Hypotension chlorpromazine

The answer is d, (Katzung, p 482.) Although many antipsychotic agents can cause orthostatic hypotension, chlorpromazine is the most likely choice of the agents above for causing this adverse effect. 

It is available in both oral and injectable forms and has a calming effect on agitated patients. Chlorpromazine should typically be started at doses no higher than lOOmg/day and increased stepwise. Otherwise, dizziness due to orthostatic hypotension is quite a problem. 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Haloperidol is a butyrophenone that is associated with a high incidence of extra pyramidal side-effects. It brings about a rapid control of agitation and restlessness and is preferred to chlorpromazine in the elderly because it causes less hypotension. 

Toxicity is remarkably low for a compound of such activity. In mice, the LDso value is about three times that of chlorpromazine [166] while none of the effects of the latter drug on the myocardium, liver, skin or eye have appeared in the studies of oxypertine. It is, however, still too early to appraise its chronic toxicity in man. As indicated earlier, dangerous interactions are likely to follow concurrent use of a MAO inhibitor, though simultaneous use of anti-Parkinsonism drugs, for example, to control the relatively minor extra-pyramidal symptoms seems to present no unusual problems. Hypotension may occasionally occur with high doses. 

CHLORPROMAZiNE Individualize dosage based on condition severity. Increase dosage until symptoms are controlled, then gradually reduce dosage to the lowest effective maintenance level. Increase parenteral dosage only if hypotension has not occurred. 

Haloperidol is less likely to cause hypotension than chlorpromazine, which has a-adrenoceptor antagonist effects. Both can cause cardiac arrhythmias if used in high dosage or in patients with pre-existing heart disease, or as an idiosyncratic reaction. There have been numerous reports of sudden and unexplained deaths, probably due to cardiac arrhythmia, in patients given chlorpromazine and other neuroleptics. The risk of serious arrhythmia is higher in the obese, and possibly in those of African ancestry. 

There are two classes of a-adrenergic receptors, aj and a2. Agents with the greatest affinity for aj blockade are chlorpromazine, thioridazine, and risperidone. There are no known beneficial effects associated with a -adrenergic receptor antagonism. However, aj-adrenergic receptor blockade can lead to hypotension, dizziness, and reflex tachycardia (Table 26.2). a2 Blockade is modest for most agents except for risperidone and clozapine. As with aj receptors, there are no benefits that have yet to be associated with a2 receptor... 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

To control hypertension, phentolamine 5 mg i.v. is recommended, with repeated doses of 0.25 to 0.5 mg i.m. every 4 to 6 hours. Alternatively, chlorpromazine 50 mg i.m. is given, followed by 25 mg i.m. every 1 to 2 hours. Nifedipine is not recommended. Blood pressure should be monitored closely to avoid overcompensation and hypotensive episodes. 

Similar to the heterocyclic antidepressants, antipsychotics must be used carefully and sparingly in this physiologically impaired population. In particular, low potency agents (most notably chlorpromazine) may cause extreme hypotension and hypothermia in these patients. 

Prochlorperazine has less potentiating effects on hypnotics than chlorpromazine and does not produce lethargy and hypotension. It may be used in the treatment of migraine, Meniere s syndrome, and other labyrinthine disturbances, and is an effective choice in PONV. 

Most patients are able to tolerate the antimuscarinic adverse effects of antipsychotic drugs. Those who are made too uncomfortable or who develop urinary retention or other severe symptoms can be switched to an agent without significant antimuscarinic action. Orthostatic hypotension or impaired ejaculation—common complications of therapy with chlorpromazine or mesoridazine—should be managed by switching to drugs with less marked adrenoceptor-blocking actions. 

The neuroleptics that are widely available may be divided into two general categories, those with low potency (such as chlorpromazine and thioridazine) and those with high potency (exemplified by haloperidol, trifluoperazine and pimozide). The former groups have a lower propensity to cause extrapyramidal side effects but are more sedative and likely to cause postural hypotension and have anticholinergic side effects. In vitro studies have shown that chlorpromazine has an affinity for all five types of dopamine receptor and has some preference for D2 and D3 receptors. By contrast, haloperidol is more potent than chlorpromazine for the D2, D3 and D4 receptors with a low affinity for the D and D5 receptors. 

Phenothiazine neuroleptics (e.g. chlorpromazine, thioridazine) + vasodilators and antihypertensive drugs —> increased hypotensive effects due to increased peripheral vasodilation. 

The introduction of the phenothiazine derivative, chlorpromazine, has started a dramatic improvement in the clinical treatment of schizophrenia. During the past four decades, beside phenothiazines, various antipsychotics having different chemical structures have been identified and introduced into clinical practice (e.g., butyrophenones and benzamides). These drugs ( typical antipsychotics ) decreased the duration of hospitalizations and, with maintenance treatment, reduced the risk of relapse and re-hospitalization. However, they had significant adverse side effects such as tardive dyskinesia, orthostatic hypotension, prolactin increase, and QT prolongation. 

Aminoalkyl compounds, such as chlorpromazine and promazine, antagonize ai-adrenoreceptors, histamine Hi-receptors and muscarinic cholinergic receptors. The blockade of ai-adrenoreceptors and histamine Hi-receptors gives chlorpromazine a sedating profile, while a i-adrenoreceptor blockage also causes hypotension. The anticholinergic activity may cause dry mouth, urinary difficulties, and constipation, while, on the other hand, offsetting the liability to produce extra pyramidal effects. 

Hypotension is the most commonly observed cardiovascular adverse effect of neuroleptic drugs, particularly after administration of those that are also potent alpha-adrenoceptor antagonists, such as chlorpromazine, thioridazine, and clozapine (34). A central mechanism involving the vasomotor regulatory center may also contribute to the lowering of blood pressure. 

ADRENERGIC NEURONE BLOCKERS PHENOTHIAZINES Variable effect some cases of t hypotensive effect other cases where hypotensive effects 1 by higher doses (> 100 mg) of chlorpromazine Additive hypotensive effect. Phenothiazines cause vasodilatation however, chlorpromazine blocks uptake of guanethidine into adrenergic neurones Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

Overdose with MAOIs can cause hypomania, coma and hypotension or hypertension. General measures are used as appropriate with minimal administration of drugs chlorpromazine for restlessness and excitement phentolamine for hypertension, no vasopressor drugs for hypotension, because of risk of hypertension (use posture and plasma volume expansion). 

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