Central Nervous System
Depressants
CNS Depressants
Sedatives
• Drugs that have an inhibitory effect on the
CNS to the degree that they reduce:
–
–
–
–
Nervousness
Excitability
Irritability
without causing sleep
CNS Depressants
Hypnotics
• Calm or soothe the CNS to the point that they
cause sleep
CNS Depressants
Sedative-Hypnotics—dose dependent:
• At low doses, calm or soothe the CNS
without inducing sleep
• At high doses, calm or soothe the CNS
• to the point of causing sleep
Sedative-Hypnotics: Barbiturates
• First introduced in 1903, standard agents
for insomnia and sedation
• Habit-forming
• Only a handful commonly used today due
in part to the safety and efficacy of:
BENZODIAZEPINES
Sedative-Hypnotics: Barbiturates
Four categories:
• Ultrashort
– mephobexital, thiamylal, thiopental
• Short
– pentobarbital, secobarbital
• Intermediate
– aprobarbital, butabarbital
• Long
– phenobarbital
Sedative-Hypnotics: Barbiturates
Barbiturates have a very narrow therapeutic index.
Therapeutic Index
• Dosage range within which the drug is effective
but above which is rapidly toxic.
Sedative-Hypnotics: Barbiturates
Mechanism of Action
• Site of action:
– Brain stem (reticular formation)
– Cerebral cortex
• By inhibiting GABA, nerve impulses traveling in
the cerebral cortex are also inhibited.
Sedative-Hypnotics: Barbiturates
Drug Effects
• Low doses:
Sedative effects
• High doses:
Hypnotic effects
(also lowers respiratory rate)
Notorious enzyme inducers
Sedative-Hypnotics: Barbiturates
Therapeutic Uses
•
•
•
•
Hypnotics
Sedatives
Anticonvulsants
Surgical procedures
Sedative-Hypnotics: Barbiturates
Side Effects
Body System
Effects
CNS
Drowsiness, lethargy, vertigo
mental depression, coma
Respiratory
Respiratory depression, apnea,
bronchospasms, cough
Sedative-Hypnotics: Barbiturates
Side Effects
Body System
GI
Other
Effects
Nausea, vomiting, diarrhea
Agranulocytosis,
vasodilation, hypotension,
Stevens-Johnson syndrome
Sedative-Hypnotics: Barbiturates
Toxicology
• Overdose frequently leads to respiratory
depression, and subsequently, respiratory arrest.
• Can be therapeutic:
– Anesthesia induction
– Uncontrollable seizures: “phenobarbital coma”
Sedative-Hypnotics: Barbiturates
Drug Interactions
• Additive effects:
– ETOH, antihistamines, benzodiazepines,
narcotics, tranquilizers
• Inhibited metabolism:
– MAOIs will prolong effects of barbiturates
• Increased metabolism:
– Reduces anticoagulant response, leading to
possible clot formation
CNS Depressants:
Benzodiazepines
Most frequently prescribed sedative-hypnotics
•
•
•
•
Most commonly prescribed drug classes
Favorable side effects
Efficacy
Safety
CNS Depressants:
Benzodiazepines
Classified as either:
• Sedative-hypnotic or Anxiolytic
(Medication that relieves anxiety)
CNS Depressants:
Benzodiazepines
Sedative-Hypnotic Type
• Long-Acting:
– flurazepam (Dalmane), quazepam (Doral)
• Short-Acting:
– estazolam (Prosom), temazepam (Restoril),
– triazolam (Halcion)
CNS Depressants:
Benzodiazepines
Anxiolytic Type
• alprazolam (Xanax)
• chloridiazepoxide (Librium)
• diazepam (Valium)
• lorazepam (Ativan)
• midazolam (Versed)
zolpidem (Ambien) and zaleplon (Sonata)
CNS Depressants:
Benzodiazepines
Mechanism of Action
• Depress CNS activity
• Affect hypothalamic, thalamic, and limbic
systems of the brain
• Benzodiazepine receptors
CNS Depressants:
Benzodiazepines
Drug Effects
• Calming effect on the CNS
• Useful in controlling agitation and anxiety
CNS Depressants:
Benzodiazepines
Therapeutic Uses
• Sedation
•
•
•
•
Sleep induction
Skeletal muscle relaxation
Anxiety relief
Treatment of alcohol withdrawal
• Agitation
• Depression
• Epilepsy
• Balanced anesthesia
CNS Depressants:
Benzodiazepines
Side Effects
• Mild and infrequent
Headache
(nervousness)
Drowsiness
Dizziness
Vertigo
Lethargy
Paradoxical excitement
“Hangover effect”
CNS Depressants:
Nursing Implications
• Before beginning therapy, perform a
thorough history regarding allergies, use
of other medications,health history, and
medical history.
• Obtain baseline vital signs and I & O,
including supine and erect BPs.
• Assess for potential disorders or conditions
that may be contraindications, and for
potential drug interactions.
CNS Depressants:
Nursing Implications
• Give 15 to 30 minutes before bedtime for
maximum effectiveness in inducing sleep.
• Most benzodiazepines (except flurazepam)
cause REM rebound and a tired feeling the
next day; use with caution in the elderly.
• Patients should be instructed to avoid
alcohol and other CNS depressants.
CNS Depressants:
Nursing Implications
• Check with physician before taking any
other medications, including OTC
medications.
• It may take 2 to 3 weeks to notice improved
sleep when taking barbiturates.
• Abruptly stopping these medications,
especially barbiturates, may cause rebound
insomnia.
CNS Depressants:
Nursing Implications
• Safety is important
– Keep side rails up
– Do not permit smoking
– Assist patient with ambulation
(especially the elderly)
– Keep call light within reach
• Monitor for side effects
CNS Depressants:
Nursing Implications
• Monitor for therapeutic effects
–
–
–
–
–
Increased ability to sleep at night
Fewer awakenings
Shorter sleep induction time
Few side effects, such as hangover effects
Improved sense of well-being because of
improved sleep
Anticonvulsants and Drugs to
Treat Other CNS Disorders
Chapter 8 Topics
•
•
•
•
•
•
•
Epilepsy
Parkinson’s Disease
Myasthenia Gravis
Attention-Deficit Disorders
Amyotrophic Lateral Sclerosis (ALS)
Multiple Sclerosis (MS)
Alzheimer’s Disease
Learning Objectives
• Develop an understanding of the
physiologic processes that occur in
epilepsy.
• Classify seizures and the goals of their
therapy.
• Understand that specific drugs are used in
different classes of seizures.
Learning Objectives
• Be familiar with Parkinson’s disease
and the drugs used in its treatment.
• Know the symptoms and treatments of
– myasthenia gravis
– attention-deficit disorders
– amyotrophic lateral sclerosis
– multiple sclerosis
– Alzheimer’s disease
Epilepsy
• Common neurologic disorder with sudden
and recurring seizures
• Caused by abnormal electrical impulses in
the brain
Epilepsy
• In the U.S., 2.5 million people are affected.
• Not all seizure disorders are epilepsy.
Epilepsy
Seizure
Abnormal electrical discharges in the cerebral cortex
caused by sudden, excessive firing of neurons
– Result in a change in behavior of which the patient is
not aware
– While conscious, the patient may or may not lose
movement control
– Loss of body control may affect one area or the entire
body
Epilepsy
Causes of Seizures
• Imbalance of excitatory and inhibitory
neurotransmitters:
– Glutamate – inhibitory
– GABA – excitatory
– Other neurotransmitters can be involved
• Neurotransmitter levels are controlled by enzymes
• Disruption in enzymes = disruption of
neurotransmitters
Epilepsy
Causes of Seizures
•
•
•
•
•
ETOH withdrawal
Cardiovascular disease
High fever
Hypocalcemia
High or low blood
sugar
• Hypoxia
• Infection (meningitis)
• Metabolic
abnormalities
• Brain tumor
• Toxic substances
• Trauma or injury to
the head
Epilepsy
Classes of Seizures
• Partial
• Generalized
Epilepsy
Classes of Seizures
• Partial
– Simple-partial
– Complex-partial
• Generalized
Epilepsy
Classes of Seizures
• Partial
– Simple-partial
– Complex-partial
• Generalized
–
–
–
–
Tonic-clonic or grand mal
Absence or petit mal
Myoclonic
Atonic
Epilepsy
Partial Seizures
• Localized in a specific area of the brain
• Occurs with 65% of epileptic patients
• Can progress to generalized seizures
Epilepsy
Partial Seizures
• Simple-Partial
• Complex-Partial
Epilepsy
Partial Seizures
• Simple-Partial
– No loss of consciousness
– May have muscle twitching or sensory
hallucinations
• Complex-Partial
Epilepsy
Partial Seizures
• Simple-Partial
– No loss of consciousness
– May have muscle twitching or sensory
hallucinations
• Complex-Partial
– Impaired consciousness
– With confusion, blank stare, and postseizure
amnesia
Epilepsy
Generalized Seizures
• Involves both hemispheres of the brain, not
one specific location
• Types
–
–
–
–
Tonic-Clonic
Absense
Myoclonic
Atonic
Generalized Seizures
Tonic-Clonic Seizures
• Tonic – body becomes rigid, lasts a minute
or less
• Clonic – initiated with muscle jerks, and
may be accompanied by shallow breathing,
loss of bladder control, and excess
salivation
Generalized Seizures
Absence
• Interruption of activities by blank stare, rotating
eyes, uncontrolled facial movements, rapid eye
blinking, and/or jerking of an arm or leg
• No generalized convulsions
• Usually lasts 30 seconds or less
• Many times it progresses to tonic-clonic as the
patient gets older
Generalized Seizures
Myoclonic
• Occurs with sudden, massive, brief muscle
jerks or non-massive, quick jerks
• Consciousness is not lost
• Can occur during sleep
Generalized Seizures
Atonic
• Begins with sudden loss of muscle tone and
consciousness
• Muscles relax, limbs go limp
• Lasts a few seconds to a minute, then
patient can resume standing and walking
Generalized Seizures
Status Epilepticus
• Continuous tonic-clonic seizures with or
without return to consciousness
• High fever and lack of oxygen severe
enough to cause brain damage or death
Discussion
What percentage of status epilepticus
patients die, regardless of treatment?
Discussion
What percentage of patients status
epilepticus patients die, regardless of
treatment?
Answer: 10%
Antiepileptic Drug Therapy
Goals of Therapy
1. Seizure control or lessen the frequency
2. Prevent emotional and behavioral changes
Discussion
Note: 30% of patients are not compliant
due to side effects (sedation and loss of
cognitive processes).
What are some possible strategies health
care providers can use to help improve
drug therapy compliance?
Antiepileptic Drug Therapy
Neuronal Activity
1. Polarized (resting)
2. Depolarized (firing)
1. Sodium and calcium enter the cell
2. When sufficient amounts cross, neurotransmitters are
released
3. Neurotransmitter release leads to firing of the neuron
3. Repolarization (return to resting)
Antiepileptic Drug Therapy
Abnormal Neuronal Activity
• Depolarization
If excessive neurotransmitters are released it
leads to uncontrollable firing of the neuron =
seizure
• Treatment
Block the firing of the neuron by raising the
threshold of depolarization
Antiepileptic Drug Therapy
• Start with monotherapy at a low dose and
titrate up slowly
• Medication must be maintained at steady
therapeutic levels (no missed doses)
• Polytherapy can be used if sufficient
response is not seen with monotherapy
Antiepileptic Drug Therapy
Problems with Therapy
• Wrong medication is used for the seizure
type
• Side effects may cause problems with
patient compliance
• If doses are missed, there is an increased
risk of seizure activity
Drug List
Anticonvulsants
•
•
•
•
•
•
•
carbamazepine (Epitol, Tegretol)
clonazepam (Klonopin)
diazepam (Valium)
divalproex (Depakote)
ethosuximide (Zarontin)
Fosphyenytoin (Cerebyx)
gabapentin (Neurontin)
Drug List
Anticonvulsants
•
•
•
•
•
•
lamotrigine (Lamictal)
levetiracetam (Keppra)
lorazepam (Ativan)
oxcarbazepine (Trileptal)
phenobarbital (Luminal Sodium)
phenytoin (Dilantin)
Drug List
Anticonvulsants
•
•
•
•
primidone (Mysoline)
topiramate (Topamax)
valproic acid (Depakene)
zonisamide (Zonegran)
Therapeutic Regimens for Seizures
Seizure Type
1st Line
2nd Line
3rd Line
Partial
Tegretol or
Dilantin
Neurontin Luminal,
or Lamictal Mysoline, or
Depakene
Absence
Zarontin or
Depakene
Depakene
Klonopin
Atonic, Atypical
Absence,
Myoclonic
Klonopin or
Lamictal
Therapeutic Regimens for Seizures
1st Line
2nd Line
Tonic-Clonic,
Tonic, Clonic
Tegretol,
Dilantin, or
Depakene
Luminal or
Mysoline
Status Epilepticus
Valium,
Ativan, or
Dilantin
Seizure Type
3rd Line
valproic acid (Depakene) and
divalproex (Depakote)
• Increases the availability of GABA
(inhibitory)
• Take with water, not a carbonated drink
• Do not use aspirin
Dispensing Issues
Warning!
• Depakote and Depakene can easily be
confused.
• Be careful with Depakote and Depakote ER.
• Depakote ER is only once a day.
phenytoin (Dilantin)
• May be used to prevent seizures
• Promotes sodium outflow from cells –
stabilizes the neuronal membrane
• Be cautious of drug interactions
• Intravenous phenytoin must be mixed
carefully
Phenytoin Side Effects
Dose Related
–
–
–
–
–
–
Ataxia
Diplopia
Dizziness
Drowsiness
Encephalopathy
Involuntary movements
Phenytoin Side Effects
Non-Dose-Related
– Gingival hyperplasia
– Peripheral neuropathy
– Vitamin deficiencies
Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
– Cerebyx (anticonvulsant)
– Celexa (antidepressant)
– Celebrex (for pain and arthritis)
carbamazepine (Epitol, Tegretol)
• Has effect on sodium channels which may
alter synaptic transmission.
• Blood monitoring must be done regularly.
• Be cautious of interactions and side effects.
gabapentin (Neurontin)
• Used in conjunction with other medications
• No significant drug interactions
• Used for many other disorders, particularly
neuropathic pain
Dispensing Issues
Warning!
Neurontin (anticonvulsant) and Noroxin
(antibiotic) are sound-alike drugs, but they
are easy to distinguish by strength.
clonazepam (Klonopin)
• Only indication is prophylaxis of seizures
• Depresses nerve transmission in the motor
cortex
• C-IV controlled substance (benzodiazepine)
Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
– Lamictal (anticonvulsant)
– Lamisil (antifungal)
– Lomotil (for diarrhea)
topiramate (Topamax)
• Is thought to alter sodium channels and
thereby increases GABA activity and
decreases glutamine activity
• Causes significant cognitive effects
• Drink fluids to decrease risk of kidney
stones
Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
– Kaletra (antiviral for HIV)
– Keflex (antibiotic)
– Keppra (anticonvulsant)
Discussion
Which neurotransmitters play
the greatest role in seizures?
Discussion
Which neurotransmitters play the greatest
role in seizures?
Answer
• Glutamate (excitatory)
• GABA (inhibitory)
Parkinson’s Disease
• Characteristic Signs
– Resting tremor
– Rigidity
– Akinesia
• Usually affects people over 60
Parkinson’s Disease
Physiology
• Result of pathologic alterations in the
extrapyramidal system (part of the CNS that
controls motor activities)
• Distinguishing feature: Lewy bodies
(protein masses) found in the midbrain
Parkinson’s Disease
Physiology
• Normal muscle movement requires balance of
dopamine (inhibitor) and ACh (stimulator)
• In the substantia nigra, enough dopamine is
released to counteract the effects of ACh
• In parkinsonism, enough dopamine is not released
which leads to excessive motor nerve stimulation
Cutaway View of the Brain
Substantia Nigra
Parkinson’s Disease
Drug Therapy
• Improves the functional ability and clinical
status of patients
• Aims at symptomatic relief, does not alter
the disease process
• Patients may have temporary or prolonged
remission
• Side effects can be a problem
Drug List
Anti-Parkinson Agents
•
•
•
•
•
•
amantadine (Symmetrel)
benztropine (Cogentin)
bromocriptine (Parlodel)
entacapone (Comtan)
levodopa (Dopar)
levodopa-carbidopa (Sinemet)
Drug List
Anti-Parkinson Agents
•
•
•
•
•
•
levodopa-carbidopa-entacapone (Stalevo)
pergolide (Permax)
pramipexole (Mirapex)
ropinirole (ReQuip)
selegiline (Eldepryl)
tolcapone (Tasmar)
levodopa (Dopar)
• Metabolized to dopamine in the brain, but
the brain does not receive a full dose
• Drug has very undesirable effects
• After about 5 years of therapy, 2/3 of
patients experience “on-off” phenomenon
levodopa-carbidopa (Sinemet)
• Probably the most common drug used for
parkinsonism
• Carbidopa allows for lower doses of
levodopa to be used which decreases side
effects
Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
– Amantadine (for Parkinson’s)
– Ranitidine (for the stomach)
– Rimantadine (for the flu)
entacapone (Comtan)
• Indicated for patients who have a
deteriorating response to levodopa
• Less toxic than tolcapone
• Take without regard to food
Discussion
What are the two primary
neurotransmitters involved in
Parkinson’s disease and what role do
they play?
Discussion
What are the two primary
neurotransmitters involved in Parkinson’s
disease and what role do they play?
Answer
• ACh (excitatory)
• Dopamine (inhibitory)
Myasthenia Gravis
• Autoimmune disorder of the neuromuscular
junction
• ACh receptors are destroyed at the motor
end plate
• Characterized by weakness and fatigability,
especially of the skeletal muscles
Motor End Plate
Myasthenia Gravis
Presenting Signs
• Ptosis (drooping eyelid)
• Diplopia (double vision)
• Dyarthria (speech)
• Dysphagia (swallowing)
Myasthenia Gravis
Treatment
Blocking the destruction of ACh causes
improvement for the patient
Drug List
Myasthenia Gravis Agents
•
•
•
•
•
azathioprine (Imuran)
cyclophosphamide (Cytoxan)
edrophonium (Enlon, Reversol)
neostigmine (Prostigmin)
pyridostigmine (Mestinon)
pyridostigmine (Mestinon)
• Blocks destruction of ACh
• Allows for ACh accumulation at the
synaptic junction
cyclophosphamide (Cytoxan)
• Prevents cell division by targeting the autoimmune portion of the disease
• Use chemotherapeutic precautions
Attention-Deficit Disorders
• Attention-Deficit Hyperactivity Disorder
(ADHD)
• Attention-Deficit Disorder (ADD)
Attention-Deficit Disorders
Attention-Deficit Hyperactivity
Disorder (ADHD)
Characterized by purposeless, chronic,
pervasive, driven behavior that affects a child
in social, emotional, and academic settings.
Attention-Deficit Disorders
Attention-Deficit Hyperactivity
Disorder (ADHD)
Characteristics for Assessment
– Hyperactivity
– Impulsivity
– Distractibility
Attention-Deficit Disorders
Attention-Deficit Disorder (ADD)
• Has less hyperactivity
• Child is more lethargic and more easily
distracted
• Both disorders are more common in boys
than girls
• Some symptoms can persist into adulthood
Drug List
Attention-Deficit Disorder
Agents
•
•
•
•
•
atomoxetine (Strattera)
clonidine (Catapres, Catapres-TTS)
desipramine (Norpramin)
dexmethylphenidate (Focalin), C-II
dextroamphetamine-amphetamine
(Adderall), C-II
Drug List
Attention-Deficit Disorder
Agents
• imipramine (Tofranil)
• methylphenidate (Concerta, Metadate,
Ritalin, Ritalin-SR), C-II
• nortriptyline (Aventyl, Pamelor)
• pemoline (Cylert), C-IV
methylphenidate (Concerta,
Metadate, Ritalin, Ritalin-SR)
• C-II controlled substance
• Drug of choice to treat ADD, ADHD, and
narcolepsy
• Increases levels of neurotransmitters in the brain
• Concerta is a QD dose – outer shell dissolves to
release medication immediately, then drug is
slowly released through pores in the tablet
dextroamphetamine-amphetamine
(Adderall)
• C-II controlled substance
• Effects last about 6 hours
• Primary side effect is depression
Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
– Adderall (ADD, ADHD)
– Inderal (anxiety, hypertension)
atomoxetine (Strattera)
• Nonstimulant inhibitor of norepinephrine
reuptake
• Controls impulsivity and activity
• Not a controlled substance, so refills can be
called in
• Side effects: weight loss and slowed growth
Dispensing Issues
Warning!
Look-Alike and Sound-Alike Drugs
– Clonidine (ADD, ADHD)
– Klonopin (seizures)
Discussion
Compare and contrast ADHD
and ADD.
Discussion
Compare and contrast ADHD and ADD.
Answer
• ADHD – hyperactivity, impulsivity, and
distractability
• ADD – more lethargic and easily
distracted
Amyotrophic Lateral Sclerosis
(ALS)
• Known as Lou Gehrig’s disease
• Progressive degenerative disease of the
nerves
• Leads to muscle weakness, paralysis, and
eventually death
• Caused by excessive levels of glutamate
Drug List
ALS Agent
• riluzole (Rilutek)
riluzole (Rilutek)
• First drug approved for ALS
• Inhibits release of glutamate
• Shown to improve survival rate by 3 months
is some patients
Multiple Sclerosis (MS)
• Autoimmune disease in which myelin
sheaths degenerate
• Patient loses use of muscles and often
eyesight is affected
• Some drugs can slow progression, but there
is no cure
Drug List
MS Agents
•
•
•
•
•
•
baclofen (Lioresal)
glatiramer acetate (Copaxone)
interferon beta-1a (Avonex, Rebif)
interferon beta-1b (Betaseron)
mitoxantrone (Novantrone)
tizanidine (Zanaflex)
interferon beta-1a (Avonex, Rebif)
•
•
•
•
Used for ambulatory patients
Reduces frequency of attacks
Delays disability
Drug should be taken at night with APAP to
prevent flu-like side effects
baclofen (Lioresal)
• Skeletal muscle relaxant
• Inhibits transmission of reflexes at the
spinal cord
• Onset requires three to four days
Alzheimer’s Disease
•
•
Degenerative disorder of the brain that
leads to progressive dementia and changes
in personality and behavior
Progression
1. Minor forgetfulness
2. Inability to complete complex tasks
3. Complete incapacitation, disorientation, and
failure to thrive
Alzheimer’s Disease
• There are no treatments that can reverse this
disease
• Depression should be treated according to
symptoms
Drug List
Alzheimer’s Agents
•
•
•
•
•
•
donepezil (Aricept)
galantamine (Reminyl)
ginkgo
memantine (Namenda)
rivastigmine (Exelon)
tacrine (Cognex)
donepezil (Aricept)
• Convenient with few side effects
• Improves memory and alertness
• Give once a day at bedtime
memantine (Namenda)
• May have fewer side effects than other
drugs
• Approved for moderate to severe conditions
• Evidence that the drug does slow disease
rivastigmine (Exelon)
• Has fewer interactions than Aricept
• More difficult to dose and administer
Discussion
How does Alzheimer’s disease affect
patients’ families? Has the disease
affected someone in your family?
Discussion
Several of the diseases presented in
this chapter are degenerative and
there is yet no known cure. How
might this affect patients with a
diagnosis of one of these conditions?