L2 | ED | PDE-5 Inhibitors

Question 1

What are some of the drugs found in this class?

Answer 1

1. Vardenafil
2. Sildenafil
3. Tadalafil

Question 2

What is their MOA?

Answer 2

They work by stimulating the nerve endings of epithelial cells of the penile erectile tissue (corpus cavernosum) which leads to the release of NO.
NO actives guanylyl cyclase within the cells which transforms guanosine triphosphate (GTP) to guanosine monophosphate (GMP) which activates protein kinase which opens up calcium channels and decreases intracellular calcium which causes smooth muscle relaxation of the corpus cavernosum allowing more blood to flow thereby causing penile erection

Question 3

What are their pharmacokinetics?

Answer 3

A. Vardenafil and Sildenafil
1. They should be taken one prior to sexual activity, and their effect lasts for up to 4 hours
2. Their bioavailability is decreased when taken with a fatty meal
3. Vardenafil is available as an ODT which should be placed on the tongue with no liquids (they decrease the bioavailability) this formulation provides a higher systemic bioavailability than enteric coated tablets (the two are not interchangeable)

B. Tidalafil
1. It has a more delayed onset of action compared to the other two however it has a half life of around 18 hours which means it could theoretically last for up to 36 hours so planning is not a major concern.
2. It is not affected by meals

• all of those phosphodiasterase inhibitors are metabolized by the hepatic enzyme P450 3A4

Question 4

What are their adverse effects?

Answer 4

Mild side effects:
Headaches, flushing, nasal congestion, dyspepsia, palpitations (all due to vasodilatation)

Severe side effects:
1. Color vision disturbance (blue/green discrimination) probably due to the inhibition of PDE-6 in the retina
2. Severe hypotension

Question 5

What are their side effects?

Answer 5

Common side effects:
Headache, flushing, dyspepsia, nasal congestion and palpitations

Severe side effects:
1. Color vision disturbance (blue/green discrimination) probably due to PDE-1 inhibition in the retina
2. Severe hypotension

Question 6

What are their contraindications?

Answer 6

1. People who are taking NO donors, nitrates or nitrites
2. People with hepatic, renal or cardiac function impairment
3. People with inherited retinal disorders.