talking about chlorpromazine with consideration of its antiemetic effect & doses in emesis lecture at Al-Mahmoudiya G. Hospital 2/10/2019

1. Chlorpromazine HCL
Alaa Fadhel Hassan
Drug information centre

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].

9. Adverse effects

10. Black box warning

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.

12. Drug interactions
Contra-
indicated
Serious - Use Alternative Monitor closely
Procainamide
Sotalol
Amiodarone, quinidine
Amitriptyline, clomipramine,
imipramine
Bromocriptine, cabergoline
Carvedilol, metoprolol,
propranolol
Clarithromycin, erythromycin,
moxifloxacin
Dopamine, epinephrine
Fentanyl, haloperidol
Fluconazole, ketoconazole
formoterol
hydrocodone
Levodopa, methyldopa
Ondansetron, prochlorperazine
tretinoin
Albuterol, salmeterol
Alprazolam, diazepam, lorazepam
Amitriptyline, clomipramine, imipramine
Anticholinergic/sedative, chlordiazepoxide, diphenoxylate hcl,
hyoscyamine, metoclopramide
Atropine, ipratropium, atracurium
Azithromycin, ciprofloxacin, levofloxacin, Trimethoprim-
sulfamethoxazole
Baclofen, orphenadrine
Caffeine, cigarette smoking
Chlorpheniramine, cyproheptadine, phenylephrine
Dobutamine, dopamine, phedrine, norepinephrine
Ethanol, haloperidol, Ketamine, vecuronium, propofol,
phenobarbital
Insulin aspart, metformin
meperidine, methadone, morphine, tramadol
Risperidone, topiramate
Hydroxyzine, itraconazole, melatonin, mifepristone,
pralidoxime, quinidine,tamoxifen, tamsulosin,

13. References
• Katzung basic & clinical pharmacology 2018
• Drugs.com website
• Medscape website

14. Thank You