Psychopharmacology and Other
Biologic Treatments
Chapter 8
Psychopharmacology
• Subspecialty of pharmacology that includes
medications affecting the brain and behavior
used to treat mental disorders including
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antipsychotics
mood stabilizers
antidepressants
antianxiety medications
stimulants
• Provides a basis for understanding specific
biologic treatments of psychiatric disorders
Pharamacodynamics:
Where Drugs Act
• Four sites of action
– Receptors (those sites to which a neurotransmitter can specifically
adhere to produce a change in the cell membranes)
– Ion channels
– Enzymes
– Carrier Proteins
• Biologic action depends on how its
structure interacts with a receptor.
Receptors
• Types of Action
– Agonist: same biologic actin
– Antagonist: opposite effect
• Interactions with a receptor
– Selectivity: specific for a receptor
– Affinity: degree of attraction
– Intrinsic activity: ability to produce a
biologic response once it is attached to
receptor
Ion Channels
• Drugs can block or open the ion channels
• Example: benzodiazepine drugs facilitate
GABA in opening the chloride ion
channel
Enzymes
• Enzymes catalyze specific biochemical
reactions within cells and are targets for
some drugs.
• Monoamine oxidase is an enzyme that
breaks down most bioamine
neurotransmitters (NE, DA, 5-HT).
• Enzymes may be inhibited to produce
greater neurotransmitter effect.
Carrier Proteins
• Transport neurotransmitters across cell
membranes
• Medications may block or inhibit this
transport.
• Example: antidepressants
Efficacy and Potency
• Efficacy - Ability of a drug to produce a response
as a result of the receptor or receptors being
occupied.
• Potency - Dose required to produce the desired
biologic response.
• Loss of effect
– desensitization (rapid decrease in drug effect)
– tolerance (gradual decrease in the effect of a drug at a
given dose)
– can lead to being treatment refractory
Target Symptoms and Side
Effects
• Target symptoms:
– Specific symptoms for each class of medication
– No drug attacks such a target symptom
• Side effects - Responses not related to target
symptoms (Table 8.1, 8.1).
• Adverse effects: Unwanted effects with
serious physiologic consequences.
Drug Toxicity
• Toxicity: Point at which concentrations of the drug
in the blood stream become harmful or poisonous
to the body.
• Therapeutic index: Ratio of the maximum
nontoxic dose to the minimum effective dose.
• High therapeutic index: Wide range between dose at which the
rug begins to take effect and dose that would be considered
toxic.
• Low therapeutic index - low range
Absorption
• From site of administration into the plasma
• Oral - (tablet and liquid) (Table 8-3)
– Most Convenient
– Most variable (food and antacids)
• First pass effect
• Decreased Gastric Motility (age, disease, medication)
• IM - Short-and long acting
• IV - Rarely used
Pharmacokinetics:
How the Body Acts on the Drug
• Absorption
• Distribution
• Metabolism
• Elimination
Bioavailability
• Amount of drug that reaches systemic
circulation unchanged
• Often used to compare one drug to another,
usually the higher the bioavailability, the
better.
Distribution
• Amount of drug found in various tissues,
especially the intended ones.
• Psychiatric drugs must pass through blood-brain
barrier (most fat-soluble)
• Factors effecting distribution
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Size of organ ( larger requires more)
Blood flow ( more, greater concentration)
Solubility (greater, more concentration)
Plasma Protein (if bound, slower distribution, stays in body longer
– Anatomic Barriers (tissues surrounding)
Crossing the Blood Brain Barrier
• Passive diffusion
– Drug must dissolve in the structure of the cell
– Lipid solubility is necessary for drugs passing through
blood brain barrier (then, can also pass through
placenta)
• Binding to other molecules
– Plasma protein binding
– The more protein binding, the less drug activity.
– Can bind to other cells, especially fat cells. Then are
released when blood level decreases.
Metabolism
• Process by which the drug is altered and
broken down into smaller substances
(metabolites) that are usually inactive.
• Lipid-soluble drugs become more water
soluble, so they may be more readily
excreted.
• Most metablism is carried out in the liver.
Cytochrome P450
• Many process carried out by enzyme class
Cytochrome P-450
– high affinity for fat-soluble drugs
– involved in metabolism of most psychiatric
medications
– Example: SSRIs inhibitors of the subfamily P4502D6
Elimination
• Clearance: Total amount of blood, serum, or
plasma from which a drug is completely removed
per unit time.
• Half-life: Time required for plasma
concentrations of the drug to be reduced by 50%.
• Only a few drugs eliminated by kidneys (lithium)
• Most excreted in the liver
– excreted in the bile and delivered to the intestine
– may be reabsorbed in intestine and “re-circulate” (up to
20%)
Dosing and Steady State
• Dosing: Administration of medication over time,
so that therapeutic levels can be achieved.
• Steady-state:
– drug accumulates and plateaus at a particular level
– rate of accumulation determined by half life
– reach steady state in about five times the elimination
half-life
Pharmacokinetics: Cultural
Considerations
• 9% of whites - genetically defective P-4502D6
• Asian descent
– Metabolize ethanol to produce higher concentrations of
acetaldehyde (flushing, palpitations)
– Require 1/2 to 1/3 dose antipsychotics and more severe
side effects
• Cardiovascular effects of propranolol
– Asian descent - more sensitive
– African descent - less sensitive
Phases of Drug Treatment
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Initiation
Stabilization
Maintenance
Discontinuation
Psychiatric Medications
• Antipsychotic Medications
• Movement Disorders Medication
• Mood Stabilizers
– Antimania
– Antidepressants
• Antianxiety and Sedative-Hypnotic
• Stimulants
Antipsychotic Medications
• Target symptoms: psychosis
• Types
– Conventional
– Atypical
• Absorption: variable
– clinical effects seen 30-60 min
– IM less variable (avoid 1st pass)
– when immobile, less absorption
• Metabolism: liver
Antipsychotic Medications
• Target symptoms: psychosis
• Types
– Conventional
– Atypical
• Absorption: variable
– clinical effects seen 30-60 min
– IM less variable (avoid 1st pass)
– when immobile, less absorption
• Metabolism: liver
• Excretion: slow
– accumulates in fatty tissues
– 1/2 life of 24 hours or more
Antipsychotic Medications
(cont..)
• Preparations
– Oral
– IM
– Depot - haloperidol and fluphenazine
• Side Effects
– Cardiovascular - orthostatic Hypertension
– Weight-gain: blocking histamine receptor
– Endocrine and sexual: block dopamine, interfere with
prolactin
– Blood Dyscrasias - agranulocytosis
Antipsychotic Medications
• Conventional
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Phenothiazines (Thorazine, Prolixin)
Thioxanthenes (Navane)
Dibenzoxazepines (Loxitane)
Haloperidol (Haldol)
• Atypical or Novel
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Clozapine (Clozaril)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Antipsychotic Side Effects
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Cardiovasular
Anticholinergic
Weight Gain
Endocrine and Side Effects
Blood Disorders
Miscellaneous
Medication-Related Movement
Disorders: Acute Syndromes
• Can occur in 90% of all patients
• Dystonia: involuntary muscle spasms,
abnormal postures, oculogyric crisis,
torticollis
• Parkinsonism: rigidity, akinesia (slow
movement), and tremor, masklike face, loss
of spontaneous movements
• Akathisia: Inability to sit still, restlessness
Movement Disorders: Acute
(cont.)
• Etiology (acute):
– Related to dopamine in nigrostrial pathway that
increases cholinergic activity
• Treatment
– Anticholinergic Medication for dystonia, parkinsonism
(Artane and Cogentin)
– Akathisia does not usually respond to anticholinergic
medication. Beta blockers have best success.
Movement Disorders: Chronic
• Tardive Dyskinesia
– Irregular, repetitive involuntary movements of mouth,
face, and tongue, including chewing, tongue protrusion,
lip smacking, puckering of the lips, and rapid eye
blinking. Abnormal finger movements are common.
• Symptoms
– Begin after 6 months, but also as antipsychotics are
withdrawn
– Irreversible - controversy
Movement Disorders: Chronic
• Etiology
– believed that chronic dopamine suppression in
the EPS causes an overactivation of the system
– increases in antipsychotic meds, suppresses
• Treatment
– prevention by using lowest possible dosage,
minimize use of PRN, closely monitor
individuals in high-risk groups
– monitoring tools
Mood Stabilizers: Antimania
Lithium Carbonate
• Action: uncertain, crosses cell membranes,
altering sodium transport, not protein bound
• Side Effects: thirst, metallic taste, increased
frequency or urination, fine head and hand tremor,
drowsiness, and mild diarrhea
• Blood levels monitored (lithium toxicity - severe
diarrhea, vomiting, drowsiness, muscular
weakness, and lack of coordination, withhold)
Lithium Carbonate
• Monitor creatinine concentrations, thyroid
hormones, and CBC every 6 months.
• Kidney damage may be a risk.
• Thyroid function may be altered usually after 6-18
months. Observe for dry skin, constipation,
bradycardia, hair loss, cold intolerance.
• Avoid during pregnancy.
Mood Stabilizers: Antimania
Anticonvulsants
• Valporate and derivatives (divalproex
sodium - Depakote)
• Carbamazapine (Tegretol)
• Gabapentin (Neurontin) (least side effects)
• Lamotrigine (Lamictal)
• Topiramate (Topamax)
Anticonvulsant Mood Stabilizers
• Only carbamazepine is approved for mania.
• Used when patients have not responded to
lithium
• Pharmacokinetics
– Highly protein bound, metabolized by P450
system (potential drug-drug interaction)
Carbamazepine
Side Effects
• Dizziness, drowsiness, tremor, visual
disturbances, nausea, and vomiting
• Minimized by treating in low doses
• Give with food
• Weight gain
• Alopecia (hair loss)
Antidepressants
Table 8.11,12
Tricyclic: Tertiary Amines
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Amitriptyline (Elavil)
Clomipramine (Anafranil)
Doxepine (Sinequan)
Imipramine (Tofranil)
Trimipramine (Surmontil)
Antidepressants
Secondary Amines
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Amoxapine (Asendin)
Desipramine (Norpramin)
Nortriptyline (Aventyl, Pamelor)
Protrypyline (Vivactil)
Side Effects -- TCAs
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Most common uncomfortable side effects
– sedation
– orthostatic hypotension
– anticholinergic
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Others
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tremors,
restlessness, insomnia, confusion
pedal edema, headache, and seizures
Blood dyscrasias
Sexual dysfunction
Adverse
– cardiotoxicity
Antidepressants
• Most antidepressants block the re-uptake of
a neurotransmitter of one or more of the
bioamines: serotonin, norepinephrine,
dopamine.
• SSRIs - selective to the serotonin
Serotonin Selective
Reuptake Inhibitors
SSRI
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Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine (Luvox)
Side Effects -- SSRIs
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Headache
Anxiety
Transient nausea
Vomiting
Diarrhea
Weight gain
Sexual dysfunction
SSRIs
• Usually given in morning, unless sedation
occurs
• Higher doses, especially fluoxetine, can
produce sedation
• Venlafaxine (Effexor), only mildly sedating.
• Paroxetine associated with weight gain
Antidepressants
Others
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Mirtazapine (Remeron)
Maprotiline (Ludiomil)
Trazodone (Desyrel)
Nefazodone (Serzone)
Bupropion (Wellbutrin)
Venlafaxine (Effexor)
Antidepressants
Monoamine Oxidase Inhibitors (MAOIs)
• Action: Inhibit enzyme responsible for the
metabolism of serotonin, dopamine,
norepinephrine, and tyramine.
• Increases levels of norepinephrine and
serontonin in the CNS
• Interacts with food -- low tyramine diet
(Table 18.3)
Antianxiety and SedativeHypnotic Medication
• Used for anxiety, not long-term
• Benzodiazepines (Table 8.14)
– diazepam (Valium)
– lorazepam (Ativan)
– alprazolam (Xanax)
• Nonbenzodiazepines
– busipirone (BuSpar)
– zolpidem (Ambien)
• Side effects
– Sedation and CNS depression
– Tolerance and dependence (Benzos)
– Avoid Benzo in elderly
Stimulants
• Amphetamines
• Used in narcolepsy, ADHD, and obesity
Electroconvulsive Therapy
• Initiate generalized seizures by an electrical
current
• Short-acting anesthetic and muscle relaxant given
• Repeat procedure 2-3 times per week
• Produces rapid relief of depressive symptoms
• Side Effects-hypo or hypertension, bradycardia or tachycardia,
and minor arrhythmias immediately after
Other Biological Treatment
• Light Therapy (Phototherapy)
– Reset circadian rhythms
– Used for SAD
• Nutritional Therapies