List indications for Sildenafil.
Erectile dysfunction
Pulmonary hypertension
Benign prostatic hyperplasia (tadalafil only)
What kind of drug is Viagra/Sildenafil?
Phosphodiesterase type 5 inhibitor
(PDE5 inhibitor)
Describe the mechanism of action of Sildenafil.
PDE5 inhibition → ↓ breakdown of cGMP → ↑ cGMP → ↑ smooth muscle relaxation in reaction to nitric oxide activation → pulmonary vasodilation, penile smooth muscle relaxation, and increased blood flow
Describe the desired effect of Sildenafil.
Decrease in pulmonary vascular resistance
↑ Blood flow in the corpus cavernosum → increase in penis size during an erection
List adverse effects of Sildenafil as a PDE5 inhibitor
Headaches, cutaneous flushing
Lightheadedness
Sildenafil: visual deficits (blue-tinted vision, or cyanopia) due to PDE-6 inhibition in the retina [6]
Runny nose, nasal congestion
Exanthema
Dyspepsia
Rarely: myocardial infarction, stroke, hearing loss, optic neuropathy
What is the contraindication of PDE5 inhibitors?
Nitrates: Use of PDE5 inhibitors with nitrates (e.g., nitroglycerin) can result in life-threatening hypotension.
Both nitrates (e.g., sublingual nitroglycerin) and PDE-5 inhibitors (e.g., vardenafil) function by increasing cGMP concentration → activation of myosin light chain phosphatase (MLCP) → dephosphorylation of light chains of myosin → smooth muscle cell relaxation in blood vessels → vasodilation
Alpha blockers: Use of PDE5 inhibitors with alpha blockers can also result in hypotension.
Sildenafil and alpha blockers should always be taken at least 4 hours apart.
Patients being treated with PDE5s should not receive nitrates in unstable angina pectoris, acute coronary syndrome, or myocardial infarction because this could result in a life-threatening decrease in blood pressure!
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