A-adrenoceptor antagonists

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

Many of the neuroleptics are a-adrenoceptor antagonists. Some, like chlorpromazine, block d postsynaptic receptors while clozapine (and risperidone) are as potent at 2 as D2 receptors. There is no evidence that either of these actions could influence striatal or mesolimbic function but NA is considered important for function of the prefrontal cortex and any increase in its release, achieved by blocking a2-mediated autoinhibition, might contribute to a reduction in negative symptoms and provide a further plus for clozapine (see Nutt et al. 1997). Centrally, however, most a2-receptors are found postsynaptically and their function, and the effect of blocking them, is uncertain. 

Milani S, Djavan B. Lower urinary tract symptoms suggestive of benign prostatic hyperplasia latest update on a, adrenoceptor antagonists. BJU Int 2005 95(Suppl 4) 29—36. 

Guh JH, Ko FN, Yu SM, Wu YC, Teng CM. Pharmacological evaluation of N-methyl-actinodaphnine, a new vascular a-adrenoceptor antagonist, isolated from Illigera luzonensis. Eur J Pharmacol 1995 279 33-41. 

Cadralazine has been launched under the trade names cadraten and cadri-lan. Pharmacological, pharmacokinetic and clinical studies on it have been reviewed [212]. A once-daily dosage of 15 mg cadralazine has been shown to be effective in the treatment of mild to severe hypertension and to be well tolerated. The therapeutic efficacy and tolerability can be improved by combining cadralazine with a -adrenoceptor antagonist [212]. 

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. 

Thus, it seems that the lack of sympathetic nervous system inhibition produced by the vasodilators, which is advantageous in some ways, can also be a disadvantage in that reflex increases in sympathetic nerve activity will lead to hemodynamic changes that reduce the effectiveness of the drugs. Therefore, the vasodilators are generally inadequate as the sole therapy for hypertension. However, many of the factors that limit the usefulness of the vasodilators can be obviated when they are administered in combination with a -adrenoceptor antagonist, such as propranolol, and a diuretic. Propranolol reduces the cardiac stimulation that occurs in response to increases in sympathetic nervous activity, and the... 

The adrenoceptor-blocking agents are described in detail in Chapter 11, although their use in the treatment of hypertension is briefly described here. Drugs of this group are subdivided into a-adrenoceptor antagonists (a-blockers) and (3-adrenoceptor antagonists ((3- blockers). 

It is another potent and selective a -adrenoceptor antagonist and quinazoline derivative. It s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds. 

Tadalafil has also been extensively evaluated in patients with cardiovascular disease and has a similar safety and efficacy profile to sildenafil (45). Studies have shown no adverse effects on cardiac contraction, ventricular repolarization, or ischemic threshold. A similar hypotensive effect has been recorded with a dose of doxazosin 8 mg so caution is needed. As hypotension does not occur in the supine position and as tadalafil has a long half-life it is suggested that tadalafil is taken in the morning and doxazosin in the evening. There is no interaction of tadalafil with the selective a-adrenoceptor antagonist tamsulosin, which can, therefore, be prescribed as an alternative to doxazosin for symptomatic benign prostate hypertrophy (46). 

The doctor is sympathetic cough is sometimes a problem for patients taking captopril she prescribes an alpha-adrenoceptor (a-adrenoceptor) antagonist, prazosin, instead. Sam has problems initially with orthostatic hypotension however, after dosage reduction, prazosin is well tolerated and Sam s BP settles at 143/87 mmHg. 

Q2 Mydriasis means the dilation of the pupil. Miosis is the constriction of the pupil. Muscarinic antagonists and alpha-adrenoceptor (a-adrenoceptor) agonists cause dilation of the pupil. However, muscarinic agonists and a-adrenoceptor antagonists cause contraction of the pupil. 

Miosis (constriction of the pupil) can be caused by muscarinic agonists and a-adrenoceptor antagonists. 

Interactions with anesthetics should be considered in patients taking a-adrenoceptor antagonists, such as risperidone (239). 

Less selective adrenoceptor agonists such as adrenaline (epinephrine), ephedrine, isoetharine, isoprenaline and orciprenaUne are less safe, being more likely to cause cardiac arrhythmias, a-adrenoceptor activity contributes to bronchoconstriction but a-adrenoceptor antagonists have not proved effective in practice. 

Antagonists with similar affinity for p,-adrenoceptor and P2-adrenoceptors include nadolol, oxprenolol, propranolol and timolol whereas acebutolol, atenolol, esmolol and metoprolol show some Pi -adrenoceptor selectivity and butoxaminc is pz-adrenoceptor preferring. Labetolol, in the racemic form used in medicine, acts as both a P-adrenoceptor and an a-adrenoceptor antagonist, though these activities reside in different isomers. Further factors determining the uses of individual agents include variations... 

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