Pulmonary Disorders II

Soluble guanylate cyclase stimulators

Riociguat exerts its effect through two mechanisms: Sensitizes endogenous soluble guanylate

cyclase by stabilizing nitric oxide–soluble guanylate cyclase bonding and directly stimulates soluble

guanylate cyclase through an auxiliary binding site. Both processes increase cyclic guanosine

monophosphate, which influences vascular tone, proliferation, fibrosis, and inflammation.

For patients on ERA/PDE5i therapy and at low-intermediate risk of death, switching from PDE5i

Elimination half-life is 12 hours. If cannot be administered for 3 days or more, retitration is required;

however, a PH specialist should always be involved for issues with access and reinitiation.

systemic hypotension, a starting dose of 0.5 mg three times daily may be used (2022 guidelines)

Adverse effects include hypotension, hemoptysis, headache, dizziness, dyspepsia, nausea, diarrhea,

vomiting, and anemia.

Contraindicated in patients receiving nitrates and phosphodiesterase inhibitors because of

hypotension; avoid with strong CYP3A4/2C8 inhibitors and inducers and with P-glycoprotein/

breast cancer resistance protein inhibitors

Riociguat risk evaluation and mitigation strategies (REMS) program for embryo-fetal toxicity

Prostacyclins

Parenteral prostacyclins (Table 8)

Mimic the actions of PGI2 (endogenous prostacyclin): Direct vasodilation of pulmonary and

systemic arterial vascular beds, inhibition of platelet aggregation, and antiproliferative effects

ii.

Continuous-infusion epoprostenol is the most thoroughly studied medication approved for

treating PAH and has been shown to prolong survival.

•

100% survival with intravenous epoprostenol compared with 80% survival with

conventional therapies at 12 weeks (p=0.003) (N Engl J Med 1996;334:296-301)

•

88% survival with intravenous epoprostenol compared with 59% expected survival in

data from historical controls at 1 year (p<0.001) (Circulation 2002;106:1477-82)

•

55% survival with intravenous epoprostenol compared with 28% survival in historical

controls at 5 years (p<0.0001) (J Am Coll Cardiol 2002;40:780-8)

iii.

Complications related to delivery include the need for a dedicated intravenous line, local

catheter/bloodstream infections, and catheter-related thrombosis.

Inhaled prostacyclins (Table 8) – Advantage over intravenous route because of selective pulmonary

vasodilation with minimal systemic effects

Sildenafil

(Revatio, Liqrev)

Sildenafil (Revatio)

Tadalafil (Adcirca, Alyq, Tadliq)

Half-life (hr)

Approved dose

20 mg oral TID

10 mg IV TID

40 mg oral daily; dose adjustment

necessary for renal impairment

Adverse effects

Headache, epistaxis, flushing, dyspepsia, hypotension, visual alterations

Drug

interactions

Contraindicated in patients receiving nitrates; avoid with strong CYP3A4 inhibitors and

inducers; contraindicated with riociguat

aKlinger JR, Elliott CG, Levine DJ, et al. Therapy for pulmonary arterial hypertension in adults. Chest 2019;155:565-86.

bGaliè N, Barberà JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med 2015;373:834-44.

IV = intravenously; TID = three times daily; WHO-FC = World Health Organization functional class; 6MWD = 6-min walk distance.