| Indication |
For the treatment of schizophrenia, control nausea and vomiting,
For relief of restlessness and apprehension before surgery, adjunct in
the treatment of tetanus, control the manifestations of the manic type
of manic-depressive illness. |
| Pharmacodynamics |
Chlorpromazine is a psychotropic agent indicated for the
treatment of schizophrenia. It also exerts sedative and antiemetic
activity. Chlorpromazine has actions at all levels of the central
nervous system-primarily at subcortical levels-as well as on multiple
organ systems. Chlorpromazine has strong antiadrenergic and weaker
peripheral anticholinergic activity; ganglionic blocking action is
relatively slight. It also possesses slight antihistaminic and
antiserotonin activity. |
| Mechanism of action |
Chlorpromazine acts as an antagonist (blocking agent) on different
postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3
and D4 - different antipsychotic properties on productive and
unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with
anxiolytic, antidepressive and antiaggressive properties as well as an
attenuation of extrapypramidal side-effects, but also leading to weight
gain, fall in blood pressure, sedation and ejaculation difficulties), on
histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo,
fall in blood pressure and weight gain), alpha1/alpha2-receptors
(antisympathomimetic properties, lowering of blood pressure, reflex
tachycardia, vertigo, sedation, hypersalivation and incontinence as well
as sexual dysfunction, but may also attenuate pseudoparkinsonism -
controversial) and finally on muscarinic (cholinergic) M1/M2-receptors
(causing anticholinergic symptoms like dry mouth, blurred vision,
obstipation, difficulty/inability to urinate, sinus tachycardia,
ECG-changes and loss of memory, but the anticholinergic action may
attenuate extrapyramidal side-effects).
Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine
reuptake, which may lead to (mild) antidepressive and antiparkinsonian
effects. This action could also account for psychomotor agitation and
amplification of psychosis (very rarely noted in clinical use). |
| Absorption |
Readily absorbed from the GI tract. Bioavailability varies due to first-pass metabolism by the liver. |
| Volume of distribution |
|
| Protein binding |
> 90% to plasma proteins, primarily albumin |
| Metabolism |
Extensively metabolized in the liver and kidneys. It is
extensively metabolized by cytochrome P450 isozymes CYP2D6 (major
pathway), CYP1A2 and CYP3A4. Approximately 10 to 12 major metabolite
have been identified. Hydroxylation at positions 3 and 7 of the
phenothiazine nucleus and the N-dimethylaminopropyl side chain undergoes
demethylation and is also metabolized to an N-oxide. In urine, 20% of
chlopromazine and its metabolites are excreted unconjugated in the urine
as unchanged drug, demonomethylchlorpromazine,
dedimethylchlorpromazine, their sulfoxide metabolites, and
chlorpromazine-N-oxide. The remaining 80% consists of conjugated
metabolites, principally O-glucuronides and small amounts of ethereal
sulfates of the mono- and dihydroxy-derivatives of chlorpromazine and
their sulfoxide metabolites. The major metabolites are the
monoglucuronide of N-dedimethylchlorpromazine and
7-hydroxychlorpromazine. Approximately 37% of the administered dose of
chlorpromazine is excreted in urine. |
| Route of elimination |
Kidneys, ~ 37% excreted in urine |
| Half life |
~ 30 hours |
| Clearance |
Not Available |
| Toxicity |
Agitation, coma, convulsions, difficulty breathing, difficulty
swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage,
irregular heart rate, low blood pressure, restlessness |
