loss of appetite. other symptoms may include restlessness, increased sweating, and trouble sleeping. less commonly there may be a feeling of the world spinning, numbness, or muscle pains. symptoms generally resolve after a short period of time. there is tentative evidence that discontinuation of antipsychotics can result in psychosis. it may also result in reoccurrence of the condition that is being treated. rarely tardive dyskinesia can occur when the medication is stopped. overdose symptoms symptoms are usually due to side effects. most often encountered are: anticholinergic side effects (dry mouth, constipation, paralytic ileus, difficulties in urinating, decreased perspiration) coma in severe cases, accompanied by respiratory depression and massive hypotension, shock hypotension or hypertension rarely, serious ventricular arrhythmia (torsades de pointes), with or without prolonged qt-time sedation severe extrapyramidal side effects with muscle rigidity and tremors, akathisia, etc. treatment treatment is mostly symptomatic and involves intensive care with stabilization of vital functions. in early detected cases of oral overdose, induction of emesis, gastric lavage, and the use of activated charcoal can be tried. in the case of a severe overdose, antidotes such as bromocriptine or ropinirole may be used to treat the extrapyramidal effects caused by haloperidol, acting as dopamine receptor agonists. ecg and vital signs should be monitored especially for qt prolongation and severe arrhythmias should be treated with antiarrhythmic measures. prognosis an overdose of haloperidol can be fatal, but in general the prognosis after overdose is good, provided the person has survived the initial phase. pharmacology haloperidol, 10-mg oral tablet haloperidol is a typical butyrophenone-type antipsychotic that exhibits high-affinity dopamine d2 receptor antagonism and slow receptor dissociation kinetics. it has effects similar to the phenothiazines. the drug binds preferentially to d2 and α1 receptors at low dose (ed50 = 0.13 and 0.42 mg/kg, respectively), and 5-ht2 receptors at a higher dose (ed50 = 2.6 mg/kg). given that antagonism of d2 receptors is more beneficial on the positive symptoms of schizophrenia and antagonism of 5-ht2 receptors on the negative symptoms, this characteristic underlies haloperidol's greater effect on delusions, hallucinations and other manifestations of psychosis. haloperidol's negligible affinity for histamine h1 receptors and muscarinic m1 acetylcholine receptors yields an antipsychotic with a lower incidence of sedation, weight gain, and orthostatic hypotension though having higher rates of treatment emergent extrapyramidal symptoms. haloperidol acts on these receptors: (ki) d1 (silent antagonist) – unknown efficiency d5 (silent antagonist) – unknown efficiency d2 (inverse agonist) – 0.7 nm d3 (inverse agonist) – 0.2 nm d4 (inverse agonist) – 5–9 nm σ1 (irreversible inactivation by haloperidol metabolite hpp+) – 3 nm σ2 (agonist): 54 nm 5ht1a receptor agonist – 1927 nm 5ht2a (silent antagonist) – 53 nm 5ht2c (silent antagonist) – 10,000 nm 5ht6 (silent antagonist) – 3666 nm 5ht7 (irreversible silent antagonist) – 377.2 nm h1 (silent antagonist) – 1,800 nm m1 (silent antagonist) – 10,000 nm α1a (silent antagonist) – 12 nm α2a (silent antagonist) – 1130 nm α2b (silent antagonist) – 480 nm α2c (silent antagonist) – 550 nm nr1/nr2b subunit containing nmda receptor (antagonist; ifenprodil site): ic50 – 2,000 nm pharmacokinetics by mouth the bioavailability of oral haloperidol ranges from 60 to 70%. however, there is a wide variance in reported mean tmax and t1/2 in different studies, ranging from 1.7 to 6.1 hours and 14.5 to 36.7 hours respectively. intramuscular injections haldol decanoate for injection into muscle the drug is well and rapidly absorbed with a high bioavailability when injected intramuscularly. the tmax is 20 minutes in healthy individuals and 33.8 minutes in patients with schizophrenia. the mean t1/2 is 20.7 hours. the decanoate injectable formulation is for intramuscular administration only and is not intended to be used intravenously. the plasma concentrations of haloperidol decanoate reach a peak at about six days after the injection, falling thereafter, with an approximate half-life of three weeks. intravenous injections the bioavailability is 100% in intravenous (iv) injection, and the very rapid onset of action is seen within seconds. the t1/2 is 14.1 to 26.2 hours. the apparent volume of distribution is between 9.5 and 21.7 l/kg. the duration of action is four to six hours. therapeutic concentrations plasma levels of five to 15 micrograms per liter are typically seen for therapeutic response (ulrich s, et al. clin pharmacokinet. 1998). the determination of plasma levels is rarely used to calculate dose adjustments but can be useful to check compliance. the concentration of haloperidol in brain tissue is about 20-fold higher compared to blood levels. it is slowly eliminated from brain tissue, which may explain the slow disappearance of side effects when the medication is stopped. distribution and metabolism haloperidol is heavily protein bound in human plasma, with a free fraction of only 7.5 to 11.6%. it is also extensively metabolized in the liver with only about 1% of the administered dose excreted unchanged in the urine. the greatest proportion of the hepatic clearance is by glucuronidation, followed by reduction and cyp-mediated oxidation, primarily by cyp3a4. history haloperidol was discovered by paul janssen. it was developed in 1958 at the belgian company janssen pharmaceutica and submitted to the first of clinical trials in belgium later that year. haloperidol was approved by the u.s. food and drug administration (fda) on 12 april 1967; it was later marketed in the u.s. and other countries under the brand name haldol by mcneil laboratories. society and culture cost haloperidol is relatively inexpensive, being up to 100 fold less expensive than newer antipsychotics. brand names haloperidol is the inn, ban, usan, aan approved name. it is sold under the tradenames aloperidin, bioperidolo, brotopon, dozic, duraperidol (germany), einalon s, eukystol, haldol (common tradename in the us and uk), halol, halosten, keselan, linton, peluces, serenace and sigaperidol. veterinary use haloperidol is also used on many different kinds of animals for nonselective tranquilization and diminishing behavioral arousal, in veterinary and other settings including captivity management.