Tyrosine hydroxylase inhibitors
Tyrosine hydroxylase inhibitors
Metirosine
Metirosine is mainly used in patients with phaeochromocytoma and is not recommended for use in essential hypertension. The manufacturer’s data sheet lists impotence and failure of ejaculation as possible side effects, but this may be related to the sedative effects of this drug. Calcium-channel blockers Calcium antagonists such as nifedipine and verapamil decrease coronary and vascular smooth muscle tone by blocking calcium influx into cells. 
There are few clinical reports of this class of drug being associated with sexual dysfunction. A report described three cases of impotence in 14 patients treated for arrhythmias and angina with verapamil and digoxin. In two patients, symptoms developed within 4 weeks.
In the remaining patient, impotence only occurred 8 months later. Another report describes a 45-year-old man admitted to hospital with suicidal depression and impotence 4 months after starting verapamil for hypertension. Within 36 hours of stopping therapy, he experienced four erections and the depression had resolved. One placebocontrolled study suggested a decrease in erectile firmness in older men on nifedipine. The mechanism of impotence is unclear. Calcium-channel blockade might be expected to relax smooth muscle, which would increase vascular engorgement of the penis and hence potentiate erection. It has been suggested that impotence may in some way be a consequence of inhibition of parasympathetic nerve function, but there is little evidence to support this.
There has been recent interest in the influence of calcium-channel blockers on sperm function, following the report of failed fertilisation of eggs at in vitro fertilisation. The man, who was taking nifedipine for hypertension, had apparently completely normal sperm parameters but no sperm were able to bind to the 15 eggs. The authors performed further studies by comparing three groups of men, fertile sperm donors, men taking calcium-channel blockers and men who had taken calcium-channel blockers but who were switched to alternative hypotensive agents at least 3 months previously. The sperm of men taking nifedipine did not undergo a spontaneous acrosome reaction, which is an essential prerequisite for fertilisation.
In the other two groups, the rate of spontaneous acrosome reaction, was normal. The acrosome reaction depends on calcium ion influx into the sperm. The authors suggested that men taking calcium channel blockers should be switched to alternative medication prior to commencing fertility treatment. Another recently published in vitro study showed that verapamil was associated with sperm damage to the head and tail regions of the sperm, associated with reduced motility. The authors even thought that the drug could have potential as a male contraceptive! Based on this evidence, it would appear a wise precaution to avoid calcium-channel blockers in men where the couple are trying to conceive.
Angiotensin-converting enzyme inhibitors
Captopril
ACE inhibitors promote vasodilatation by inhibiting the formation of angiotensin 2. As there is no specific effect on the autonomic nervous system, a low incidence of sexual side effects is to be expected. There are no reports indicating sexual dysfunction with captopril alone. In a study comparing the effect of captopril, propranolol and methyldopa on patients’ distress over their sexual symptoms, those on captopril reported the least change from pretreatment symptoms. Although 19% complained of worsening symptoms, the same percentage reported an improvement. 
Another large study looked at 30 000 patients (53% women) and noted improvements in sexual function in patients of both sexes when captopril was substituted for other antihypertensive medication. In one multicentre study of 900 men with mild hypertension, the incidence of difficulty in obtaining and maintaining erections was the same in men taking the ACE inhibitor enalapril as in those taking placebo. Benoff et al recommend using ACE inhibitors rather than calcium-channel blockers for men in whom fertility may be a problem.
