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Block 2: Antipsychotic Drugs


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Can you name all the drugs to remember for this lecture? :)
2 old antipsychotics
4 atypical antipsychotics
DA system stabilizer
2 anticholinergic
antihistamine w/ anticholinergic
old antipsychotics: chlorpromazine, haloperidol

newer atypical antipsychotics: risperidone, clozapine, olanzapine, quetiapine

Domanine system stabilizer: aripiprazole


antihistamine w/ anticholinergic: diphenhydramine
Hypothesis of Schizophrenia
DA excess- DA receptor blockers make better/agonists make worse
Neuroleptic syndrome
lack of initiative and disinterest caused by antipsychotic drugs
Antipsychotic admin
oral or im
Time of action
Full effect of anti-psychs several hours to weeks after admin
Generalized side effects
Mostly due to blockade of cholinergic and alpha adrenergic receptors in addition to DA receptor block (not associated with benefits)
Which side effect is not reversible?
Tardive dyskinesia
What are the non-neurological side effects?
Orthostatic hypotension, altered sexual fxn, increased prolactin, wt. gain, sedation, seizures, anticholinergic effects, phototoxicity, blood dyscrasias
Characterize orthostatic hypotension
Due to alpha adrenergic block, prevents NE from constricting arterioles
*can cause reflex tachycardia
Characterize altered sexual fxn
name two drugs that play a role
decreased sex drive
Thioridazine (thI'-er-rid'-ez-zine') & chlorpromazine (chlor-prO'-me-zine') may prevent ejaculation
Characterize increased prolactin
Caused by block of DA receptors on PL secreting cells, loss of inhibitory signal. Women-glactorrhea/amenorrhea Men- gynecomastia (man boobs)
Characterize weight gain
May be severe enough to cause DM type 2
Characterize seizures
All antipsychs lower seizure threshold
Characterize anticholinergic effects
nasal congestion, dry mouth, blurred near vision, constipation, and urinary retention
Characterize phototoxicity
Extreme sensitivity, more suceptible to burns
Characterize blood dyscrasias
leukopenia, usually within first two months of treatment
Neurological side effects or Extrapyramidal (involuntary motor activity)
Parkinsonism syndrome, dystonias, akathisias, tardive dyskinesia
How many treated patients get neuro side effects?
Characterize Parkinsonism syndrome
Caused by blockade of DA receptors, symptoms identical to that of idiopathing Parkinson's
One more time for kicks...symptoms of Parkinson's
akinesia, rigidity, alteration of posture, tremor, mask like face, shuffling gait, loss of associative movement, hypersalivation
Control of anti-psych induced parkinson's
Co-admin of an anticholinergic drug (benztropine or trihexphenidyl)
Characterize dystonias
Uncoordinated, bizarre, jerking or spastic movements of the neck, face, eyes, tongue, torso, arms, or legs.
Control of dystonias
I.V. or I.M. benztropine or an antihistamine w/anti-chol properties: diphenhydramine
Characterize akathisias
discomforting feeling of restlessness and agitation/patients unable to sit still
Control of akathisias
Characterize Tardive Dyskinesia
Irreversible! Coordinated rhythmic, abnormal, involuntary sucking, chewing, licking, and pursing movements of the tongue and mouth
When will tardive appear?
Months or years after treatment
New atypical antipsychs
Risperidone, Clozapine, Olanzapine
Properties of new anti-psychs
As effective of positive symptoms as haloperidol, more effective at relieving negatives.
Block D2 and 5HT2 receptors
Cause more severe weight gain
Risperidone vs. Haloperidol
(causes __, high doses cause __)
Causes some elevation of prolactin, high dose cause extrapyrimidal effects
Clozapine vs. Haloperidol
(no__ and ___, may cause ___)
No prolactin elevation, no Tardive
Can cause agranulocytosis (possibly fatal), WBC count every week
D4 receptor
Expressed in the mesolimbic system not the striatum. Binds clozapine 10X more than other DA receptors
Olanzapine vs. Haloperidol
(no __ or __)
Binds to the same receptors as clozapine including 5HT2 and D4
No Tardive or hematologic abnormalities
Quetiapine vs. Haloperidol
Greater affinity for 5HT2 than for D2. Antagonizes H1, alpha 1 and 2 receptors.
Dopamine system stabilizer drug
Aripiprazole (ah-re-pip'-ra-zole), partial DA agonist and some serotonin receptors
Antagonist at D2, DA, alpha-adrenergic, cholinergic receptors
Effect of Cholorpromazine and Haloperidol
Ameliorates the positive symptoms of schizophrenia
What are the symptoms of schizophrenia?
thought disorder, flat affect, autism, hallucinations, and delusions
D2 receptor antagonist
Side effects of cholorpromazine and haloperidol
orthostatic hypotension, hyperprolactinemia, wt gain, sedation (Chlor>Halo), antichol effects, blood dyscrasias, parkinosims, dystonias, akathisias, tardive
Blocks D2 and 5HT2 receptors
Effect of risperidone
effective for both +/- symptoms
Side effects of risperidone
hyperprolactinemia and extrapyrimidal effects at high doses
Blocks D4 receptors>>D2 and 5HT2 receptors
Effect of clozapine
best drug for relieving symptoms
Side effects of Clozapine
very mild extrapyramidal effects but AGRANULOCYTOSIS
Blocks D2 and D4 receptors equally and 5HT2
Effect of olanzapine
Both +/- symptoms
Side effects of olanzapine
Some extrapyramidal, some prolactin elevation
Blocks 5HT2 > D2, also blocks H1
Effect of Quetiapine
Both +/- symptoms
Side effects of Quetiapine
Some elevated prolactin, some extrapyramidal
Partial DA agonist and some 5HT receptor agonist
Effect of aripiprazole
As good as atypical anti-psychs
Side effects of aripirazole
?? We don't know
Lauren's middle name?
Discovery of Chlorpromazine
Delay and Deniker 1952
Antipsychs are also called
The atomic number of Carbon

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