PDE5I & GCs

Question 1

Sildenafil MOA?

Answer 1

• selectively blocks PDE type V, an enzyme that breaks down cGMP, and important intracellular mediator of sm m relaxation

Question 2

Sildenafil (viagra) & tadalafil, effects?

Answer 2

• ↑ exercise tolerance & slows sx progression

Question 3

Clinical applications of sildenafil?

Answer 3

• PAH, ED

Question 4

PK of sildenafil?

Answer 4

PO, half life ~ 4 hrs

Question 5

Toxicities of sildenafil?

Answer 5

• well tolerated, w/ HA, flushing, and dyspepsia
• rarely see priapism
• can cause visual disturbances (like lack of color discrimination) and sudden hearing loss
• Causes mild hypotension when used alone, but much greater ↓ seen if used with alpha-blockers for HTN or nitrates for anginal pain

Question 6

Benefits to tadalafil?

Answer 6

• AKA cialis

- Longer half life

Question 7

MOA of riociguat?

Answer 7

• Guanylate Cyclase Sensitizer
• Dual MOA
• Sensitizes soluble guanylate cyclase (sGC) to endogenous NO by stabilizing the NO-sCG binding
• directly stimulates sGC independent of NO
• ↑ generation of cGMP –> ↑ vasodilation

Question 8

Clinical applications of riociguat?

Answer 8

PAH and type 4 PH

Question 9

Toxicities of riociguat?

Answer 9

• hypotension, HA, dizziness, dyspepsia; rare severe bleed
• May cause fetal harm so no preggers and stop > 1month prior to getting preggers
• Should not be administered with nitric oxide donors or type V PDE-Is
• Multiple potential drug interactions at both transporters and cyto P450