Introduction to PDE5 Inhibitors Pharmacology

Phosphodiesterase type 5 inhibitors – or PDE5 inhibitors – are used in the treatment of erectile dysfunction and primary pulmonary hypertension. Here, we review the essential pharmacology that you need to know.

Examples of PDE5 inhibitors include:

  • Sildenafil
  • Tadalafil
  • Vardenafil

All three medicines are used to treat erectile function. Sildenafil and tadalafil are also used to treat pulmonary hypertension.

The original PDE5 inhibitor – sildenafil – was discovered as a potential treatment option for angina pectoris.

Mechanism of action

Phosphodiestesterase type 5 is an enzyme predominantly found in the smooth muscle of the corpus cavernosum of the penis and the arteries of the lung.

PDE5 inhibitors work by protecting cyclic guanosine monophosphate (cGMP) from degradation by the enzyme, PDE5.

As nitric oxide binds to guanylate cyclase receptors, it increases levels of cGMP. Greater levels of cGMP are linked to smooth muscle relaxation in the penile gland and the arteries of the lung.

Smooth muscle relaxation leads to vasodilation. More vasodilation means increased blood flow to the affected glands, leading to an erection.

By preventing degradation of cGMP, PDE5 inhibitors lead to greater vasodilation in both the penile gland and the arteries of the lung.

Side effects

Side effects associated with PDE5 inhibitors include:

  • Flushing
  • Headache
  • Dizziness
  • Nasal congestion
  • Hypotension
  • Tachycardia
  • Palpitations
  • Impaired vision

In a small number of cases, prolonged erections – priapism – may occur, which is considered a medical emergency.

Clinical considerations

When we talk about the clinical pharmacology of PDE5 inhibitors, we need to think about the following factors:

  • That PDE5 inhibitors should be avoided in patients with cardiovascular disease – due to the increased risk of heart attack and stroke.
  • That PDE5 inhibitors should be avoided alongside other drugs which can precipitate dangerously low blood pressure levels – such as vasodilators, calcium channel blockers and other hypotensive agents.
  • That PDE5 inhibitors should be avoided, or, at the very least, given at lower doses, in patients with hepatic or renal impairment.
  • PDE5 inhibitors should not be taken alongside nitric oxide donors, organic nitrates and nitrates – such as nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, sodium nitroprusside and alkyl nitrites (known colloquially as “poppers”).
  • Levels of PDE5 inhibitors are increased by CYP 450 inhibitors such as amiodarone, erythromycin, cimetidine, diltiazem, protease inhibitors and fluconazole.
  • Onset of effect of PDE5 inhibitors is delayed when taken with food.

PDE5 inhibitors pharmacology means understanding how the drug works not only at the penile level, but in the body as a whole. Inhibiting PDE5 has significant bodily effects and this becomes more serious when you consider potential drug interactions.

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