NCM 106 - PHARMACOLOGY
LECTURE #3: DRUGS AFFECTING THE NERVOUS SYSTEM
BSN 2103 1ST SEMESTER AY 2023-2024
TRANSCRIBERS: Kyla Mae Arago, Angelo dela Paz, Nicole Carolai Zara, Sheira Atienza
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SOURCE: PPT and NOTES
CHECKER: Rod H. Maranan
Structure and Function of Autonomic
Synapse
TOPICS
Drugs Affecting the Autonomic Nervous
System
Drugs for Anxiety and Insomnia
Drugs for Seizures
Drugs for Emotional, Mood, and Behavioral
Disorders
Drugs for Psychoses
Drugs for the Control of Pain
Drugs for Local and General Anesthesia
Drugs for Degenerative Diseases of the
Nervous System
Drugs for Neuromuscular Disorders
Two primary neurotransmitters of the autonomic nervous
system:
1. Norepinephrine (NE)
2. Acetylcholine (Ach)
Basic structure of the autonomic pathway
NOREPINEPHRINE AND ADRENERGIC
TRANSMISSION
Overview of the Nervous System
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NE is released at almost postganglionic nerves
(except sweat glands (Ach)
Natural catecholamines: epinephrine and dopamine
All of these drugs bind to the same target tissues as
adrenalin
The receptors at the ends of postganglionic
sympathetic neurons are called adrenergic, which
comes from the word adrenalin.
Adrenergic reactions: alpha receptors (α receptors)
and beta receptors (β receptors)
ACETYLCHOLINE AND CHOLINERGI
TRANSMISSION
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Nerves releasing Ach are called cholinergic nerves.
Cholinergic receptors: Nicotinic and Muscarinic
RECEPTORS IN THE ANS
1) DRUGS AFFECTING THE AUTONOMIC
NERVOUS SYSTEM
Autonomous Nervous System
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involuntary control of the body
homeostasis
regulates the functions of internal organs such as the
heart, stomach, and also controls our smooth and
cardiac muscles, and our glands
Sympathetic and Parasympathetic Divisions
TYPES OF AUTONOMIC RECEPTORS
CLASSIFICATION AND NAMING OF
AUTONOMIC DRUGS
1. Stimulation of the sympathetic nervous system
• These drugs are called adrenergic agents or
sympathomimetics, and they produce the classic
symptoms of the fight-or-flight response. Natural or
synthetic agents that produce a sympathomimetic
response
include
the
catecholamines
and
noncatecholamines.
Example:
Sympathomimetic drugs: Phenylephrine
Sympathetic Effect: Bind to adrenergic receptors or
mimics sympathetic action in some other way.
Parasympathetic Effect: No effect
Overall result: Increase sympathetic tone
2. Inhibition of the sympathetic nervous system
• These drugs are called adrenergic-blocking
agents or adrenergic antagonists, and they
produce actions opposite those of the
sympathomimetics. The term sympatholytics is
another name for adrenergic antagonists.
Example:
Sympatholytic drugs: β-blockers such as propanolol or
metoprolol; α-agonists such as clonidine
Sympathetic Effect: Block binding to adrenergic drug or
decrease adrenergic signals
Parasympathetic Effect: No effect
Overall result: Increase parasympathetic tone
4. Inhibition of the parasympathetic nervous system
These drugs are called cholinergic-blocking agents,
anticholinergics, parasympatholytics, or muscarinic
blockers, and they produce actions opposite those of
the cholinergic drugs.
Example:
Anticholinergics/muscarinic antagonists: Atropine,
scopolamine, dimenhydrinate
Sympathetic Effect: No effect
Parasympathetic Effect: Block muscarinic receptors and
parasympathetic function
Overall result: Increase sympathetic tone
•
2) DRUGS FOR ANXIETY AND INSOMNIA
ANXIETY
The International Classification of Diseases 10th edition
defines anxiety as a feeling of "apprehension, tension or
unease brought on by the expectation of a threat whose
origin is mainly unknown or unrecognized.
TYPES OF ANXIETY DISORDERS
Situational Anxiety
Generalized
anxiety disorder
(GAD)
Panic Disorder
3. Stimulation of the parasympathetic nervous system
• These
drugs
are
called
cholinergic
or
parasympathomimetics, and they produce the
characteristic symptoms of the rest-and-digest
response.
Example:
Parasymphathomimetics/
muscarinic
agonists:
Pilocarpine
Sympathetic Effect: No effect except on sweat glands
Parasympathetic Effect: Bind to muscarinic receptor,
similar to ACh
Overall result: Increase parasympathetic tone
Phobias
Social Anxiety
Disorder
Obsessive–
Compulsive
Disorder (OCD)
the anxiety experienced by people
faced with a stressful environment.
- nawawala rin after the event
is difficult to control, it’s an
excessive anxiety that lasts 6
months or more.
second category of intense anxiety,
characterized by intense feelings of
immediate
apprehension,
fearfulness, terror, or impending
doom, accompanied by increased
autonomic nervous system activity.
- madaming iniisip
- why panic? because there’s fast
information
- hyperactivity of CNS
are fearful feelings attached to
situations or objects.
a.k.a. social phobia. Means fear of
crowds.
recurrent, intrusive thoughts or
repetitive behaviors that interfere
with
normal
activities
or
relationships.
Posttraumatic
stress disorder
(PTSD)
is a type of extreme situational
anxiety that develops in response to
reexperiencing a previous life
event.
- trauma
SPECIFIC REGIONS OF THE BRAIN RESPONSIBLE
FOR ANXIETY AND WAKEFULNESS
The limbic system is an area in the middle of the brain. It
is responsible for emotional expression, learning, and
memory. The limbic system serves as a conduit for signals
that get to the hypothalamus. Emotional states associated
in this connection are anxiety, fear, rage, aggression,
remorse, depression, sexual desire, and euphoria.
The reticular activating system (RAS) is a larger area
where reticular formation is found. The RAS is responsible
for sleeping and wakefulness and performs an alerting
function for the entire cerebral cortex. It helps a person
focus attention on individual tasks by transmitting
information to higher brain centers.
ANXIETY MANAGEMENT THROUGH
PHARMACOLOGIC AND
NONPHARMACOLOGIC STRATEGIES
Model for Stress Management
INSOMNIA AND ITS LINK TO ANXIETY
Why is sleep important?
1. Inactivity during sleep gives the body time to
repair itself.
2. Sleep is a function that evolved as a protective
mechanism. Throughout history, night-time was
the safest time of day.
3. Sleep deals with “electrical” charging and
discharging of the brain.
INSOMNIA
or sleeplessness, is a disorder sometimes associated with
anxiety. It’s a condition characterized by a patient’s inability
to fall asleep or remain asleep.
Major types of insomia:
1. Short-term or behavioral insomnia: acute,
mostly adults, lasts for days or weeks; caused by
stress
2. Long-term insomnia: for 3 or more times a week;
last for months
3. Rebound insomnia: withdrawal symptom
(pagtigil ng pagtake ng substance like cigarettes)
USE OF THE ELECTRO-ENCEPHALOGRAM
TO DIAGNOSE SLEEP DISORDERS
a tool for diagnosing sleep
Electrodisorders,
seizure
activity,
encephalogram
depression, and dementia. Four
(EEG) *one word, no dash types of brain waves— alpha,
Two distinct types of
sleep identified with an
EEG:
1. Nonrapid eye
movement
(NREM) sleep
2. Rapid eye
movement
(REM) sleep
beta, delta, and theta— are
identified
by
their
shape,
frequencies, and height on a
graph.
- heartbeat, eye movements,
brain waves, and breathing
activity begin to taper down.
Motor movements also diminish.
Stage IV NREM sleep appears to
be linked to repair and restoration
of the physical body, whereas
- eyes move around rapidly in a
range of directions, but don't send
any visual information to the
brain.
- often called paradoxical sleep
since the brain wave pattern of
this stage is similar to that when
persons are drowsy but awake.
- associated with learning,
memory, and the capacity to
adjust
to
changes
in the
environment.
Anxiolytics
drugs having the ability to relieve anxiety, are quite
effective. These include medications found within a number
of therapeutic categories. It provides treatment for these
conditions:
• phobias
• post-traumatic stress disorder
• generalized anxiety disorder
• obsessive–compulsive disorder
• panic attack
*The body requires the dream
state associated with REM sleep
to keep the psyche functioning
normally. When a person is
deprived of REM sleep, they
experience a sleep debt and
become frightened,
irritable,
paranoid, and even emotionally
disturbed.
5 STAGES OF SLEEP
STAGE 1
- very light sleep
- sleep activity slow down
STAGE 2
- breathing pattern and heart rate slows
down
- body temperature decreases slightly
STAGE 3
- deep sleep starts
- brain starts to generate slow delta
waves
- body heals itself
STAGE 4
- very deep sleep
- muscle activity is limited
STAGE 5
- rem sleep
- brain waves speed up and dreams
occur
- heart rate increases
Stage 1-4: NREM
Stage 5: REM (frightened, paranoid, etc.)
SSRIs. Safer than other classes of antidepressants; less
common sympathomimetic effects (increased heart rate
and hypertension) and fewer anticholinergic effects; SSRIs
can cause weight gain and sexual dysfunction;
an overdose of this medication can cause confusion,
anxiety, restlessness, hypertension, tremors, sweating,
fever, and lack of muscle coordination.
Atypical antidepressants like serotonin–norepinephrine
reuptake inhibitors (SNRIs). Adverse effects include
abnormal dreams, sweating, constipation, dry mouth, loss
of appetite, weight loss, tremor, abnormal vision,
headaches, nausea and vomiting, dizziness, and loss of
sexual
MAOIs
- Patients must strictly avoid foods containing tyramine, a
form of the amino acid tyrosine, to avoid a hypertensive
crisis and should refrain from caffeine intake; MAOIs
potentiate the effects of insulin and other diabetic drugs;
common adverse effects include orthostatic hypotension,
headache, and diarrhea; rarely used because of the
potential for serious adverse effects.
TREATING ANXIETY AND INSOMNIA WITH
CNS DRUGS
1. Sedatives:
2. Sedative–
hypnotic:
Medications that depress the CNS,
they have the ability to sedate or relax
a patient. At higher doses, some of
these drugs are called hypnotics
since they can induce sleep.
A term used to describe a drug with
the ability to produce a calming effect
at lower doses and the ability to
induce sleep at higher doses.
3. Tranquilizer:
Older term; describes a drug that
produces a calm or tranquil feeling.
4.
Antidepressants:
used mainly to treat depression or
depression
that
accompanied
anxiety.
*need prescription
Many CNS depressants can cause
physical
and
psychological
dependence.
The
withdrawal
syndrome for some CNS depressants
can cause life-threatening neurologic
reactions.
ANTIDEPRESSANTS FOR SYMPTOMS OF
PANIC AND ANXIETY
TCAs
- Not recommended in patients with a history of heart
attack, heart block, or arrhythmia; patients of ten have
annoying anticholinergic effects such as dry mouth, blurred
vision, urine retention, and hypertension.
- patients with asthma, GI disorders, alcoholism,
schizophrenia, or bipolar disorder should take TCAs with
extreme caution.
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Steven Johnson Syndrome – maselan and skin; may
develop rashes, blisters, etc.
Adverse effects are more on GI factors.
TREATING ANXIETY AND INSOMNIA WITH
BENZODIAZEPINES
Benzodiazepines
- The benzodiazepines are one of the most widely
prescribed drug classes.
- preferred drugs for various anxiety disorders and for
insomnia.
- about 15 benzodiazepines are available, and all have the
same actions and adverse effects and differ primarily in
their onset and duration of action.
• do not produce life-threatening respiratory
depression or coma if taken in excessive
amounts. Death is unlikely, unless the
benzodiazepines are taken in large quantities in
combination with other CNS depressants, or if the
patient suffers from sleep apnea.
3) DRUGS FOR SEIZURES
SEIZURES
a disturbance of electrical activity in the brain that may
affect consciousness, motor activity, and sensation. As a
valuable tool in measuring uncontrolled neuronal activity,
the electroencephalogram (EEG) is useful in diagnosing
seizure disorders.
- nagambala ang neurons
- biglaan/hindi mapigilang electrical charges
USE OF BARBITURATES AS SEDATIVES
Barbiturates
Barbiturates are drugs derived from barbituric
acid. They are powerful CNS depressants prescribed for
their sedative, hypnotic, and antiseizure effects that have
been used in pharmacotherapy since the early 1900s.
Barbiturates are capable of depressing CNS
function at all levels.
SEIZURE AND CONVULSION
OTHER CNS DEPRESSANTS FOR ANXIETY
AND SLEEP DISORDERS
The final group of CNS depressants used for anxiety and
sleep disorders consists of miscellaneous agents that are
chemically unrelated to either benzodiazepines or
barbiturates.
Other drugs used mainly for treatment of social anxiety
symptoms include:
• valproate (Depakote)
• propranolol (Inderal)
• atenolol (Tenormin)
Other drugs used mainly for insomnia therapy include:
• zaleplon (Sonata)
• eszopiclone (Lunesta)
• zolpidem (Ambien)
Commonly prescribed for their anxiolytic effects:
• Buspirone (BuSpar)
• zolpidem (Ambien)
Used primarily for their hypnotic effects:
• Zolpidem (Ambien)
• ramelteon (Rozerem)
• eszopiclone (Lunesta)
When many neurons fire out Convulsions specifically
of
sequence refer to involuntary, violent
simultaneously,
this spasms of the large skeletal
produces a disorganized muscles of the face, neck,
electrical discharge that can arms, and legs.
short-circuit your brain
activity. This discharge
spreads through a part of
your brain and a seizure * involuntary movement of
results.
the body
• The terms seizure and convulsion are not
synonymous.
• Thus, it may be stated that all convulsions are
seizures, but not all seizures are convulsions.
CAUSES OF SEIZURES
Infectious
diseases
Trauma
Metabolic
disorders
Vascular
diseases
Pediatric
disorders
Acute infections such as meningitis and
encephalitis can cause inflammation in
the brain.
Physical trauma such as direct blows
to the skull may increase intracranial
pressure; chemical trauma such as
the presence of toxic substances or the
ingestion of poisons may cause brain
injury.
Changes in fluid and electrolytes such
as hypoglycemia, hyponatremia, and
water intoxication may cause seizures
by
altering
electrical
impulse
transmission at the cellular level.
Changes in oxygenation such as those
caused by respiratory hypoxia and
carbon monoxide poisoning, and
changes in perfusion such as those
caused by hypotension, cerebral
vascular accidents, shock, and cardiac
dysrhythmias may be causes.
Rapid increase in body temperature
may result in a febrile seizure.
Neoplastic
disease
Tumors, especially rapidly growing
ones, may occupy space, increase
intracranial pressure, and damage
brain tissue by disrupting blood flow.
DRUGS THAT POTENTIATE GABA ACTION
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TYPES OF SEIZURES
The differing presentation of seizures relates to their signs
and symptoms. Determining the cause of recurrent
seizures is important for planning appropriate drug
selection and treatment options. Proper diagnosis,
therefore, is essential. Epilepsies are typically identified
using the International Classification of Epileptic
Seizures nomenclature as:
Partial (focal) – only specific part of the brain are affective
Generalized – 2 electric discharged
Special epileptic syndromes -
GENERAL CONCEPTS OF ANTI SEIZURE
PHARMACOTHERAPHY
The choice of drug for anti seizure pharmacotherapy
depends on signs presented by the patient, the patient’s
previous medical history, and associated pathologies.
Seizures are likely to occur if antiseizure drugs are
abruptly withdrawn, the medication is usually
discontinued over a period of 6 to 12 weeks. The newer
antiseizure drugs offer advantages over the traditional
drugs, because they exhibit fewer troublesome side
effects. Some antiseizure drug combinations may actually
increase the incidence of seizures due to unfavorable drug
interactions.
Several important antiseizure drugs act by changing
the action of gamma-aminobutyric acid (GABA), the
primary inhibitory neurotransmitter in the brain.
Newer drugs are agents that inhibit GABA-degrading
enzymes. Barbiturates, benzodiazepines, and
several newer drugs reduce seizure activity by
intensifying GABA action.
TREATING SEIZURES WITH
BARBITURATES
Barbiturates are organic compounds derived from
barbituric acid. These drugs intensify the effect of GABA in
the brain and generally depress the firing of CNS neurons.
Overall barbiturates are effective against all major seizure
types except absence seizures.
PHENOBARBITAL
The antiseizures properties of
phenobarbital were discovered
in 1912. Phenobarbital is able to
suppress abnormal neuronal
discharges without causing
sedation.
Phenobarbital
is
sometimes a preferred drug for
the
pharmacotherapy
of
neonatal seizures.
MEPHOBARBITAL
It is occasionally used for
(Mebaral)
epilepsy
treatment.
Mephobarbital is converted to
phenobarbital in the liver and
offers no significant advantages
over phenobarbital.
TREATING SEIZURES WITH
BENZODIAZEPINES
Benzodiazepines
Like barbiturates, benzodiazepines intensify the effect of
GABA in the brain. The benzodiazepines bind directly to
the GABA receptor, suppressing abnormal neuronal
foci. Benzodiazepines used in treating epilepsy include
clonazepam (Klonopin), clorazepate (Tranxene),
lorazepam (Ativan), and diazepam (Valium). Indications
include absence seizures and myoclonic seizures.
Tolerance may begin to develop after only a few months of
therapy with benzodiazepines, seizures may recur unless
the dose is periodically adjusted.
Valium
– taken with empty stomach
- it should be exact amount; spoon is not applicable
because they are different in sized
- use a cup or spoon with right measurement
MECHANISMS OF ACTION OF ANTI
SEIZURES DRUGS
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Antiseizure pharmacotherapy is directed at
controlling the movement of electrolytes across
neuronal membranes or affecting neurotransmitter
balance. The goal of antiseizure pharmacotherapy is
to suppress neuronal activity just enough to prevent
abnormal or repetitive firing.
* goal is suppress/reduce the electro discharge
3 GENERAL MECHANISMS by which antiseizure drugs
act:
• Stimulating an influx of chloride ions, an effect
associated with the neurotransmitter gammaaminobutyric acid (GABA).
• Delaying an influx of sodium.
• Delaying an influx of calcium.
These drugs are generally not used alone in seizure
pharmacotherapy, but instead serve as adjuncts to other
antiseizure drugs for short-term seizure control. The
benzodiazepines are one of the most widely prescribed
classes of drugs, used not only to control seizures but
also for anxiety, skeletal muscle spasms, and alcohol
withdrawal symptoms.
TREATING SEIZURES WITH HYDANTOINS
AND RELATED DRUGS
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Several drugs dampen CNS activity by delaying an
influx of sodium ions across neuronal membranes.
Hydantoins and related antiseizure drugs act by
this mechanism.
Sodium ion movement is the major factor that
determines whether a neuron will undergo an action
potential. If these channels are temporarily
inactivated, neuronal activity will be suppressed.
With hydantoin and phenytoin-like drugs, sodium
channels are not blocked; they are just
desensitized.
The oldest and most commonly prescribed antiseizure medication is phenytoin (Dilantin). Approved
in the 1930s, phenytoin is a broad-spectrum hydantoin
drug, useful in treating all types of epilepsy except
absence seizures. Phenytoin and fosphenytoin are
first-line drugs in the treatment of status epilepticus.
DRUGS THAT SHARE A MECHANISM OF
ACTION SIMILAR TO THAT OF THE
HYDANTOIN
Carbamazepine
produces
Carbamazepine
Oxcarbazepine
Valproic Acid
Depakene/Depakote
Lamotrigine
(Lamictal)
Levetiracetam
(Keppra)
zonisamide
(Zonegran)
and
fewer adverse effects than
other phenytoin-related drugs
or phenobarbital, it is a
preferred drug for tonic
clonic and partial seizures.
Oxcarbazepine is slightly
better
tolerated
than
carbamazepine
although
serious skin and organ
hypersensitivity
reactions
have been noted.
Valproic acid is a preferred
drug for absence and
myoclonic seizures and is
used in combination with
other drugs for partial
seizures.
Depakene/Depakote
are
used for generalized tonic–
clonic, myoclonic, partial,
and absence seizures.
These can be taken as
monotherapy
or
in
combination
with
other
antiseizure drugs.
It has become a first-line drug
for adjunctive control of
partial, absence, and tonicclonic seizures and is also
FDA approved for bipolar
disorder.
They are approved for
adjunctive therapy of partial
seizures in adults.
SUCCINIMIDES
-medications that suppress seizures by delaying calcium
influx into neurons. They are generally only effective
against absence seizures. Without calcium influx,
neuronal transmission would not be possible. Succinimides
delay entry of calcium into neurons by blocking lowthreshold calcium channels, increasing the electrical
threshold of the neuron, and reducing the likelihood that an
action potential will be generated. By raising the seizure
threshold, succinimides keep neurons from firing too
quickly, thus suppressing abnormal foci.
ETHOSUXIMIDE
Ethosuximide (Zarontin) is the most commonly
prescribed drug in this class. It remains a preferred
choice for absence seizures.
TREATING SEIZURES WITH AMINO ACID
COMPOUNDS
Some amino acid compounds reduce brain excitability by
suppressing positive ion influxes in a manner differently
from the other seizure medications. For infants with
epilepsy, administration of natural amino acids (e.g.,
taurine) has supported mental and speech development,
which often suffers because of repeated seizures.
DRUGS IN AMINO ACID COMPOUND
Acetazolamide
(Diamox)
and
lacosamide
(Vimpat) are two drugs with properties useful in the
treatment of a range of conditions and seizures.
Acetazolamide
Acetazolamide is a carbonic hydrase
inhibitor approved for the symptomatic
relief of glaucoma, for altitude sickness,
and for a range of conditions including
nausea, dizziness, drowsiness, and
fatigue. Its main nervous system
application is the treatment of absence
and myoclonic seizures.
Lacosamide
Lacosamide is used in combination
with other drugs to treat adult patients
with partial-onset seizures. Drawbacks
to amino acid therapy are potential
allergic
reactions,
drowsiness,
dizziness, irregular heartbeat, and
problems with coordination.
TREATING DEPRESSION WITH TRICYCLIC
ANTIDEPRESSANTS
• TCAs act by inhibiting the presynaptic reuptake of
4) DRUGS FOR EMOTIONAL, MOOD, AND
BEHAVIORAL DISORDERS
Two Major Categories of Mood disorder
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Depression
Bipolar disorder
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DEPRESSION
Side Effects
• TCAs produced fewer side effects and were less
Characteristics
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Major Depressive Disorder or Clinical Depression
Feelings of despair, guilt, and misery; lack of selfworth.
Obsessed with death (expressing a wish to die or
to commit suicide)
Avoiding
psychosocial
and
interpersonal
interactions.
Lack of interest in personal appearance or sex.
Delusions or hallucinations
Difficulty sleeping or sleeping too much.
Extremely tired; without energy.
Abnormal eating patterns (eating too much or not
enough)
Vague physical symptoms (gastrointestinal [GI]
pain, joint/muscle pain, or headache).
Inability to concentrate or make decisions.
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Situational Depression
Dysthymic Disorder
Postpartum Depression
Seasonal Affective Disorder (SAD)
Psychotic Depression
ASSESSMENT AND TREATMENT OF
DEPRESSION
Assessment
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Treatment
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Counseling therapies and behavioral
therapies
Interpersonal and cognitive-behavioral
therapies
Psychodynamic therapies
Electroconvulsive therapy (ECT)
Repetitive transcranial magnetic stimulation
(RTMS)
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Depression - imbalance of neurotransmitters in regions of
the brain
• MONOAMINE OXIDASE (MAO) ENZYMES
• TRICYCLIC ANTIDEPRESSANTS
ATYPICAL ANTIDEPRESSANTS
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MECHANISM OF ACTION
•
slowing the reuptake of
norepinephrine
blocking
the
enzymatic
norepinephrine
serotonin
breakdown
and
of
a natural neurotransmitter in the CNS, found in high
concentrations within neurons of the hypothalamus,
limbic system, medulla, and spinal cord.
important to several body functions, including cycling
between non rapid eye movement (NREM) and rapid
eye movement (REM) sleep, pain perception, and
emotional states.
Lack of adequate serotonin in the CNS can lead to
depression.
5-hydroxytryptamine (5-HT)
Take Note!
•
Increased levels of serotonin in the synaptic gap
induce complex neurotransmitter changes in
presynaptic and postsynaptic neurons. Presynaptic
receptors become less sensitive, and postsynaptic
receptors become more sensitive
ANTIDEPRESSANTS
•
amitriptyline (Elavil)
amoxapine (Asendin)
clomipramine (Anafranil)
desipramine (Norpramin)
doxepin (Silenor)
imipramine (Tofranil)
maprotiline (Ludiomil)
nortriptyline (Aventyl, Pamelor)
protriptyline (Vivactil)
trimipramine (Surmontil)
Serotonin
Complete Health Examination
•
dangerous than MAO inhibitors
orthostatic hypotension
most serious adverse effect occurs when TCAs
accumulate in cardiac tissue is cardiac
dysrhythmias
Sedation
Anticholinergic effects, such as dry mouth,
constipation,
urinary
retention,
excessive
perspiration, blurred vision, and tachycardia, are
common.
TRICYCLIC ANTIDEPRESSANTS
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Forms
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both norepinephrine and serotonin
Clomipramine (Anafranil) is approved for
treatment of obsessive–compulsive disorder
doxepin (Sinequan) for generalized anxiety
disorders.
The atypical antidepressants do not neatly fit into the
other antidepressant medication classes when it
comes to classification. In this instance, "atypical"
actually refers to the distinctive chemical structures
that are represented in the group.
Treating Depression with Atypical Depressants
- They are each unique medications that work in
different ways from one another.
•
duloxetine (Cymbalta)
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TYRAMINE
Venlafaxine (Effexor)
Bupropion (Wellbutrin)
Mirtazapine (Remeron)
Nefazodone (Serzone)
Trazodone (Desyrel, Oleptro)
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TREATING DEPRESSION WITH MAO
INHIBITORS
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limit the breakdown of norepinephrine, dopamine,
and serotonin in the CNS.
these drugs are reserved for patients who have
not responded to TCAs or SSRIs
The action of norepinephrine at adrenergic
synapses is terminated through two means:
(1) reuptake into the presynaptic nerve
(2) enzymatic destruction by the enzyme MAO.
By decreasing the effectiveness of the enzyme
MAO, the MAOIs limit the breakdown of
norepinephrine,dopamine, and serotonin in the
CNS.
This
creates
higher
levels
of
these
neurotransmitters in the brain to facilitate
neurotransmission and alleviate the symptoms of
depression.
MAOIs are now reserved for patients who are not
responsive to other antidepressant classes.
CRISIS
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MAOI + SSRI = serotonin syndrome
MAOI + antihypertensives = severe hypotension
MAOI + insulin and oral antidiabetic drugs =
hypoglycemic effectsn
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Avocados
Bananas
Raisins
Papaya products
Canned figs
Cheese (cottage
cheese is okay)
Sour cream
Yogurt
Beer
Wines
Beef/ chicken liver
•
•
MAOI + Tyramine (mechanism of action)
•
•
•
The group of drugs called monoamine oxidase
inhibitors (MAOIs) inhibits monoamine oxidase.
tyramine enters the bloodstream in high
concentrations
result is a sudden release of norepinephrine,
causing acute hypertension.
Symptoms (minutes occur)
•
occipital headache, stiff neck,
palpitations, diaphoresis, and nausea.
flushing,
Consequences:
•
Myocardial infarctions (heart attack) and cerebral
vascular accidents (brain attack)
ANTIDOTE: Calcium Channel Blockers
•
•
•
excessive or abnormal sweating for no
apparent reason.
Brain attack
•
interruption in the flow of blood to cells in the brain.
•
once known as manic depression
characterized by episodes of depression
alternating with episodes of mania.
likely results from abnormal functioning of
neurotransmitters or
a mental illness that causes unusual shifts in a
person's mood, energy, activity levels, and
concentration. receptors in the brain.
BIPOLAR DISORDER
•
•
TREATING DEPRESSION WITH SRIS
amitriptyline (Elavil)
amoxapine (Asendin)
clomipramine (Anafranil)
desipramine (Norpramin)
doxepin (Silenor)
imipramine (Tofranil)
maprotiline (Ludiomil)
nortriptyline (Aventyl, Pamelor)
protriptyline (Vivactil)
trimipramine (Surmontil)
MAOI + foods containing tyramine (amino acid
tyrosine)
MAOI + meperidine (Demerol), dextromethorphan
(Pedia Care and others), and TCAs =
Hyperpyrexia (elevation of body temperature)
•
•
•
•
•
Paté
Meat extracts
Pickled or kippered
herring
Pepperoni
Salami
Sausage
Bologna/hot dogs
Pods of broad beans
(fava beans)
Soy Sauce
Chocolate
All yeast or yeast
extracts
Diaphoresis
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Characteristics
Depressive Stage
•
patients exhibit the symptoms of major depression
•
a condition in which you have a period of
abnormally elevated, extreme changes in your
mood or emotions, energy level or activity level.
•
emotional state; high psychomotor activity and
irritability.
•
•
•
•
•
•
Inflated self-esteem (grandiosity)
Decreased need for sleep
Increased talkativeness
Flight of ideas
Distractibility
Increased goal-directed activity or psychomotor
agitation.
Excessive involvement in pleasurable activities;
high potential for painful consequence
Mania
Display signs of mania
Signs of Mania
•
Flight of Ideas
•
•
Immediate transition of ideas from one to another
Characterized by a sudden shift or fast shifting of
ideas
DRUGS FOR BIPOLAR
•
Mood Stabilizers
•
have the ability to moderate extreme shifts in
emotions between mania and depression
✓
✓
Anti-seizure drugs
Atypical antipsychotic drugs
•
•
•
Lithium (Eskalith)
•
•
Traditional Treatment as monotherapy or in
combination with other drugs.
Effective for purely manic or purely depressive
episodes
•
•
Effective for purely depressive episodes
May be even more effective than lithium.
•
Helpful for patients with chronic depression and
have not received effective treatment with the
other mood stabilizers.
Lamotrigine (Lamictal)
Lamotrigine
Antiseizure agents:
•
•
•
•
•
•
gabapentin (Neurontin)
oxcarbazepine (Trileptal)
topiramate (Topamax)
zonisamide (Zonegran)
valproic acid (Depakene, Depakote)
carbamazepine (Tegretol
Agranulocytosis
•
a deficiency of granulocytes in the blood, causing
increased vulnerability to infection.
they may not be able to interact with others
appropriately at home, school, or on the
playground.
Boys are usually more overt when it comes to
activity.
Girls show less aggression and impulsiveness
but more anxiety, mood swings, social
withdrawal, and cognitive and language delays.
Girls tend to be older at the time of diagnosis.
Symptoms of ADHD
•
•
•
•
•
•
•
•
•
•
Easy distractibility.
Failure to receive or follow instructions properly.
Inability to focus on one task at a time and jumping
from one activity to another.
Difficulty remembering.
Frequent loss or misplacement of personal items.
Excessive talking and interrupting other children
in a group.
Inability to sit still when asked to do so repeatedly.
Impulsiveness.
Sleep disturbance.
Pharmacotherapy of ADHD
Drugs prescribed for ADHD;
•
include d- and l-amphetamine racemic mixture
(Adderall)
•
dexmethylphenidate (Focalin)
•
dextroamphetamine (Dexedrine)
•
lisdexamfetamine (Vyvanse)
•
methamphetamine (Desoxyn)
•
methylphenidate (Ritalin)
•
•
Management of Symptoms
Family support
Psychological support
Atypical antipsychotics
- high risk in agranulocytosis
Example: Clozapine (Clozaril)
Less risk for agranulocytosis
•
•
•
•
aripiprazole (Abilify)
A (Zyprexa)
quetiapine (Seroquel)
risperidone (Risperdal)
ATTENTION- DEFICIT/HYPERACTIVITY
DISORDER
•
•
A condition characterized by poor attention span,
behavior control issues, and/or hyperactivity.
The etiology of ADHD is not clear. For many
years, scientists described this disorder as mental
brain dysfunction and hyperkinetic syndrome,
focusing on abnormal brain function and
overactivity.
Characteristics of ADHD
•
•
•
ADHD is neither an emotional disorder nor a mood
disorder.
ADHD is characterized by developmentally
inappropriate behaviors involving difficulty in
paying attention or focusing on tasks. ADHD may
be diagnosed when the child’s hyperactive
behaviors significantly interfere with normal play,
sleep, or learning activities
Hyperactive children usually have increased
motor activity.
CNS STIMULANTS
•
Adverse reaction to the ADHD patient
includeinsomnia, nervousness, anorexia, and
weight loss.
• Occasionally, a patient may experience dizziness,
depression, irritability, nausea, or abdominal pain.
NON CNS STIMULANTS
•
exhibit less efficacy, but generally these drugs
are more effective as adjunctive therapy
CNS STIMULANTS DRUGS
• d- and l-amphetamine racemic mixture
•
(Adderall, Adderall-XR)
• dexmethylphenidate (Focalin)
• dextroamphetamine (Dexedrine)
• lisdexamfetamine (Vyvanse)
• methamphetamine (Desoxyn)
• methylphenidate (Ritalin,
• Concerta, Daytrana, Metadate, Methylin)
•
•
•
•
•
•
•
•
•
•
•
ADVERSE EFFECTS
Irritability
nervousness
restlessness
insomnia,
euphoria
palpitations
Sudden death (reported in children with
structural cardiac abnormalities)
circulatory collapse,
exfoliative dermatitis
anorexia
liver failure
NON STIMULANTS DRUGS
•
•
•
tomoxetine (Strattera)
clonidine (Kapvay)
guanfacine (Intuniv)
•
•
•
•
•
•
Headache
insomnia
upper abdominal pain
vomiting
decreased appetite
Severe liver injury (rare)
•
Catatonic
ayaw ng maraming nakakalat, hindi pwedeng
maglagay ng any kalat or basura
ADVERSE EFFECTS
CAUSE
5) DRUGS FOR PSYCHOSES
THE NATURE OF PSYCHOSES
PSYCHOSES
•
It refers to a collection of symptoms that affect the
mind, where there has been some loss of contact
with reality (NIMH).
delusions
hallucinations
illusions
disorganized behavior
social withdrawal
paranoia
•
•
•
•
•
•
The exact cause of schizophrenia is unknown, but there are
a few leading theories.
• genetic factors
• imbalances in brain chemicals
Can schizophrenia go back?
•
Yes, once the patient is not adhering to the
medication administered to them
•
Pag naranasan ang similar scenario before
How to determine if psychotic patients can be
discharged?
•
Pag nagagawa na ang ADL
•
Pag nakakausap na
Classifications
Characteristics
duration of
symptoms
Onset
Acute
Less than one
month
Sudden
one month or
longer
one month or
longer
Chronic
One month or
longer
Gradual or
sudden
one month or
longer
PSYCHOSES
•
It can be a symptom of a number of different
mental health conditions. The most common is
schizophrenia.
•
It is the most common psychotic disorder that
affects how a person thinks, feels, and behaves.
SCHIZOPHRENIA
SYMPTOMS
•
•
•
overstimulation of dopamine receptors may be
responsible for schizophrenia
“schizoaffective disorder”
•
Mechanism of action of antipsychotic drugs
When schizophrenia is active, symptoms can
include delusions, hallucinations, disorganized
speech, trouble with thinking, and lack of
motivation.
What symptoms should the nurse look for when
observing a patient with schizophrenia?
Positive
Negative
•
symptoms that
add on to normal
behavior
abnormally
present
•
symptoms that
subtract
from
normal behavior
abnormally
absent
TYPES OF SCHIZOPHRENIA
•
•
•
Paranoia
Overthinker
bawal mag-bulungan sa harap
Disorganized
mga taong grasa
PHARMACOLOGIC MANAGEMENT OF
PSYCHOSES
PHENOTHIAZINES
•
Each phenothiazine has a slightly different sideeffect spectrum and some have a broader
spectrum of application than just psychoses.
EXTRAPYRAMIDAL SIDE EFFECTS
•
•
Mechanism of action of antipsychotic drugs
TREATING PSYCHOSES WITH
PHENOTHIAZINES
1. Conventional Antipsychotic Drugs
•
•
•
first generation
typical antipsychotics
includes phenothiazine and phenothiazine-like
drugs
PHENOTHIAZINES - most effective at treating positive
signs of schizophrenia
A particularly serious set of adverse reactions to
antipsychotic drugs. EPS include acute dystonia,
akathisia, parkinsonism, and tardive dyskinesia.
Examples:
• acute dystonias
• akathisia
• parkinsonism
• tardive dyskinesia
TARDIVE DYSKINESIA
•
one obvious symptom of catatonic (hindi ganon
ka-violent), you cannot establish conversation
with them
•
their movements are disorganized
TREATING PSYCHOSES WITH NONPHENOTHIAZINES
Conventional Antipsychotic Drugs
NONPHENOTHIAZINES
• It causes less sedation and fewer anticholinergic
adverse effects than chlorpromazine, but exhibit
an equal or even greater incidence of
extrapyramidal signs.
TREATING PSYCHOSES WITH ATYPICAL
ANTIPSYCHOTICS
ATYPICAL ANTIPSYCHOTIC DRUGS
•
•
•
•
second generation
broader spectrum of action
control both negative and positive symptoms
clozapine (Clozaril) is the first atypical
antipsychotic drug
NEUROPATHIC PAIN
This type of pain results from injury to the nerves and is
typically described by patients as burning, shooting, or
numb pain.
NONPHARMACOLOGIC TECHNIQUES FOR PAIN
MANAGEMENT
ATYPICAL ANTIPSYCHOTIC DRUGS
They block different receptors and at therapeutic doses,
they exhibit their antipsychotic actions without producing
the EPS effects of the conventional drugs.
•
•
•
•
•
•
•
weight gain
diabetes
stroke
menstrual irregularities
reduced libido
osteoporosis
impotence
●
●
●
●
●
●
●
●
●
●
●
●
●
Acupuncture
Biofeedback therapy
Massage
Heat or cold packs
Meditation or prayer
Relaxation therapy
Art or music therapy
Imagery
Chiropractic manipulation
Hypnosis
Physical Therapy
Therapeutic or physical touch
Transcutaneous electrical nerve stimulation (TENS)
THE NEURAL MECHANISMS OF PAIN
TREATING PSYCHOSES WITH DOPAMINE
SYSTEM STABILIZERS
DOPAMINE SYSTEM STABILIZERS
•
•
third generation
dopamine partial agonists
ARIPIPRAZOLE
•
•
•
a lower incidence of extrapyramidal symptoms
and fewer weight-gain issues
virtually non-existent anticholinergic adverse
effect
low incidence of adverse effect
6) DRUGS FOR PAIN
PAIN
•
•
an experience characterized by unpleasant feelings,
usually associated with trauma or diseases.
Anxiety, fatigue, and depression can increase the
perception of pain. Positive attitude and support from
caregivers may reduce the perception of pain
PAIN MAY BE CLASSIFIED AS:
ACUTE PAIN
an intense pain occurring over a brief period, usually from
injury to recovery.
CHRONIC PAIN
persists over a longer time. Six months is considered the
standard. It interferes continuously with daily activities.
NOCICEPTIVE PAIN
This type of pain is injury to tissue. It can be described as
somatic pain (sharp, localized sensations) or visceral pain
(dull, throbbing, or aching sensation
CLASSIFICATION OF OPIOIDS
ANALGESICS
it is a natural or synthetic morphine like substance
responsible for reducing moderate to severe pain.
OPIOIDS AGONISTS
bind to opioid receptors and produce multiple responses
throughout the body.
TREATMENT FOR OPIOID DEPENDENCE
1
One method of treating opioid dependence has been
to switch the patient from IV and inhalation forms of
illegal drugs to methadone (Dolophine)
2
A newer treatment option is to administer
buprenorphine (Buprenex, Butrans, Suboxone), a
mixed opioid agonist–antagonist, by the sublingual or
transdermal route
3
Buprenorphine is used early in opioid abuse therapy to
prevent opioid withdrawal symptoms. Suboxone
contains both buprenorphine and naloxone and is
used later in the maintenance of opioid addiction.
NOTE:
●
Opioids are narcotic substances
Did you know?
●
●
●
Opioids can cause sedation, which may be either
therapeutic or determine a side effect, depending on
the patient’s disease state.
All opioids have the potential to cause physical and
psychological dependence.
One method available is patient-controlled analgesia
(PCA). During PCA, patients are allowed to selfmedicate with opiate medication by pressing a
button. Safe levels of scheduled pain medication are
delivered with an infusion pump.
NONOPIOID ANALGESICS
OPIOIDS ANTAGONISTS
●
are blockers of opioid activity. They are often used to
reverse the symptoms of opioid addiction, toxicity, and
overdose.
Symptoms
●
●
Sedation
Respiratory distress
●
Any opioid may be abused for its psychoactive effects;
however, morphine, meperidine, oxycodone and heroin
are preferred because of their potency. Although heroin
is currently available as a legal analgesic in many
countries, it is deemed too dangerous, and also its a
major drug abuse.
OPIOIDS WITH MIXED AGONIST- ANTAGONIST
Activity
NONSTEROIDAL ANTI-INFLAMMATORY
- Narcotic opioids that have mixed agonist–antagonist activity
stimulate the opioid receptor; thus, they cause analgesia.
●
Symptoms
●
- the withdrawal symptoms or adverse effects are not as
intense due to partial activity of receptor subtypes.
act by inhibiting pain mediators at the nociceptor level.
When tissue is damaged, chemical mediators
are released locally, including histamine, potassium ion,
hydrogen ion, bradykinin, and prostaglandins
PHARMACOTHERAPY WITH NSAIDS
●
●
●
act by inhibiting pain mediators at the nociceptor
level. When tissue is damaged, chemical mediators
are released locally, including histamine, potassium ion,
hydrogen ion, bradykinin, and prostaglandins
DRUGS ASSOCIATED WITH NSAIDS
1
2
3
•
•
Aspirin
Ibuprofen
COX-2 Inhibitors
Aspirin and Ibuprofen are available OTC and are
inexpensive. They are safe and well tolerated by most
patients when used at low to moderate doses.
COX-2 enzyme is more specific for the synthesis of
inflammatory prostaglandins, the selective COX-2
inhibitors provide more specific and peripheral pain
relief
CLASSIFICATION OF HEADACHES
Tension Headache
● most common type of headache
● occurs when muscles of the head and neck become
very tight because of stress, causing a steady and
lingering pain.
● can usually be effectively treated with OTC
analgesics such as aspirin, ibuprofen or
acetaminophen
Migraine
● most painful type of headache
● characterized by throbbing or pulsating pain, and
sometimes preceded by an aura. Most migraines are
accompanied by nausea and vomiting.
NOTE
●
●
Auras are sensory cues to let the patient know that
a migraine attack is coming soon.
Headaches - most common complaint by patients
NONOPIOID FOR TREATMENT OF TENSION
HEADACHES
1
2
3
4
5
Ascomp (aspirin)
Fioricet (acetaminophen)
Phrenilin (acetaminophen)
Phrenilin Forte (acetaminophen)
Ibuprofen
DRUG THERAPY FOR MIGRAINE HEADACHES
7) DRUGS FOR LOCAL AND GENERAL
ANESTHESIA
Anesthesia
A medical procedure performed by administering drugs that
cause loss of sensation.
occurs when sensation is lost to a limited
Local
anesthesia part of the body without loss of
consciousness.
requires different classes of drugs that
General
anesthesia cause loss of sensation to the entire body,
usually resulting in loss of consciousness.
Mechanism of action
The concentration of sodium ions usually is higher on the
outside of neurons than on the inside. - During a medical
or surgical procedure, it is essential that the action of the
anesthetic last long enough to complete the procedure.
Sodium hydroxide is sometimes added to anesthetic
solutions to increase the effectiveness of the anesthetic
in regions that have extensive local infections or
abscesses. Bacteria tend to acidify an infected site, and
local anesthetics are less effective in this type of
environment. Adding alkaline substances such as sodium
hydroxide or sodium bicarbonate neutralizes the region and
creates a more favorable environment for the anesthetic.
ADDITIONAL INFORMATION
Local anesthetic treatments are more accurately called
surface anesthesia or regional anesthesia, depending
on how the drugs are administered and their resulting
effects.
The method employed is dependent on the location and
extent of the desired anesthesia. For example, some
local anesthetics are applied topically before a needlestick
or for minor skin surgery. Others are used to block
sensations to large areas such as a limb or the lower
abdomen.
Local anesthetics
Local anesthetics are drugs that produce a rapid loss of
sensation to a limited part of the body. They produce their
therapeutic effect by blocking the entry of sodium ions
into neurons.
Methods of local anesthetic administration
Epidural
anesthesia
•
Infiltration
(field
block)
anesthesia
•
Nerve
block
anesthesia
•
Spinal
anesthesia
•
Topical
(surface)
anesthesia
•
•
•
•
•
Injection into the epidural space of the
spinal cord.
•
Most commonly used in obstetrics
during labor and delivery.
Direct injection into tissue immediate
to the surgical site.
Drug diffuses into tissue to block a
specific group of nerves in a small area
close to the surgical site.
Direct injection into tissue that may be
distant from the operation site.
Drug affects nerve bundles serving the
surgical area; used to block sensation
in a limb or large area of the face.
Injection into the cerebral spinal fluid
(CSF).
Drug affects a large, regional area
such as the lower abdomen and legs.
Creams, sprays, suppositories, drops,
and lozenges.
Applied to mucous membranes
including the eyes, lips, gums, nasal
membranes, and throat; very safe
unless absorbed.
Classification for local anesthetics
AMIDES
•
•
•
Amides have largely replaced the esters because they
produce fewer side effects and generally have a longer
duration of action. Lidocaine (Xylocaine) is the most
widely used amide for short surgical procedures
requiring local anesthesia.
Drug:
articaine (Septocaine, Zorcaine)
bupivacaine(Marcaine,Sensorcaine)
dibucaine (Nupercainal)
lidocaine (Anestacon, Dilocaine, Xylocaine,
others)
mepivacaine (Carbocaine, Isocaine, Polocaine)
prilocaine
ropivacaine (Naropin)
General adverses effects:
Burning, stinging and redness at topical
application sites.
Difficulty breathing or swallowing, respiratory
depression and arrest, convulsions,
anaphylactoid reaction, burning, contact
dermatitis.
ESTERS
•
Cocaine was the first local anesthetic widely used for
medical procedures. Cocaine is a natural ester, found
in the leaves of the plant Erythroxylon coca, native to
the Andes Mountains of Peru. As late as the 1880s,
cocaine was routinely used for eye surgery, nerve
blocks, and spinal anesthesia. Although still available
for local anesthesia.
•
•
Drug:
benzocaine (Americaine, Anbesol, Solarcaine,
others)
chloroprocaine (Nesacaine)
procaine (Novocain)
proparacaine (Alcaine, Ophthetic) tetracaine
(Pontocaine
General adverses effects:
CNS depression and burning, stinging and
redness at topical application sites.
Respiratory
arrest,
anaphylactoid reaction.
circulatory
failure,
General anesthesia
loss of sensation throughout the
accompanied by loss of consciousness
entire
body,
magbasa ka nang
maayos jan…
TWO PRIMARY METHODS OF INDUCING
GENERAL ANESTHESIA
INHALED DRUGS
These drugs produce their effects by preventing the flow
of sodium into neurons in the CNS, thus delaying nerve
impulses and producing a dramatic reduction in neural
activity. The exact mechanism is not exactly known,
although it is likely that gamma-aminobutyric acid
(GABA) receptors in the brain are activated. It is not the
same mechanism as is known for local anesthetics.
Gas
The only gas used routinely for anesthesia is nitrous
oxide, commonly called laughing gas. Nitrous oxide is
used for brief obstetric and surgical procedures and for
dental procedures. It may also be used in conjunction with
other general anesthetics, making it possible to decrease
their dosages with greater effectiveness.
Volatile liquids
Volatile anesthetics are liquid at room temperature but are
converted into a vapor and inhaled to produce their
anesthetic effects. Commonly administered volatile agents
are enflurane (Ethrane) and isoflurane (Forane).
INTRAVENOUS DRUGS
IV anesthetics are used alone, for short procedures, or in
combination with inhalation anesthetics.
Inhaled general anesthetics
ADDITIONAL INFORMATION
General anesthetics are drugs that rapidly produce
unconsciousness and total analgesia. To supplement the
effects of a general anesthetic, adjunct drugs are given
before, during, and after surgery.
Characteristics of General anesthesia
•
•
Signs of general anesthesia include total
analgesia and loss of consciousness,
memory, and body movement
General anesthesia is rarely achieved with a
single drug, instead multiple medications.
Balanced Anesthesia
• allows a lower dose of inhalation anesthetic, thus
making the procedure safer for the patient
Stages of General Anesthesia
Pharmacotherapy with IV general
anesthetics
IV general anesthetics are important supplements to
general anesthesia. Although occasionally used alone,
they are often administered with inhaled general
anesthetics. When IV anesthetics are administered alone,
they are generally reserved for medical procedures that
take less than 15 minutes.
Neuroleptanalgesia
Opioids offer the advantage of superior analgesia.
Combining the opioid fentanyl (Sublimaze) with the
antipsychotic agent droperidol (Inapsine) produces a state
known as neuroleptanalgesia.
Intravenous General Anesthetics
Adjuncts to anesthesia
A number of drugs are used either to complement the
effects of general anesthetics or to treat anticipated side
effects of the anesthesia.
PARKINSON’S DISEASE
Drugs as adjuncts to surgery
Preoperative drugs are given to relieve anxiety and to
provide mild sedation.
Neuromuscular Neuromuscular blockades cause
paralysis
without
loss
of
blockers
consciousness, which means that
without a general anesthetic, patients
would be awake and without the
ability to move. Remember, breathing
muscles are skeletal muscle.
Selected adjuncts to anesthesia
-
Other term: Parkinsonism
one of the most common degenerative disease of the
nervous system
-
a progressive and degenerative disorder of the CNS
caused :
Dopamine
Acetylcholine
feel-good
primary neurotransmitter
neurotransmitter
associated with Motor
Neurons
plays an important
role
in
the plays a role in memory,
coordination of body
learning,
attention,
movements
arousal and involuntary
muscle movement.
*Normal mechanism:
substantia nigra = nigrostriatal pathway = corpus striatum
substantia nigra – part of the basal ganglia that supply
dopamine
corpus striatum - region of the brain that controls
unconscious muscle movement: Balance, posture, muscle
tone, and involuntary muscle movement
* depend on the proper balance of the neurotransmitters :
dopamine (inhibitory) and acetylcholine (stimulatory) in the
corpus striatum.
Very good! Natapos
mo na reviewhin ang
part na to, wag
kakalimutang uminom
ng
tubig
para
marefresh ang ating
brain.
* If dopamine is absent, acetylcholine has a more dramatic
stimulatory effect (cholinergic activity)
cholinergic activity- arises whenever the neurotransmitter
acetylcholine is used in the body.
Thus, when the brain experiences a loss of dopamine
within the substantia nigra or an overactive
cholinergic influence in the corpus striatum,
parkinsonism results.
CHARACTERISTICS OF PARKINSONISM
8) DRUGS FOR DEGENERATIVE
DISEASES
-
affects older than 50 years of age
Men are affected slightly more than women
Progressive of full symptoms that takes years to
develop.
Degenerative Diseases
-
-
-
characterized by progressive, often irreversible
deterioration, and loss of function in the organs or
tissues.
often difficult to deal with pharmacologically bcs there
is no cure but these drugs can slow down and offer
symptomatic relief.
Etiology: unknown
Early stage: very subtle signs and symptoms
(difficulties in diagnosing)
Later stage: profound neurologic, cognitive, or sensory
and motor deficits.
3 COMMON DEBILITATING AND PROGRESSIVE
CONDITIONS
Parkinson’s
disease
Alzheimer’s
disease
Multiple
Sclerosis
SIGNS AND SYMPTOMS
Tremors
(pill-rolling)
Muscle rigidity
Bradykinesia
(slow
movements)
Akinesia
(freeze-ups)
The hands and head develop a palsylike motion or shakiness when at rest;
“pill rolling” is a common behavior in
progressive states, in which patients
rub the thumb and forefinger together
as if a pill were between them.
Stiffness may resemble symptoms of
arthritis; patients often have difficulty
bending over or moving limbs. These
symptoms may be less noticeable at
first but progress to become more
obvious in later years.
The most noticeable of all symptoms,
marked by difficulty chewing,
swallowing (drolling), or speaking.
the inability to voluntarily move one's
muscles and limbs
Postural
instability
Patients may be humped over slightly
and easily lose their balance.
Stumbling results in frequent falls
with associated injuries.
Affective
flattening
patients often have a “masked face”
where there is little facial expression
or blinking of the eyes.
loss of smell
constipation
depression
Non-Motor
inhibit the action of acetylcholine in
the brain
Anticholinergic
Drugs
GOAL OF PHARMACOTHERAPY:
* increase to perform normal ADLs (activities of daily living
(ADLs) such as eating, walking, dressing, and bathing)
* attempts to restore the functional balance of dopamine
and acetylcholine in the corpus striatum
DRUGS FOR PARKINSON’S DISEASE
Antiparkinsonism
drugs
Dopaminergic
drugs
given to restore the balance of DA
and ACh in specific regions of the
brain.
either restore dopamine function in
the area or stimulate dopamine
receptors
primary use as dopamine agonists
for the initial treatment of
Parkinson’s disease cholinergic
blockers (anticholinergic)
Drug of choice for
(Parcopa, or Sinemet)
•
2nd approach to balance between
dopamine and acetylcholine
atropine - first drugs used to treat parkinsonism
•
•
•
•
•
benztropine (Cogentin)
biperiden (Akineton)
diphenhydramine (Benadryl)
procyclidine (Kemadrin)
trihexyphenidyl (Artane)
TAKE NOTE
Centrally acting anticholinergics are not as effective as
levodopa at relieving severe parkinsonism symptoms.
They are used early in the course of the disease when:
symptoms are less severe
in patients who cannot tolerate levodopa
in combination therapy with other antiparkinsonism
Drugs
NURSING INTERVENTION
* Teach the patient to take the medication on an empty
stomach or to avoid taking together with a high-protein
meal.
Absorption of levodopa decreases with high protein meal
and eating foods or vitamins with vitamin B6 [pyridoxine]
* Be particularly cautious with older adults who are at an
increased risk for falls
DOPAMINERGIC DRUGS
levodopa with
carbidopa
used early in the course of therapy
for Parkinson’s disease.
Parkinsonsim
* Teach the patient to rise from lying to sitting or standing
slowly to avoid dizziness or falls
* Class Medications: CNS agent
* amino-acid precursor of dopamine
synthesis
levodopa
* effectiveness: “boosted” by combining
it with carbidopa.
* works by being converted to
dopamine in the brain.
* class of medications: decarboxylase
inhibitors.
Carbidopa
Carbidopa
alone
(Lodosyn)
* works by preventing levodopa from
being broken before it reaches the
brain.
*can also increase the concentration
of dopamine and levodopa in the brain
DRUGS THAT INHIBIT ENZYMES THAT NORMALLY
DESTROY LEVODOPA & DOPAMINE
•
Tolcapone (Tasmar),
•
Entacapone (Comtan)
•
Rasagiline (Azilect)
•
Selegiline (Eldepryl, Zelapar)
•
Directly activate the dopamine receptor (dopamine
agonists- mimicks the action)
•
Apomorphine (Apokyn)
•
Bromocriptine (Parlodel)
•
Pramipexole (Mirapex)
•
Ropinirole (Requip)
ALZHEIMER’S DISEASE (AD)
-
affects memory, thinking, and behavior.
one of the forms of dementia
patient generally lives 5 to 10 years following diagnosis
Etiology: unknown
10% cases AD: gene defects on chromosome 1, 14, or
21
degenerative disorder which is the loss of cognitive
functioning — thinking, remembering, and reasoning.
Known Etiology: multiple cerebral infarcts, severe
infections, & toxins.
Most Etiology: unknown
It usually associated with cerebral atrophy or other
structural changes within the brain.
ADDITONAL INFO:
Brain Damage Causes:
•
Chronic inflammation
•
excess free radicals
inflammation
- is part of the body's defense mechanism.
free radicals
- unstable atoms that can damage cells, causing illness
and aging.
Patients with AD (Found within the brain at autopsy):
* Amyloid plaques
* neurofibrillary tangles
Current Hypothesis
inflammatory activity = increase of amyloid (killing healthy
neurons)
memantine and cholinesterase inhibitors, can be taken
in combination.
ultimately reducing microglial cells which removes amyloid
plaques.
MULTIPLE SCLEROSIS
\
•
•
•
•
•
•
•
SYMPTOMS
Impaired memory and judgment
Confusion or disorientation
Inability to recognize family or friends
Aggressive behavior
Depression
Psychoses, including paranoia and delusions
Anxiety
-
chronic, inflammatory, autoimmune disorder found
most prevalent among young adults.
-
Sensory and motor deficits become progressively
worse as the patient grows older.
-
Etiology: unknown
-
characterized by damaged myelin located in the CNS
* inflammation
* scarring
which will lead to decrease in nerve transmission.
DRUGS FOR AD
acetylcholinesterase
inhibitors
glutamatergic
inhibitors
NSAIDs
vitamin E
Monoamine oxidase
inhibitor
most widely used class of
drugs for treating AD
memantine (Namenda)
Most effective: intensify the effect of acetylcholine at the
cholinergic receptor if there are functioning neurons
present
Ineffective: severe stages of this AD, probably because
many neurons have died.
Progression: discontinued; therapeutic benefit does not
outweight
tacrine (Cognex) * rarely prescribed (possible liver damage)
Donepezil
(Aricept)
•
•
•
•
•
•
•
•
impaired cognitive ability
disruption of balance and coordination
bowel and bladder symptoms
sexual dysfunction
Dizziness
Vertigo
visual impairment
slurred speech
selegiline
Acetylcholinesterase Inhibitors
Rivastigmine
(Exelon)
•
SYMPTOMS
Fatigue
Heat sensitivity (heat hypersensitivity occurs when
you experience excessive sweating and discomfort as
your body tries to cool down when exposed to heat.)
Neuropathic pain (affects that carry sensations to
your brain)
Spasticity (feelings of pain or tightness)
•
•
*Cause weight loss
*potentially serious side effect in some
older adults.
* are approved for the treatment of
progressive AD
Caprylidene
(Axona)
•
TYPES OF MULTIPLE SCLEROSIS
Clinically Isolated
Syndrome (CIS)
first episode of neurologic
symptoms
Relapsingremitting Multiple
Sclerosis (RRMS)
clearly defined attacks of new or
increasing neurologic symptoms
Secondary
Progressive
Multiple Sclerosis
(SPMS)
Primary
Progressive
Multiple Sclerosis
(PPMS)
Galantamine
(Razadyne,
Reminyl)
follows the initial relapsing-remitting
course
neurologic function worsens
DRUG CLASS FOR MULTIPLE SCLEROSIS
Immunomodulators
Glutamatergic Inhibitors
Memantine (Namenda)
treatment of moderate to severe AD.
Reduces the abnormally high levels of glutamate
* Too much glutamate in the brain can cause nerve cells to
become overexcited which result in brain cell death
Immunosuppressants
Potassium Channel
Blockers
change immune system to
works more effectively.
inhibit the intensity of the
immune response.
improve nerve conduction
IMMUNOMODULATORS
Patients with relapse–remitting MS and secondary–
progressive MS
2 categories of immune-modulating drugs
a. glatiramer (Copaxone)
b. interferon beta
* interferon beta-1a (avonex, rebif)
* interferon beta-1b (Betaseron, Extavia)
IM: Avonex
SQ: Rebif and Betaseron
- Both reduce the severity of symptoms
Adverse side effects
-
-
flulike symptoms
Anxiety
discomfort
experienced at the
injection site
liver toxicity
POTASSIUM CHANNEL BLOCKER
Dalfampridine (Ampyra)
1st FDA-approved oral drug (walking impairment)
Most adverse side effect: seizure activity
contraindicated in patients with prior history of
seizures.
It exerts an effect through its broad-spectrum
potassium channel blockade and has been shown to
increase nerve conduction and improve walking
speed.
Adverse side effects:
•
hair loss,
•
GI discomfort (nausea and vomiting)
•
allergic symptoms (pruritus, rash, hypotension)
Common side effects
-
Flushing
chest pain
Weakness
Infection
Pain
Nausea
joint pain
anxiety
muscle stiffness
caution when taking immunomodulators in combination of:
• chemotherapeutic agents
• bone marrow-suppressing drugs
Patients with relapsing forms of MS
Fingolimod (Gilenya)
• decreases the number of MS flare-ups
• slows down the development of physical impairment
caused by MS.
Glatiramer (Copaxone)
• synthetic protein that simulates myelin basic protein
• an essential part of the nerve’s myelin coating
OVERVIEW
PARKINSONS DISEASE
Dopaminergic drugs
amantadine (Symmetrel)
apomorphine
bromocriptine (Parlodel)
entacapone (Comtan)
levodopa-carbidopa (Parcopa, Sinemet)
levodopa-carbidopa-entacapone (Stalevo)
pramipexole (Mirapex)
rasagiline (Azilect)
ropinirole (Requip)
selegiline (Eldepryl, Zelapar)
tolcapone (Tasmar)
Anticholinergic Drugs
benztropine (Cogentin)
biperiden (Akineton)
diphenhydramine (Benadryl)
procyclidine (Kemadrin)
trihexyphenidyl (Artane)
DRUGS FOR ALZHEIMER’S DISEASE
donepezil (Aricept)
Copaxone
• available in prefilled syringes
IMMUNOSUPPRESANTS
acetylcholinesterase
inhibitors
rivastigmine (Exelon)
Patients with progressive-relapsing MS
Mitoxantrone (Novantrone) (IV)
no response to interferon or glatiramer acetate
therapy.
more toxic than the immune-modulating drugs.
* Toxicity is a concern due to irreversible cardiac injury and
potential harm to the fetus.
Adverse side effects:
•
hair loss,
•
GI discomfort (nausea and vomiting)
•
allergic symptoms (pruritus, rash, hypotension)
galantamine
•
Razadyne
•
Reminyl)
tacrine (Cognex)
glutamatergic
inhibitors
NSAIDs
vitamin E
Monoamine oxidase
inhibitor
memantine (Namenda)
Selegiline
DRUG CLASS FOR MULTIPLE SCLEROSIS
Immunomodulators
•
glatiramer (Copaxone)
•
interferon beta-1a (avonex, rebif)
•
interferon beta-1b (Betaseron, Extavia)
•
natalizumab (Tysabri)
•
fingolimod (Gilenya)
•
teriflunomide (Aubagio)
Immunosuppressants
•
mitoxantrone (Novantrone)
Potassium Channel Blockers
•
dalfampridine (Ampyra)
9) DRUGS FOR NEUROMUSCULAR
DISORDERS
-
Not antispasmodic drugs but do relax skeletal muscles via
a central mechanism of action:
•
Neuromuscular Disorders
group of conditions affecting the nerves that control
muscle function in the voluntary muscles
DIFFERENCE
MUSCLE SPASM
a protracted and painful
contraction that can limit
movement and function.
-
•
•
•
•
•
•
a quick and moderate
contraction that does not
hurt.
•
CAUSES
Excessive use of the skeletal muscle
Local injury of the skeletal muscle
Overmedication with antipsychotic drug
(antipyschotic drugs contains high level of dopamine)
Epilepsy
Hypocalcemia
SYMPTOMS
•
•
•
•
•
Edema (Swelling caused due to excess fluid)
Inflammation of the affected muscle
Pain in the affected muscle
Loss of coordination
Reduced mobility
Pharmacologic and Nonpharmacologic treatment of
muscle spasms
Nonpharmacologic
treatment
• Immobilization of
affected muscle
Pharmacologic treatment
the
• Application of heat or
cold
• Hydrotherapy
• Therapeutic ultrasound
• Supervised exercises
• Massages
SPASTICITY
MUSCLE CRAMPS
MUSCLE SPASMS
refers to the sudden, involuntary contraction and
relaxation of a muscle or group of muscles.
May include combinations
of:
• Analgesics
• anti-inflammatory drugs
• centrally acting skeletal
muscle relaxants.
Most skeletal muscle
relaxants drugs do so by
reducing the symptoms of
stiffness and rigidity in the
muscles that come from
muscular trauma.
CENTRALLY ACTING SKELETAL MUSCLE
RELAXANTS
Treating Muscle Spasms at the Level of the Central
Nervous system
Antispasmodic drugs
• baclofen (Lioresal)
•
cyclobenzaprine (Amrix, Flexeril)
•
Tizanidine (Zanaflex)
•
vigabatrin (Sabril)
benzodiazepines such as
* diazepam (Valium)
* clonazepam (Klonopin)
* lorazepam (Ativan).
•
•
•
•
•
a condition in which certain muscle groups
remain in a continuous state of contraction,
usually resulting from damage to the CNS.
The contracted muscles become stiff with
increased muscle tone.
CAUSES
Cerebral palsy
Severe head injury or lesions
Stroke
(dystonia- characterized by involuntary muscle
contraction that forces body parts into
abnormal, occasionally painful movements or
SIGNS & SYMPTOMS
•
•
•
•
•
Mild to severe pain
Exaggerated deep tendon reflexes
Muscle spasms
Scissoring (involuntary crossing of the legs
Fixed joints
TREATMENT OF MUSCLE SPASTICITY
TREATMENT
Includes both physical therapy and medications.
Medications alone are not adequate in reducing the
complications of spasticity.
PHYSICAL THERAPHY
•
Muscle stretching
•
Muscle-group strengthening exercises
•
Repetitive-motion exercises
In extreme cases:
Surgery to release tendon or to sever the nerve-muscle
pathway
Drugs effective in the treatment of spasticity include
several classifications of antispasmodics that act at the
level of the CNS, neuromuscular junction, or muscle
tissue
The direct-acting drugs produce an antispasmodic effect
at the level of the neuromuscular junction and skeletal
muscle.
TREATING MUSCLE SPASMS DIRECTLY AT THE
MUSCLE TISSUE (DIRECT-ACTING DRUGS)
•
•
•
•
•
•
baclofen (Lioresal)
diazepam (Valium)
dantrolene (Dantrium)
onabotulinumtoxinA (Botox, Dysport)
rimabotulinumtoxinB (Myobloc)
incobotulinumtoxinA (Xeomin)
-
BOTULINUM TOXIN
a highly potent neurotoxin that is produced from the
bacteria Clostridium botulinum
-
produces its effect by blocking the release of
acetylcholine from cholinergic nerve terminals
-
To circumvent major problems with mobility or posture,
botulinum toxin is often applied to small muscle groups
-
administered with centrally acting oral medications to
increase functional use of a range of muscle groups
BLOCKING THE EFFECT OF ACETYLCHOLINE AT
THE RECEPTOR
neuromuscular blockers bind to nicotinic receptors located
on the surface of skeletal muscle fibers.
neuromuscular blocking agents are classified into two:
•
nondepolarizing blockers
•
depolarizing blockers
neuromuscular blocking drugs are different from
ganglionic blocking drugs that target the autonomic
nervous system.
GANGLIONIC BLOCKERS
* dampen parasympathetic tone and
produce effects like increased heart rate, dry mouth,
urinary retention, and reduced gastrointestinal activity.
* They also dampen sympathetic tone, resulting in
reduced sweating and less norepinephrine being released
from postsynaptic nerve terminals
NONDEPOLARIZING BLOCKERS
Tubocurarine are used to relax the muscles of patients
being prepared for longer surgical procedures.
Concerns of tubocurarine-like treatment are overrelaxation of muscles.
DEPOLARIZING BLOCKERS
used primarily to relax the muscles of patients receiving
electroconvulsive therapy (ECT) and for shorter surgical
procedures
Succinylcholine (Anectine, Quelicin)
NCM 106 - PHARMACOLOGY
LECTURE #: TOPIC NAME
BSN 2103 1ST SEMESTER AY 2023-2024
TRANSCRIBERS: Arago, Dela Luna, Magpili, Palma, Rosales
\
SOURCE: PPT, NOTES/OTHER INFO, BOOK
CHECKER: Rod H. Maranan
1.1 INNATE (NONSPECIFIC) BODY DEFENSES
AND THE IMMUNE RESPONSE
TOPIC OUTLINE
1
2
3
4
5
6
Drugs for Immune System Modulation
Drugs for Inflammation and Fever
Drugs for Bacterial Infection
Drugs for Fungal, Protozoans, and Helminthic
Infections
Drugs for Viral Infections
Drugs for Neoplasta
I. Drugs for Immune System Modulation
•
•
•
•
•
•
•
•
Innate (Nonspecific) Body Defense
First line of protection from pathogens.
Serve as general barriers to microbes or
environmental hazards.
Also called nonspecific defenses.
Other innate defenses are phagocytes, natural killer
(NK) cells, the complement system, fever, and
interferons.
From a pharmacologic perspective, one of the most
important of the innate defenses is inflammation.
Adaptive (Specific) Defenses
Second line of defense that is specific to particular
threats.
Commonly known as immune response.
Primary cell of the immune response is the
lymphocyte.
TWO TYPES OF LYMPHOCYTES
T lymphocytes
(T cells)
B lymphocytes
(B cells)
• These cells regulate the body's
immune response and actively
seek out and eliminate cancerous
and infectious cells.
• These cells produce antibodies,
which are proteins that primarily
attack bacteria, viruses, and other
foreign pathogens.
ANTIGENS
•
•
Microbes and foreign substances that elicit an immune
response
Foreign proteins, such as those present on the
surfaces of pollen grains, bacteria, nonhuman cells,
and viruses, are the strongest antigens
TWO PRIMARY DIVISIONS OF THE IMMUNE
RESPONSE
Antibodymediated
(humoral)
immunity
Cellmediated
immunity
IMMUNOMODULATOR
•
The general term referring to any drug or therapy that
affects body defenses.
TWO CATEGORIES OF IMMUNOMODULATORS
•
•
•
•
Immunostimulants
Used to stimulate body defenses so that microbes or
cancer cells can be more effectively attacked.
Strengthen the body's resistance to infections by
increasing the immune system's baseline response,
which is especially significant in those who have a
weakened immune system.
Immunosuppressants
Inhibit or decrease the intensity of the immune
response in the body.
Suppress body defenses to prevent a transplanted
organ from being rejected by the immune system.
• This occurs when foreign material or
antigens are detected in the body. This
process is predominantly driven by B cell
lymphocytes, a kind of immune cell that
generates antibodies in response to antigen
recognition.
• This isn't reliant on antibodies to perform
adaptive immune processes. Cell-mediated
immunity is predominantly driven by mature T
cells, macrophages, and the production of
cytokines in response to an antigen.
•
Peak production of antibodies occurs about 10 days after an initial
Steps in the Humoral and Cell-mediated Immune
antigen challenge.
Response
Function of Antibodies
IMMUNIZATION AGENTS
•
•
Antibodies
Biologic agents used to stimulate the immune system.
One of the most important medical interventions for the
prevention of serious infectious disease.
1.3 ADMINISTRATION OF VACCINES
Vaccination/Immunization
Process of introducing foreign proteins or inactive cells
(vaccines) into the body to trigger immune activation
before the patient is exposed to the real pathogen.
•
Results in the formation of memory B cells.
•
Whereas some immunizations are needed only once,
most require follow-up doses, called boosters, to
provide sustained protection.
Titer The effectiveness of most vaccines can be
assessed by measuring the amount of antibody
produced after the vaccine has been
administered through this quantity
•
The goal of vaccine administration is to induce longlasting immunity to a pathogen without producing an
illness in an otherwise healthy person.
•
1.2 HUMORAL IMMUNE RESPONSE AND
ANTIBODIES
Humoral Immune Response
Initiated when an antigen encounters a type of
lymphocyte known as a B cell.
•
The B cell becomes activated and divides rapidly to
form millions of copies, or clones, of itself.
•
Most cells in this clone are called plasma cells whose
primary function is to secrete antibodies specific to the
antigen that initiated the challenge.
Antibodies
culating through the body also known as immunoglobulins (Ig), which
ysically interact with the antigens to neutralize or mark them for
struction by other cells of the immune response.
•
FOUR METHODS OF PRODUCING SAFE AND
EFFECTIVE VACCINES
1
2
Attenuated (live) vaccines contain microbes that are
alive but weakened (attenuated) so they are unable to
produce
disease
unless
the
patient
is
immunocompromised. Some attenuated vaccines
cause a mild or subclinical case of the disease.
Inactivated (killed) vaccines contain microbes that
have been inactivated by heat or chemicals and are
unable to replicate or cause disease. Boosters may be
necessary to prolong immunity.
3
4
Toxoid vaccines contain bacterial toxins that have
been chemically modified to be incapable of causing
disease. When injected, toxoid vaccines induce the
formation of antibodies that are capable of neutralizing
the real toxins.
Recombinant technology vaccines are those that
contain partial organisms or bacterial proteins that are
generated in the laboratory using biotechnology.
TYPES OF IMMUNITY
•
•
•
•
•
•
•
•
Active Immunity
Type of response induced by the real pathogen, or its
vaccine.
The body produces its own antibodies in response to
exposure. The active immunity induced by vaccines
closely resembles that caused by natural exposure to
the antigen, including the generation of memory cells.
Passive Immunity
Occurs when preformed antibodies are transferred or
“donated” from one person to another.
Drugs for passive immunity are usually administered
when the patient has already been exposed to a
virulent pathogen, or the patient is at very high risk of
exposure and there is not sufficient time to develop
active immunity.
Patients who are immunosuppressed may receive
these medications to prevent infections.
Memory cells are not produced.
Protective effects will disappear within several weeks
to several months after the infusions are discontinued.
Second indication for the use of passive immunity is
for situations where the activation of the immune
system and the development of memory are not
desirable
Immune Globulin Preparations
Mechanisms of Active and Passive Immunity
•
•
•
•
•
•
•
•
•
•
•
•
Vaccines
Administered with the goal of preventing illness.
Anthrax vaccine has been used to immunize people
who are at high risk for exposure to anthrax from a
potential bioterrorism incident.
In human immunodeficiency virus (HIV), experimental
HIV vaccines are given after infection has occurred for
the purpose of enhancing the immune response,
rather than preventing the disease.
Vaccines are not without adverse effects.
Although
severe
reactions
are
uncommon,
anaphylaxis is possible.
Vaccinations are contraindicated for patients who have
a weakened immune system or who are currently
experiencing symptoms such as diarrhea, vomiting, or
fever.
Most vaccines are pregnancy category C and
vaccinations are often delayed in pregnant patients
until after delivery to avoid any potential harm to the
fetus.
Effective vaccines have been produced for a number
of debilitating diseases.
Widespread use has prevented serious illness in
millions of patients, particularly children.
Nurses play a key role in encouraging patients to be
vaccinated according to established guidelines.
Although vaccinations have proved to be a resounding
success in children, many adults die of diseases that
could be prevented by vaccination.
The Centers for Disease Control and Prevention
(CDC) publishes an adult immunization schedule that
contains
both
age-based
and
risk-based
recommendations.
The Shingles Vaccination
Selected Vaccines and Their Schedule
Prototype Drug: Hepatitis B Vaccine
(Engerix-B, Recombivax HB)
1.4 CELL-MEDIATED IMMUNITY AND
CYTOKINES
•
•
T-Cells
destroy pathogens by sending signals
mature in the thymus gland
TWO MAIN TYPES OF T-CELLS
•
•
•
•
•
•
•
•
Helper T-cell
contains CD4 receptor
helps or induce immune response
recognize antigen in association with class II MHC
macrophages are activated to kill microorganisms by
secreting cytokines.
Cytotoxic T-cell
contains CD8 receptor
predominantly cytotoxic
recognize antigen in association with class I MHC
destroy directly
CYTOKINES
•
•
•
regulate the intensity and duration of immune
response
mediate cell-to-cell communication
regulate inflammation in the body
TYPES
Interferons
signal cells to put defense
against invading virus
Interleukins
Tumor Necrosis Factor
(TNF)
Colony-Stimulating
Factors (CSF)
modulate
growth,
differentiation, and activation
during immune response
regulate inflammation and
signals immune cells to kill
tumor cells
act as “cellular booster”, help
produce more white blood cell
1.5 PHARMACOTHERAPY WITH BIOLOGIC
RESPONSE MODIFIERS
•
•
•
•
Immunostimulants
are drugs designed to improve the body’s resilience to
infections by boosting the immune system’s baseline
response
Biologic Response Modifier
can either be endogenous or exogenous
alter the body’s normal response to disease or
infection
are
biopharmaceuticals,
including
interferons,
interleukins, monoclonal antibodies, and colonystimulating factors.
BIOLOGIC RESPONSE MODIFIERS
•
•
•
•
•
•
•
•
•
•
•
Interferons
are cytokines secreted by lymphocytes and
macrophages
cannot protect infected cell
attach to an uninfected cell to induce protective
antiviral properties.
antiviral, anticancer, anti-inflammatory properties.
alpha interferons include IFN alfa-2b, IFN alfacon-1,
IFN alfa-n3, pegIFN alfa-2a, and pegIFN alfa-2b
beta interferon consists of beta-1a and beta-1b
gamma interferon includes IFN gamma-1b
Interleukins
Synthesized primarily by lymphocytes, monocytes and
macrophages
stimulation of cytotoxic T-cell activity against tumor
cell, increased B-cell and plasma cell production
Interleukin-2 aldesleukin (Proleukin) which is
treatment for metastatic renal carcinoma and
metastatic melanoma
Interleukin-11 marketed as oprelvekin (Neumega)
used to stimulate platelet production
Note: Italics indicate common adverse effects; underlining
indicates serious adverse effects.
OTHER BIOLOGIC RESPONSE MODIFIER
DRUGS
Levamisole (Ergamisole)
to stimulate production of B-cell, T-cell, and
macrophages in patients with colon cancer.
Bacillus Calmette-Geurin (BGC)
•
vaccine is used for pharmacotherapy of certain types
of bladder cancer.
Filgrastim (Neupogen) and Sargramostim (Leukin)
•
promote the production of white blood cells which is
used to shorten the length of neutropenia in patients
with cancer and have had bone marrow transplant.
•
1.6 IMMUNOSUPPRESSANTS FOR PREVENTING
TRANSPLANT REJECTION AND FOR TREATING
INFLAMMATION
•
•
Immunosuppressants
are drugs used to inhibit or dampen the immune
response of the body, it is used for transplanting
organs and treating severe inflammatory disorders.
given one or more immunosuppressant drugs before
surgery and are continued several months after.
TRANSPLANTATION
•
Transplant Rejection
a process in which a transplant recipient’s immune
system attacks the transplanted organ or tissue.
THREE TYPES OF REJECTION
IMMUNOSTIMULANTS
Hyperacute
Rejection
Acute Rejection
Chronic Rejection
occurs a few minutes after the
transplant when the antigen is
completely unmatched.
may occur any time from the first
week after the transplant to 3
months afterwards.
can take place over many years.
The body’s constant immune
response against the new organ
damages the transplanted organ.
ACUTE INFLAMMATORY DISORDERS
•
•
•
severe inflammation is characterized by autoimmune
disorders
examples are rheumatoid arthritis, systemic lupus
erythematosus, myasthenia gravis, and Hoshimoto’s
thyroiditis.
immunosuppressants are usually given for brief period
in high doses to control relapses
DRUG CLASSES OF IMMUNOSUPPRESSANTS
Corticosteroid
inhibit inflammation; short term
therapy of severe inflammation
Antimetabolites
Calcineurin
such as sirolimus (Rapamune) and
azathioprine
(Imuran)
inhibit
aspects of lymphocyte replication
Cyclosporine
(Gengraf,
Sandimmune,
Neoral)
and
tacrolimus (Prograf) disrupts T-cell
function
IMMUNOSUPPRESSANTS
PROTOTYPE DRUG: CYCLOSPORINE
(GENGRAF, NEORAL, SANDIMMUNE)
II. Drugs for Inflammation and Fever
CHEMICAL MEDIATORS OF INFLAMMATION
33.1 INFLAMMATION
•
a nonspecific defense system of the body. Through the
process of inflammation, a large number of potentially
damaging chemicals and microorganisms may be
neutralized
•
Inflammation is a body defense mechanism that
occurs in response to many different stimuli, including
physical injury, exposure to toxic chemicals, extreme
heat, invading microorganisms, or death of cells. It is
considered an innate (nonspecific) defense
mechanism because inflammation proceeds in the
same manner, regardless of the cause that triggered
it.
The central purpose of inflammation is to contain the
injury or destroy the microorganism. By neutralizing
the foreign agent and removing cellular debris and
dead cells, repair of the injured area is able to proceed
at a faster pace. Signs of inflammation include
swelling, pain, warmth, and redness of the affected
area.
FUNCTIONS OF INFLAMMATION
•
CLASSIFICATION OF INFLAMMATION
•
•
•
•
•
1. Acute Inflammation
Acute inflammation has an immediate onset and 8 to
10 days are normally needed for the symptoms to
resolve and for repair to begin.
If the body cannot contain or neutralize the damaging
agent, inflammation may continue for long periods and
become chronic.
2. Chronic Inflammation
has a slower onset and may continue for prolonged
periods.
In autoimmune disorders such as systemic lupus
erythematosus (SLE) and rheumatoid arthritis (RA),
chronic inflammation may persist for years, with
symptoms becoming progressively worse over time.
Other chronic disorders such as seasonal allergy arise
at predictable times during each year, and
inflammation may produce only minor, annoying
symptoms.
STEPS IN ACUTE INFLAMMATION
33.2 THE ROLES OF CHEMICAL MEDIATORS IN
INFLAMMATION
Chemical mediators of inflammation include:
•
Histamine
•
Leukotrienes
Histamine
•
is a key chemical mediator of inflammation.
•
It is stored primarily within mast cells located in tissue
spaces under epithelial membranes such as the skin,
bronchial tree, digestive tract, and along blood
vessels.
•
Mast cells detect foreign agents or injury and respond
by releasing histamine, which initiates the
inflammatory response within seconds.
•
•
•
General Strategies for Treating Inflammation
Inflammation is not a disease, but a symptom of an
underlying disorder. Whenever possible, the cause of
the inflammation should be identified and treated.
The inflammation should be identified and treated.
Inflammation is a natural process for ridding the body
of antigens, and it is usually self-limiting. For mild
symptoms, nonpharmacologic treatments such as ice
packs and rest should be used whenever applicable.
Topical drugs should be used when applicable
because they cause few adverse effects. Inflammation
of the skin and mucous membranes of the mouth,
nose, rectum, and vagina are best treated with topical
drugs. These include anti-inflammatory creams,
ointments, patches, suppositories, and intranasal
sprays. Many of these products are available over the
counter (OTC).
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
•
NSAIDs such as aspirin and ibuprofen have analgesic,
antipyretic, and anti-inflammatory properties. They are
widely prescribed for mild to moderate inflammation.
SELECTED NONSTEROIDAL ANTIINFLAMMATORY DRUGS
INHIBITION OF CYCLOOXYGENASE1 AND 2
•
•
Salicylates
Aspirin belongs to the chemical family known as the
salicylates. Since the discovery of salicylates in 1828,
aspirin has become one of the most highly used drugs
in the world. Aspirin binds to both COX-1 and COX-2
enzymes, changing their structures and preventing
them from forming inflammatory prostaglandins.
Ibuprofen and Ibuprofen-like NSAIDs
Ibuprofen (Motrin, Advil) and a large number of
ibuprofen-like drugs are NSAIDs that were developed
as alternatives to aspirin. Like aspirin, they exhibit their
effects through inhibition of both COX-1 and COX-2,
although the inhibition by these drugs is reversible.
PROTOTYPE DRUG: IBUPROFEN
(ADVIL, MOTRIN, OTHERS)
FEVER
•
•
Like inflammation, fever is a natural defense
mechanism for neutralizing foreign organisms. Many
species of bacteria are killed by high fever. Often, the
health care provider must determine whether the fever
needs to be dealt with aggressively or allowed to run
its course. Drugs used to treat fever are called
antipyretics.
Treating Fever with Antipyretic
In most patients, fever is more of a discomfort than a
life-threatening problem. Prolonged, high fever,
however, can become dangerous, especially in young
children in whom fever can stimulate febrile seizures.
In adults, excessively high fever can break down body
tissues, reduce mental acuity, and lead to delirium or
coma, particularly among elderly patients. In rare
instances, an elevated body temperature may be fatal.
PROTOTYPE DRUG: ACETAMINOPHEN
(TYLENOL, OTHERS)
Therapeutic Class: Antipyretic and analgesic
Pharmacologic Class: Centrally acting COX inhibitor
CORTICOSTEROIDS (GLUCOCORTICOIDS)
•
•
Corticosteroids
have
numerous
therapeutic
applications. One of their most useful properties is the
ability to suppress severe inflammation. Because of
potentially serious adverse effects, however, systemic
corticosteroids are reserved for the short-term
treatment of severe disease. Corticosteroids are often
referred to as glucocorticoids.
Treating Acute and Severe Inflammation using
Corticosteroid
Corticosteroids are natural hormones released by the
adrenal cortex that have powerful effects on nearly
every cell in the body. When corticosteroids are used
as drugs to treat inflammatory disorders, the doses are
many times higher than the amount naturally present
in the blood.
SELECTED CORTICOSTEROID FOR SEVER
INFLAMMATION
III. Drugs for Bacterial Infection
3.1 PATHOGENECITY & VIRULENCE
•
•
•
•
•
•
•
Pathogens
any microbes or organisms that are capable of causing
diseases
enters through broken skin, ingestion, inhalation, or
contact with mucous membrane.
Human Pathogens
Viruses
Bacteria
Fungi
Unicellular organisms
Multicellular animals
PATHOGENECITY VS. VIRULENCE
•
•
•
Pathogenecity
ability of an organism to
cause infection
•
Virulence
severity or harmfulness
of a disease
How do pathogens cause disease?
Invasiveness
Production of toxins
COMMON BACTERIAL PATHOGENS AND
DISORDERS
3.2 DESCRIBING AND CLASSIFYING BACTERIA
•
•
•
Methods of Classifying Bacteria
Examining the microscopically after a crystal violet
gram stain is applied.
Cellular shape
Ability to use oxygen.
Terms in Methods of Classifying Bacteria
Gram – positive
bacteria
Gram –
negative
bacteria
Bacilli
Cocci
spirilla
Aerobic
Anaerobic
Some bacteria contain a thick cell wall
and retain a purple color after staining
Bacteria that have thinner cell walls
will lose the violet stain
Rod shapes
Spherical shapes
Spirals
Bacteria that thrive in an oxygen-rich
environment
Bacteria that grow best without
oxygen
GRAM STAINING
CELLULAR SHAPE
3.3 CLASSIFICATION OF ANTI-INFECTIVE
DRUGS
•
•
•
•
•
•
•
•
Anti-infective Drugs
any drug that is effective against pathogens
most frequent term used is “antibiotic”
Chemical Class
aminoglycosides
fluoroquinolone
sulfonamides
Pharmacological Class
cell wall inhibitors
folic acid inhibitors
reverse transcriptase inhibitor
3.4 ACTIONS OF ANTI-INFECTIVE DRUGS
Primary Goal
Bactericidal
Bacteriostatic
assist the body’s defense in eliminating
pathogens
medication that kills bacteria
growth slowing drugs
MECHANISMS OF ACTION OF ANTIMICROBIAL
DRUGS
!!! REMEMBER !!!
In acquired resistance the patient is not the one who
becomes resistant but rather the bacteria.
The longer the antibiotic is used in a population and
the more often it is prescribed the larger the
percentage of resistant strains.
•
•
HEALTH CARE ACQUIRED INFECTIONS (HAIS)
•
•
infections that are acquired from the hospital.
often resistant to antibiotics.
TYPES
MRSA
VRE
methicillin-resistant
Staphylococcus aureus
vantomycin-resistant
enterococci
5 PRINCIPLES RECOMMENDED BY CDC
1
2
3
4
5
•
Prevent infections when possible.
Use the right drug for the infection.
Restrict the use of antibiotics to those conditions
deemed medically unnecessary.
Advise patients to take anti-infective for the full length
of therapy.
Prevent transmission of pathogens.
DID YOU KNOW?
Antibiotics can also be given to prevent infection; this
practice
is
called
prophylactic
or
chemoprophylaxis.
3.6 SELECTION OF AN EFFECTIVE ANTIBIOTIC
3.5 ACQUIRED RESISTANCE
•
•
•
•
•
Microorganisms have the ability to replicate rapidly in
a rapid condition.
This rapid replication can cause a random mutation
which can result for a bacteria to survive in a harsher
condition.
When antibiotics are given to the patient with mutated
microorganism, the medication will only kill the
pathogens that are susceptible to the drug thus leaving
the mutated bacteria behind.
This resistant bacteria will have plenty of room to
divide.
The result of this division are also bacterias that are
resistant to antibiotics.
•
•
•
selection of antibiotics is an important task for
healthcare providers as selecting an incorrect drug will
delay proper treatment.
Laboratory Test
examination of the patient urine, stool, spinal fluid,
sputum, blood, or purulent drainage of microorganism
Culture and Sensitivity Testing
process of growing the pathogens and identifying the
most effective antibiotics.
More info. about selection of an effective antibiotic
If the infection is severe, therapy may begin in a
broad-spectrum antibiotic, which are drugs effective
against a wide variety of pathogens.
•
Upon identification of pathogens, therapy is shifted to
narrow-spectrum antibiotic, one that is effective
•
against a smaller group of microbes or isolated
species.
PENICILLINS
COMMON ADVERSE EFFECT OF ANTIINFECTIVE DRUG
•
•
•
•
•
•
•
Superinfection
appearance of secondary infection
occurs when normal body microorganisms (host flora)
are destroyed.
Signs & Symptoms
diarrhea
bladder pain
painful urination
abnormal vaginal discharge
ADDITIONAL INFO
Host flora themselves can cause disease if allowed to
proliferate without control or if established in colonies
in abnormal locations.
OPPORTUNISTIC ORGANISM
host flora that become pathogenic if the patient’s
immune system is suppressed.
Example •
Herpes virus
•
Fungi
•
3.7 HOST FACTORS
•
•
•
•
•
•
Host Defense
In some cases, antibiotics alone may not be enough.
Patient’s immune system and phagocytic cells will be
needed to completely rid the body of the infectious
agent.
Local Tissue Conditions
Local conditions at the infection should be considered
as it can hinders the drug from reaching t microbes and
limits therapeutic success. Excessive pus formation or
hematomas from injury or inflammation can block
drugs from reaching their targets.
Allergy History
Severe allergic reactions to antibiotics, although not
common, may be fatal. If severe allergy anti-infective
is established, it is best to avoid all drugs in the same
chemical class.
Other Patient Variables
Age
Pregnancy status
Genetics
CEPHALOSPORINS
•
•
•
•
•
comprise the largest antibiotic class.
act by essentially the same mechanism as the
penicillins and have similar pharmacological
properties.
The primary therapeutic use of the cephalosporins is
for gram-negative infections and for patients who
cannot tolerate the less expensive penicillins.
Like the penicillins, many cephalosporins contain a
beta-lactam ring that is responsible for their
antimicrobial activity
bactericidal and act by attaching to penicillin-binding
proteins to inhibit bacterial cell-wall synthesis.
3.8 PHARMACOTHERAPY WITH PENICILLINS
•
•
•
•
•
Penicillins
first mass-produced antibiotic
was isolated from the fungus penicillium in 1941
kills bacteria by disrupting their cell walls
gram positive bacteria are the most commonly affected
by the penicillins
indicated for the treatment of pneumonia, meningitis;
skin, bone, and joint infections; stomach infections;
blood, and valve infections; gas gangrene; tetanus;
anthrax; and sickle-cell anemia in infants.
GENERATION OF CEPHALOSPORINS
•
•
•
•
First Generation
most effective drugs in this class against gram-positive
organisms.
Bacteria that produce beta-lactamase will usually be
resistant to these drugs.
Second Generation
more potent, are more resistant to beta-lactamase,
and exhibit a broader spectrum against-negative
organisms than the first-generation drugs.
Third Generation
exhibit an even broader spectrum against gramnegative bacteria than the second-generation drugs.
They generally have a longer duration of action and
are resistant to beta lactamase.
•
Fourth Generation
capable of entering the cerebrospinal fluid (CSF) to
treat central nervous system (CNS) infections.
Fifth Generation
designed to be effective against MRSA infections.
•
are the most frequent adverse effect.
•
are a common sign of allergy and may appear several
days following the initiation of therapy.
•
TETRACYCLINES
Allergic Reactions
Skin Rashes
CEPHALOSPORINS
MACROSLIDES
•
Erythromycin (EryC, Erythrocin, others), the first
macrolide
antibiotic,
was
isolated
from
Streptomyces in a soil sample in 1952.
•
safe alternatives to penicillin, although they are drugs
of choice for relatively few infections.
•
inhibit protein synthesis by binding to the bacterial
ribosome
•
At low doses = a bacteriostatic effect
•
At higher doses = macrolides may be bactericidal
•
are effective against most gram-positive bacteria and
many gram negative species.
Common Indications:
•
whooping cough
•
Legionnaires’ disease
•
And infections by streptococcus, H. influenza, and M.
pneumoniae
Drugs in this class are used against bacteria residing inside
host cells, such as Listeria, Chlamydia, Neisseria, and
Legionella.
Side Effects:
•
Mild Gl upset
•
Diarrhea
•
Abdominal pain
•
superinfections
MACROSLIDES
TETRACYCLINES
•
•
•
•
•
•
•
•
•
•
•
•
First tetracyclines were extracted from Streptomyces
soil microorganisms in 1948.
effective against a large number of different gramnegative and gram-positive organisms and have one
of the broadest spectrums of any class of antibiotics
act by inhibiting bacterial protein synthesis.
By binding to the bacterial ribosome, which differs in
structure from a human ribosome, the tetracyclines
slow microbial growth and exert a bacteriostatic effect.
All tetracyclines have the same spectrum of activity
and exhibit similar adverse effects.
Gastric distress is relatively common with
tetracyclines so patients tend to take them with food.
Because these drugs bind metal ions such as calcium
and iron, tetracyclines should not be taken with milk
or iron supplements.
Calcium and iron can decrease the drug’s absorption
by as much as 50%.
Direct exposure to sunlight can result in severe
photosensitivity during therapy.
may cause permanent yellow-brown discoloration of
the permanent teeth in young children
affect fetal bone growth and teeth development
should be avoided during pregnancy
AMINOGLYCOSIDES
•
•
•
•
First aminoglycoside, streptomycin, was named
after Streptomyces griseus, the soil organism from
which it was isolated in 1942.
more toxic than other antibiotic classes
have important therapeutic applications for the
treatment of aerobic gram-negative bacteria,
mycobacteria, and some protozoans
bactericidal and act by inhibiting bacterial protein
synthesis.
•
•
•
•
•
•
•
FLUOROQUINOLONES
normally reserved for serious systemic infections
caused by aerobic gram-negative organisms,
including those caused by E. coli, Serratia, Proteus,
Klebsiella, and Pseudomonas.
Enterococcal infections
administered
concurrently
with
a
penicillin,
cephalosporin, or vancomycin for treatment.
Systemic bacterial infections
given parenterally because they are poorly absorbed
from the GI tract.
Ototoxicity
recognized by hearing impairment, dizziness, loss of
balance, persistent headache, and ringing in the ears.
aminoglycosides are usually discontinued when
symptoms of hearing impairment first appear.
Nephrotoxicity
recognized by abnormal urinary function tests, such as
elevated serum creatinine or BUN.
Nephrotoxicity is usually reversible.
AMINOGLYCOSIDES
SULFONAMIDES
•
FLUOROQUINOLONES
•
•
•
•
•
•
•
•
•
•
•
The first drug in this class, nalidixic acid (NegGram),
was approved by the FDA in 1962. Its use was
restricted to UTIs.
were once reserved only for UTIs because of their
toxicity
bactericidal and affect DNA synthesis by inhibiting
two bacterial enzymes: DNA gyrase and
topoisomerase IV.
have activity against gram-negative pathogens;
newer ones are significantly more effective against
gram-positive microbes
Clinical applications include infections of the
respiratory, GI, and genitourinary tracts, and some skin
and soft-tissue infections.
Most are well absorbed orally and may be
administered either once or twice a day.
may be taken with food, they should not be taken
concurrently with multivitamins or mineral
supplements
most common side effects: nausea, vomiting, and
diarrhea
serious
adverse
effects:
dysrhythmias
(moxifloxacin) and potential hepatotoxicity
Most widely used fluoroquinolone, ciprofloxacin
(Cipro), is an drug of choice for the postexposure
prophylaxis of Bacillus anthracis, the organism
responsible for causing anthrax.
discovery of the sulfonamides in the 1930s heralded a
new era in the treatment of infectious disease.
•
significantly reduced mortality from susceptible
microbes and earned their discoverer a Nobel Prize in
Medicine.
•
bacteriostatic and active against a broad spectrum
of microorganisms
•
suppress bacterial growth by inhibiting the synthesis
of folic acid, or folate.
•
for the treatment of Pneumocystis carinii
pneumonia and shigella infections of the small
bowel.
Side Effects
•
formation of crystals in the urine
•
hypersensitivity reactions
•
nausea, and vomiting.
Not common but potentially fatal blood abnormalities
•
aplastic anemia
•
acute hemolytic anemia
•
Agranulocytosis
SULFONAMIDES
URINARY ANTISEPTICS
•
•
•
•
drugs given by the PO route for their antibacterial
action in the urinary tract.
their actions are specific to the urinary system.
able to treat local infections in the urinary tract without
reaching high levels in the blood that might produce
systemic toxicity
Although not considered first-line drugs for UTI, they
serve important roles as secondary medications,
especially in patients who present with infections
resistant to TMP-SMZ or the fluoroquinolones.
URINARY ANTISEPTICS
•
•
•
Linezolid
for severe infections from S. aureus and S.
pneumoniae.
Daptomycin
treatment of serious skin and skin-structure infections
Telithromycin
prescribed for respiratory infections.
TUBERCULOSIS
•
•
•
•
•
•
highly contagious infection caused by the organism
Mycobacterium tuberculosis
Mycobacterium tuberculosis
invades the lung
activates the body’s immune defenses
have a cell wall that is resistant to penetration by antiinfective drugs.
Additonal Info
For medications to reach the microorganisms isolated
in the tubercles, therapy must continue for 6-12
months
For patients with multidrug-resistant infections and
require therapy for as long as 24 months.
TYPICAL REGIMEN FOR PATIENTS WITH NO
COMPLICATING FACTORS
•
•
•
ANTITUBERCULAR DRUGS
OTHER ANTIBACTERIAL DRUGS
•
•
•
•
•
•
•
•
•
•
CARBAPENEMS
Imipenem (Primaxin), ertapenem (Invanz), doripenem
(Doribax), and meropenem (Merrem IV) belong to a
relatively new class of antibiotics
bactericidal and have some of the broadest
antimicrobial spectrums of any class of antibiotics.
They contain a beta-lactam ring and kill bacteria by
inhibiting construction of the cell wall. The ring in
carbapenems is very resistant to destruction by betalactamase.
Imipenem
broadest antimicrobial spectrum and is the most widely
prescribed drug in this small class.
always administered in a fixed-dose combination with
cilastatin, which increases the serum levels of the
antibiotic.
Meropenem
approved only for peritonitis and bacterial meningitis
Ertapenem
narrower spectrum but longer half-life than the other
carbapenems
approved for the treatment of serious abdominopelvic
and skin infections, community-acquired pneumonia,
and complicated UTI
Clindamycin
for abdominal infections caused by bacteroides.
Metronidazole
anti-infective that is effective against anaerobes.
Quinupristin
C: Streptogramins, treatment of vancomycin-resistant
Enterococcus faecium infections.
Initial Phase
2 months of daily therapy with isoniazid, rifampin
(Rifadin, Rimactane), pyrazinamide (PZA), and
ethambutol (Myambutol).
If C&S testing reveals that the strain is sensitive to the
first three drugs, ethambutol is dropped from the
regimen.
Continuation Phase
4 months of therapy with isoniazid and rifampin, two to
three times per week.
•
•
•
First-line Drugs
Generally, the most effective and best tolerated by
patients
Second-line Drugs
more toxic and less effective than the first-line agents
used when resistance develops
ANTITUBERCULOSIS DRUGS
FUNGAL INFECTIONS
•
•
•
•
•
•
•
•
•
•
•
Characteristics of Fungi
Fungi - are single-celled or multicellular organisms
whose primary role on the planet is to serve as
decomposers of dead plants and animals, returning
their elements to the soil for recycling.
Yeasts
which include the common pathogen
Candida albicans, are unicellular fungi.
Most exposure to pathogenic fungi occurs through
inhalation of fungal spores or by handling
contaminated soil.
The lungs serve as a route for invasive fungi to enter
the body and infect internal organs.
Unlike bacteria, which grow rapidly to overwhelm
hosts’ defenses, fungi grow slowly, and infections
may progress for many months before symptoms
develop.
The human body is remarkably resistant to infection by
these organisms, and patients with healthy immune
systems experience few serious fungal diseases.
Patients who have a suppressed immune system,
however, such as those infected with HIV, may
experience frequent fungal infections, some of
which may require aggressive pharmacotherapy
Patients with intact immune defenses are afflicted
with community acquired infections:
Blastomycosis
Histoplasmosis
Sporotrichosis
Coccidioidomycosis
Opportunistic Fungal Infections
acquired in a nosocomial setting are more likely to be
candidiasis, aspergillosis, cryptococcosis, and
mucormycosis
FUNGAL PATHOGENS
IV. Drugs for Fungal, Protozoan, and
Helminthic Infections
CLASSIFICATION OF MYCOSES
•
Fungal infections are called mycoses. A simple and
useful method of classifying mycoses is to consider
them as either superficial or systemic.
Superficial mycoses
It affects the scalp, skin, nails, and mucous
membranes such as the oral cavity and vagina.
Mycoses of this type are often treated with topical
drugs because the incidence of adverse effects is
much lower using this route of administration.
Systemic mycoses
Systemic mycoses are those affecting internal organs,
typically the lungs, brain, and digestive organs.
Although much less common than superficial
mycoses, systemic fungal infections affect multiple
body systems and are sometimes fatal to patients with
suppressed immune systems.
Mycoses of this type require aggressive oral or
parenteral medications that produce more adverse
effects than the topical agents.
•
•
•
•
•
•
•
•
AZOLES
•
MECHANISM OF ACTION OF ANTIFUNGAL
DRUGS
•
•
•
•
•
Biologically, fungi are classified as eukaryotes; their
cellular structure and metabolic pathways are more
similar to those of humans than to bacteria.
Anti-infectives that are efficacious against bacteria
are ineffective in treating mycoses because of these
differences in physiology. Thus, an entirely different
set of drugs is needed to eliminate fungal infections.
One important difference between fungal cells and
human cells is the steroid used in constructing
plasma membranes.
The largest class of antifungal drugs, the azoles,
inhibits ergosterol biosynthesis, causing the fungal
plasma membrane to become porous or leaky.
Ergosterol
is
present
in
fungi.
→ Amphotericin B (Fungizone), terbinafine
(Lamisil), and nystatin (Mycostatin) also act by
this mechanism.
•
PHARMACOTHERAPY OF SYSTEMIC FUNGAL
DISEASES
•
•
•
•
The AIDS epidemic, however, has resulted in the
frequent clinical occurrence of previously rare
mycoses,
such
as
cryptococcosis
and
coccidioidomycosis.
Opportunistic fungal disease in patients with AIDS
spurred the development of several new drugs for
systemic fungal infections over the past 20 years.
Others who may experience systemic mycoses
include those patients who are receiving prolonged
therapy
with corticosteroids,
experiencing
extensive burns, receiving antineoplastic drugs,
having indwelling vascular catheters, or having
recently received organ transplants.
There are relatively few drugs available for treating
systemic mycoses. Amphotericin B has been the
preferred drug for systemic fungal infections since the
1960s.
The azole drugs consist of two different chemical
classes, the imidazoles and the triazoles. Azole
antifungal drugs interfere with the biosynthesis of
ergosterol, which is essential for fungal cell
membranes. Depleting fungal cells of ergosterol
impairs their growth.
PHARMACOTHERAPY WITH THE AZOLE
ANTIFUNGALS
•
Fluconazole (Diflucan), itraconazole (Sporanox),
ketoconazole (Nizoral), and voriconazole (Vfend)
are used for both systemic and topical infections.
•
The systemic azole drugs have a spectrum of
activity similar to that of amphotericin B, are
considerably less toxic, and have the major
advantage that they can be administered PO.
Because of these characteristics, azoles have
replaced amphotericin B in the pharmacotherapy of
less serious systemic fungal infections.
→ The most common adverse effects of the
systemic azoles are nausea and vomiting.
Anaphylaxis and rash have been reported. Fatal
drug-induced
hepatitis
has
occurred
with
ketoconazole, although the incidence is rare and has
not been reported with the other systemic azoles.
Itraconazole has begun to replace ketoconazole in
the therapy of systemic mycoses because it is less
hepatotoxic and may be given either orally or
intravenously.
Posaconazole (Noxafil) is used to prevent invasive
Candida
and
Aspergillus
infections
in
immunosuppressed patients.
Azoles may affect glycemic control in patients with
diabetes. Various reproductive abnormalities have
been reported with systemic azoles, including
menstrual irregularities, gynecomastia in men, and a
decline in testosterone levels. Decreased libido and
temporary sterility in men are other potential side
effects. The azoles should be used with caution in
pregnant patients.
SYSTEMIC AZOLES
ANTIFUNGAL DRUGS
Drugs for Systemic Fungal Infections
Systemic or invasive fungal disease may require
intensive pharmacotherapy for extended periods.
Amphotericin B (Fungizone) and fluconazole
(Diflucan) are preferred drugs for these serious
infections.
The newer azole drugs such as itraconazole are
considerably safer and have become preferred drugs
for less severe infections.
Flucytosine (Ancobon) is sometimes combined with
amphotericin B to treat septicemia or pulmonary and
urinary tract infections due to Candida and
Cryptococcus species. Flucytosine can cause
immunosuppression, renal impairment, and liver
toxicity.
β-glucan synthesis inhibitors have been added to
the treatment options for systemic mycoses.
Caspofungin (Cancidas), anidulafungin (Eraxis),
and micafungin (Mycamine) are important
alternatives to amphotericin B in the treatment of
invasive candidiasis.
→ Adverse effects include phlebitis,
headaches,
and possible renal or hepatic
impairment.
•
•
•
•
TOPICAL AZOLES
•
Clotrimazole (Mycelex, others) is a preferred drug
for superficial fungal infections of the skin, vagina,
and mouth. Fluconazole and itraconazole are
additional options for oral candidiasis. Several of the
azoles are available to treat vulvovaginal candidiasis,
including
tioconazole,
miconazole.
butoconazole,
and
PHARMACOTHERAPY OF SUPERFICIAL
FUNGAL INFECTIONS
•
•
Antifungal drugs applied topically are much safer
than their systemic counterparts because penetration
into the deeper layers of the skin or mucous
membranes is poor and only small amounts are
absorbed into the circulation.
Adverse effects are generally minor and limited to
the region being treated. Burning or stinging at the
site of application, drying of the skin, rash, or contact
dermatitis are the most frequent side effects from the
topical agents.
PHARMACOTHERAPY OF NON MALARIAL
PROTOZOAN INFECTIONS
•
•
•
•
PROTOZOAN INFECTIONS
•
•
•
Protozoa
single-celled organisms that inhabit water, soil, and
animal hosts
These parasites often thrive in conditions where
sanitation and personal hygiene are poor and
population density is high. In addition, protozoan
infections often occur in patients who are
immunosuppressed, such as those with AIDS or who
are receiving antineoplastic drugs.
•
HELMINTHIC INFECTIONS
ANTIPROTOZOAL DRUGS
•
•
•
Pharmacotherpay of Malaria
Drug therapy of protozoan infections is difficult. When
faced with adverse conditions, protozoans can form
cysts. With few exceptions, antibiotic, antifungal, and
antiviral drugs are ineffective against protozoans.
Malaria is caused by four species of the protozoan
Plasmodium. Malaria is the second most common
fatal infectious disease in the world, with 300 to 500
million cases occurring annually.
→ It begins with a bite from an infected female
Anopheles mosquito, which is the carrier for the
parasite. Plasmodium multiplies in the liver and
transforms into progeny called merozoites. The
merozoites infect red blood cells, which eventually
rupture, releasing more merozoites, and causing
severe fever and chills. This phase is called the
erythrocytic stage of the infection
Pharmacotherapy of malaria attempts to interrupt the
complex life cycle of Plasmodium.
•
Prevention of the disease
Treatment of acute attacks
Prevention of relapse
•
The Food and Drug Administration (FDA) approved
the use of a fixed-dose combination of artemether/
lumefantrine (Coartem) to treat acute, uncomplicated
malaria infections.
Artemether is prepared from substances obtained
from the Chinese herb Artemisa annua, which had
been known to have antimalarial properties for over a
thousand years.
Lumefantrine extends the half-life of the combination
drug. Coartem is significant because it is very
effective and offers an additional option for treating
chloroquine-resistant infections. This drug is
approved for treatment, not prevention, of malaria.
•
•
Helminths
consist of various species of parasitic worms, which
have more complex anatomy, physiology, and life
cycles than the protozoans.
PHARMACOTHERAPY OF HELMINTHIC
INFECTIONS
•
•
•
•
GOALS OF ANTIMALARIAL THERAPY
•
•
•
These infections include amebiasis, toxoplasmosis,
giardiasis,
cryptosporidiosis,
trichomoniasis,
trypanosomiasis, and leishmaniasis.
Protozoans can invade nearly any tissue in the body.
→ Examples: Plasmodia prefer erythrocytes,
Giardia the colon, and Entamoeba travels to the
liver
In such regions, parasitic infections are endemic and
contribute significantly to mortality, especially in
children, who are often more susceptible to the
pathogens. Several of these infections occur in
severely immunocompromised patients
Caused by the protozoan Entamoeba histolytica,
amebiasis is common in Africa, Latin America, and
Asia
E. histolytica can invade the liver and create
abscesses. The primary symptom of amebiasis is
amebic dysentery, a severe form of diarrhea.
Metronidazole (Flagyl) has been the traditional drug
of choice for non malarial protozoan infections. In
2005, tinidazole (Tindamax) was approved by the
FDA for treatment of trichomoniasis, giardiasis, and
amebiasis.
•
Helminths
are
classified
as
roundworms
(nematodes), flukes (trematodes), or tapeworms
(cestodes).
For ascariasis, oral mebendazole (Vermox) for 3 days
is the standard treatment.
Pharmacotherapy of enterobiasis includes a single
dose of mebendazole, albendazole (Albenza) or
pyrantel (Antiminth, Ascarel, Pin-X, Pinworm
Caplets).
Not all helminthic infections require pharmacotherapy
When the infestation is severe or complications
occur, pharmacotherapy is initiated. Complications
caused by extensive infestations may include
physical obstruction in the intestine, absorption,
increased risk for secondary bacterial infections, and
severe fatigue.
Pharmacotherapy is targeted at killing the parasites
locally in the intestine and systemically in the tissues
and organs they have invaded. Some anthelmintics
have a broad spectrum and are effective against
multiple organisms, whereas others are specific for a
certain species. Resistance has not yet become a
clinical problem with anthelmintics.
V. DRUGS FOR VIRAL INFECTIONS
VIRUSES
•
tiny infectious agents capable of causing disease in
humans and other organisms. They are nonliving
agents that infect bacteria, plants, and animals.
Viruses contain none of the cellular organelles
necessary for self-survival that are present in living
organisms.
T4 lymphocyte.The virus uncoated and the genetic
material of HIV,single-stranded RNA, enters the host
cell. HIV converts its RNA strands to double-stranded
DNA, using the viral enzyme reverse transcriptase.
The viral DNA eventually enters the nucleus of the T4
lymphocyte where it becomes incorporated into the
host’s chromosomes. This action is performed by HIV
integrase, another enzyme unique to HIV. It may
remain in the host DNA for many years before it
becomes activated to begin producing more viral
particles. The new virions eventually bud from the
host cell and enter the bloodstream. The new virions,
however, are not yet infectious. As a final step, the
viral enzyme protease cleaves some of the proteins
associated with the HIV DNA, enabling the virion to
infect other T4 lymphocytes. Once budding occurs,
the immune system recognizes that the cell is
infected and kills the T4 lymphocyte. Unfortunately,it
is too late; a patient who is infected with HIV may
produce as many as 10 billion new virions every day,
and the patient’s devastated immune system is
unable to remove them.
CHARACTERISTICS OF VIRUSES
Capsid
Viral
Envelope
•
•
•
•
•
Surrounded by a protective protein coat
contains glycoprotein and protein
“spikes” that are recognized as foreign
by the host’s immune system and trigger
body defenses to remove the invader
Virion
A mature infective particle
They infect their host by locating and entering a target
cell and then using the machinery inside that cell to
replicate.
Intracellular Parasites
They must be inside a host cell to cause infection.
The host organism and cell are often very specific; it
may be a single species of plant, bacteria, or animal,
or even a single type of cell within that species. Most
often viruses infect only one species.
Rhinoviruses
cause the common cold, are self-limiting and require
no medical intervention.
Hepatitis B virus
can cause permanent liver damage and increase a
patient’s risk of hepatocellular carcinoma.
REPLICATION OF HIV
ANTIVIRAL PHARMACOTHERAPY
•
•
Antiviral pharmacotherapy can be extremely
challenging because of the rapid mutation rate of
viruses, which can quickly render drugs ineffective.
Complicating therapy
the intracellular nature of the virus, which makes it
difficult to eliminate the pathogen without giving
excessively high doses of drugs that injure normal
cells.
THREE BASIC STRATEGIES USED FOR
ANTIVIRAL PHARMACOTHERAPY
1
2
3
Prevent viral infections through the administration of
vaccines
Treat active infections with drugs such as acyclovir
(Zovirax) that interrupt an aspect of the virus’s
replication cycle.
For prophylaxis, use drugs that boost the patient’s
immune response (immunostimulants) so that the
virus remains in latency with the patient symptom
free.
HIV-AIDS
Human Immunodeficiency Virus (HIV)
Antiretroviral drugs slow the growth of the causative
agent for AIDS, the human immunodeficiency virus
(HIV), by several mechanisms. Resistance to these
drugs is a major clinical problem, and a
pharmacologic cure for HIV-AIDS is not yet
achievable.
Acquired Immune Deficiency Syndrome (AIDS)
•
Acquired immune deficiency syndrome (AIDS) is
characterized by profound immunosuppression that
leads to opportunistic infections and malignancies not
commonly found in patients with healthy immune
defenses.
•
GENERAL PRINCIPLES OF HIV
PHARMACOTHERAPY
•
•
REPLICATION OF HIV
•
Shortly after entry into the body, the virus attaches to
its preferred target—the CD4 receptor on T4 (helper)
lymphocytes. During this early stage, structural
proteins on the surface of HIV fuse with the CD4
receptor. Coreceptors known as CCR5 and CXCR4
have been discovered that assist HIV in binding to the
All living organisms make RNA from DNA. Because
of their “backward” or reverse synthesis, these
viruses are called retroviruses, and drugs used to
treat HIV infections are called antiretrovirals.
•
•
Latent Phase
patients are asymptomatic and may not even realize
they are infected.
Symptomatic Phase
The decision to begin therapy during the symptomatic
phase is much easier because the severe symptoms
of AIDS can rapidly lead to death. Thus, therapy is
nearly always initiated during this phase when the
CD4 T-cell count falls below 200 cells/mcL or when
AIDS-defining symptoms become apparent.
Viral Load
determined by measuring the amount of HIV RNA in
the blood.
CLASSIFICATION OF DRUGS FOR HIV-AIDS
•
Highly Active Antiretroviral Therap (HAART)
The goal of HAART is to reduce the plasma HIV RNA
to its lowest possible level. It must be understood,
however, that HIV is harbored in locations other than
the blood, such as lymph nodes; therefore,
elimination of the virus from the blood is not a cure.
The simultaneous use of drugs from several classes
reduces the probability that HIV will become resistant
to treatment.
HIV-AIDS antiretrovirals are classified into the
following groups, based on their mechanisms of
action:
•
•
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•
•
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•
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•
PHARMACOTHERAPY WITH REVERSE
TRANSCRIPTASE INHIBITORS
Basic Postexposure Prophylaxis treatment includes
one of the following regimens, conducted over a 4week period
•
Zidovudine and lamivudine.
•
Zidovudine and emtricitabine.
•
Lamivudine and tenofovir.
•
Tenofovir and emtricitabine
Herpesviruses
•
Herpes simplex viruses (HSVs) are a family of DNA
viruses that cause repeated blister-like lesions on the
skin, genitals, and other mucosal surfaces. Antiviral
drugs can lower the frequency of acute herpes
episodes and diminish the intensity of acute disease.
The reverse transcriptase inhibitors block HIV
replication at the level of the reverse transcriptase
enzyme. These include the NRTIs, NNRTIs, and the
NtRTIs.
Drugs in the NNRTI class act by binding near the
active site, causing a structural change in the enzyme
molecule. The enzyme can no longer bind
nucleosides and is unable to construct viral DNA.
As a class, the NRTIs are well tolerated, although
nausea, vomiting, diarrhea, headache, and fatigue
are common during the first few weeks of therapy.
The NNRTIs are also generally well tolerated and
exhibit few serious adverse effects.
Drugs in the protease inhibitor class block the viral
enzyme protease, which is responsible for the final
assembly of the HIV virions. They have become key
drugs in the pharmacotherapy of HIV infection.
The protease inhibitors inhibit the final assembly of
the HIV virion. They are always used in combination
with other antiretrovirals.
Atazanavir and darunavir Ritonavir
ritonavir boosting Addition of small amounts of
ritonavir allows less frequent dosing intervals and
increases the plasma concentration of the primary
protease inhibitor.
ENTRY INHIBITORS AND INTEGRASE
INHIBITOR
•
Entry inhibitors prevent the entry of the viral nucleic
acid into the T4 lymphocyte. HIV Integrase inhibitors
prevent integrase enzymes from inserting its viral
DNA strand into the human chromosome.
Enfuvirtide (Fuzeon)
Maraviroc (Selzentry)
•
•
PHARMACOTHERAPY WITH PROTEASE
INHIBITOR
•
•
Nucleoside/nucleotide
reverse
transcriptase
inhibitors (NRTIs/NtRTIs).
Non-Nucleoside reverse transcriptase inhibitors
(NNRTIs).
Protease inhibitors (PIs).
Entry inhibitors (includes fusion inhibitors and CCR5
antagonists).
Integrase inhibitors.
Initial Therapy of HIV Infection
NNRTI-based regimen: efavirenz + tenofovir +
emtricitabine.
PI-based regimens: • atazanavir (ritonavir-boosted) +
tenofovir + emtricitabine. • darunavir (ritonavirboosted) + tenofovir + emtricitabine.
Integrase
inhibitor–based
regimen:
raltegravir+tenofovir +emtricitabine.
Reverse Transcriptase Inhibitors
(NRTIs, NNRTIs, and NTRTIs)
This class includes nonnucleoside reverse
transcriptase inhibitors, which bind directly to the viral
enzyme reverse transcriptase and inhibit its function,
and nucleotide reverse transcriptase inhibitors.
PROTEASE INHIBITORS
•
PHARMACOTHERAPY WITH ENTRY INHIBITORS
AND INTEGRASE INHIBITORS
Because HIV develops resistance to most of the
frequently prescribed antiretrovirals, scientists have
been looking intensively for unique mechanisms of
drug action.
PREVENTION OF HIV INFECTION
•
Scientists are still far from developing a vaccine to
prevent AIDS. A few HIV vaccines are currently in
clinical trials, but none is expected to cause a major
impact on the HIV epidemic. At best, the HIV vaccines
produced thus far only boost the immune response;
they are unable to prevent the infection or its fatal
consequences. Although the immune response boost
may help a patient already infected with the virus to
better
PREVENTION OF PERINATAL TRANSMISSION
•
The risk of perinatal transmission of HIV can be
markedly reduced by implementing drug therapy of
the mother during pregnancy and the newborn
following birth.
POSTEXPOSURE PHROPHYLAXIS OF HIV
INFECTION FOLLOWING OCCUPATIONAL
EXPOSURE
PHARMACOTHERAPY OF HERPESVIRUS
INFECTIONS
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•
•
•
Herpesviruses are usually acquired through direct
physical contact with an infected person, but they
may also be transmitted from infected mothers to
their newborns,sometimes resulting in severe CNS
disease.
Oral antiviral therapy
acyclovir (Zovirax)
famciclovir (Famvir) valacyclovir (valtrex)
HERPESVIRUS FAMILY
•
•
•
•
•
•
HSV-1. Primarily infections of the eye, mouth, and
lips, although the incidence of genital infections is
increasing.
HSV-2 Primarily genital infections.
Cytomegalovirus (CMV). Affects multiple body
systems in immunosuppressed patients.
Varicella-zoster virus (VZV). Shingles (zoster) and
chickenpox (varicella).
Epstein–Barr virus (EBV). Infectious mononucleosis
and a form of cancer called Burkitt’s lymphoma.
Herpesvirus-type 6. Roseola in children and hepatitis
or encephalitis in immunosuppressed patients.
VI. Drugs for Neoplasia
INFLUENZA
•
Influenza is a viral infection characterized by acute
symptoms that include sore throat, sneezing,
coughing, fever, and chills. The infectious viral
particles are easily spread via airborne droplets. In
immunosuppressed patients, an influenza infection
may be fatal.
PHARMACOTHERAPY OF INFLUENZA
•
•
•
•
•
Drugs are available to prevent and to treat influenza
infections. Vaccination is the best choice, because
drugs are relatively ineffective once influenza
symptoms appear.
Amantadine (Symmetrel)
Chemoprophylaxis with amantadine (Flumadine)
Oseltamivir
zanamivir
VIRAL HEPATITIS
•
Viral hepatitis is a common infection caused by a
number of different viruses: Hepatitis A, Hepatitis B,
and
Hepatitis. All hepatitis viruses cause
inflammation and necrosis of liver cells and produce
similar symptoms.
PHARMACOTHERAPY OF VIRAL HEPATITIS
•
•
•
•
•
•
Hepatitis A and B are best treated through
immunization. Newer drugs for HBV are pies for
chronic hepatitis.
Hepatitis A
Hepatitis A virus (HAV) is spread by the oral–fecal
route and causes epidemics in regions of the world
having poor sanitation. Outbreaks in the United
States are most often sporadic events caused by the
consumption of contaminated food.
Hepatitis A Vaccine (Havrix, VAQTA)
HA Ig
Hepatitis B
Hepatitis B virus (HBV) in the United States is
transmitted
primarily
through
exposure
to
contaminated blood and body fluids. Major risk
factors for HBV infection include injected drug abuse,
sex with an HBV-infected partner, and sex between
men. Health care workers are at risk because of
accidental exposure to HBV-contaminated needles or
body fluids.
Hepatitis B Vaccine
CANCER
•
•
•
•
one of the most feared diseases in the society
No symptoms Painful Treatments
May strike at an early age.
No cure
ANTICANCER DRUGS, ANTINEOPLASTICS, OR
CANCER CHEMOTHERAPEUTIC AGENTS
•
Medications used to treat cancer.
CHARACTERISTICS OF CANCER
•
•
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Cancer
Also known as carcinoma
Characterized by abnormal, uncontrolled cell
division.
Due to the damage in genes controlling cell growth.
Ultraviolet (UV) Light
known cause of skin cancer.
Metastasis
Invasion of abnormal or cancer cells to distant sites
to populate new tumors.
Tumors
A swelling, abnormal enlargement, or a mass due to
cancer cells.
Neoplasm is oftentimes used interchangeably with it.
Can be solid masses or widely disseminated through
the blood.
Named according to their tissue of origin, generally
with the suffix -oma.
CLASSIFICATION AND NAMING OF TUMORS
THREE DIFERENT THERAPIES FOR CHRONIC
HBV PHARMACOTHERAPY
•
•
•
•
Interferon alfa or PEG
Between 30% to 40% of patients respond to 4 months
of therapy. However, 5% to 10% of these patients
relapse after completion of therapy.
interferon Lamivudine (Epivir)
Between 25% to 45% of patients respond to therapy,
which lasts 1 year or longer. Emergence of resistant
viral strains is becoming a clinical problem.
Adefovir (Hepsera)
Approximately 50% of patients respond to 48 weeks
of therapy. The drug is new, and long-term studies are
in progress.
Hepatitis C and Other Hepatitis Viruses
The hepatitis C, D, E, and G viruses are sometimes
referred to as non A–non B viruses. Of the non A–non
B viruses, Hepatitis C has the greatest clinical
importance.
CAUSES OF CANCER
•
•
•
Carcinogens
Factors that are known to cause or to be associated
with a higher risk of acquiring cancer.
Chemical Carcinogens
Tobacco smoke Alcohol ingestion (esophageal, oral,
breast, and liver cancers) Exposure to asbestos and
benzene
Physical Factors
Attributed to Cancer exposure to large amounts of Xrays – leukemia UV (Ultraviolet rays) – skin cancer
•
The site of cancer may be distant from the entry
location, as with bladder cancer caused by the
inhalation of certain industrial chemicals. It is
estimated that viruses are associated with about 15%
of all human cancers. Examples include:
1. herpes simplex types I and II
2. Epstein-Barr
3. Human papillomavirus(HPV)
4. Cytomegalovirus
5. Human T-lymphotropic viruses
Factors that suppress the immune system, such as
HIV or drugs given after transplant surgery, may
encourage the growth of cancer cells. Some cancers
have a strong genetic component.
•
Tumor suppressor genes - may inhibit the formation
of tumors and damage to these genes may result in
cancer
•
Damage to the suppressor gene p53 is associated
with cancers of the breast, lung, brain, colon, and
bone.
•
Although the development of cancer has a genetic
component, it is also greatly influenced by factors in
the environment.
•
Maintaining or adopting healthy lifestyle habits can
reduce the risk of acquiring cancer
•
Following proper nutrition, avoiding chemical and
physical risks, and maintaining a regular schedule of
health checkups can help prevent cancer from
developing into a fatal disease.
•
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•
Lifestyle factors regarding cancer prevention or
diagnosis:
Eliminate tobacco use and exposure to secondhand
smoke.
Limit or eliminate alcoholic beverage use.
Maintain a healthy diet low in fat and high in fresh
vegetables and fruit.
Choose most foods from plant sources; increase fiber
in the diet.
Exercise regularly and maintain body weight within
recommended guidelines.
Self-examine your body monthly for abnormal lumps
and skin lesions.
Avoid chronic or prolonged exposure to direct
sunlight and/or wear protective clothing or sunscreen.
Have periodic diagnostic testing performed at
recommended intervals:
→ Women should have periodic mammograms,
according to the schedule recommended by their
health care provider.
→ Men should receive prostate screening, as
recommended by their health care provider.
→ Both men and women should receive a
screening colonoscopy, according to the schedule
recommended by their health care provider.
→ Women who are sexually active or have
reached age 18 should have a Pap test every 3-5
years, or as directed by their health care provider.
GOALS OF CANCER CHEMOTHERAPY: CURE,
CONTROL, AND PALLIATION
•
•
•
Chemotherapy
also known as the pharmacotherapy of cancer
it can reach cancer cells virtually in any location of the
body.
Chemotherapy has three general goals: cure, control,
and palliation.
THREE GENERAL GOALS
Cure
Control
Palliation
The primary goal desired by most patients
is to achieve a complete cure; that is,
permanent removal of all cancer cells from
the body.
When cancer has progressed and a cure is
not possible, a second goal of
chemotherapy is to control or manage the
disease.
It is used in times when cure or control may
not be achievable. Reduce the size of the
tumor and ease the severity of pain and
other tumor symptoms, thus improving the
quality of life.
GOALS OF CANCER CHEMOTHERAPY: CURE,
CONTROL, AND PALLIATION
Chemotherapy
can be used alone or in combination with other
treatment modalities such as surgery or radiation
therapy.
Surgery
•
useful for removing solid tumors that are localized.
Radiation Therapy
•
Approximately 50% of patients with cancer receive
this as part of their treatment since it is the most
successful and produces the fewest adverse effects
for cancers that are localized. It is prescribed
postoperatively
Adjuvant Chemotherapy
•
administration of antineoplastic drugs after surgery or
radiation therapy.
•
Drugs are given as chemoprophylaxis but it is
uncommon since most of the drugs used have
potentially serious adverse effects.
Example:
•
patients who have had a primary breast cancer
removed may receive tamoxifen, even if there is no
evidence of metastases because there is a high
likelihood that the disease will recur.
•
GROWTH FRACTION AND SUCCESS OF
CHEMOTHERAPY
•
Normal and cancerous cells go through a sequence
of events known as the cell cycle.
STAGES OF THE CELL CYCLE
G0 Phase
also known as the resting stage
phase during which cells conduct their everyday
activities such as metabolism, impulse conduction,
contraction, or secretion.
G1 Phase
•
occurs when the cell receives a signal to divide the
synthesis of the RNA, proteins, and other
components needed to duplicate its DNA during the
S phase.
G2 Phase
•
Also known as the pre mitotic phase Follows after the
duplication of the DNA 4. M phase. The phase where
the cells divide The cells reenter the G0 phase until
further notice
•
The actions of many of the antineoplastic drugs are
specific to certain phases of the cell cycle, whereas
others are mostly independent of the cell cycle.
Examples: Mitotic Inhibitors like Vincristine (Oncovin) – M
Phase Antimetabolites like Fluorouracil (Efudex) – S
•
•
Phase Alkylating agents like cyclophosphamide (Cytoxan)
- generally independent of the phases of the cell cycle.
•
•
Sometimes the optimum dosing schedule must be
delayed until the patient sufficiently recovers from the
drug toxicities, especially bone marrow suppression.
The specific dosing schedule depends on the type of
tumor, the stage of the disease, and the patient’s
overall condition.
TOXICITY OF ANTINEOPLASTIC DRUGS
•
GROWTH FRACTION AND SUCCESS OF
CHEMOTHERAPY
•
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Growth Fraction
measure of the number of cells undergoing mitosis in
a tissue.
ratio of the number of replicating cells to the number of
resting cells.
Antineoplastic Drugs
much more toxic to tissues and tumors with high
growth fractions.
Low Growth Fractions
Less sensitive to antineoplastic drugs
Solid Tumors such as Breast and Lung Cancer
High Growth Fractions
Highly sensitive to chemotherapy = greater
antineoplastic success rate
Certain leukemias and lymphomas
!!!!Take note!!!!
Hair follicles, bone marrow, and the gastrointestinal
(GI) epithelium, also have a high growth fraction which
means that they are more sensitive to the effects of the
antineoplastics.
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ACHIEVING A TOTAL CANCER CURE
•
•
•
Every cancer cell should be eliminated to cure a
patient but doing so is a very difficult task. An example
is a small breast tumor which may contain 1 billion
cancer cells.
No drug can totally kill 100% of all the cancer cells
however, it can decrease the burden sufficiently so that
the immune system can fend off the cancerous cells
on its own.
This idea reinforces the importance of diagnosing and
treating tumors at an early stage when the number of
cancer cells is smaller.
SPECIAL CHEMOTHERAPY PROTOCOLS AND
STRATEGIES
•
Tumor cells exhibit a high mutation rate that continually
changes their genetic structure.
•
Complicating the chances for a cure is that cancer
cells often develop resistance to antineoplastic drugs.
•
The effectiveness of such drugs deteriorates over time
because the tumor becomes “refractory” to treatment.
Combination Chemotherapy
•
The use of multiple drugs affects different stages of the
cancer cell’s life cycle. It attacks the various clones
within the tumor via several mechanisms of action
which increases the percentage of cells killed.
•
Allows lower dosages of antineoplastics, reducing
toxicity and slowing the development of resistance.
Example:
cyclophosphamide-methotrexate-fluorouracil
(CMF) for breast cancer cyclophosphamide-doxorubicin
vincristine (CDV) for lung cancer
Dosing Schedules
•
Specific dosing schedules, or protocols, have been
found to increase the effectiveness of antineoplastic
drugs.
•
•
•
All anticancer drugs have the potential to cause
serious toxicity. High dosages always result in adverse
effects on the patient, affecting normal cells. Because
of these, they are classified according to their emetic
potential. Some of these effects include:
1. Alopecia – hair loss
2. Mucositis – inflammation of the epithelial lining of
the digestive tract
3. Nausea and Vomiting
Before starting therapy with the highest emetic
potential medications, patients may be pretreated with
antiemetic drugs such as:
1. ondansetron (Zofran)
2. prochlorperazine (Compazine)
3. metoclopramide (Reglan, others)
4. lorazepam (Ativan)
Stem cells in the bone marrow may be destroyed by
antineoplastics, causing anemia, leukopenia, and
thrombocytopenia. Severe bone marrow suppression
is a contraindication to therapy with most
antineoplastics.
Each antineoplastic drug has a documented nadir, the
lowest point at which the erythrocyte, neutrophil, or
platelet count is depressed by the drug. Although
chemotherapy decreases all types of white blood cells,
neutrophils are the type most affected. A patient is
diagnosed with neutropenia when the neutrophil count
is less than 1,500 cells/mL, leaving them very
susceptible to infections. These patients are placed in
reverse isolations
Efforts to minimize bone marrow toxicity may include
bone marrow transplantation, platelet infusions, or
therapy with growth factors such as epoetin alfa
(Epogen, Procrit), filgrastim (Neupogen), or oprelvekin
(Neumega). When possible, antineoplastics are given
locally by topical application or through direct
instillation into a tumor site to minimize systemic
toxicity. Most antineoplastics, however, must be
administered intravenously.
Because of this effect, antineoplastics are sometimes
classified by their emetic potential.
Each antineoplastic drug has a documented nadir, the
lowest point to which the erythrocyte, neutrophil, or
platelet count is depressed by the drug.
VESICANTS
•
•
•
•
Many antineoplastics fall under this classification
Agents can cause serious tissue injury if they escape
from an artery or vein during an infusion or injection.
Extravasation from an injection site can produce
severe tissue and nerve damage, local infection, and
even loss of a limb.
Central line or Subclavian vein should be used with
vesicants whenever possible.
ANTINEOPLASTICS WITH THE STRONGEST
VESICANT ACTIVITY ACTIVITY INCLUDE:
•
Busulfan, Carmustine, Dacarbazine, Dactinomycin,
Daunorubicin,
Idarubicin,
Mechlorethamine,
Mitomycin, Plicamycin, Streptozocin, Vinblastine,
Vincristine, and Vinorelbine.
•
Cancer survivors face several possible long-term
consequences from chemotherapy.
Example:
Alkylating agents – associated with infertility in both male
and female patients.
PHARMACOTHERAPY WITH HORMONES AND
HORMONE ANTAGONISTS
•
The second concern for long-term survivors is the induction
of secondary malignancies caused by antineoplastic drugs.
The most common is acute nonlymphocytic leukemia
THESE AGENTS MAY BE CLASSIFIED INTO
FOUR GENERAL GROUPS
CLASSIFICATION OF ANTINEOPLASTIC DRUGS
•
•
Drugs used in cancer chemotherapy come from
diverse pharmacologic and chemical classes. Some of
the drug classes attack macromolecules in cancer
cells, such as DNA and proteins, whereas others
poison vital metabolic pathways of rapidly growing
cells.
Classification of the various antineoplastics is quite
variable. The mechanisms by which some
antineoplastics act are not completely understood.
•
•
•
CLASSIFICATION OF ANTINEOPLASTIC DRUGS
•
The primary classifications include:
1. Alkylating agents
2. Antimetabolites
4. Antitumor antibiotics
5. Natural products
6. Hormones and hormone antagonists
7. Biologic response modifiers and
therapies
8. Miscellaneous antineoplastic drugs
•
targeted
•
•
The first alkylating agents, the nitrogen mustards, were
developed in secrecy as chemical warfare agents
during World War II. Although the drugs in this class
have different chemical structures, all share the
common characteristic of forming bonds or linkages
with DNA, a process called alkylation.
Antimetabolites are antineoplastic drugs that
chemically resemble essential building blocks of cells.
These drugs interfere with aspects of the nutrient or
nucleic acid metabolism of rapidly growing tumor cells.
•
•
PHARMCAOTHERAPY WITH ANTITUMOR
ANTIBIOTICS
•
Antitumor antibiotics
Antitumor antibiotics are drugs obtained from bacteria
that have the ability to kill cancer cells. Although not
widely used, they are very effective against certain
tumors.
PHARMACOTHERAPY WITH NATURAL
PRODUCTS
•
•
•
•
Plants have been a valuable source for antineoplastic
drugs. These natural products act by preventing the
division of cancer cells.
subdivisions of natural products used as
antineoplastics:
Vinca alkaloids
Taxanes - cabazitaxel (Jevtana), paclitaxel (Taxol),
and docetaxel (Taxotere)
Topoisomerase I inhibitors - antineoplastics cause
strand breaks that accumulate and permanently
damage the tumor DNA.
Biologic response modifiers are drugs that are used to
enhance the ability of body defenses to destroy cancer
cells.
BRMs include interferons, interleukins, and certain
other cytokines. Some drugs in this class are
immunostimulants.
PHARMACOTHERAPY WITH BIOLOGIC
RESPONSE MODIFIERS AND TARGETED
THERAPIES
PHARMACOTHERAPY WITH ANTIMETABOLITES
•
Corticosteroids
the natural ability of corticosteroids to suppress cell
division in lymphocytes
Gonadal Hormones
Gonadal hormones are used to treat tumor cells that
possess specific hormone receptors.
Estrogen Antagonists
(Antiestrogents)
Secreted by the ovary and the adrenal gland, estrogen
is a hormone that has profound metabolic actions on
many organs.
Androgen Antagonists
Growth of prostatic carcinoma is usually androgen
dependent.
BIOLOGIC RESPONSE MODIFIERS AND
TARGETED THERAPIES
PHARMACOTHERAPY WITH ALKYLATING
AGENTS
•
Use of hormones or their antagonists as antineoplastic
agents is a strategy used to slow the growth of
hormone, dependent tumors. Hormonal therapy is
limited to treating hormone-sensitive tumors of the
breast or prostate.
•
Biologic response modifiers are drugs that are used to
enhance the ability of body defenses to destroy cancer
cells. BRMs include interferons, interleukins, and
certain other cytokines. Some drugs in this class are
immunostimulants.
Target Therapy
an antineoplastic drug that has been specially
engineered to attack these cancer antigens. Unlike
interferons and interleukins, which are considered
general immunostimulants, targeted therapies are
engineered to attack only one specific type of tumor
cell.
Monoclonal antibodies (MABs)
are BRMs that are a type of targeted therapy. Once the
MAB binds to its target cell, the cancer cell dies, or is
marked for destruction by other cells of the immune
response.
MISCELLANEOUS ANTINEOPLASTICS
•
Certain anticancer drugs act through mechanisms
other than those previously described
NCM 106 - PHARMACOLOGY
LECTURE #: DRUGS AFFECTING ENDOCRINE SYSTEM
BSN 2103 1ST SEMESTER AY 2023-2024
TRANSCRIBERS: ARAGO, DELA LUNA, MAGPILI, PALMA, & ROSALES
TOPIC OUTLINE
1
2
3
4
Drugs for Pituitary, Thyroid, and Adrenal Glands
Drugs for Diabetes Mellitus
Drugs for Disorders and Conditions of the Female
Reproductive System
Drugs for Disorders and Conditions of the Male
Reproductive System
Of the remaining, growth hormone and antidiuretic hormone
have the most clinical utility.
Growth Hormone
•
also called somatotropin, stimulates the growth and
metabolism of nearly every tissue in the body. Deficiency
of this hormone in children can cause short stature, a
condition characterized by significantly decreased
physical height compared with the norm of a specific
age group. Severe deficiency results in dwarfism.
Short stature is caused by many conditions other than
GH deficiency, however, and often a specific cause
cannot be identified.
•
can be detected in 20 weeks of gestation (5 months)
through an ultrasound
can be diagnosed from 7-10 years old (stage of growth
influence of child)
symptoms that can be seen in ultrasound:
➢ not proportion of the upper and lower
extremities
➢ Big head
Treating dwarfism with Growth Hormone Therapy is not
applicable since it is not curable.
➢ No human being can manipulate the growth of
infants during pregnancy
➢ It is a genetic factor
Endocrine System
•
•
consists of glands that secrete hormones, chemical
messengers that are released in response to a change
in the body’s internal environment.
The role of hormones is to maintain homeostasis; to
keep physiologic processes within a normal range.
Dwarfism
•
•
•
I. DRUGS FOR PITUITARY, THYROID, AND
ADRENAL DISORDERS
NOTE:
•
Same with anemia, not all anemic can be considered
hypotensive
Hypothalamus and Pituitary Gland
•
•
Two endocrine structures in the brain, the hypothalamus
and the pituitary gland, deserve special recognition
because they control many other endocrine glands.
The hypothalamus secretes releasing hormones that
travel via blood vessels a short distance to the pituitary
gland.
•
•
•
Two Distinct Regions of Pituitary Gland
1. Anterior Pituitary (Adenohypophysis)
•
consists
of
glandular
tissue
and
secretes
adrenocorticotropic hormone (ACTH), TSH, growth
hormone, prolactin, follicle-stimulating hormone (FSH),
and luteinizing hormone (LH).
•
contains nervous tissue rather than glandular tissue.
Neurons in the posterior pituitary store antidiuretic
hormone (ADH) and oxytocin, which are released in
response to nerve impulses from the hypothalamus.
2. Posterior Pituitary (Neurohypophysis)
•
Pharmacotherapy with Hypothalamic and Pituitary
Hormones
•
Out of the 15 different hormones secreted by the
pituitary and the hypothalamus, only a few are used in
pharmacotherapy. It is usually more effective to give
drugs that directly affect secretion at the target organs.
The only hypothalamic hormone used clinically is
gonadotropin-releasing hormone (GnRH). Leuprolide
(Lupron), goserelin (Zoladex), and nafarelin (Synarel)
are analogs of GnRH that are used to treat
endometriosis, a common cause of infertility. Leuprolide,
histrelin (Supprelin LA), goserelin, degarelix (Firmagon),
and triptorelin (Trelstar) are used for the palliative
treatment of advanced prostate cancer. Two pituitary
hormones, prolactin and oxytocin, affect the female
reproductive system. Corticotropin affects the adrenal
gland and is discussed later in this chapter.
SOURCE: PPT, BOOK, DISCUSSION/NOTES
CHECKER: ROD H. MARANAN
Increased release GH = Giantism
Decreased release GH = Dwarfism
Mecasermin (Increlex) has the same actions as GH
and is indicated for the long-term treatment of growth
failure in children with severe deficiency of insulin-like
growth factor (IGF) or for those who have developed
neutralizing antibodies to GH. It is administered once
daily by the subcutaneous route. It should not be
administered to adults, after the epiphyses have closed.
Adverse effects include hypoglycemia, headache,
dizziness, vomiting, and tonsillar hypertrophy.
Excess secretion of GH in adults is known as
acromegaly. Acromegaly is a rare disorder caused by a
GH-secreting tumor of the pituitary gland. Because the
epiphyseal plates are closed in adults, bones become
deformed rather than elongated with this disorder. The
onset is gradual, with enlargement of the small bones of
the hands, feet, face, and skull; broad nose; protruding
lower jaw; and slanting forehead.
Antidiuretic Hormone (ADH)
•
•
•
•
It is essential that the amount of fluids in the body be
maintained within narrow limits. Loss of large amounts
of water leads to dehydration, whereas too much body
fluid leads to congestion, edema, and water intoxication.
Antidiuretic hormone (ADH) is one of the most
important means the body has to maintain fluid
homeostasis
released by the pituitary gland
regulates antidiuretic, urination/urine flow (meaning,
binabawasan ang pag-ihi)
ADH Concept is always associated Diabetes Insipidus
Diabetes Insipidus (DI)
•
•
•
•
the decreased number or lack of ADH
low amount of ADH result in an excessive amount of
urination (polyuria)
not the same with Diabetes Mellitus
3P’s of Diabetes:
➢ Polydipsia
➢ Polyuria
➢ Polyphagia
Polyuria
•
•
first major symptoms of DM that is being acquired by the
person who has DI
Two ADH preparations are available for the treatment of
diabetes insipidus: desmopressin (DDAVP) and
vasopressin.
Desmopressin
•
a famous drug given to patients with ADH problems
Is a synthetic form of human ADH that acts on the pipeline to
increase the reabsorption of water
Why does reabsorption of water happen?
•
In cases of DI, once a patient has fluid intake, it
automatically goes straight into the urinary bladder
which will be considered a form of urine. No absorption
of water happens
Desmopressin (DDAVP, Noctiva, Stimate)
NOTE:
•
No problem with the bladder and sphincter but there
is less absorption of fluid because of the decreased
ADH level.
•
As nurses, do not diagnose the patient who is having
frequent urination as a Diabetes or problem with the
bladder, reassessment is a must.
•
Frequent urination can be associated with:
> DI
> Bladder prob: maluwag na urethral sphincter
which is why there is no control in urination, tuloy
tuloy
> DM
•
A series of tests is a must for us to be able to identify
if there is a decrease in the level of ADH that leads to
the patient acquiring polyuria
Serum Sodium Concentration
•
an electrolyte that must be tested and the result must be
normal before the administration of desmopressin
•
focus in the result of sodium = should be in equal
amount
•
- increased in Na= there is attraction of water *during
urination, sodium joins the urine
NOTE:
•
The sodium must be in normal in taking
desmopressin
•
Patient’s urine has no connection with sodium activity,
kaya nagka-polyuria because of decreased ACH.
•
Insipidus = no taste
•
If the result is decreased sodium, and uminom ng
demospressin (not natural ADH) = isasama ang
sodium palabas sa urine, and may lead to
hyponatremia (decreased level of sodium in the body)
•
Hyponatremia lead to the release of the fluid from
intracellular going out and result to edema.
Vasopressin
•
a synthetic drug that has a structure identical to that of
human ADH. It acts on the renal collecting tubules to
increase their permeability to water, thus enhancing
water reabsorption.
•
•
•
Reabsorption of water (Tuloy tuloy ang pag ihi)
Decrease AH
Not natural (Synthetic)
•
Actions and Uses Desmopressin is a synthetic form of
human ADH that acts on the kidneys to increase the
reabsorption of water. It is used to control the acute
symptoms of DI in patients who have insufficient ADH
secretion. The oral (PO) route is preferred, although
intranasal and parenteral forms are available.
Action and Uses
Administration Alert
Before starting therapy, ensure that serum sodium
concentration is normal.
• Following an IV injection, fluids must be restricted and
carefully monitored to prevent serious water intoxication.
•
Pregnancy category B
Adverse Effect
•
Desmopressin can cause symptoms of water
intoxication: drowsiness, headache, and listlessness,
progressing to convulsions and coma.
•
Desmopressin participates in very few drug–drug
interactions. Increased antidiuretic action can occur with
chlorpropamide and nonsteroidal anti-inflammatory
drugs (NSAIDs). Decreased antidiuretic action can occur
with lithium, alcohol, heparin, and epinephrine.
Interaction (Drug-Drug)
Thyroid Glands
•
The thyroid gland secretes hormones affecting almost
every cell in the body. Thyroid hormone increases
basal metabolic rate, influencing cellular functions
and raising body temperature. It is crucial for the
normal growth and development of infants and children,
impacting mental development and sexual maturity. The
thyroid also influences cardiovascular, respiratory, GI,
and neuromuscular function.
•
is attached to a carrier protein, thyroxine-binding
globulin (TBG), which protects it from degradation.
Thyroid Hormone
TYPE OF CELLS THAT SECRETE HORMONES
Parafollicular Cells
•
secrete calcitonin, involved in calcium homeostasis.
•
secrete thyroid hormone, consisting of thyroxine (T4)
and triiodothyronine (T3). Iodine is essential for hormone
synthesis, obtained through dietary intake.
•
THYROXINE (T4) is the major hormone but is converted
to the more biologically active T3. Thyroid hormone in
the blood is attached to thyroxine-binding globulin (TBG)
and is regulated by negative feedback.
•
Hypothalamus and anterior pituitary regulate secretion
through a negative feedback loop. TRH stimulates TSH
release, which, in turn, stimulates thyroid hormone
production. Negative feedback suppresses TSH and
TRH secretion as blood levels of thyroid hormone
increase.
Follicular Cells
Conversion and Biological Activity
Regulation of Thyroid Hormone Secretion
Pharmacotherapy of Hypothyroidism
•
In
the
pharmacotherapy
of
hypothyroidism,
levothyroxine (T4) and liothyronine (T3) are commonly
used, with treatment requiring individualized and
periodic adjustments. Levothyroxine is the standard
choice, but a combination with liothyronine is an option.
Monitoring involves evaluating serum TSH levels, and
caution is exercised in initiating therapy for older adults.
Treatment is generally lifelong, and patients are advised
against switching medication brands.
•
Antithyroid drugs like propylthiouracil (PTU) and
methimazole (Tapazole) inhibit iodine incorporation into
T3 and T4. Methimazole is often preferred due to its less
frequent dosing and fewer adverse effects. Surgical
removal of the thyroid gland or radioactive iodine (I-131)
administration may be necessary in severe cases. I-131
results in a permanent solution but may lead to
hypothyroidism, requiring levothyroxine therapy. Nonradioactive iodine, such as Lugol's solution and
potassium iodide, is used for specific thyroid conditions.
Treatment choices depend on the severity and cause of
hyperthyroidism, with consideration of individual patient
factors.
NOTE:
•
Hypothyroidism
➢ Decrease of T3 and T4 levels (TH)
•
T3 and T4 is responsible for metabolic activity
(ginagamitan ng energy)
•
Weight Gain
➢ First manifestation of hypothyroidism
➢ because of low level of hormone (MR)
Disease Associated with Hypothyroidism
Hashimoto Disease
•
•
•
Less release of thyroid hormone
Miss Japan: hashimoto, apelido ng japanese
Signs and Symptoms of severe condition: Myxedema
•
refers to a severe form of hypothyroidism than can occur
when the condition is left untreated or is not treated
sufficiently.
Lumulobo ang mukha
Billugin ang braso at hita
Nag-iipon ng tubig para magmukhang panda
Factors Influencing Thyroid hormone Production
•
Conditions causing decreased plasma proteins can
increase
free
thyroid
hormone,
leading
to
hyperthyroidism. High levels of iodine and exposure to
cold can impact thyroid activity.
Myxedema (panda)
•
•
•
its secretion being norepinephrine. The adrenal release
of epinephrine is triggered by activation of the
sympathetic division of the autonomic nervous system.
Only Drug for Hypothyroidism
•
Levothyroxine
•
•
Increased T3 and T4 levels
Weight loss with diaphoresis (payat na pawisan)
(maasim? Pwede)
Hyperthyroidism
Adrenal Cortex
•
Disease Associated of Hyperthyroidism
Grave’s Disease
•
•
•
Thyroid storm (exceed of thyroid hormone)
Grave (grabe = sobra)
Symptoms of Severe context: Thyroid storm
•
•
Thyroid Storm
a life-threatening health condition that is
associated with untreated or undertreated
hyperthyroidism.
sobrang payat, pagbagyong thyroid dahil sa grave
graveng release of TH
Three Classes of Steroid Hormones
Gonadocorticoids
•
secreted by the adrenal cortex are mostly androgens
(male sex hormones), though small amounts of estrogen
are also produced. The amounts of these adrenal sex
hormones are far less than the levels secreted by the
testes or ovaries. The adrenal glands are also the
primary
source
of
endogenous
estrogen
in
postmenopausal women. Tumors of the adrenal cortex
can cause hypersecretion of Gonadocorticoids, resulting
in hirsutism and masculinization, which are signs that
are more noticeable in females than males.
•
Aldosterone accounts for more than 95% of the
mineralocorticoids secreted by the adrenals. The
primary function of aldosterone is to regulate plasma
volume by promoting sodium reabsorption and
potassium excretion by the renal tubules. When plasma
volume falls, the kidney secretes renin, which results in
the production of angiotensin II. Angiotensin II then
causes aldosterone secretion, which promotes sodium
and water retention. Attempts to modify this pathway led
to the development of the angiotensin converting
enzyme (ACE) inhibitor class of medications, which are
often preferred drugs for treating HTN and heart failure.
Certain adrenal tumors cause excessive secretion of
aldosterone, a condition known as hyperaldosteronism,
which is characterized by HTN and hypokalemia.
•
More than 30 glucocorticoids are secreted from the
adrenal cortex, including cortisol, corticosterone, and
cortisone. Cortisol, also called hydrocortisone, is
secreted in the highest amount and is the most
important pharmacologically. Glucocorticoids affect the
metabolism of nearly every cell and prepare the body for
long-term stress.
4 Drugs: LIP-Tint
•
•
•
•
secretes three classes of steroid hormones: the
glucocorticoids,
mineralocorticoids,
and
gonadocorticoids. Collectively, the glucocorticoids and
mineralocorticoids are called corticosteroids or
adrenocortical hormones. The terms corticosteroid and
glucocorticoid are often used interchangeably in clinical
practice. However, it should be understood that the term
corticosteroid implies that a drug has both glucocorticoid
and mineralocorticoid activity.
Lugol’s solution (non-radioactive therapy)
Iodine 131 half-life (radioactive therapy)
propylthiouracil (PTU)
Tapazole
Mineralocorticoids
Glucocorticoids
The effects of glucocorticoids are diverse and
include the following:
•
Adrenal Glands, Adrenal Drugs, Antiadrenal Drugs
Adrenal Glands
•
•
•
•
The small adrenal glands secrete hormones that have
an impact on every bodily tissue. Disorders of the
adrenal glands can be caused by either insufficient or
excessive hormone secretion. Which part of the adrenal
gland is causing the abnormal secretion determines the
specific pharmacotherapy.
•
Normal Function of Adrenal Glands
•
Weighing only two-tenths of an ounce, each adrenal
gland is divided into two major portions: an inner
medulla and an outer cortex.
Regulation of Corticosteroid Secretion
•
Adrenal Medulla
•
secretes 75% to 80% epinephrine, with the remainder of
Increase the level of blood glucose (hyperglycemic
effect) by inhibiting insulin secretion and promoting
gluconeogenesis, the synthesis of carbohydrates from
lipid and protein sources
Increase the breakdown of proteins and lipids and
promote their utilization as energy sources
Suppress the inflammatory and immune responses.
Increase the sensitivity of vascular smooth muscle to
norepinephrine and angiotensin II • Increase the
breakdown of bony matrix, resulting in bone
demineralization
Promote bronchodilation by making bronchial smooth
muscle more responsive to sympathetic nervous system
activation.
Control of corticosteroid levels in the blood begins with
corticotropin-releasing factor (CRF), secreted by the
hypothalamus. CRF travels to the pituitary, where it
causes the release of adrenocorticotropic hormone
(ACTH). ACTH then travels through the blood to reach
the adrenal cortex, causing it to release corticosteroids.
When the serum level of cortisol rises, it provides
negative feedback to the hypothalamus and the pituitary
to shut off further release of corticosteroids.
Addison’s Disease
•
Adrenocortical Insufficiency
•
Lack of adequate corticosteroid production, known as
adrenocortical insufficiency, may be caused by either
hyposecretion of the adrenal cortex or inadequate
secretion of ACTH from the pituitary. Cosyntropin
(Cortrosyn) closely resembles ACTH and is used to
diagnose the cause of the adrenocortical insufficiency.
For this test, a small dose of cosyntropin is injected IV
and plasma cortisol levels are measured 30 to 60
minutes later. If the adrenal gland responds by secreting
corticosteroids after the cosyntropin injection, the
pathology lies at the level of the pituitary or
hypothalamus (secondary adrenocortical insufficiency).
If plasma cortisol levels fail to rise after the injection, the
pathology is at the level of the adrenal gland (primary
adrenocortical insufficiency).
ADRENAL DRUGS
Pharmacotherapy with Corticosteroids
•
•
The corticosteroids are used as replacement therapy for
patients with adrenocortical insufficiency and to dampen
inflammatory
and
immune
responses.
The
corticosteroids, listed in Table 44.4, are one of the most
widely prescribed drug classes.
Primary adrenocortical insufficiency, known as
Addison’s disease, is quite rare and includes a
deficiency of both corticosteroids and mineralocorticoids.
Autoimmune destruction of both adrenal glands is the
most common cause of Addison’s disease. Secondary
adrenocortical insufficiency is more common than
primary and can occur when corticosteroids are
suddenly withdrawn during pharmacotherapy. When
corticosteroids are taken as medications for prolonged
periods, they provide negative feedback to the pituitary
to stop secreting ACTH. Without stimulation by ACTH,
the adrenal cortex shrinks and stops secreting
endogenous corticosteroids, a condition known as
adrenal atrophy. If the corticosteroid medication is
abruptly discontinued, the shrunken adrenal glands will
not be able to secrete sufficient corticosteroids, and
symptoms of acute adrenocortical insufficiency will
appear. Symptoms include nausea, vomiting, lethargy,
confusion, and coma. Immediate administration of IV
therapy with hydrocortisone is essential because shock
may quickly result if symptoms remain untreated. Acute
adrenocortical insufficiency can be prevented by
discontinuing corticosteroids gradually.
Other possible causes of acute adrenocortical
insufficiency include infection, trauma, and cancer. The
development of adrenal atrophy following corticosteroid
administration is shown in Pharmacotherapy Illustrated
44.1.
•
For chronic adrenocortical insufficiency, replacement
therapy with corticosteroids is indicated. The goal of
replacement therapy is to achieve the same
physiological level of hormones in the blood that would
be present if the adrenal glands were functioning
properly. Patients requiring replacement therapy usually
must take corticosteroids their entire lifetime, and
concurrent therapy with a mineralocorticoid such as
fludrocortisone (Florinef) is necessary.
•
In
addition
to
treating
adrenal
insufficiency,
corticosteroids are prescribed for a large number of
nonendocrine disorders. Their ability to quickly and
effectively suppress the inflammatory and immune
responses gives them tremendous therapeutic utility to
treat a diverse set of conditions. Indeed, no other drug
class is used for so many different indications.
Nonendocrine indications for pharmacotherapy with
corticosteroids:
➢ Allergies, including allergic rhinitis. • Asthma.
➢ Cancer,
including
Hodgkin’s
disease,
leukemias, and lymphomas.
➢ Edema associated with hepatic, neurologic,
and renal disorders
Corticosteroids
Adrenocortical Insufficiency
•
Symptoms of adrenocortical insufficiency include
hypoglycemia, fatigue, hypotension, increased skin
pigmentation, and GI disturbances such as anorexia,
vomiting, and diarrhea. Low plasma cortisol,
accompanied by high plasma ACTH levels, is diagnostic
because this indicates that the adrenal gland is not
responding to ACTH stimulation.
•
➢
•
•
•
Inflammatory GI disease, including ulcerative
colitis and Crohn’s disease.
➢ Inflammatory
joint
disorders,
including
rheumatoid arthritis, ankylosing spondylitis, and
bursitis.
➢ Inflammatory skin disorders, including contact
dermatitis and rashes.
➢ Shock.
➢ Transplant rejection prophylaxis.
More than 20 corticosteroids are available as
medications, and choice of a particular drug depends
primarily on the pharmacokinetic properties of the drug.
The duration of action, which is often used to classify
these drugs, ranges from short to long acting. Some,
such as hydrocortisone, have mineralocorticoid activity
that causes sodium and fluid retention; others, such as
prednisone, have no such effect.
Corticosteroids interact with many drugs. Their
hyperglycemic effects may decrease the effectiveness of
antidiabetic drugs. Combining corticosteroids with other
ulcer-promoting drugs such as aspirin and other NSAIDs
markedly increases the risk of peptic ulcer disease.
Administration with non–potassium-sparing diuretics
may lead to hypocalcemia and hypokalemia. High doses
of corticosteroids taken for prolonged periods offer a
significant risk for serious adverse effects. These
adverse effects can affect nearly any body system.
The following strategies are used to limit the incidence
of serious adverse effects from corticosteroids:
➢ Keep doses to the lowest possible amount that
will achieve a therapeutic effect.
➢ Administer corticosteroids every other day
(alternate day dosing) to limit adrenal atrophy.
➢ For acute conditions, give patients large
amounts for a few days and then gradually
decrease the drug dose until it is discontinued.
Give the drugs locally by inhalation, intraarticular injections, or topical applications to the
skin, eyes, or ears, when feasible, to diminish
the possibility of systemic effects.
ANTIADRENAL DRUGS
Pharmacotherapy of Cushing’s Syndrome
•
•
Cushing’s syndrome occurs when high levels of
corticosteroids are present in the body over a
prolonged period. If the hypersecretion is caused by a
pituitary gland tumor producing excess amounts of
ACTH, the condition is called Cushing’s disease. The
most common cause of Cushing’s syndrome is longterm therapy with high doses of systemic corticosteroids
used as medications. Signs and symptoms include
adrenal atrophy, osteoporosis, HTN, increased risk of
infections, delayed wound healing, acne, peptic ulcers,
general obesity, and a redistribution of fat around the
face (moon face), shoulders, and neck (buffalo hump).
Mood and personality changes may occur, and the
patient may become psychologically dependent on the
drug.
Some of these drugs, including hydrocortisone, also
have mineralocorticoid activity and can cause retention
of sodium and water. Because of their anti-inflammatory
properties, corticosteroids may mask signs of infection,
and a resulting delay in antibiotic therapy may result.
Because Cushing’s syndrome has a high mortality rate,
the primary therapeutic goal is to identify and treat the
cause of the excess corticosteroid secretion. If the
patient is receiving high doses of a corticosteroid
medication, gradual discontinuation of the drug is
usually sufficient to reverse the syndrome.
Ketoconazole (Nizoral)
•
When the cause of the hypersecretion is an adrenal
tumor or perhaps an ectopic tumor secreting ACTH,
surgical removal is indicated. When removal of the
tumor is not possible, a secondary option is to
administer medications to reduce the excess cortisol
secretion. The antifungal drug ketoconazole (Nizoral)
has been the traditional drug for patients with Cushing’s
syndrome who need long-term therapy. Used off-label
for this indication, ketoconazole rapidly blocks the
synthesis of corticosteroids, lowering serum levels.
Unfortunately, patients often develop tolerance to the
drug and corticosteroids eventually return to abnormally
high levels. Ketoconazole should not be used during
pregnancy because it has been shown to be teratogenic
in animals.
Pasireotide (Signifor)
•
A newer approach to treating Cushing’s syndrome is the
drug pasireotide (Signifor), for treating patients for whom
pituitary surgery is not an option. Pasireotide is closely
related to somatostatin (GH-inhibiting hormone).
Pasireotide causes inhibition of ACTH secretion by the
pituitary and subsequently corticosteroid secretion from
the adrenals. Given by the subcutaneous route, several
weeks or months of therapy may be needed for optimal
suppression of corticosteroid secretion. Signifor LAR is a
depot form of this drug that is given IM once every 4
weeks for the management of acromegaly.
•
Mitotane (Lysodren) is an antineoplastic drug that is
specific for cells of the adrenal cortex. It is approved to
treat inoperable tumors of the adrenal gland. Although
not specifically approved for Cushing’s syndrome, it will
reduce symptoms of this disorder if they are caused by
adrenal cancer. GI symptoms such as anorexia, nausea,
and vomiting will occur in most patients. CNS adverse
effects, including depression, lethargy, and dizziness,
occur in 40% of patients.
Mitotane (Lysodren)
II. DRUGS FOR DIABETES MELLITUS
Diabetes
•
can lead to serious acute and chronic complications,
including heart disease, stroke, blindness, chronic
kidney disease (CKD), acute kidney injury (AKI), and
amputations. Because nurses frequently care for
patients with diabetes, it is imperative that the disorder,
its treatment, and possible complications are well
understood.
Regulation of Blood Glucose Levels
Pancreas
•
Located behind the stomach and between the
duodenum and spleen. an organ essential to both the
digestive and endocrine systems. It is responsible for
the secretion of several enzymes into the duodenum
that assist in the chemical digestion of nutrients.
•
are responsible for its endocrine function: the secretion
of glucagon and insulin.
•
One of the body’s most essential molecules. The body
prefers to use glucose as its primary energy source. The
brain relies almost exclusively on glucose for its energy
needs. Because of this need, blood levels of glucose
must remain relatively constant throughout the day.
Islets of Langerhans
Glucose
Two Pancreatic Hormones
Insulin
Glucagon
•
acts to decrease blood
glucose level
•
acts to increase blood
glucose level
•
•
Cells may be virtually surrounded by glucose but they
are unable to use it until insulin arrives. It may be helpful
to visualize insulin as a transporter or “gatekeeper.”
When present, insulin swings open the gate,
transporting glucose inside cells: no insulin, no entry.
Thus, insulin is said to have a hypoglycemic effect,
because its presence causes glucose to leave the blood
and serum glucose to fall.
•
The physiological actions of insulin can be
summarized as follows:
•
•
•
•
Promotes the entry of glucose into cells.
Provides for the storage of glucose, as glycogen.
Inhibits the breakdown of fat and glycogen.
Increases
protein
synthesis
and
inhibits
gluconeogenesis: the production of new glucose from
noncarbohydrate molecules (protein and lipid).
•
Physiologic Action of Insulin
•
•
•
•
•
•
Promotes the entry of glucose into cells Provides for the
storage of glucose, as glycogen in skeletal muscle and
the liver Inhibits the breakdown of fat and glycogen
Increases
protein
synthesis
and
inhibits
gluconeogenesis: the production of new glucose from
noncarbohydrate molecules (protein and lipid).
The pancreas also secretes glucagon, which has actions
opposite those of insulin. When levels of blood glucose
fall, glucagon is secreted. Its primary function is to
maintain adequate serum levels of glucose between
meals. Thus, glucagon has a hyperglycemic effect
because its presence causes blood glucose to rise.
Blood glucose levels are usually kept within a normal
range by insulin and glucagon; however, other
hormones and drugs can affect glucose metabolism.
Hyperglycemic hormones include epinephrine, thyroid
hormone, growth hormone, and glucocorticoids.
Common drugs that can raise the level of blood glucose
include corticosteroids, nonsteroidal anti-inflammatory
drugs (NSAIDs), and diuretics.
Drugs with a hypoglycemic effect include alcohol,
lithium, angiotensin-converting enzyme (ACE) inhibitors,
and beta-adrenergic blockers. It is important that serum
glucose be periodically monitored in patients who are
receiving medications and who exhibit hypoglycemia or
hypoglycemic effects.
Diabetes Mellitus is a metabolic disorder in which
there is deficient insulin secretion or decreased
sensitivity of insulin receptors on target cells, resulting in
hyperglycemia. The etiology of DM includes a
combination of genetic and environmental factors. The
recent increase in the frequency of the disease is
probably the result of trends toward more sedentary and
stressful lifestyles, increasing consumption of highly
caloric foods with resultant obesity, and increased
longevity.
Etiology and Characteristics of Type 1 Diabetes
Mellitus
Type 1 Diabetes Mellitus
•
accounts for 5% to 10% of all cases of DM and is one of
•
•
the most common diseases of childhood. Type 1 DM
was previously called juvenile-onset diabetes because it
is often diagnosed between the ages of 11 and 13.
Because approximately 25% of patients with type 1 DM
develop the disease in adulthood, however, this type of
diabetes is more accurately referred to as insulin
dependent diabetes mellitus.
The signs and symptoms of type 1 DM are consistent
from patient to patient, with the most diagnostic sign
being sustained hyperglycemia. Following are the typical
signs and symptoms:
➢ Hyperglycemia—fasting blood glucose greater
than 126 mg/dL on at least two separate
occasions
➢ Polyuria - excessive urination
➢ Polyphagia - increased hunger
➢ Polydipsia - increased thirst
➢ Glucosuria - high levels of glucose in the urine
Weight loss Fatigue.
Laboratory tests are required for proper diagnosis. The
primary blood tests for diagnosing diabetes include the
following:
➢ Hemoglobin A1C. As serum glucose
increases, more glucose becomes bound to
hemoglobin. A value of 6.5% or higher indicates
diabetes. The advantage of A1C is that it does
not require fasting, and it provides an average
measure of glucose control over the 8 to 12
weeks prior to the test.
➢ Fasting plasma glucose (FPG). Obtained
following a fast of at least 8 hours. A value of
126 mg/dL or higher indicates diabetes.
➢ Oral glucose tolerance test (OGTT). A
loading dose of 75 g of glucose is ingested and
the plasma glucose level is obtained 2 hours
later. A value of 200 mg/dL or higher indicates
diabetes.
Lipids are used as an energy source and ketones, also
called ketoacids, because glucose unable to enter cells.
Keto Acids can give the patient’s breath an acetone like,
fruity odor. More important, high levels of ketoacids
lower the pH of the blood, causing diabetic ketoacidosis
(DKA). DKA typically develops over several days with
symptoms such as polyuria, polydipsia, nausea,
vomiting, and severe fatigue, progressing to stupor,
coma, and possibly death. DKA occurs primarily in
patients with type 1 DM.
Pharmacotherapy for Type 1 Diabetes Mellitus
•
•
•
•
•
In 1922, Insulin first became available as a medication
type 1 DM.
Increased insulin availability and improvements in insulin
products, personal blood glucose monitoring devices,
and the insulin pump.
Patients with type 1 DM are severely deficient in insulin
production; thus, Insulin Replacement Therapy is
required in normal physiologic amounts.
The fundamental principle to remember about insulin
therapy is that the right amount of insulin must be
available to cells when glucose is present in the blood.
Pharmacologists have modified human insulin to create
certain pharmacokinetic advantages, such as a more
rapid onset of action (Humalog) or a more prolonged
duration of action (Lantus).
•
•
•
•
•
Some patients require two or more injections daily for
proper
diabetes
management.
For
ease
of
administration, two different compatible types of insulin
may be mixed, using a standard method.
Examples of premixed insulin combinations include the
following:
➢ Humulin 70/30 and Novolin 70/30: contain 70%
NPH insulin and 30% regular insulin
➢ Humulin 50/50: contains 50% NPH insulin and
50% regular insulin
➢ NovoLog Mix 70/30: contains 70% insulin
aspart protamine and 30% insulin aspart
➢ Humalog Mix 75/25: contains 75% insulin lispro
protamine and 25% insulin lispro.
Insulin Pump
•
The primary adverse effect of insulin therapy is
overtreatment; insulin may remove too much glucose
from the blood,resulting in hypoglycemia. This occurs
when a patient with type 1 DM has more insulin in the
blood than is needed to balance the amount of
circulating blood glucose. Hypoglycemia may occur
when the insulin level peaks, during exercise, when the
patient receives too much insulin due to a medication
error, or if the patient skips a meal.
The hormone glucagon is also used for the emergency
treatment of severe hypoglycemia in patients who are
unable to take IV glucose.
A common clinical problem occurring during insulin
therapy is administering too much insulin relative to what
the body needs.
Patient is hypoglycemic including pale, cool, moist skin,
confusion, lightheadedness, weakness, and anxiety, with
blood glucose less than 50 mg/dL.
Other adverse effects of insulin include:
•
•
•
Localized allergic reactions at the injection site
Generalized urticaria
Swollen lymph glands
Insulin Adjunct
•
•
The use of therapeutic agents other than insulin – is one
strategy aimed at improving outcomes.
Pramlintide (Symlin) - is an antihyperglycemic
•
•
Etiology and Characteristics of Type 2 Diabetes
Mellitus
•
•
The primary physiologic characteristic of type 2 DM is
insulin resistance.
The majority of people with type 2 DM have obesity and
dyslipidemias.
Hyperosmolar hyperglycemic state (HHS)
•
•
is a serious, acute condition with a mortality rate of 20%
to 40% that occurs in persons with type 2 DM.
Pharmacotherapy for Type 2 Diabetes Mellitus
•
Type 2 DM is usually managed with non-insulin
antidiabetic drugs, which are prescribed after diet and
exercise have failed to reduce blood glucose to normal
levels. As the disease progresses, insulin may become
necessary or it may be required temporarily during times
of stress, such as illness or loss. These drugs are
sometimes referred to as oral hypoglycemic drugs.
SIX PRIMARY GROUPS OF ANTIDIABETIC DRUGS
FOR T2DM
1. Sulfonylureas
•
•
•
the first oral hypoglycemics available divided into firstand second-generation categories act by stimulating the
release of insulin from pancreatic islet cells and by
increasing the sensitivity of insulin receptors on target
cells
The most common adverse effect of sulfonylureas is
hypoglycemia, which is usually caused by taking too
much medication or not eating enough food. Other
adverse effects include weight gain, hypersensitivity
reactions, GI distress, and hepatotoxicity.
When alcohol is taken with these sulfonylureas, some
patients experience a disulfiram-like reaction that
includes flushing, palpitations, and nausea.
2. Alpha-glucosidase Inhibitors
•
•
•
5. Meglitinides
•
•
•
•
•
•
include acarbose (Precose) and miglitol (Glyset) act by
blocking enzymes in the small intestine that are
responsible for breaking down complex carbohydrates
into monosaccharides do not produce hypoglycemia
when used alone, hypoglycemia may occur when these
drugs are combined with insulin or a sulfonylurea
These drugs are usually well tolerated and have minimal
adverse effects that include abdominal cramping,
diarrhea, and flatulence. Liver function should be
monitored because a small incidence of liver impairment
has been reported.
•
•
better known as metformin
type of oral diabetes medication that helps lower blood
sugar levels for people with Type 2 diabetes by
decreasing the amount of glucose your liver produces
and releases into your bloodstream
Healthcare providers prescribe this medication for other
conditions, as well, like PCOS and gestational diabetes
In PCOS, biguanides decrease insulin levels, which then
decrease luteinizing hormone and androgen levels.
act by affecting the incretin–glucose control mechanism
signals the pancreas to increase insulin secretion and
the liver to stop producing glucagon these drugs
or glitazones
reduce blood glucose by decreasing insulin resistance
and inhibiting hepatic gluconeogenesis
Optimal lowering of blood glucose may require 3 to 4
months of therapy
rosiglitazone (Avandia) and pioglitazone (Actos), contain
black box warnings for heart failure and for increased
risk for myocardial ischemia. These drugs are usually
combined with other antidiabetic drugs in the
management of blood glucose
The most common adverse effects are fluid retention,
headache, and weight gain. Hypoglycemia does not
occur with drugs in this class. Liver function should be
monitored because thiazolidinediones may be
hepatotoxic. Because of their tendency to promote fluid
retention, thiazolidinediones are contraindicated in
patients with serious heart failure or pulmonary edema.
III. DRUGS FOR DISORDERS AND
CONDITIONS OF THE FEMALE
REPRODUCTIVE SYSTEM
Hypothalamic and Pituitary Regulation of Female
Reproductive Function
•
4. Incretin mimetics
•
repaglinide (Prandin) and nateglinide (Starlix), act by
stimulating the release of insulin from pancreatic islet
cells in a manner similar to that of the sulfonylureas.
short durations of action of 2 to 4 hours.
efficacy is equal to that of the sulfonylureas, and they
are well tolerated
6. Thiazolidinediones
•
•
3. Biguanides
•
•
decrease food intake by increasing the feeling of satiety
in the patient, and they also slow gastric emptying,
which delays glucose absorption exenatide (Byetta,
Bydureon) and liraglutide (Victoza), activate a receptor
called GLP-1.
A major disadvantage is that the drugs must be
administered subcutaneously and they have a high
incidence of nausea, vomiting, and diarrhea
The newer drugs in this class, such as semaglutide
(Ozempic), may be administered once weekly. Incretin
enhancers, such as saxagliptin (Onglyza), are drugs that
slow the breakdown of incretin, allowing natural incretin
levels to rise and produce a greater response. They
accomplish this by inhibiting the enzyme dipeptidyl
peptidase-4 (DPP-4). They are taken orally. They work
well with other antidiabetic drugs; several are included in
fixed-dose combinations with metformin.
Bromocriptine (Parlodel) is an older drug, originally
approved to treat Parkinson’s disease, pituitary
adenoma, acromegaly, and for women with amenorrhea
and infertility caused by excessive prolactin secretion.
The drug acts on the central nervous system to increase
levels of the neurotransmitter dopamine. Later approved
for type 2 diabetes as Cycloset, the exact mechanism by
which it improves glycemic control remains unclear.
The most frequent adverse effects associated with
bromocriptine are nausea, fatigue, dizziness, vomiting,
and headache.
•
Regulation of the female reproductive system is
achieved by hormones from the hypothalamus, pituitary
gland, and ovary. The hypothalamus secretes
gonadotropin-releasing hormone (GnRH), which
travels a short distance to the pituitary to stimulate the
secretion of follicle-stimulating hormone (FSH) and
luteinizing hormone (LH). Both of these pituitary
hormones act on the ovary and cause immature ovarian
follicles to begin developing. The rising and falling levels
of pituitary hormones create two inter- related cycles
that occur on a periodic, monthly basis: the ovarian and
uterine cycles.
secretion causes one follicle to expel its oocyte, a
process called ovulation. The ruptured follicle, minus its
oocyte, remains in the ovary and is transformed into the
hormone-secreting corpus luteum.
•
feedback to shut off GnRH, FSH, and LH secretion.
Estrogen and progesterone are used as drugs to
achieve several therapeutic goals. The most widespread
pharmacologic use of the female sex hormones is to
prevent pregnancy. They are also prescribed to treat
dysfunctional uterine bleeding, severe symptoms of
menopause, and certain neoplasms.
Oral Contraceptives
•
are drugs used in low doses to prevent pregnancy.
Commonly referred to as “the pill,” they prevent
fertilization by inhibiting ovulation.
•
Estrogen and progesterone are used as drugs to
achieve several therapeutic goals. The most widespread
pharmacologic use of the female sex hormones is to
prevent pregnancy. They are also prescribed to treat
dysfunctional uterine bleeding, severe symptoms of
menopause, and certain neoplasms.
Hormonal contraceptives (HCs) are drugs used in low
doses to prevent pregnancy. The oral formulations are
commonly referred to as “the pill” or oral contraceptives.
The HCs prevent fertilization by inhibiting ovulation.
Hormonal Contraceptives
•
Estrogens and Progestins as Oral Contraceptives
Estrogen
Progestin
•
•
•
•
ethinyl estradiol
•
norethindrone
Daily doses of estrogen contained in oral contraceptives
(OCs) have declined from 150 mcg, 40 years ago, to
20–35 mcg in modern formulations.
Common problem with OCs, and likely the most frequent
reason for treatment failure or pregnancy, is forgetting to
take the medication daily.
Begins on day 5 of menstruations until 21th day and
takes dummy pills on the 7th day of the end of the
month.
Estrogens and Progestine Hormonal
Contraceptions
•
estrogen-progestin HCs act by preventing ovulation.
•
These drugs are sometimes prescribed to promote
timely and regular monthly cycles and to reduce the
incidence of dysmenorrhea.
Ovarian Control of Female Reproductive Function
4
TYPES OF ESTROGEN-PROGESTIN OCs
1. Monophasic
•
constant dose of estrogen & progestin through 21-day
treatment
•
constant estrogen but increase progestin
•
amount of estrogen and progestin vary
•
have synthetic estrogen and progestin
•
first HC to be approved to treat heavy menstruation,
bleeding.
2. Biphasic
3. Triphasic
•
•
As ovarian follicles mature, they secrete the female sex
hormones estrogen and progesterone. Estrogen is
actually a general term for three different hormones:
estradiol, estrone, and estriol. Estrogen is responsible
for the maturation of the female reproductive organs and
for the appearance of secondary sex characteristics
In the last half of the ovarian cycle, the corpus luteum
secretes a class of hormones called progestins, the
most abundant of which is progesterone. In combination
with
estrogen,
progesterone
promotes
breast
development and regulates the monthly changes of the
uterine cycle. Under the influence of estrogen and
progesterone, the uterine endometrium becomes
vascular and thickens in preparation for receiving a
fertilized egg. High progesterone and estrogen levels in
the finalthird of the uterine cycle provide negative
4. Quadriphasic
Natazia
•
•
•
Sub-q Provera injected every 3 months
Irreversible
12 months after the discontinuation, fertility will restore.
•
•
single rod containing the progestin etonogestrel
3 years of contraceptive protection.
•
•
containing ethinyl estradiol and norelgestromin.
The patch is changed every 7 days for the first 3 weeks,
followed by a patch-free week 4.
The serum estrogen levels of patients who use the patch
are 60% higher compared to those of patients who take
combination OCs.
Subdermal Implants
Progestin-Only OCs
•
•
•
•
•
•
•
•
•
•
mini pills
produce thick, viscous mucus at the entrance of uterus
no penetration of sperm
inhibit implantation of fertilized egg
less effective
effects: higher incidence of menstrual irregularities such
as amenorrhea, prolonged menstrual bleeding or
spotting.
reserved for patients who have estrogen intolerance
reduced risk for thromboembolic events
no effect on breast cancer
pregnancy category X.
Transdermal Patch
•
Vaginal Ring
•
•
5- to 7.5-cm (2–3 in) diameter ring containing estrogen
and progestin
Inserted to the vagina and provide 3 weeks of
protection.
Intrauterine Devices
LARCs (Long-Acting Reversible Contraceptives)
Depot Injections
•
•
IM Injection of medroxyprogesterone
3 months of protection
•
•
T-shape that are safe, inexpensive, and reliable
methods of contraception
Results from a thickening of the endometrium and
increased cervical mucus that slows down sperm
•
•
motility.
Fertility returns quickly after removal of the device.
Liletta, Mirena,
Kyleena,
and
Skyla
contain
levonorgestrel, which is released very slowly to prevent
conception for 3–6 years, depending on the product.
Extended-Regimen OCs
Seasonale
•
•
consists of tablets containing levonorgestrel and ethinyl
estradiol that are taken for 84 consecutive days
allows for continuous contraceptive protection
Seasonique
•
similar, but instead of inert tablets for 7 days, the patient
takes low-dose estrogen tablets. LoSeasonique is a
lower dose formulation of Seasonique.
Emergency Contraception and Pharmacologic
Abortion
Emergency Contraception (EC)
•
•
•
•
did not experience an increased risk
for breast cancer or MI.
is the prevention of implantation following unprotected
intercourse or contraceptive failure.
Pharmacologic abortion is the removal of an embryo by
the use of drugs after implantation has occurred.
Drugs for Emergency Contraception and
Termination of Early Pregnancy
Abortifacients
•
drugs used to induce abortion
Prototype Drug – Conjugated Estrogens (Cenestin,
Enjuvia, Premarin)
Conjugated Estrogens (Premarin)
• contain a mixture of different natural estrogens.
Conjugated estrogen A (Cenestin) & Conjugated
estrogen B (Enjuvia)
•
contain a mixture of 9–10 different synthetic plant
estrogens.
•
The primary indication for conjugated estrogens has
been to treat moderate to severe symptoms of
menopause
drug is approved for the palliative treatment of certain
types of breast cancer, vulvar or vaginal atrophy and
dyspareunia (pain during intercourse).
treatment of female hypogonadism and use after
oophorectomy.
exert several positive metabolic effects, including an
increase in bone density and a reduction in LDL
cholesterol.
lower the risk of coronary artery disease and colon
cancer
Action and Uses
•
•
•
•
Adverse Effects
Hormone Replacement Therapy
Menopause
•
•
progressive decrease in estrogen secretion by the
ovaries, resulting in the permanent cessation of menses.
natural consequence of aging
Unpleasant Symptoms
•
hot flashes, night sweats, irregular menstrual cycles,
vaginal dryness, and bone mass loss.
•
to treat unpleasant symptoms of menopause and to
prevent the long-term consequences of estrogen loss.
offer relief from the immediate, distressing menopausal
symptoms, prevents osteoporosis-related fractures, and
may offer some degree of protection from colorectal
cancer.
Hormone Replacement Therapy (HRT)
•
Results of the study:
Estrogen-Progestin Combination HRT
•
•
increased risk of MI, stroke, breast cancer, dementia,
and venous thromboembolism
decreased risk of hip fractures and colorectal cancer
•
increased risk of stroke and thromboembolic disorders.
Estrogen alone
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
nausea,
fluid retention,
edema,
breast tenderness,
abdominal cramps
bloating,
acute pancreatitis,
appetite changes,
acne,
mental depression,
decreased libido,
headache,
fatigue,
nervousness,
weight gain.
Newer Drug
Duavee
•
•
•
•
•
contains conjugated estrogens with bazedoxifene,
belongs to selective estrogen receptor modifiers
(SERMs).
preventing intense hot flashes
first HRT to include a SERM
increased risk of endometrial cancer and DVT
oral (PO) route
Ospemifene (Osphena)
•
•
a SERM that acts by increasing the thickness of the
vaginal epithelium.
to treat dyspareunia
Prasterone (Intrarosa)
•
•
consists of dehydroepiandrosterone (DHEA), a natural
hormone
to treat dyspareunia
Pharmacologic Management of Uterine
Contractions
Labor and Breast-feeding
(Imvexxy) vaginal low dose estradiol insert
•
•
to treat menopause-related moderate to severe
dyspareunia
risks for cardiovascular disorders, probable dementia,
and endometrial and breast cancers.
Pharmacotherapy with Progestins
Uterine Abnormalities
Dysfunctional Uterine Bleeding
•
•
is a condition in which hemorrhage occurs on a
noncyclic basis or in abnormal amounts. It is the most
frequent health care problem reported by women and is
a common reason for hysterectomy.
can have a number of causes, including early abortion,
pelvic neoplasms, thyroid disorders, pregnancy, and
infection. Types of dysfunctional uterine bleeding include
the following:
➢ Amenorrhea — absence of menstruation.
➢ Endometriosis — abnormal location of
endometrial tissues.
➢ Oligomenorrhea — infrequent menstruation.
➢ Menorrhagia — prolonged or excessive
menstruation.
➢ Breakthrough bleeding — hemorrhage
between menstrual periods.
➢ Premenstrual syndrome (PMS) — symptoms
develop during the luteal phase.
➢ Postmenopausal bleeding — hemorrhage
following menopause.
➢ Endometrial carcinoma — cancer of the
endometrium.
•
Several drugs are used to manage uterine contractions
and to stimulate lactation
•
are drugs that stimulate uterine contractions to promote
the induction of labor.
•
are used to inhibit uterine contractions during premature
labor.
•
are local hormones that act directly at the site where
they are secreted. Although the body makes dozens of
different prostaglandins, only a few have clinical utility. In
the uterus, prostaglandins cause intense smooth muscle
contractions.
Oxytocis
Tocolytics
Prostaglandis
Pharmacotherapy of Female Fertility
Female Infertility
Infertility
•
is the inability to become pregnant after at least 1 year
of frequent unprotected intercourse. Infertility is a
common disorder, with as many as 25% of couples
experiencing difficulty in conceiving children at some
point during their reproductive lifetimes. It is estimated
that females contribute to approximately 60% of infertility
disorders.
hormone (ICSH) in the male reproductive system,
regulates the production of testosterone.
Androgens
•
are considered male sex hormones.
•
•
Secreted by testes
the primary androgen responsible for maturation of the
male sex organs and the secondary sex characteristics
of men.
Testosterone
Hypothalamic and Pituitary Regulation of Male
Reproductive Function
Pharmacotherapy of Female Hypoactive Sexual
Desire Disorder
Female Hypoactive Sexual Desire
Female Hypoactive Sexual Desire Disorder (HSDD)
•
is a condition in which a woman experiences a low level
of sexual libido or desire to have sexual relations.
•
•
Lack of sufficient testosterone secretion by the testes
can result in male hypogonadism.
•
when the condition is caused by a testicular disorder
•
without sufficient FSH and LH secretion by the pituitary,
the testes will lack their stimulus to produce
testosterone.
Primary Hypogonadism
Secondary Hypogonadism
Flibanserin
•
Hypogonadism
•
is the first drug approved to treat female hypoactive
sexual desire disorder, a condition characterized by
diminished libido that can decrease the quality of life in
some women.
In 2015 the U.S. Food and Drug Administration (FDA)
approved the first drug for HSDD in women.
Common side effects:
➢ dizziness
➢ sleepiness
➢ nausea
➢ fatigue
➢ dry mouth
Pharmacotherapy with Androgens
Androgens
•
•
•
testosterone and related hormones that support male
reproductive function.
androstenedione and dehydroepiandrosterone (DHEA).
used therapeutically to treat hypogonadism and certain
cancers.
Pharmacotherapy of Hypogonadism
Endometriosis
•
•
a common cause of infertility, is characterized by the
presence of endometrial tissue that has implanted
outside the uterus in locations such as the surface of
pelvic organs or the ovaries. Being responsive to
hormonal stimuli, this abnormal tissue can cause pain,
dysfunctional bleeding, and dysmenorrhea.
IV. DRUGS FOR DISORDERS AND
CONDITIONS OF MALE REPRODUCTIVE
SYSTEM
Hypothalamic and Pituitary Regulation of Male
Reproductive Function
Follicle-Stimulating Hormone (FSH)
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This hormone regulates sperm production in men.
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more
Luteinizing Hormone (LH)
accurately
called
interstitial
cell–stimulating
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replacement therapy with testosterone or other
androgens at levels normally found in healthy men.
-androgens improve libid
o and correct erectile dysfunction caused by abnormally
low testosterone levels.
Male sex characteristics reappear, a condition called
masculinization or virilization.
Depression resolves and muscle strength rapidly
improves.
return serum testosterone to normal levels.
Testosterone
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promotes the synthesis of erythropoietin
has a profound anabolic effect on skeletal muscle
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are testosterone-like compounds with hormonal activity
that are taken inappropriately by athletes who hope to
build muscle mass and strength, thereby obtaining a
competitive edge.
raise cholesterol levels and may cause low sperm
counts and impotence in men.
In female athletes, menstrual irregularities are likely with
an obvious increase in masculine appearance.
Oral androgens are hepatotoxic, and permanent liver
damage
Behavioral changes include aggression and psychologic
dependence.
illegal and strongly discouraged by healthcare providers
and athletic associations.
Schedule III drugs on the Drug Enforcement
Administration list
of controlled substances.
Anabolic Steroids
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Pharmacotherapy of Male Infertility
Male Infertility
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30% to 40% of infertility among couples is caused by
difficulties with the male reproductive system.
Men may have a psychologic etiology, which should be
ruled out before pharmacotherapy is considered.
Male infertility may have a number of complex causes.
The most obvious etiology is lack of sufficient sperm
production.
Oligospermia
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fewer than 20 million sperm/mL of ejaculate, considered
abnormal and can lower reproductive success.
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complete absence of sperm in an ejaculate.
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Infections such as mumps, chronic tuberculosis, and
sexually transmitted infections can contribute to
infertility.
The possibility of erectile dysfunction must be
considered and treated.
Infertility may occur with or without signs of
hypogonadism.
Azoospermia
Male Infertility
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Pharmacotherapy of Male Infertility
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The goal of endocrine pharmacotherapy of male
infertility is to increase sperm production.
Therapy often begins with IM injections of human
chorionic gonadotropin (HCG)
3 times per week over 1 year
Human Chorionic Gonadotropin (HCG)
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identical to those of LH: increased testosterone
secretion and spermatogenesis
Sperm counts are conducted periodically to assess
therapeutic progress.
If unsuccessful, therapy with menotropins (Menopur,
Repronex) may be attempted.
Menotropin consists of a mixture of purified FSH and
LH.
Treatment for Male Infertility
Antiestrogens
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such as tamoxifen (Nolvadex) and clomiphene (Clomid)
have been used to block the negative feedback of
estrogen (from the adrenal glands) to the pituitary and
hypothalamus, thus increasing the levels of FSH and
LH.
Testolactone (Teslac)
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an aromatase inhibitor, has been administered to block
the metabolic conversion of testosterone to estrogen.
Various nutritional supplements have been tested,
such as zinc, L-arginine, and vitamins C and E .
Penile Injections
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Drug therapy of male infertility is not as successful as
fertility pharmacotherapy in women.
5% of infertile men have an endocrine etiology for their
disorder.
Large number of injections needed, other means of
conception may be explored, such as in vitro fertilization
or intrauterine insemination.
Pharmacotherapy of Erectile Dysfunction
Erectile Dysfunction
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Also known as impotence
Common disorder in men
Increases with age although it may occur in men of any
age
Consistent inability to either obtain an erection or to
sustain an erection long enough to achieve successful
intercourse
Certain diseases are associated with a higher incidence
of this condition such as:
➢ Atherosclerosis
➢ Diabetes
➢ Chronic Kidney Disease (CKD)
➢ Stroke
➢ Hypertension
Smoking is one of the biggest causes, increasing the
risk of ED by 30% to 60%, in a dose-dependent manner.
Psychogenic causes may include depression, fatigue,
guilt, or fear of sexual failure.
Low testosterone secretion can cause an inability to
develop an erection due to loss of libido.
Penile erection has both neuromuscular and vascular
components. Autonomic nerves dilate arterioles leading
to the major erectile tissues of the penis, called the
corpora cavernosa.
The corpora have vascular spaces that fill with blood to
cause rigidity. Constriction of veins draining blood from
the corpora allows the penis to remain rigid long enough
for successful penetration.
After ejaculation, the veins dilate, blood leaves the
corpora, and the penis quickly loses its rigidity.
Common drugs cause impotence as an adverse
effect
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Thiazide diuretics
Phenothiazine
Selective serotonin reuptake inhibitors (SSRIs)
Tricyclic antidepressants (TCAs)
Beta- and alpha adrenergic antagonists
Angiotensin-converting enzyme (ACE) inhibitors.
Drugs for Erectile Dysfunction
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cause pain and reduce the spontaneity associated with
pleasurable intercourse
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use is rare, although it may be used for patients in whom
PDE-5 inhibitors are contraindicated.
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do not cause an erection.
Other PDE-5 Inhibitors:
➢ Vardenafil (Levitra, Staxyn)
➢ Tadalafil (Cialis)
➢ Avanafil (Stendra)
Alprostadil
PDE-5 Inhibitor
Pharmacotherapy of Benign Prostatic Hyperplasia
Benign Prostatic Hyperplasia
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is the most common benign neoplasm in men.
also called benign prostatic hypertrophy or benign
prostatic obstruction.
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a condition in men in which the prostate gland is
enlarged and not cancerous.
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is characterized by enlargement of the prostate gland
that decreases the outflow of urine by obstructing the
urethra, causing difficult urination.
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Symptoms include:
➢ increased urinary frequency (usually with small
amounts of urine)
➢ increased urgency to urinate
➢ postvoid leakage
➢ excessive nighttime urination (nocturia)
➢ decreased force of the urine stream
➢ sensation that the bladder did not empty
completely.
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The urinary outlet obstruction can lead to serious
complications, such as urinary infections or acute kidney
injury (AKI).
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In advanced cases, a surgical procedure called
transurethral resection is needed to restore the patency
of the urethra.
Note:
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BPH is not considered to be a precursor to prostate
carcinoma.
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Only a few medications are available for the
pharmacotherapy of BPH.
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Early in the course of the disease, drug therapy may
relieve some symptoms.
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Drugs for BPH have limited effectiveness and have
value only in treating mild-to-moderate disease as an
alternative to surgery.
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Because pharmacotherapy alleviates the symptoms but
does not cure the disease, these medications must be
taken for the remainder of the patient’s life, or until
surgery is indicated.
restricting fluids close to bedtime, may be sufficient to
achieve symptomatic improvement.
Pathogenesis of Benign Prostatic Hyperplasia
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involves two components: static and dynamic.
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Relate to anatomic enlargement of the prostate gland.
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due to excessive numbers of alpha1 adrenergic
receptors located in smooth-muscle cells in the neck of
the urinary bladder and in the prostate gland.
Static factors
Dynamic factors
Notes:
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Certain frequently used medications can worsen
symptoms of BPH.
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Alpha-adrenergic antagonists or blockers, which include
decongestants such
as
pseudoephedrine and
phenylephrine.
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Drugs
with
anticholinergic
effects,
such
as
antihistamines, tricyclic antidepressants (TCAs), or
phenothiazines.
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Testosterone and other anabolic steroids may increase
prostate enlargement.
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Older men should avoid drugs that worsen symptoms of
BPH.
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The goal of treatment for patients with BPH focuses on
minimizing the urinary obstruction and preventing
complications.
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Not all BPH is progressive, and many patients never
experience moderate or advanced symptoms.
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Patient education such as avoiding caffeine or alcohol
intake, eliminating drugs that worsen BPH, and