#10 Psychopharmacology 10-20-06

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psychopharmacology include

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1) antidepressants
2) anxiolytics
3) lithium
4) antipsychotics

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treatment goal is

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to be able to treat pts on an outpatient basis

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3 classes of antidepressants

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1) TCA
2) MAOI
3) SSRIs

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older agent- 1st generation
Tricyclic antidepressants (TCA's)

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1) Amitriptyline (Elavil, Endep)
2) Imipramine (Tofranil)
3) Desipramine (Norpramine)
4) Doxepin (Sinequan)
5) Clomipramine (Anafranil, also a SSRI)
6) Maprotiline (Ludiomil)
7) Nortriptyline (Aventyl, Pamelor)
8) Protriptyline (Vivactil)

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older agent
Monoamine oxidase inhibitors (MAO-I's)

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1) Phenelzine (Nardil)
2) Tranylcypromine (Parnate)
3) Clorgyline (specific for MAO type A, research only)
4) Isocarboxazid (Marplan)

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second generation
not including SSRIs

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1) Amoxapine (Asendin)
2) Bupropion (Wellbutrin)
3) Nefazodone (Serzone)
4) Trazodone (Desyrel)
5) Mirtazapine (Remeron)

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Serotonin-specific reuptake inhibitors (SSRIs)

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1) Fluoxetine (Prozac)
2) Clomipramine (Anafranil)
3) Sertraline (zoloft)
4) Venlafaxine (Effexor)
5) Paroxetine (Paxil)
6) Citalopram (Celexa)
7) Escitalopram (Lexapro)

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Norepinephrine-specific reuptake inhibitors

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1) Atomoxetine (Strattera) for ADHD

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TCA's are thought to enhance the actions of?

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biogenic amines by inhibiting reuptake

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Imipramine (Tofranil)

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1) prototype TCA
2) blocks norepinephrine reuptake

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Clomipramine (Anafranil)

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1) TCA
2) prominent actions on the serotonin system
3) for obsessive complusive disorder

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Fluoxetine (Prozac)

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1) SSRI
2) relatively selective in their effect

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Venlafaxine (Effexor)

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1) SSRI
2) #1 antidepressant
3) has actions at both serotonin and NE
4) 5 times greater selectivity for serotonin

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Venlafaxine (Effexor) is linked to

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overdose (>suicide)

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Paroxetine (Paxil)

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1) SSRI
2) 10:1 = serotonin:NE

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most common SE of SSRI's

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1) nausea
2) headeche
3) insomnia
4) nervousness
5) fatigue
6) sexal dysfunction

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less common SE of SSRI's

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1) inappropriate ADH secretion
2) rashes
3) extrapyrmidal effects

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SE of TCA's

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1) urinary retention
2) constipation
3) wt gain
4) sexal dysfunction
5) confusion/delirium
6) orthostatic hypotension
"anticholinergic"

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SE of MAOI's

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1) sleep disturbances
2) orthostatic hypotension
3) wt gain
4) sexal dysfunction
5) drug/food interactions

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MAOI with serotonergic agents or narcotics (Merpiridine) can cause

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serotonin syndrome

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s/s of serotonin syndrome

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1) hyperpyrexia
2) agitation
3) neuromuscular irritability
4) hypotension
5) coma
6) death

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Venlafaxine (Effexor) SE

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1) similar to SSRI
2) high dose = increase in DBP

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Bupropion (Wellbutrin) SE

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high dose = seizure

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Trazodone (Desyrel) SE

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1) priatism

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TCA's + MAOI =

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1) hypertensive crisis
2) tahcycardia
3) seizures

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SSRI's + tryptophan =

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1) agitation
2) restlessness

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MAOI's + tyramine containing foods =

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hypertensive crisis

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mania is a syndrome that may include

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1) sustained, abnormal clear mood elevation
2) extreme, unrealistic confidence
3) acceleration of psychomotor function

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drug tx for mania

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1) lithium
2) haloperidol
3) benzodiazepines

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for pts not responding to litium

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1) Valproic acid (Depakene, Depakote)
2) Carbamazepine (Tegretol)

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lithium

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1) taken up through Na channel
2) increases the reuptake of NE
3) inhibits the release of NE and serotonin
4) inhibits adenylate cyclase
5) increases GABA
6) decreases glutamate
7) alter the 2nd messenger system = decrease neuronal excitability

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effective therapeutic level of lithium

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1.0 mEq/l

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toxic level

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over 1.5 mEq/l

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over 2mEq/l

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1) hypotension
2) cardiac arrhythmias
3) seizures

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schizophrenia
positive symptoms

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1) conceptual disorganization
2) delusions
3) hallucinations

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schizo
negative symptoms = 33%
asso. with poor long-term outcome

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1) loss of function
2) anhedonia
3) decreased emotional expression
4) impaired concentration
5) diminished socialization

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1) catatonic type

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1) major change in motor activity
2) negativism

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2) paranoid type

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1) siginificant preoccupation with a specific delusional system

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3) disorganized type

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1) disorganized speech/behavior asso. with superficial or silly affect

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4) residual type disease

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negative symptomatology in the absence of
1) illusions
2) hallucinations
3) motor disturbance

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schizo. 3 principal risk factors

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1) genetic
2) early development damage
3) winter births

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antipsychotic
phenothiazine compounds
1) aliphatic derivative

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1) Chlorpromazine (Thorazine)

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2) piperidine derivatives

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1) Thioridazine (Mellaril)

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3) Piperazine derivatives

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1) Fluphenazine (Prolixin)

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Thioxanthene compound

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1) Thiothixene (Navane)

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Butyrophenones

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1) Haloperidol (Haldol)

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antipsychotics
miscellaneous structures

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1) Pimozide (Orap)
2) Molindone (Moban)
3) Clozapine (Clozaril)
4) Olanzapine (Zyprexa)
5) Quetiapine (Seroquel)
6) Risperidone (Risperdal)
7) Ioxapine (Loxitane)
8) Ziprasidone (Geodon)

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phenothiazine prototype

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Chlorpromazine (Thorazine)

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Chlorpromazine blocks

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1) dopamine - cnetral focus
2) alpha adrenergic receptor
3) serotonin (5-HT2)

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antipsychotic induced endocrine change due to
blockade of dopamine-mediated tonic inhibiton of?

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prolactin secretion

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adverse effect of antipsychotic = extrapyramidal reactions

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1) early in treatment
2) Parkinson's syndrome
3) akisthisia
4) acute dystonic reactions
5) tx = antimuscarinic (Benadryl)

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extrapyramidal reactions
occurrence late in tx

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1) Tardive dyskinesia = choreoathenoid move.

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SE antipsychotics
ocular effects

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1) Cholrpromazine = cornea and lens deposits
2) Thioridazine (Mellaril) = retinal deposits

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malignant neuroleptic syndrome

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1) life-threatening
2) initial symptom = muscle rigidity
3) fever
4) irregu. pulse, unstable BP
5) > creatinine kinase
6) TX = antiparkinson drug and muscle relaxants

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Clozapine (Clozaril) cause

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1) agranulocytosis

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additive effects of antipsychotics

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1) alpha adrenergic blockade
2) anticholinergic effects
3) quinidine-like effects (Thioridazine)

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indications for antipsychotic drugs

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1) schizo.
2) schizoaffective disorder
3) manic
4) Tourette's syndrome
5) senile dementia asso. wtih Alzheimer's
6) antiemetic
7) relief of puritis