Cpz Plus (anp)

Uses

Chlorpromazine is used for Psychoses, Nausea and vomiting, Psychoses, Intractable hiccup, Psychoses.

Trihexyphenidyl Hydrochloride is used for an adjunct treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic & idiopathic). Additionally, it is used for the control of extrapyramidal disorders caused by central nervous system drugs such as dibenzoxazepines, phenothiazines, thioxanthenes & butyrophenones.

Cpz Plus (anp) is also used to associated treatment for these conditions: Acute Intermittent Porphyria (AIP), Apprehension, Mania, Nausea and vomiting, Oppositional Defiant Disorder, Restlessness, Schizophrenia, Tetanus, Intractable singultus, Severe behavioural problems, Short term HyperactivityExtrapyramidal disorder, Extrapyramidal symptoms caused by butyrophenones, Extrapyramidal symptoms caused by dibenzoxazepines, Extrapyramidal symptoms caused by phenothiazines, Extrapyramidal symptoms caused by thioxanthenes, Idiopathic Parkinson's Disease, Parkinsonism post encephalitic, Arteriosclerotic Parkinsonism

How Cpz Plus (anp) works

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).

Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M1 subtype. In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally. Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum. Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated.

Dosage

Cpz Plus (anp) dosage

Oral: Psychoses:

• Adult: 25 mg tid; may be given as a single 75 mg dose at night. Maintenance: 25-100 mg tid increased to ≥1 g daily as required in psychotic patients.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

Oral: Intractable hiccup:

• Adult: Initially, 25-50 mg 3-4 times daily for 2-3 days; if unresponsive, may admin 25-50 mg via IM inj. If still necessary, 25-50 mg in 500-1000 ml of normal saline may be given via slow IV infusion.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

Intramuscular: Psychoses:

• Adult: 25-50 mg repeated every 6-8 hr. Substitute with oral therapy as soon as possible.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

Intramuscular: Nausea and vomiting:

• Adult: Initially, 25 mg via IM inj, followed by 25-50 mg every 3-4 hr until vomiting stops.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether Trihexyphenidyl may best be given before or after meals should be determined by the way the patient reacts.

Idiopathic Parkinsonism: 1 mg of Trihexyphenidylmay be administered the first day. The dose may then be increased by 2 mg increments at intervals of three to five days.

Drug-Induced Parkinsonism: Commence therapy with a single 1 mg dose increase the total daily dosage to 5-15 mg range if the extrapyramidal manifestations are not controlled.

Concomitant Use with Levodopa: When Trihexyphenidyl is used concomitantly with levodopa, the usual dose is 3-6 mg daily.

May be taken with or without food. May be taken with meals to reduce GI discomfort.

Side Effects

Tardive dyskinesia (on long-term therapy). Involuntary movements of extremities may also occur. Dry mouth, constipation, urinary retention, mydriasis, agitation, insomnia, depression and convulsions; postural hypotension, ECG changes. Allergic skin reaction, amenorrhoea, gynaecomastia, weight gain. Hyperglycaemia and raised serum cholesterol.

Minor side effects such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness. Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Potential side effects are constipation, drowsiness, urinary hesitancy or retention, pupil dilation, increased intraocular tension, vomiting and headache.

Toxicity

Agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, restlessness

Symptoms of overdose include mydriasis, dryness of mucous membranes, red face, atonic states of bowels and bladder, and hyperthermia in high doses. Trihexyphenidyl causes agitation, confusion, and hallucinations due to its effects on the central nervous system. Untreated overdose may result in death, especially in children. Respiratory depression and cardiac arrest may be seen as premortal signs.

Patients experiencing an overdose of trihexyphenidyl may experience dry mouth, anhidrosis, mydriasis, nausea, vomiting, tachycardia, hyperpyrexia, reduced gastrointestinal motility, urinary hesitancy or retention, rash, hyperthermia, confusion, restlessness, agitation, poor coordination, paranoia, psychosis, delirium, hallucinations, coma, respiratory failure, circulatory failure, and death. Patients should be treated with symptomatic and supportive care which may include airway maintenance and the use of physostigmine.

Precaution

Parkinson's disease; CV disease; renal or hepatic impairment; cerebrovascular and respiratoty disease; jaundice; DM; hypothyroidism; paralytic ileus; prostatic hyperplasia or urinary retention; epilepsy or history of seizures; myasthenia gravis; pregnancy; elderly (especially with dementia), and debilitated patients. Avoid direct sunlight.

Patients with cardiac, liver, or kidney disorders, or with hypertensioon, should closely be monitored. Since trihexyphenidyl has parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy. Trihexyphenidyl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson’s disease. Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided.

Interaction

Potentiation of anticholinergic effects of antiparkinson agents and TCAs may lead to an anticholinergic crisis. Additive orthostatic hypotensive effect in combination with MAOIs. Reverses antihypertensive effect of guanethidine, methyldopa and clonidine.

Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with trihexyphenidyl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with trihexyphenidyl may cause increased sedative effects. It may be contraindicated in patients taking monoamine oxidase inhibitors & tricycllic antidepressants.

Volume of Distribution

• 20 L/kg

Elimination Route

Readily absorbed from the GI tract. Bioavailability varies due to first-pass metabolism by the liver.

Trihexyphenidyl is absorbed from the gastrointestinal tract. Trihexyphenidyl reaches a C_max of 7.2 ng/mL, with a T_max of 1.3 hours, and an AUC of 201 ng*h/mL.

Half Life

~ 30 hours

The mean elimination half life of trihexyphenidyl is 3.2 ± 0.3 hours.

Elimination Route

Kidneys, ~ 37% excreted in urine

Data regarding the route of elimination of trihexyphenidyl are not readily available. However, it is likely eliminated predominantly in the urine.

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Pregnancy Category C. It is not known whether the drug is excreted in human milk and therefore trihexyphenidyl should only be used if the expected benefit to the mother outweighs the potential risk to the infant.

Contraindication

Hypersensitivity; preexisting CNS depression, coma, bone-marrow supression; phaeochromocytoma; lactation

Trihexyphenidyl is contraindicated in patients with hypersensitivity in patients to trihexyphenidyl HCl or to any of the tablet or elixir ingredients. Trihexyphenidyl is also contraindicated in patients with narrow angle glaucoma. Blindness after long-term use due to narrow angle glaucoma has been reported.

Acute Overdose

Symptoms include somnolence, coma, hypotension and extrapyramidal symptoms. Other possible manifestations include agitation and restlessness, convulsions, fever, autonomic reactions such as dry mouth and ileus, EKG changes and cardiac arrhythmias.

Treatment is symptomatic and supportive. Early gastric lavage may be helpful. Observe patient and maintain an open airway.

Overdosage with trihexyphenidyl produces typical central symptoms of atropine intoxication ( the central anticholinergic syndrome). Signs & symptoms are: dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of mouth, pharynx, nose and bronchi, foul smelling breath, tachycardia etc. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations etc. The condition can progress to stupor, coma, paralysis, cardiac, respiratory arrest and death.

Storage Condition

Store at 15-30°C.

Innovators Monograph

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