Haloperidol 1 Haloperidol Haloperidol Systematic (IUPAC) name 4-[4-(4-Chlorophenyl)-4-hydroxy-1-piperidyl]-1-(4-fluorophenyl)-butan-1-one Clinical data Trade names Haldol AHFS/Drugs.com [1] monograph MedlinePlus [2] a682180 Pregnancy cat. C (AU) C (US) Legal status Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US) Routes Oral, IM, IV, depot (as decanoate ester) Pharmacokinetic data Bioavailability 60-70% (Oral) Protein binding ~90% Metabolism Liver-mediated Half-life 14-26 hours (IV), 20.7 hours (IM), 14-37 hours (oral) Excretion Biliary (hence in faeces) and in urine Identifiers CAS number [3] 52-86-8 ATC code [4] N05AD01 PubChem [5] CID 3559 IUPHAR ligand [6] 86 DrugBank [7] DB00502 ChemSpider [8] 3438 UNII [9] J6292F8L3D KEGG [10] D00136 ChEBI [11] CHEBI:5613 Haloperidol 2 ChEMBL [12] CHEMBL54 Chemical data Formula C H ClFNO 21 23 2 Mol. mass 375.9 g/mol [13] (what is this?) (verify) Haloperidol /hæloʊpɛridɒl/ (INN, BAN, USAN, AAN; most common brand names: Haldol, Serenace) is an antipsychotic medication used in the treatment of schizophrenia, acute psychosis, mania, delirium, tics in Tourette syndrome, choreas, nausea and vomiting in palliative care, intractable hiccups, agitation and severe anxiety. Haloperidol is a butyrophenone derivative and functions as an inverse agonist of dopamine. It is classified as a typical antipsychotic and has pharmacological effects similar to the phenothiazines. A long-acting decanoate ester of haloperidol is used as an injection given every four weeks to people with schizophrenia or related illnesses who have poor adherence to medication regimens (most commonly due to them forgetting to take their medication, or due to poor insight into their illness) and suffer frequent relapses of illness, or to overcome the drawbacks inherent to its orally administered counterpart. It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system. Medical uses Haloperidol is used in the control of the symptoms of: •• Schizophrenia • Acute psychosis, such as drug-induced psychosis caused by LSD, psilocybin, amphetamines, ketamine, and phencyclidine, and psychosis associated with high fever or metabolic disease • Hyperactivity, aggression • Hyperactive delirium (to control the agitation component of delirium) •• Otherwise uncontrollable, severe behavioral disorders in children and adolescents • Agitation and confusion associated with cerebral sclerosis •• Adjunctive treatment of alcohol and opioid withdrawal • Treatment of severe nausea and emesis in postoperative and palliative care, especially for palliating adverse effects of radiation therapy and chemotherapy in oncology • Treatment of neurological disorders, such as tic disorders, Tourette syndrome, and chorea • Therapeutic trial in personality disorders, such as borderline personality disorder • Treatment of intractable hiccups •• Also used in aquaculture to block dopamine receptors to enable GnrHA function for ovulation use in spawning fish •• Alcohol-induced psychosis Haloperidol was considered indispensable for treating psychiatric emergency situations, although the newer atypical drugs have gained greater role in a number of situations as outlined in a series of consensus reviews published between 2001 and 2005. It is enrolled in the World Health Organization list of Essential Medicines. A multiple-year study suggested this drug and other neuroleptic antipsychotic drugs commonly given to Alzheimer's patients with mild behavioural problems often make their condition worse that its withdrawal was even beneficial for some cognitive and functional measures. Haloperidol 3 Pregnancy and lactation Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. In humans, no controlled studies exist. Unconfirmed studies in pregnant women revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy. In addition, there have been reports that neonates exposed to antipsychotic drugs are at risk for extrapyramidal and/or withdrawal symptoms following delivery such as agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Following accepted general principles, haloperidol should be given during pregnancy only if the benefit to the mother clearly outweighs the potential fetal risk. Haloperidol, when given to lactating women, is found in significant amounts in their milk. Breastfed children sometimes show extrapyramidal symptoms. If the use of haloperidol during lactation seems indicated, the benefit for the mother should clearly outweigh the risk for the child, or breastfeeding should be stopped.Wikipedia:Citation needed Other considerations During long-term treatment of chronic psychiatric disorders, the daily dose should be reduced to the lowest level needed for maintenance of remission. Sometimes, it may be indicated to terminate haloperidol treatment gradually. In addition, during long-term use, routine monitoring including measurement of BMI, blood pressure, fasting blood sugar, and lipids, is recommended due to the risk of side-effects. Other forms of therapy (psychotherapy, occupational therapy/ergotherapy, or social rehabilitation) should be instituted properly.Wikipedia:Citation needed PET imaging studies have suggested low doses are preferable. Clinical response was associated with at least 65% occupancy of D2 receptors, while greater than 72% was likely to cause hyperprolactinaemia and over 78% associated with Skeletal formula of haloperidol decanoate: The decanoate group is highlighted in blue. extrapyramidal side effects. Doses of haloperidol greater than 5 mg increased the risk of side effects without improving efficacy. Patients responded with doses under even 2 mg in first episode psychosis. For maintenance treatment of schizophrenia, an international consensus conference recommended a reduction dosage by about 20% every 6 months until a minimal maintenance dose is established. • Depot forms are also available; these are injected deeply IM at regular intervals. The depot forms are not suitable for initial treatment, but are suitable for patients who have demonstrated inconsistency with oral dosages.Wikipedia:Citation needed The decanoate ester of haloperidol (haloperidol decanoate, trade names Haldol decanoate, Halomonth, Neoperidole) has a much longer duration of action, so is often used in people known to be noncompliant with oral medication. A dose is given by intramuscular injection once every two to four weeks.[14] The IUPAC name of haloperidol decanoate is 4-(4-chlorophenyl)-1-1[4-(4-fluorophenyl)-4-oxobutyl]-4 piperidinyl decanoate. Topical formulations of haloperidol should not be used as treatment for nausea because research does not indicate that this therapy is more effective than alternatives.[15] Haloperidol 4 Adverse effects Sources for the following lists of adverse effects[16][17][18][19] Common (>1% incidence) •• Extrapyramidal side effects such as: (as haloperidol is a high potency typical antipsychotic it tends to produce significant extrapyramidal side effects. According to a recent meta-analysis of the comparative efficacy and tolerability of 15 antipsychotic drugs it was the most prone of the 15 for causing extrapyramidal side effects.) - Dystonia - Muscle rigidity - Akathisia - Parkinsonism •• Hypotension • Anticholinergic side effects such as: (Note: these adverse effects are less common than with lower potency typical antipsychotics) - Constipation - Dry mouth - Blurred vision • Somnolence (which is not a particularly prominent side effect, as is supported by the results of the aforementioned meta-analysis.) Unknown frequency •• Prolonged QT interval •• Orthostatic hypotension •• Increased respiratory rate •• Anaemia •• Visual disturbances •• Headache Rare (<1% incidence) •• Jaundice •• Hepatitis •• Cholestasis •• Acute hepatic failure •• Liver function test abnormal •• Hypoglycaemia •• Hyperglycaemia •• Hyponatraemia •• Anaphylactic reaction •• Hypersensitivity •• Agranulocytosis •• Neutropaenia •• Leukopaenia •• Thrombocytopaenia •• Pancytopaenia •• Psychotic disorder •• Agitation •• Confusional state Haloperidol 5 •• Depression •• Insomnia •• Seizure •• Torsades de pointes •• Ventricular fibrillation •• Ventricular tachycardia •• Extrasystoles •• Bronchospasm •• Laryngospasm •• Laryngeal oedema •• Dyspnoea •• Nausea •• Vomiting •• Leukocytoclastic vasculitis •• Dermatitis exfoliative •• Urticaria •• Photosensitivity reaction •• Rash •• Pruritis •• Hyperhidrosis •• Urinary retention •• Priapism •• Gynaecomastia •• Sudden death •• Face oedema •• Oedema •• Hypothermia •• Hyperthermia •• Injection site abscess •• Anorexia •• Pulmonary embolism •• Tardive dyskinesia •• Cataracts •• Retinopathy •• Neuroleptic malignant syndrome Haloperidol has been shown to dramatically increase dopamine activity, up to 98%, in test subjects after two weeks on a "moderate to high" dose compared to chronic schizophrenics. In another study, a live survey of a patient showed the person has 90% more dopamine receptors, of the D2 subtype, than before treatment with haloperidol. The long-term effect of this is unknown, but the first study concludes this upregulation is positively associated with severe dyskinesias (more upregulation, more dyskinesia). Some research studies have suggested effects of haloperidol on brain tissue. In a 2005 placebo-compared study of six macaques receiving haloperidol for up to 27 months,