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Glossary of Antipsychotic Drugs-CNS Pharm

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What is a neuroleptic drug?
refers to the production of extrapyramidal SE and often used to describe 1st generation antipsychotics.
What is Chlorpromazine?
1st generation antipsychotic
Structure: Phenothiazine
What are the properties of Chlorpromazine?
lipid soluble, 90% plasma bound, long half-life ~30hrs
Where does Chlorpromazine act?
1. D2R antag-potent (def. propr)
2. a1 antag-fairly potent
3. weahe cholinergic antag
4. weak H1 antag
5. noncompetitvive channel blocker (ca and na)
What are the rapidly developing effects of Chlorpromazine?
sedation, disinterest in environment, psychomotore slowing, emotional quieting.
"chemical straightjacket"
What is Chlorpromazine used for?
treat acute psychotic symptoms, includes schizo and mania
What are the delayed effects of Chlorpromazine?
Anti-Schizo effects 92-3wks later)
*alleviates: tension, hyperactivity, combativenes, hostilility, hallucinations, acute delusions, anorexia, negativism and smts withdrawal. Less improved cognitive functions
What are the early onset SE of Chlorpromazine?
Extrapyramidal SE
*Parkinson like sx
*Akathisia
*Acute dystonic reactions
***more common kids and young soon after start
What are the late onset SE of Chlorpromazine?
Extrapyramidal:not reversible
*Tardive dyskinesia--prob. due to Receptor regulation
What is the mechanism of Chlorpromazine?
Therapeutic and neuroleptic SE due to D@-R blocking by inc. conductance of K and reducing cAMP.
Where does Chlorpromazine work in the CNS?
Targets the frontal cortex and limbic system. i.e. Cortex, hippocampus, Nucleus accumbens, VTA...principlly the VTA that stretches to the other spots
Why are their extrapyramidal SE?Chlorpromazine
D2-R block in the striatum.
1. inc. anticholin. activity of striatum.
2. (late) change is genetic in receptors
Other SE of Chlorpromazine?
Oversedation, OD in kids, Seizure with hx, CVS: a1blcok-ortho Hypotension, quinidine-like;dec. contract, reflex tachy; drymouth, inhibit ejeact, galactorrhea, amenorrhea
***neuroleptic malignant syndrome
What is Neuroleptic malignant syndrome?
hyperthermia, diffuse muscle rigidity, autonomic sx-HTN,incontinence.

TX-dantrolene IV (muscle relax) then bromocriptine (d2 agonist)
How do you manage the early EP SE of Chlorpromazine?
1.anticholinergic antipark drugs: diphenhydramine, trihexiphenidyl, benztropine
What are the other 1st generation antipsychotic drugs?
Depot form: fluphenazine decanoate
Low potency: Chlorpromazine, Thioridazine
Intermed: Trifluoperazine, Perphenazine, Thiothixene
High Pot: Haloperidol, Fluphenazine
What are the uses of 1st generation antipsychotics?
1. Schizo
2. Gilles de la Tourette Syndrome
3. Huntington's Chorea
4. Acute manic episodes while on Li being built up
5. Schizo-affective disorders
6. Emesis
What is Clozapine?
2nd generation antipsychotic/Atypical antipsych.
What is different about 2nd generation anti-psychotics?
*relatively little EPS, and more effective at negative sx
*antagonize 5-HT2R, D2, D2,(and/or)D4
What are the properties of Clozapine?
more anticholinergic than most antipsy, low affinity for D2R
What are the SE of Clozapine?
MAJOR: 1-2% Agranulocytosis, fatal if unchecked
minor:can cause weight gain and induce/exacerbate DM2, HTN, sleep apnea
What are the other 2nd generation Antipsy, that are diff. from Clozapine?
olanzapine (zyprexa)
risperidone (Risperidal)
quetiapine (Seroquel)
sertindole (ziprasidone)

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