Pulmonary Arterial Hypertension

Question 1

List six (6) drugs that can cause Pulmonary Arterial Hypertension

Answer 1

1. Cocaine
2. SSRI use during pregnancy (increase risk for newborn)
3. Weight loss drugs (diethylpropion, lorcaserin, phendimetrazine, phentermine)
4. Methamphetamines
5. Dasatinib (Sprycel)
6. Diazoxide (Proglycem)

Question 2

MOA of Prostacyclin Analogues (Prostanoids) and Receptor Agonists?

Answer 2

Prostacyclin synthase is reduced in patients with PAH, causing decreased production of prostacyclin I2, a vasodilator with anti-proliferative effects, in pulmonary artery smooth muscle cells. Prostacyclin analogues are potent vasodilators and inhibitors of platelet aggregation.

Question 3

List two (2) prostacyclin analogs given by continuous IV infusion

Answer 3

1. Epoprostenol (Flolan, Veletri), central catheter

2. Treprostinil (Remodulin), SC or central

Question 4

List two prostacyclin analogs given by inhalation

Answer 4

1. Treprostinil (Tyvaso)

2. Iloprost (Ventavis)

Question 5

List two prostacyclin analogs given orally

Answer 5

1. Treprostinil (Orenitram), oral ER tablet

2. Selexipag (Uptravi), tablet

Question 6

MOA of endothelin receptor antagonists?

Answer 6

Endothelin is a vasoconstrictor with cellular proliferative effects. ERAs block endothelin receptors on pulmonary artery smooth muscle cells.

Question 7

List three (3) endothelin receptor antagonists

Answer 7

1. Bosentan (Tracleer), tablet
2. Ambrisentan (Letairis), tablet
3. Macitentan (Opsumit), tablet

Question 8

MOA of phosphodiesterase-5 inhibitors in PAH?

Answer 8

PDE-5 is responsible for the degradation of cyclic guanosine monophosphage (cGMP); increased cGMP concentrations lead to pulmonary vasculature relaxation and vasodilation.

Question 9

List a PDE-5 inhibitors given IV in PAH

Answer 9

1. Sildenafil (Revatio) tablet, oral suspension, IV

Question 10

List PDE-5 inhibitor given orally in PAH

Answer 10

1. Sildenafil (Revatio) tablet, oral suspension, IV

2. Tadalafil (Adcirca) tablet

Question 11

MOA of soluble guanylate cyclase stimulator

Answer 11

Soluble guanylate cyclase (sGC) is a receptor for endogenous nitric oxide. Riociguat sensitizes sGC to endogenous nitric oxide and directly stimulates the receptor at a different binding site. This increases cGMP, leading to relaxation and anti-proliferative effects.

Question 12

List soluble guanylate cyclase simulator

Answer 12

Riociguat (Adempas), tablet

Question 13

List six (6) drugs that can cause Pulmonary Fibrosis

Answer 13

1. Amiodarone
2. Bleomycin
3. Dronedarone
4. Methotrexate
5. Nitrofurantoin
6. Sulfasalazine

Question 14

Two (2) contraindications for prostacyclin analogs

Answer 14

1. Epoprostenol: heart failure with decreased LVEF

2. Troprostinil (oral): severe hepatic impairment (Child-Pugh Class C)

Question 15

List three (3) warnings for prostacyclin analogs

Answer 15

1. Rebound Pulmonary Hypertension, increased risk of bleeding
2. Chronic IV infusions carry risk of sepsis and blood stream infections
3. Troprostinil oral (Orenitram) does not dissolve and can lodge in diverticuli

Question 16

List three (3) side effect considerations (Hint: General, IV/SC infusions, Inhaled)

Answer 16

1. General: Vasodilation reactions (hypotension, headache, dizziness, flushing, N/V/D), edema, jaw pain, MSK pain, tachycardia, flu-like syndrome, anxiety, tremor, thrombocytopenia
2. IV/SC: infusion-site pain, especially SC Remodulin
3. Inhalation: cough and mouth/throat irritation (Tyvaso & Ventavis)

Question 17

List eight (8) miscellaneous notes for prostacyclin analogs (Hint: potency, interruptions in therapy, dose reductions, photosensitivity, ice packs, infusion-site pain, infection risk, hepatic considerations)

Answer 17

1. parenteral agents are considered the most potent of all PAH medications
2. avoid interruptions in therapy (epo half life 6 minutes vs. trepro half life 4 hours)
3. Avoid large, sudden reductions in dose (decrease gradually)
4. Epoprostenol must be protected from light before reconstitution and during infusion (Flolan & Veletri)
5. Flolan: reconstituted solutions require use of ice packs. Valetri is thermostable.
6. Remodulin: infusion site pain in 85% of patients with SC administration, may need analgesic. No ice pack needed.
7. Carefully instruct patient on sterile technique to decrease infection risk (e.g. when they are infusion it themselves)
8. Treprostinil oral (Orenitram) contraindicated in Child Pugh Class C; Selexipag (Uptravi) avoid use in Child Pugh Class C; for both drugs, mild-to-moderate hepatic impairment, lower starting doses requires.

Question 18

List three (3) boxed warnings for endothelin receptor antagonists

Answer 18

1. Embryo-fetal toxicity (women of childbearing potential must have a negative pregnancy test prior to initiation of therapy and monthly thereafter)
2. Bosentan: hepatic toxicity (increased ALT/AST and liver failure)
3. Available only through individual REMS programs (Tracleer REMS Program, Letairis REMS Program and Opsumit REMS Program)

Question 19

List three (3) contraindications to ERA

Answer 19

1. Pregnancy
2. Bosentan: use with cyclosporine or glyburide
3. Ambrisentan: idiopathic pulmonary fibrosis

Question 20

List two (2) warnings for ERA

Answer 20

1. Hepatotoxicity (only Bosentan has BBW), decreased Hgb/Hct, fluid retention (e.g. pulmonary edema, peripheral edema), decreased sperm counts
2. Bosentan: hypersensitivity reactions (e.g. rash, angioedema, anaphylaxis, DRESS)

Question 21

List four (4) side effects of ERA (hint: Neuro, Pulmo, Derm, CV)

Answer 21

1. Headache
2. Upper respiratory tract infections (e.g. nasal congestion, cough, bronchitis)
3. Flushing
4. Hypotension

Question 22

List four (4) monitoring parameters for ERAs (hint: Hepato, Hemato, Ob/gyn)

Answer 22

1. LFTs
2. Bilirubin
3. Hgb/Hct
4. Pregnancy tests

Question 23

List two (2) contraindications to PDE-5 inhibitors

Answer 23

1. use with nitrates or riociguat

2. Revatio: avoid taking with protease inhibitors (e.g. atazanavir, ritonavir, others)

Question 24

List two (2) warnings for PDE-5 inhibitors

Answer 24

1. Hearing loss (with or without tinnitus and dizziness), vision loss (rare but may be due to nonarteritic anterior ischemic optic neuropathy [NAION]), priapism, hypotension, pulmonary edema
2. Revatio: not recommended for pediatric use due to increased mortality

Question 25

List six (6) side effects (hint: neuro, derm, GI times two, pain, unusual)

Answer 25

1. Headache
2. Flushing
3. Dyspepsia & N/D
4. Extremity or back pain
5. Epistaxis

Question 26

List boxed warnings for soluble guanylate cyclase stimulator

Answer 26

1. Embryo-fetal toxicity must have a pregnancy test prior to initiation of therapy and monthly thereafter.

Question 27

List two contraindications to riociguat

Answer 27

1. Pregnancy

2. Use of PDE-5 inhibitors or nitrates

Question 28

List three (3) warnings for Adempas

Answer 28

1. Hypotension
2. Bleeding
3. Pulmonary edema

Question 29

List four (4) side effects for Adempas

Answer 29

1. Headache
2. Dyspepsia
3. Dizziness
4. N/V/D

Question 30

List 7ish drug classes used in PAH

Answer 30

1. warfarin
2. loop diuretics
3. oxygen
4. digoxin
5. ERAs
6. Prostacyclin analogs or receptor agonists
7. PDE-5 inhibitors/sGC stimulators