Haloperidol nervous system

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

Hong J-S, Tilson HA, Yoshikawa K Effects of lithium and haloperidol administration on the rat brain levels of Substance P. J Pharmacol Exp Ther 224 590-597, 1983 Honig A, Bartlett JR, Bouras N, et al Amino acid levels in depression a preliminary investigation. J Psychiatr Res 22 159-164, 1989 Honjo H, Ogino Y, Natitoh K, et al In vivo effects by estrone sulphate on the central nervous system on senile dementia [Alzheimer s type). Journal of Steroid Biochemistry 34 521-525, 1989... 

Multiple sites in the CNS are affected by LSD. The drug shows serotonin (5-HT) agonist activity at presynaptic receptors in the midbrain, binding to both 5-HT and 5-HT2 receptors. Activation of the sympathetic nervous system occurs, which causes pupillary dilation, increased blood pressure, piloerection, and increased body temperature. Taken orally, low doses of LSD can induce hallucinations with brilliant colors, and mood alteration occurs. Tolerance and physical dependence have occurred, but true dependence is rare. Adverse effects include hyperreflexia, nausea, and muscular weakness. Sometimes high doses produce long-lasting psychotic changes in susceptible individuals. Haloperidol (see p. 127) and other neuroleptics can block the hallucinatory action of LSD and quickly abort the syndrome. 

Juhl, R., Tsuang, M., Perry, P. (1977). Concomitant administration of haloperidol and lithium carbonate in acute mania. Diseases of the Nervous System, 38, 675-676. 

CIMETIDINE ANTIPSYCHOTICS -CHLORPROMAZINE, CLOZAPINE, HALOPERIDOL, OLANZAPINE, PERPHENAZINE, RISPERIDONE, SERTINDOLE, THIORIDAZINE, ZUCLOPENTHIXOL T plasma concentrations of these antipsychotics, with risk of associated adverse effects - Drugs Acting on the Nervous System, Antipsychotics Cimetidine is an inhibitor of CYP3A4 (sertindole, haloperidol, risperidone) CYP2D6 (chlorpromazine, risperidone, zudopenthixol, thioridazine, perphenazine) and CYP1A2 (clozapine, olanzapine, sertindole, haloperidol) Avoid concomitant use. Choose alternative acid suppression... 

If the user s bad trip is due to overdose of an antimuscarinic drug, natural or synthetic, then diazepam is specially preferred, or a neuroleptic with no or minimal antimuscarinic effects, e.g. haloperidol. A dose of an anticholinesterase that penetrates the central nervous system (physostig-... 

Flaloperidol is well absorbed orally with a bioavailability of 60-65% due to first-pass hepatic metabolism. It has a reversible oxidation/reduction metabolic pathway it is metabolized via reduction to reduced haloperidol, which is biologically inactive. Both agents are rapidly absorbed after intramuscular injection, peaking within 10 min. Butyrophenones are metabolized in the liver to inactive metabolites. Concentrations of butyrophenones are found in the liver, central nervous system, and throughout the body. Flaloperidol is 92% protein bound. Haloperidol is 15% eliminated through the bile. The elimination half-life is 14-41 h. The half-life of droperidol is 2 h 10% is recovered unchanged in the urine. 

The exact mechanism of mescaline has not been clearly defined. The central nervous system effects of mescaline appear to involve stimulation of both serotonin and dopamine receptors. In experimental studies, these effects can be blocked by either serotonin antagonists such as methysergide or dopamine antagonists such as haloperidol. Mescaline is structurally related to the amphetamines and cathine (khat). Sympathomimetic effects can occur and are thought to be centrally mediated. Mescaline does not appear to inhibit monoamine oxidase. 

Factors that inhibit or alter the activity of the mixed function oxidase enzymes may increase the risk from exposure to the indicator compounds in the aromatic EC5-EC9 fraction (the BTEXs), the aromatic EC>16-EC35 fraction (the carcinogenic PAHs in this fraction) and a constituent of the aliphatic I < C5IiCH fraction (//-hexane). For example, concurrent alcohol consumption may increase the risk of central nervous system depression from the BTEXs, ototoxicity from toluene, and hematotoxicity from benzene. Acetone exposure may increase the risk of peripheral neuropathy of n-hexane. People who take haloperidol, acetaminophen, or aspirin, or who have a nutritionally inadequate diet, may also be more susceptible to the toxicity of these agents. ATSDR (1995f) noted that a substantial percentage of children consume less than the recommended dietary allowances of certain nutrients. 

A. Haloperidol and droperidol potentiate central nervous system-depressant effects of opioids, antidepressants, phenothiazines, ethanol, barbiturates, and other sedatives. 

Casamenti et al. [1399] developed a method for screening 11 central nervous system drugs (phenobarbital, olanzapine, clozapine, risperidone, loxapine, haloperidol, imipramine, amitriptyline, fluoxetine, chlorpromazine, paroxetine) on a Cjg column (A = 230 nm) using a 20/11.7 water (0.4g tetramethylammonium perchlorate with 0.2 mL of 7% (m/m) HCIO4 to pH 2.8 with ammonia)/acetonitrile mobile phase. Keep in mind that perchlorates, when concentrated with some metals, are hazardous. Elution was complete in 35 min with good resolution for most compounds. Plots of the effects of mobile phase modifier level and percent acetonitrile on overall retention are presented. Linear ranges of 25-5000 ng/mL with detection limits of 10-250 ng/mL (analyte dependent) are reported. 

Nervous system A study comparing somnolence with asenapine, olanzapine, risperidone and haloperidol relative to placebo evaluated 10 clinical trials of patients with schizophrenia or bipolar disorder [36 -]. The duration and incidence of somnolence was greatest for asenapine and olanzapine (maximal for olanzapine) and with shorter time to onset than the other antipsychotics and placebo patients with bipolar disorder were the most sensitive. 

Nervous System Parkinsonism was present in 46% of 150 elderly patients being treated with haloperidol and xmrelated to plasma concentrations or duration of use [151 ]. Two cases of neuroleptic-induced catatonia following the administration of intravenous haloperidol are described both patients recovered following discontinuation of haloperidol [152 ]. A case of neuroleptic malignant syndrome in a 48-year-old male is reported with index exposure to intravenous haloperidol that resolved on discontinuation [153 ]. Obsessive-compulsive symptoms are associated with a number of SGAs particularly clozapine however a case report describes the development of obsessive-compulsive symptoms in a learning disability patient treated with haloperidol [154 ]. 

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