Haloperidol

Haloperidol(中文:[[ ]]) is a typical antipsychotic medication. It is used in the treatment of various psychoses including:

• Schizophrenia
• Bipolar disorder
• Delirium
• in Tourette’s syndrome and severe tics
• in intractable hiccups
• in severe anxiety including for sedation of patients in intensive care or palliative care
• in the management of nausea and vomiting of various causes

It may be used by mouth. A long-acting formulation may be used as an injection every 4 weeks in people with schizophrenia, who either forget or refuse to take the medication by mouth. Doses are expressed in terms of the equivalent amount of haloperidol. Haliperidol decanoate 141 mg is equivalent to about 100 mg of haloperiodl. Dosages should be reduced in elderly or debilitated patients; a usual starting dose is half the normal adult dose.

Pronunciation

Haloperidol 1.5mg

Haloperidol 10mg

Haloperidol 1mg

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Haloperidol Tab 1 mg	HALO14	P1S1S3
Haloperidol Tab 1.5 mg	HALO03	P1S1S3
Haloperidol Tab 5 mg	HALO05	P1S1S3
Haloperiodl Drops 2mg/ml 30ml	HALO16	P1S1S3
Haloperidol IM Injection 5mg/ml 1ml	HALO08	P1S1S3

Mechanism of Action

Haloperidol is a typical antipsychotic that blocks dopamine D2 receptor with high affinity. The presumed effectiveness of antipsychotic drugs relied on their ability to block dopamine receptors. This assumption arose from the dopamine hypothesis that maintains that both schizophrenia and bipolar disorder are a result of excessive dopamine activity. In addition, haloperidol also acts as an antagonist (blocking agent) on different postsynaptic and presynaptic receptors:

• Dopamine receptors (subtypes D1, D2, D3, D4 and D5), which account for its antipsychotic properties
• Serotonin receptors (5-HT2, 5-HT6 and 5-HT7), with anxiolytic, antidepressant, and anti-aggressive properties
• Histamine receptors (H1 receptors) accounting for sedation, antiemetic effect
• α1- and α2-adrenergic receptors accounting for lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction
• M1 muscarinic acetylcholine receptors causing anticholinergic symptoms such as dry mouth, blurred vision, constipation, difficulty to urinate, sinus tachycardia, and loss of memory.

Dosage

Indication	Dose
Schizophrenia Psychoses Mania	By mouth ADULT: Initially 2 - 20 mg once daily, or Initially 2 – 20 mg in divided doses Maintenance 1 – 3 mg 3 times a day, adjusted according to response ELDERLY or debilitated patients: Initially 1 – 10 mg once daily, or Initially 1 – 10 mg daily in divided doses; Maintenance 1 – 3 mg 3 times a day, adjusted according to response Maximum 20 mg per day CHILD 3 to 12 years: Initially 500 micrograms daily Increased to a usual dose of 1 to 4 mg daily Maximum of 6 mg daily CHILD 13 to 17 years: Initially 500 micrograms daily Increased to a usual dose of 1 to 6 mg daily (Maximum of 10 mg daily By intramuscular injection ADULT: 2 – 5 mg, repeated dose given according to response and tolerability. ELDERLY or debilitated patients: 1 – 2.5 mg, repeated dose given according to response and tolerability. Maximum 12 mg per day
Agitation and restlessness in the elderly	By mouth ADULT: 0.75 – 1.5 mg 2-3 times a day, adjusted according to response
Tourette syndrome Severe tics Intractable hiccup	By mouth ADULT: 1.5 – 3 mg 2 -3 times daily Maintenance 0.5 – 3 mg 3 times daily ELDERLY or debilitated patients: 0.75 – 1.5 mg 2-3 times daily Maintenance 0.5 – 1 mg 3 times daily
Nausea and vomiting of terminal illness	By mouth ADULT: 1.5 mg 1-2 times daily, increased to 5 – 10 mg daily in divided doses if necessary

During long-term treatment of chronic psychiatric disorders, the daily dose should be reduced to the lowest level needed for maintenance of remission. Doses of haloperidol greater than 5mg increased the risk of side effects without improving efficacy.

Side Effects

Comparing to other typical antipsychotic, Haloperidol is less likely to cause sedation, hypotension, or antimuscarinic effects, but is associated with a higher incidence of movement disorder known as tardive dyskinesia which may be permanent. Neuroleptic malignant syndrome and QY interval prolongation may occur. In older people with psychosis due to dementia it results in an increased risk of death.

Possible side effects include:

Common (>1% incidence)
Extrapyramidal side effects including	Akathisia (motor restlessness) Dystonia (continuous spasms and muscle contractions) Muscle rigidity Parkinsonism
Orthostatic Hypotension
depression
Weight loss
Anticholinergic side effects such as	Dry mouth Constipation Difficulty to urinate Blurred vision Mydriasis Tachycardia
Rare (< 1% incidence)	Bronchospasm Hypoglycemia Inappropriate antidiuretic hormone secretion Photosensitivity reactions pigmentation
Frequency not known	stevens- Johnson syndrome toxic epidermal necrolysis prolonged QT intervals

Pharmacokinetics

Oral bioavailability	Haloperidol is readily absorbed after oral doses.
Onset of action	There is wide intersubject variation in plasma concentrations of haloperidol. In practice, no strong correlation has been found between plasma concentrations of haloperidol and its therapeutic effect. Peak plasma concentrations range from 1.7 to 6.1 hours after ingestion.
Metabolism	It is extensively metabolized in the liver via CYP-mediated oxidation, primarily by CYP3A4.
Elimination half-life	It is excreted in the urine and faeces. Owing to the first-pass metabolism in the liver, plasma concentrations after oral doses are much lower than those after intramuscular doses. The plasma half-life of ranging from about 12 to 38 hours after oral dose. Moreover, there is wide intersubject variation in plasma concentrations of haloperidol. In practice, no strong correlation has been found between plasma concentrations of haloperidol and its therapeutic effect. The decanoate ester of haloperidol is very slowly absorbed from the injection site and is therefore suitable for depot injection. The plasma concentrations reach a peak at about 6 days after the injection, falling thereafter, with an approximate half-life of 3 weeks.

Drug Management

Monitoring:

Baseline ECG required before treatment – assess need for further ECGs during treatment on an individual basis. During long-term use, routine monitoring includes:

• measurement of BMI
• blood pressure
• fasting blood sugar and lipids

Drug interaction

The metabolism of haloperidol is mediated by the cytochrome P450 system, particularly the isoenzymes CYP3A4 and CYP2D6. Therefore, there is the potential for interactions between haloperidol and other drugs that induce, inhibit, or act as a substrate for these isoenzymes, resulting in altered plasma haloperidol concentrations. It may be necessary to amend the dosage of haloperidol when given with sch drugs. Haloperidol itself is also an inhibitor of CYP2D6 and may increase the plasma concentrations of tricyclic antidepressants by inhibiting their metabolism. Haloperidol must be used with extreme caution in patients receiving lithium; an encephalopathic syndrome has been reported after their use together.

Drugs given with haloperidol	Potential Effect
CNS-depressant drugs including alcohol, hypnotics, anxiolytics, and opioids.	Potentiates the sedative effect. The doses of concomitantly used opioids for chronic pain can be reduced by 50%.
Lithium	An encephalopathic syndrome characterized by delirium, seizures, or an increased incidence of extrapyramidal symptom, and coma
Tricyclic antidepressants	Metabolism and elimination of tricyclics significantly decreased, increased toxicity such as anticholinergic and cardiovascular side effects, and lowering seizure threshold.
Levodopa	In theory, antipsychotics with dopamine-blocking activity and dopaminergic drugs such as those used to treat parkinsonism may be mutually antagonistic.
Methyldopa Drugs metabolized by the CYP3A4 enzyme system: inducers such ass carbamazepine, phenobarbitone and rifampicin	Increased risk of extrapyramidal side effects Decreases plasma levels of haloperidol
Drugs metabolized by the CYP3A4 enzyme system: inhibitors such as quinidine, buspirone and fluoxetine	Increases plasma levels of haloperidol
Drugs that prolong the QT interval e.g. amiodarone	An increased risk of ventricular arrhythmias – avoid concomitant use.