(6.2) Pulmonary HTN Drugs

Question 1

First gene linked to PAH

Answer 1

BMPR2

Question 2

Weight loss drug associated with PAH

Answer 2

fenfluramine/phentermine

Question 3

Vasopressor test is positive

Answer 3

Pulmonary Artery pressure falls >= 10

mPAP <= 40

Cardiac output is unchanged

Question 4

Prostanoid MoA

Answer 4

Mimics action of endogenous prostacyclin

vascular relaxation

inhibits grown of smooth muscle cells and platelet aggregation

increases cAMP

used in PAH to lower

Question 5

Epoprostenol class/effect

Answer 5

“Prost”

prostanoid

used in PAH to lower Pulmonary arterial resistance

decrease PAP

increase exercise tolerance

increase short term survival

Question 6

epoprostenol kinetics/concerns

Answer 6

6 min half life so needs continuous IV admin

sepsis due to catheter/risky if pump is clogged

nause/vomiting
headache
flushing
jaw pain

Question 7

treprostinil class/effect

Answer 7

‘prost’

prostanoid

used in PAH to lower Pulmonary arterial resistance

decrease PAP

increase exercise tolerance

increase short term survival

Question 8

treprostinil kinetics/concerns

Answer 8

initially subQ but that is really painful

1:2 dilution for IV use with a 4hour half life and does not need refrigeration

qid inhalation available now

SubQ site pain/ jaw pain/ diarrhea/ edema/ nausea

inhalation has cough/headache/throat irritation/some nausea, flushing, and dizziness

Question 9

iloprost class/effect

Answer 9

‘prost’

prostanoid

used in PAH to lower Pulmonary arterial resistance

decrease PAP

increase exercise tolerance

increase short term survival

Question 10

iloprost kinetics/concerns

Answer 10

inhalation 6-9 times a day

fainting due to hypotension (SBP <85)

cough/headache/flushing/jaw pain

Question 11

selexipag class/effect

Answer 11

prostanoid

used in PAH to lower Pulmonary arterial resistance

decrease PAP

increase exercise tolerance

increase short term survival

Question 12

selexipag kinetics/concerns

Answer 12

oral admin BID
tablets are 225-350 each

headache/flushing/diarrhea/vomiting/jaw and limb pain/skin rash

Question 13

Bosentant class and MoA

Answer 13

‘entan’
endothelin antagonist

non-specifically binds ETa and ETb endothelin receptors

improves exercise tolerance and slows symptom progression

Question 14

Bosentan kinetics/concerns

Answer 14

oral drug

50% availability regardless if eaten with a meal

metabolized by liver

hepatotoxic (11% fatal) and teratogenic

headache/flushing/edema/nasal congestion/anemia/decreased sperm

accelerates warfarin metabolism and oral BC

increases cyclosporin and glyburide drug levels

Question 15

ambrisentan class and MoA

Answer 15

‘entan’ andothelin antagonist

selectively blocks ETa receptors that cause vasoconstriction and promote proliferation

improves execise tolerance and slows symptom progression

Question 16

ambrisentan kinetics and concerns

Answer 16

oral drug

teratogenic but is NOT hepatotoxic

edema/nasal congestion/anemia/decreased sperm

Question 17

macitentan

Answer 17

18hr half life endothelin antagonist

CYP450 effects similar to bosentan

Question 18

sildenafil class and MoA

Answer 18

PDEV inhibitor

imrpoves exercise tolerance and slows progression of symptoms

Question 19

sildenafil kinetics and concerns

Answer 19

oral drug with 4 hr half life

well tolerated with headahce/flushing/dyspnea

priapism

visual disturbances and hearing loss

mild hypotension if used alone and will cause more with alpha antagonist or nitrates

Question 20

Riociguat class and MoA

Answer 20

guanylate cyclase sensitizer to exogenous NO

also directly stimulates sGC independent of NO

increases cGMP production and dilation

improves exercise tolerance

Question 21

Riociguat kinetics/concerns

Answer 21

oral drug with 12 hr half life

hypotension/headache/dizziness/dyspepsia
may cause fetal harm avoid pregnancy for 1 mo after cessation

do not use with nitrates and PDEV

CYP450 and transporter interactions