PAH- RAT

Question 1

Synthetic Prostacyclin and Prostacyclin Analogs: MOA and Drugs

Answer 1

Direct vasodilator of systemic and pumonary vascular beds, also inhbits platelet aggregation

• Epoprostenol
• Treprostinil
• Iloprost

Question 2

Synthetic Prostacyclin and Prostacyclin Analogs: adverse effects

Answer 2

Flushing, jaw pain, headache, skeletal pain, diarrhea

Hypotension, thrombocytopenia, catheter-related infection, pump malfunction, infusion site pain (mostly with SC formulation) and thrombosis may occur with parenteral formulations

Cough and throat irritation may occur with the inhaled formulations

Question 3

Endothelin Receptor Antagonists (ERAs): MOA

Answer 3

Antagonism of endothelin receptors, leading to vasodilation

Question 4

Endothelin Receptor Antagonists (ERAs): Drugs

Answer 4

Bosentan (Tracleer®)
Ambrisentan (Letairis®)
Macitentan (Opsumit®)

Question 5

Endothelin Receptor Antagonists (ERAs): Adverse effects

Answer 5

Headache, flushing, ↑LFTs (more likely with bosentan), edema (especially if >65 years old), ↓hemoglobin/hematocrit

Teratogenic (Category X)

Bosentan has a black box warning for liver injury (monitors LFTs at baseline and monthly)

Question 6

Phosphodiesterase-5 (PDE-5) Inhibitors: MOA

Answer 6

↑intracellular concentration of cGMP, leading to vasorelaxation and antiproliferative effects on vascular smooth muscle cells

Question 7

Phosphodiesterase-5 (PDE-5) Inhibitors: Drugs

Answer 7

Sildenafil (Revatio®)

Tadalafil (Adcirca®)

Question 8

Phosphodiesterase-5 (PDE-5) Inhibitors: Adverse effects

Answer 8

Headache, flushing, dyspepsia, epistaxis, rash, vision changes

Question 9

Soluble Guanylate Cyclase Stimulator: MOA

Answer 9

Sensitizes soluble guanylate cyclase to endogenous nitric oxide and stimulates nitric oxide and soluble guanylate cyclase binding
↑ cGMP leading to vasodilation

Question 10

Soluble Guanylate Cyclase Stimulator: Drugs

Answer 10

Riociguat (Adempas®)

Question 11

Soluble Guanylate Cyclase Stimulator: : Adverse effects

Answer 11

Hypotension, dizziness, headache, bleeding, edema, dyspepsia

Teratogenic (Category X)

Question 12

Soluble Guanylate Cyclase Stimulator: Comments

Answer 12

Use is contraindicated with PDE-5 inhibitors

Available through REMS program due to teratogenicity

May use in functional classes II through IV

Question 13

Selective Prostacyclin IP Agonist: MOA

Answer 13

Activation of the IP receptor leads to smooth muscle cell vasodilation through ↑cAMP

Inhibition of proliferation and platelet aggregation

Question 14

Selective Prostacyclin IP Agonist: Drugs

Answer 14

Selexipag (Uptravi)

Question 15

Selective Prostacyclin IP Agonist: Adverse Effects

Answer 15

Flushing, headache, diarrhea, nausea, vomiting

Less common: hyperthyroidism, ↓ hemoglobin

Question 16

Selective Prostacyclin IP Agonist: Comments

Answer 16

Studied in functional class II and III

May monitor thyroid function tests

Question 17

Calcium Channel Blockers: MOA

Answer 17

Blocks influx of extracellular calcium, leading to vasodilation

Question 18

CCB: Drugs

Answer 18

Nifedipine (Procardia®)
Diltiazem (Cardizem®)
Amlodipine (Norvasc®)

Question 19

CCB: Adverse Effects

Answer 19

Peripheral edema, headache, dizziness, constipation, flushing

Question 20

CCB: Comments

Answer 20

Diltiazem is a negative inotrope

Use is dependent upon positive response in vasodilator testing