Acetylcholine, hypotensive effect

The primary cardiovascular effects of muscarinic agonists are reduction in peripheral vascular resistance and changes in heart rate. The direct effects listed in Table 7-3 are modified by important homeostatic reflexes, as described in Chapter 6 Introduction to Autonomic Pharmacology and depicted in Figure 6-7. Intravenous infusions of minimal effective doses of acetylcholine in humans (eg, 20-50. g/min) cause vasodilation, resulting in a reduction in blood pressure, often accompanied by a reflex increase in heart rate. Larger doses of acetylcholine produce bradycardia and decrease atrioventricular node conduction velocity in addition to the hypotensive effect. 

It is a potent alpha-adrenergic blocking agent and only haloalkylamine used clinically. It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease. It interferes with the reflex adjustment of blood pressure and produces postural hypotension. It increases the cardiac output and decreases the total peripheral resistance. It also antagonizes cardiac arrhythmias provoked by catecholamines. Apart from these effects, phenoxybenzamine has other actions also e.g. antagonism of acetylcholine, histamine, 5-hydroxytryptamine (serotonin). However, the vasodilatation produced by phenoxybenzamine is because of alpha blockage. Adverse reactions are miosis, dryness of mouth, inhibition of ejaculation, palpitation, nasal stuffiness and in higher doses, postural hypotension and reflex bradycardia. 

Carbachol is a quaternary ammonium compound that shares both the muscarinic and nicotinic actions of acetylcholine but is much more slowly deactivated. Carbachol has been used topically in ophthalmology and systemically (subcutaneously, for example in doses of 2 mg/day) for urinary retention. Severe cholinergic effects can result. In one instance they primarily involved the gastrointestinal tract and the patient died of esophageal rupture (1). In other cases patients have experienced extreme bradycardia with hypotension, requiring treatment with intravenous atropine. As carbachol is not destroyed by cholinesterase, a cumulative effect is possible in patients who receive regular doses at short intervals in one case, hypotension only developed on the third treatment day (2). 

The pharmacological properties of hydroxyzine are quite similar to those of chlorpromazine. It has antihistamine and anti-acetylcholine actions as have, indeed, most of the derivatives listed. Like chlorpromazine, hydroxyzine is anticonvulsive, it potentiates the action of hypnotics, it produces hypothermia and hypotension, it depresses the reticular system and it has some anti-adrenaline action. Extrapyramidal side effects do not, apparently, occur, perhaps because of the drug s rather powerful anti-acetylcholine action which probably also explains such side effects as dryness of the mouth and the occasional occurrence of central excitation. Epileptiform seizures have also been seen during hydroxyzine therapy. The fact that anti-acetylcholine and antihistamine activity is found with many of the diphenylmethane derivatives, whether depressant or excitatory, suggests that the tranquillizing effect of hydroxyzine cannot be due to its antagonizing the action of acetylcholine or histamine. 

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