05.01.2.1 Pharmacodynamic Interactions

An example of a pharmacodynamic interaction is considered. Atherosclerosis is usually the underlying cause of angina (coronary artery disease) and erectile dysfunction. Men who develop atherosclerosis often have angina and erectile dysfunction. Nitroglycerin is used to relieve or prevent attacks of angina. Sildenafil (Viagra) is used to treat erectile dysfunction. Nitroglycerin acts by mimicking endogenous nitric oxide to stimulate the enzyme guanylate cyclase to convert GTP to cGMP, which after a few more steps leads to vasodilation to relieve the angina (Figure 5.1). There is only a small decrease in blood pressure with nitroglycerin.

Figure 5.1 Pharmacodynamic drug interaction (Copyright QUT, Sheila Doggrell)

Normally, erectile function is mediated by endogenous nitric oxide that stimulates the guanylate cyclase to increase the levels of cGMP in the corpus carvenosum, which produces relaxation, and blood rushes in to cause penile erection. The effects of cGMP are short-lived as it is rapidly inactivated by the enzyme phosphodiesterase V. When men take nitroglycerin for angina and sildenafil for erectile dysfunction, the sildenafil will inhibit phosphodiesterase V in the corpus carvenosum and blood vessels to increase the effect of nitroglycerin (Figure 5.1). Thus, the effects of nitroglycerin are increased, and there is a large decrease in blood pressure with postural hypotension (dizziness and fainting when standing up). As a result of this interaction, sildenafil is contraindicated in men taking nitroglycerin.