Drugs for Neuroleptics (Anti-psychotic)

Drug Clinical Extra pyramidal Muscarinic Sedative effect Hypotensive effect Advantages Disadvantages
potency effects effects (Histamine receptor) (adrenergic receptor)
TYPICAL blocking DA receptor
Chlorpromazine ↓ ++ +++ +++ +++ Inexpensive, parenteral form available Many AE especially ANS effect
Thioridazine ↓ + +++ +++ +++ Slight EPS, inexpensive Dose limited, no parenteral form, cardiotoxicity
Trifluoperazine ↑ +++ + + +
Haloperidol ↑ +++ + + + Parenteral form, depot available for poor Severe EPS, Cannot withdraw rapidly if patient
compliance patient, inexpensive develop problems, dose adjustment difficult
Flupentixol ↑ +++ + + +
Pimozide ↑ +++ + ++ +
ATYPICAL Act on D2 / D2-like & 5HT receptor
Clozapine Medium ± ++ +++ +++ For treatment resistant patients, ↓ EPS Agranulocytosis (need to do blood count), cost
Risperidone ↑ +/+++ ++ +++ +++ Broad efficacy, ↓ EPS with ↓ dose (< 8mg/dl) EPS, hypotension with ↑ dose, cost
Olanzapine ↑ + + ++ ++ Effective against –ve & +ve symptoms, ↓ EPS Weight gain
Quetiapine ↓ ± ++ + +
Aripiprazole ↑ ± ± + +

ADME: Selection of drug in psychosis

• Readily but incompletely absorbed
• Significant first pass metabolism
• Highly lipid soluble and protein bound
– Vd large.
– Generally have longer duration of action than
estimated plasma t ½
– Full relapse may not occur until 6 weeks after
discontinuation
• Metabolized mainly in the liver
• Excreted mainly through urine and bile
– May persist weeks after last dose of
chronically administered drug
General Use of drugs:
• Generally control +ve symptoms better than -ve
– -ve symptoms – use atypical neuroleptics
• Symptomatic
– Do not remove cause of illness
– Long term Rx required
• Choice of drug is empirical, guided by
– presenting symptom
– associated features & mood states
– type of S/E that is acceptable to patient
• Difference response to each drugs
– no way to predict
• In pregnancy, small increase in teratogenic risk
1) Agitated, combative voilent
CPZ, triflupromazine, haloperidol
2) Withdrawn & apathetic
Trifluperazine, flupenazine
3) Mainly negative symptoms & resistant cases
Clozapine, olanzapine
4) If EPS must be avoided
Thioridazine, clozapine, olanzapine
5) Elderly patients (prone to sedation, mental confusion,
hypotension)
More potent atypical drugs
Other adverse effects:
• Toxic or allergic reactions
–Agranulocytosis – especially with clozapine
–Cholestatic jaundice
–Skin eruptions
• Ocular complications
–Deposits in cornea and lense, cataract-CPZ
–Retinal deposits (thioridazine)
• Cardiac toxicity
–ECG changes (direct negative inotropic and
quinidine-like effect to heart) Adverse Effect for Anticholinergic Agonist:
• ↑ QT, PR interval (thioridazine) ~ Dry mouth, hot & flushed skin, ↑ body temperature, constipation
• ST depression ~ Blurred vision, “sandy” eyes, ↑ IOP- induce glaucoma
–Ventricular arrhythmia, heart block (thioridazine) ~ CNS: restlessness, confusion, delirium
~ mad as a hen, blind as a bat, hot as a hare, dry as bone, red as beet