RESP: PHOSPHODIESTERASE (TYPE 5) INHIBITORS

Question 1

PHOSPHODIESTERASE (TYPE 5) INHIBITORS: INDICATIONS

Answer 1

• Erectile Dysfxn

- Primary Pulmonary HTN

Question 2

PHOSPHODIESTERASE (TYPE 5) INHIBITORS: MOA

Answer 2

• Selective for PDE type-5 that is found predominantly in the smooth muscle of the corpus cavernosum of the penis and arteries of the lung
• For an erection to occur, sexual stimulation is required. This releases nitric oxide, which stimulates cyclic guanosine monophosphate (cGMP) production, causing arterial smooth muscle relaxation, vasodilatation and penile engorgement.
• As PDE5 is responsible for the breakdown of cGMP, inhibition of this enzyme by sildenafil increases cGMP concentrations, improving penile blood flow and erection quality.
• It is worth noting sildenafil does not cause an erection without sexual stimulation. In the pulmonary vasculature, sildenafil causes arterial vasodilatation by similar mechanisms so is used to treat primary pulmonary hypertension

Question 3

PHOSPHODIESTERASE (TYPE 5) INHIBITORS: ADVERSE EFFECTS

Answer 3

• Flushing
• HA
• Dizziness
• Nasal Congestion
• Hypotension
• Tachycardia
• Palpitations
• Small associated risk of Vascular Events (MI, Stroke)
• If the erection fails to subside for a prolonged period despite absence of stimulation (priapism), urgent medical assistance is required to prevent penile damage.
• Visual disorders including colour distortion are due to inhibition of PDE6 in the retina and should prompt urgent medical review

Question 4

PHOSPHODIESTERASE (TYPE 5) INHIBITORS: WARNINGS

Answer 4

• Stroke
• ACS
• CVDx
• Should be avoided at a lower dose in people with severe hepatic or renal impairment

Question 5

PHOSPHODIESTERASE (TYPE 5) INHIBITORS: INTERACTIONS

Answer 5

• Do not prescribe sildenafil for people taking any drug that increases nitric oxide, particularly nitrates or nicorandil, as their combined effects on cGMP can cause marked arterial vasodilatation and cardiovascular collapse.
• Vasodilators including α-blockers (should not be taken within 4 hours of sildenafil) and calcium channel blockers, as there is an increased risk of hypotension.
• Plasma concentrations and adverse effects of sildenafil are increased by cytochrome P450 inhibitors, e.g. amiodarone, diltiazem and fluconazole

Question 6

PHOSPHODIESTERASE (TYPE 5) INHIBITORS: EXAMPLES

Answer 6

• Sildenafil