Pulm. HTN

Question 1

Epoprostenol

Answer 1

Prostanoid = Mimics Prostacylin (uses G-protein to increase cAMP)

• Prostacyclin = - Potent vasodilator
  - Suppresses growth of Smooth m of vasculature
  - Inhibits platelet aggregation
• Effects: -Lowers pulm arterial resistance and BP
  - Increases exercise tolerance
  - Increases short term survival
• *** Serious adverse effects
  
  • VERY SHORT 1/2 life = ~6mins
• *- Needs to be a CONTINUOUS IV with a PUMP to keep COLD!
• • can cause sepsis due to chronic catherter
• • catherter can become clogged and be life-threatening

Common Side effects: Headache, nausea, flushing, jaw pain

Question 2

Treprostinil

Answer 2

Prostanoid = Mimics Prostacyclin (uses G-protein to increase cAMP)

• Prostacyclin = - Potent vasodilator
  - Suppresses growth of Smooth m of vasculature
  - Inhibits platelet aggregation
• Effects: -Lowers pulm arterial resistance and BP
  - Increases exercise tolerance
  - Increases short term survival
• *** Initially given as SUBCUTANEOUS INFUSION = BUTTT was very PAINFUL!
• • Now given like Epoprostenol (iv pump)
• • Has longer 1/2 life tho = ~4hrs

Adverse effects

• Sepsis from chronic catheter
• Site pain from subcutaneous infusion
• Jaw pain, diarrhea, Edema, Nausea

Question 3

Iloprost

Answer 3

Prostanoid = Mimics Prostacyclin (uses G-protein to increase cAMP)

• Prostacyclin = - Potent vasodilator
  - Suppresses growth of Smooth m of vasculature
  - Inhibits platelet aggregation
• Effects: -Lowers pulm arterial resistance and BP
  - Increases exercise tolerance
  - Increases short term survival

** Administered via INHALATION!!!!

Adverse effects:

• Fainting if pt has hypotension (if systolic BP is below 85)
• Cough, headache, flushing, jaw pain

Question 4

Selexipag

Answer 4

Prostanoid = Mimics Prostacyclin (uses G-protein to increase cAMP)

• “new kid on the block”
• Prostacyclin = - Potent vasodilator
  - Suppresses growth of Smooth m of vasculature
  - Inhibits platelet aggregation
• Effects: -Lowers pulm arterial resistance and BP
  - Increases exercise tolerance
  - Increases short term survival

** Administered ORALLY, BID (tablets are 225-350 each!!!!!!)

common side effects:
- headache, flushing, diarrhea, nausea, vomit, jaw/limb/muscle pain, skin rash

Question 5

Bosentan

Answer 5

Endothelin Antagonist

“Is an ugly drug to take!”

** NONSPECIFICALLY blocks ETa and ETb endothelin receptors!!!!

• Effects: Increases exercise tolerance and slows sx progression!
• Given Orally
• ***- SERIOUS Adverse Effects
  - Hepatotoxicity (potentially fatal)
  - Teratogenesis (FDA category X)
• Other adverse effects
  • Headache, flush, edema, nasal congestion, anemia, reduced sperm count
• *- Drug interactions:
  
  • Increases Metabolism of: Wafarin and Oral contraceptives (need 2 forms of contraception!)

Question 6

Ambrisentan

Answer 6

Endothelin Antagonist

**“Drug of first choice!!!!” (Even tho it is expensive - about 300 per pill)

**- SPECIFICALLY blocks Eta receptors (these cause vasoconstriction and promote proliferation)

• Effects: Increases exercise tolerance and slows sx progression!
• Given Orally

** SERIOUS Adverse Effects:
- Teratogenesis (FDA category X)
…..DOES NOT effect the liver

• Other Adverse Effects
  
  • Edema, nasal congestion, anemia, reduced sperm

** Does not accelerate metabolism of Warfarin or Oral contraceptives

Question 7

Macitentan

Answer 7

Endothelin Antagonist

• NONSPECIFICALLY blocks ETa and ETb

~18 hour 1/2 life so one pill a day

Similar adverse effects of Bosentan

Question 8

Sildenafil

Answer 8

PDE-5 Inhibitor

“Viagra for ED, Revatio for PAH!”

**- Selectively blocks PDE-5 so INCREASES cGMP which causes Vascular Sm. M relaxation!!

• Effects: - Improves exercise tolerance, and slows sx progression

Is well tolerated, BUT:

• can cause visual/hearing disturbances (if blood shunts there)
• ***- Be careful if combining with HTN/angina meds like: alpha adrenergic antagonists or nitrates Could cause severe drop in BP!!!

Question 9

Tadalafil

Answer 9

PDE-5 Inhibitor

“Cialis for ED, Adcirca for PAH”

Same as Sildenafil but LONGGGG 1/2 life!

Question 10

Riociguat

Answer 10

Guanylate Cyclase Sensitizer

Dual mode of action:

• Sensitizes Guanylate Cyclase (GC) by stabilizing NO-GC binding!
• Directly Activates Guanylate Cyclase without NO!

Oral drug 12 hr 1/2 life

Adverse Effects:

• hypotension, headache, dizzy, dyspepsia (indigestion)
• may cause fetal harm
• DO NOT give with NO donors or PDE-5 inhibitors!