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
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
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 P-
4502D6
 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
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
Phenothiazines (Thorazine, Prolixin)
Thioxanthenes (Navane)
Dibenzoxazepines (Loxitane)
Haloperidol (Haldol)
Atypical or Novel
Clozapine (Clozaril)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
 Antipsychotic Side Effects
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
Amitriptyline (Elavil)
Clomipramine (Anafranil)
Doxepine (Sinequan)
Imipramine (Tofranil)
Trimipramine (Surmontil)
 Antidepressants
Secondary Amines
Amoxapine (Asendin)
Desipramine (Norpramin)
Nortriptyline (Aventyl, Pamelor)
Protrypyline (Vivactil)
 Side Effects -- TCAs
Most common uncomfortable side effects
sedation
orthostatic hypotension
anticholinergic
Others
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

Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine (Luvox)
 Side Effects -- SSRIs
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
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 Sedative-
Hypnotic 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