Parkinsonism haloperidol

The antipsychotics are contraindicated in patients with known hypersensitivity to the drug s, in comatose patients, and in those who are severely depressed, have bone marrow depression, blood dysera ias, Parkinson s disease (haloperidol), liver impairment, coronary artery disease, or severe hypotension or hypertension. 

Another indication of the importance of DA in motor control is the observation that in humans its precursor levodopa, and DA agonists like bromocriptine, not only overcome the akinesia of Parkinsonism but in excess will actually cause involuntary movements, or dyskinesia (Chapter 14). Also it is well known that DA antagonists like chlorpromazine and haloperidol produce Parkinsonian-like symptoms in humans (and catalepsy in animals) and, as indicated above, reduce the dyskinesia of Huntington s Chorea. Thus DA seems to sit on a knife edge in the control of motor function (Fig. 7.8). 

The answer is b. (Hardman, pp 282—283J Central dopamine receptors are divided into Dt and D2 receptors. Antipsychotic activity is better correlated to blockade of D2 receptors. Haloperidol, a potent antipsychotic, selectively antagonizes at Dz receptors. Phenothiazine derivatives, such as chlorpromazine, fluphenazine, and promethazine, are not selective for D2 receptors. Bromocriptine, a selective D2 agonist, is useful in the treatment of parkinsonism and hyperprolactinemia. It produces fewer adverse reactions than do nonselective dopamine receptor agonists... 

The answer is b. (Katzung, p 4822) Haloperidol, a butyrophenone, is by far the most likely antipsychotic to produce extrapyramidal toxicides Other agents, such as piperazine (an aromatic phenothiazine), thiothixene (a thioxanthene), and pimozide (a diphenylbutyropiperidine) are comparitively less likely to produce extrapyramidal toxicity than haloperi-dol. The antagonism of dopamine in the nigrostriatal system might explain the Parkinson-like effects Both haloperidol and pimozide act mainly on D2 receptors, whereas thioridazine and piperazine act on ooadrenergie receptors, and have a less potent but definite effect on D2 receptors. 

Iwahashi K, Anemo K, Nakamura K, Fukunishi 1, Igarashi K. 2001. Analysis of the metabolism of haloperidol and its neurotoxic pyridinium metabolite in patients with drug-induced parkinsonism. Neuropsychobiology 44 126. 

Drugs that are successful in treating the disease act as dopamine receptor blockers and are known as antipsychot-ics or neuroleptics (e.g. chlorpromazine, haloperidol). Antipsychotic drags reduce some of the symptoms, especially the delusions and hallucinations. A side-effect of the drugs is that they can result in symptoms similar to those seen in patients with Parkinson s disease. This is not surprising, since the hypothesis to explain Parkinson s disease is too low a concentration of dopamine in a specific area of the brain (see below). 

Haloperidol is indicated for schizophrenia, severe anxiety, motor tics and intractable hiccup. It is not indicated in the treatment of parkinsonism, which may be aggravated through its use, as haloperidol tends to cause extra pyramidal symptoms. 

In the international, multicenter, double-blind trial of olanzapine, the Simpson-Angus Scale and the Barnes Akathisia Scale were used to monitor treatment-emergent EPS. The acute phase was followed by a 52-week, double-blind, maintenance phase, during which there were significantly lower rates of treatment-emergent Parkinsonism and akathisia (p > 0.001), as well as TD (p < 0.003) in comparison with haloperidol (117). These results suggest that olanzapine has a substantially lower propensity than neuroleptics to evoke EPS, and perhaps TD. 

Temazepam is rarely beneficial in patients with psychoses and may induce paradoxical reactions. It may exacerbate myasthenia gravis, Parkinson s disease, and chronic obstructive pulmonary disease. Temazepam may decrease plasma levels of haloperidol. 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

AccessMedicine Print Chapter 28. Pharmacologic Management of Parkinsonism Other Movement Disorders Haloperidol, other neuroleptics Sometimes helpful... 

Haloperidol Blocks central D2 Reduces vocal Tourette s syndrome Oral Toxicity Parkinsonism, other... 

Attention has been focused on dopamine because of its relationship to neurological diseases and to addiction (discussed in Section 10). Dopamine receptors constitute a large family, which are classified into two main subfamilies. The D, subfamily consists of D1a and D1B (D5) receptors and the D2 subfamily of D2, D3, and D4 receptors.763 764 The D, receptors, which are prominent in the prefrontal cortex and also in the striatum, are more abundant than the D2 receptors, which are also present in the striatum and the pituitary and are targets for antipsychotic drugs such as haloperidol (Fig. 30-33).765 The recently discovered and less numerous D3 receptors are present in only a few regions of the brain. However, a deficiency of D3 receptors may also be involved in addiction, schizophrenia, and Parkinson disease.766 767... 

Circunstantial evidence directly implicating dopamine in the pathogenesis of duodenal ulcer in man is the unusual incidence of peptic ulcer disease in dopamine-deficient disorders. From purely descriptive clinical and epidemiologic studies we know that patients with Parkinson s disease, before the introduction of dopamine therapy, had an excess of ulcer disease (72). One report even comments on the curiosity that after initiation of L-DOPA administration the ulcer symptoms have virtually disappeared (72 ). On the other hand, less clearly, schizophrenia which is associated with dopamine excess and/or receptor hyperactivity is accompanied by virtual lack, or decreased prevalence, of peptic ulcer (73-76). Schizophrenia associated with ulcer disease has been viewed as a reportable curiosity in medical literature (75). At present, possibly because of the widespread therapeutic application of neuroleptics, the lack of peptic ulcer disease in schizophrenics is less striking than in the past. On the other hand, we recently observed in our autopsy series perforated duodenal ulcers in two schizophrenic patients who had been on large doses of haloperidol therapy (Szabo, unpublished observation). Thus, even in man, dopamine may indeed be implicated in the pathogenesis of duodenal ulcer disease. 

Secondary parkinsonism Parkinsonian symptoms infrequently follow viral encephalitis or multiple small vascular lesions. Drugs such as the phenothiazines and haloperidol (see p. 127), whose major pharmacologic action is blockade of dopamine receptors in the brain, may also produce parkinsonian symptoms. These drugs should not be used in parkinsonian patients. 

D2-receptor activation gives Gai-mediated inhibition of adenylate cyclase (decreasing cAMP) and these receptors are involved in schizophrenia and Parkinson s disease and in control of motor function, cardiovascular function and behaviour by the CNS. The well-known antipsychotics chlorpromazine and haloperidol are D2-R antagonists. A number of hallucinogenic indole alkaloids from ergot-infected grasses and cereals are D2-R agonists (Table 5.4). 

Patients taking olanzapine reported a low incidence of dystonias, which may be about 0.3% (SEDA-22, 56). In the light of two new cases of acute dystonia associated with olanzapine in patients with previous history of dystonia or parkinsonism related to antipsychotic treatment, comparative figures have been reported. Acute dystonia occurred in 1.4% of patients who took olanzapine, compared with 5.0-6.3% of those taking haloperidol (84). 

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