2. Pharmacodynamic
• 1st G (Typical) antipsychotic phenoththiazine of low clinical
potency.
• blocks postsynaptic mesolimbic dopaminergic receptors in the
brain; exhibits a strong α-adrenergic, muscarinic & H1-receptor
blocking effect and depresses the release of hypothalamic and
hypophyseal hormones (α1 = 5-HT2A > D2 > D1).
• Its strong antiemetic effect due to dopamine-receptor blockade,
both centrally (in the chemoreceptor trigger zone of the medulla)
and peripherally (on stomach receptors).
3. Pharmacodynamics
• Its toxicity attributed to the effects on α and M receptors while blockade of
dopamine receptors may result in akathisia, dystonia, parkinsonian
symptoms, tardive dyskinesia, and hyperprolactinemia.
• Longacting injectable formulations may cause some blockade of D2
receptors 3–6 months after the last injection. They generally have a much
longer clinical duration of action than would be estimated from their
plasma half-lives, in parallel to the prolonged occupancy of D2 dopamine
receptors in the brain.
• Time to recurrence of psychotic symptoms is highly variable after
discontinuation of antipsychotic drugs. The average time for relapse in
stable patients with schizophrenia who discontinue their medication is 6
months.
4. Indications
• Behavioral problems in children (1-12 yr) marked by combativeness
&/or explosive hyperexcitable. Short-term treatment of hyperactive
children with excessive motor activity accompanying conduct disorders.
• Manic episodes associated with bipolar disorder, schizophrenia &
psychotic disorders.
• Management of nausea and vomiting, intractable hiccups & acute
intermittent porphyria.
• Management of restlessness and apprehension prior to surgery.
• Adjunctive therapy in the treatment of tetanus.
• [Off Label Uses] nausea and vomiting of pregnancy, psychosis/
agitation associated with dementia.
5. Pharmacokinetics
• Readily & incompletely absorbed, oral doses availability is (25–35%)
& duration of 4-6 hr.
• Plasma half-life is biphasic, initial (children: 1.1 hr & adults: ~2 hr);
terminal (children: 7.7 hr & adults: ~30 hr).
• Highly lipid soluble and protein bound (92–99%), tend to have large
volumes of distribution (usually < 7 l/kg), crosses blood-brain barrier.
• Metabolism: extensively hepatic by demethylation (followed by
glucuronide conjugation) & amine oxidation, catalyzed by liver
microsomal CYP450 enz. [CYP2D6, CYP1A2, & CYP3A4].
• Excretion: urine (<1% as unchanged drug) within 24 hr., metabolites
may excreted weeks after the last dose of chronic administration.
6. Dosage
• Psychotic disorders: minimum effective therapeutic dose 100 mg
while usual range of daily dose 100-1000 mg.
• Nausea and vomiting: 10 to 25 mg every 4 to 6 hr (oral/prn) & 25
mg; initial then 25 to 50 mg every 3 to 4 hr (I.M./ prn until vomiting
stops, if no hypotension occurs).
• During surgery: 12.5 mg; repeat in 30 min. if necessary & if no
hypotension occurs &/ 2 mg per fractional injection at 2 min.
intervals using a 1 mg/mL solution (I.V).
• Nausea and vomiting of pregnancy, refractory: 25 to 50 mg every 4
to 6 hr (I.M/I.V) & 10 to 25 mg every 4 to 6 hr (oral).
7. Dosage II
• Geriatric: in the lower range of recommended adult dosing.
• Nausea and vomiting, treatment for infants ≥6 months, children, &
adolescents weighing ≤45.5 kg: (Oral, I.M, I.V): 0.55 mg/kg/dose q 6-8 hr as
needed.
• Usual maximum daily dose (I.M, I.V) for children <5 yr/ weighing <22.7 kg is
40 mg/day while for children ≥5 yrs & adolescents/ weighing 22.7 to 45.5 kg is
75 mg/day
• For Adolescents weighing >45.5 kg (Oral) 10-25 mg q 4 to 6 hr as needed/ &
(I.M, I.V) 25 mg; if tolerated (no hypotension), then may give 25 to 50 mg q -6
hours as needed.
• Cyclic vomiting syndrome; abortive therapy: infants ≥6 months, children, &
adolescents(I.V) 0.5-1 mg/kg/dose q 6 hr; maximum dose 50 mg in
combination with diphenhydramine (for possible dystonic reactions).
8. Reconstitution & administration
• Its reconstituted with N/S to a maximum conc. of 1 mg/ml (direct I.V
inj.) while diluting 25-50 mg of chlorpromazine with 500-1000 ml N/S
is recommended for treatment of intractable hiccups [manufacturer].
• Diluted solution administered slow I.V. at a rate not exceed 1
mg/min while given as a slow I.V inf. for intractable hiccups.
• [To reduce the risk of hypotension, patients must remain lying down
during and for 30 min. after the inj].
• I.M inj. Given slowly, deep into upper outer quadrant of buttock.
• Injection solution must be protected from light and freezing [A
slightly yellowed solution does not indicate potency loss, but a
markedly discolored solution should be discarded].
11. Preganancy & lactation
• Jaundice or hyper- or hyporeflexia have been reported.
• Use during the third trimester of pregnancy has a risk for abnormal
muscle movements (EPS) and withdrawal symptoms in newborns
following delivery. Symptoms may include [agitation, feeding
disorder, hypertonia, hypotonia, respiratory distress, somnolence,
and tremor].
• Pregnancy category C, as an adjunctive treatment of nausea and
vomiting in pregnant women would be reserved for women with
dehydration with persisting symptoms.
• Lactation: Drug enters breast milk; not recommended.