Tamsulosin is a competitive α1 antagonist with a structure quite different from that of most other α1-receptor blockers. It has high bioavailability and a half-life of 9–15 hours. It is metabolized extensively in the liver. Tamsulosin has higher affinity for α1A and α1D receptors than for the α1B subtype. Evidence suggests that tamsulosin has relatively greater potency in inhibiting contraction in prostate smooth muscle versus vascular smooth muscle compared with other α1-selective antagonists. The drug’s efficacy in BPH suggests that the α1A subtype may be the most important α subtype mediating prostate smooth muscle contraction. Furthermore, compared with other antagonists, tamsulosin has less effect on standing blood pressure in patients. Nevertheless, caution is appropriate in using any α antagonist in patients with diminished sympathetic nervous system function (see http://www .bmj.com/content/347/bmj.f6320). Recent epidemiologic studies suggest an increased risk of orthostatic hypotension shortly after initiation of treatment. A recently recognized and potentially serious adverse effect of oral tamsulosin in patients undergoing cataract surgery is that they are at increased risk of the intraoperative floppy iris syndrome (IFIS), characterized by the billowing of a flaccid iris, propensity for iris prolapse, and progressive intra-operative pupillary constriction. These effects increase the risk of cataract surgery, and complications are more likely in the ensuing 14 days if patients are taking these agents.
Alfuzosin is an α1-selective quinazoline derivative that is approved for use in BPH. It has a bioavailability of about 60%, is extensively metabolized, and has an elimination half-life of about 5 hours. It may increase risk of QT prolongation in susceptible individuals. Silodosin resembles tamsulosin in blocking the α1A receptor and is also used in the treatment of BPH. Indoramin is another α1selective antagonist that also has efficacy as an antihypertensive. It is not available in the USA. Urapidil is an α1 antagonist (its primary effect) that also has weak α2-agonist and 5-HT1A-agonist actions and weak antagonist action at β1 receptors. It is used in Europe as an antihypertensive agent and for BPH. Labetalol and carvedilol have both α1-selective and β-antagonistic effects; they are discussed below. Neuroleptic drugs such as chlorpromazine and haloperidol are potent dopamine receptor antagonists but are also antagonists at α receptors. Their antagonism of α receptors probably contributes to some of their adverse effects, particularly hypotension. Similarly, the antidepressant trazodone has the capacity to block α1 receptors. Ergot derivatives, eg, ergotamine and dihydroergotamine, cause reversible α-receptor blockade, probably via a partial agonist action (see Chapter 16).
Yohimbine is an α2-selective antagonist. It is sometimes used in the treatment of orthostatic hypotension because it promotes norepinephrine release through blockade of α2 receptors in both the CNS and the periphery. This increases central sympathetic activation and also promotes increased norepinephrine release in the periphery. It was once widely used to treat male erectile dysfunction but has been superseded by phosphodiesterase-5 inhibitors like sildenafil (see Chapter 12). Yohimbine can greatly elevate blood pressure if administered to patients receiving norepinephrine transport-blocking drugs. Yohimbine reverses the anti-hypertensive effects of α2-adrenoceptor agonists such as clonidine. It is used in veterinary medicine to reverse anesthesia produced by xylazine, an α2 agonist used to calm animals. Although yohimbine has been taken off the market in the USA solely for financial reasons, it is available as a “nutritional” supplement and through compounding pharmacies.