40. Pulmonary Arterial Hypertension Flashcards by Yerin M

Drug list that can cause pulmonary arterial HTN

Cocaine
Fenfluramine
Methamphetamine/amphetamine
SSRI use during pregnancy (increase risk of persistent pulmonary hypertension of a newborn (PPHN))
Weight-loss drugs (diethylpropion, phendimetrazine, phentermine)

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Pulmonary HTN is characterized by mPAP ≥____ (normal range is ___)

≥25mmHg
Normal range 8-20 mmHg

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PAH stems from an imbalance in vasoconstrictor and vasodilator substances. Vasoconstrictor substances (e.g. ____) are increased and vasodilating substances (e.g. ____) are decreased

vasoconstrictor = endotheline-1, TXA2
Vasodilator = prostacyclins

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____ is the most common cause of death in pts who have PAH

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S/sx of PAH

Fatigue, dyspnea
Others: chest pain syncope edema, tachycardia and/or Raynaud’s phenomenon

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T/F: There is no cure for PAH but there are treatment options and in some cases, a lung or heart transplant may be an option for younger patients

True

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Non-drug treatments for PAH

Sodium restriction (<2.4 grams/day)
Avoid meds that increase sodium/water retention (NSAIDs)
Influenza and pneumococcal vaccines recommended

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____ is performed to confirm the diagnosis of PAH

Right heart catheterization

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During a right heart catheterization, what meds are administered for vasoreactivity testing?

short-acting vasodilators (e.g. inhaled nitric oxide, IV epoprostenol, IV adenosine)

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What makes someone a responder during vasoreactivity testing? What treatment do you recommend for responders?

If mPAP falls by at least 10mmHg to an absolute value <40mmHg
Treatment: oral CCB

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What are common CCBs used in responders?

Long-acting nifedipine, diltiazem, and amlodipine
Verapamil is NOT recommended d/t more pronounced negative inotropic effects compared to diltiazem

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What are treatment options for non-responders or responders who failed CCBs?

Prostacyclin analogues and receptor agonists, endothelin receptor antagonists (ERAs), PDE-5i, and/or soluble guanylate cyclase (sGC) stimulator

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Parenteral prostacyclin analogues, specifically ___, have shown to decrease mortality

IV epoprostenol

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Supportive therapies for PAH may include ___ (for volume overload) and ___ (to improve cardiac output or control HR in Afib)

Loop diuretics
Diogxin

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T/F: PAH leads to a higher risk of bleeding

False - leads to a pro-thrombic state and increased risk of blood clots

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What is the preferred anticoagulation if needed in PAH pts?

Warfarin

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MOA of prostacycline analogues

Potent vasodilators and inhibitors of platelet aggregation

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Which prostacyclin analogues can be administered by continuous IV at home using an ambulatory infusion pump?

Epoprostenol and treprostinil

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Treprostrinil (Remodulin) starting dose

1.25ng/kg/min, titrate

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Epoprostenol (Flolan) starting dose

2ng/kg/min, titrate

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CI with epoprostenol

HF with decreased LVEJ

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CI with treprostinil (oral)

severe hepatic impairment (Child-Pugh C)

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Warnings for prostacyclin analogues

Vasodilation reactions (hypotension, flushing, HA, dizziness)
Rebound pulmonary HTN (with interruption or large decreases in dose, can be fatal)
Chronic IV infusions: sepsis and bloostreen infections
Treprostinil (Orenitram): PO ghost shell, can lodge in diverticulum

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Side effects of prostacyclin analogues

Hypotension, flushing, jaw pain, HA, dizziness, N/V/D, edema, myalgia, tachycardia, flu-like syndrome, anxiety, tremor, thrombocytopenia
IV/SC infusions: infusion-site pain (esp SC Remodulin)
Treprostinil (inhaled) and iloprost: cough and mouth/throat irritation

Parenteral prostacyclin analogues (___,____,____) are very potent vasodilators; aoid interruptions and sudden large dose reductions

Epoprostenol - Flolan, Veletri Treprostinil - Remodulin

Which prostacyclin analogues require light protection before reconstitution and during infusion? Which ones require ice packs for stability?

Epoprostenol - protect from light before and during infusion Flolan (epoprostenol) - use ice packs for stability; Veletri and Remodulin are thermostable (no need for ice packs)

ng to mg conversion

1,000,000 ng = 1 mg

Endothelin receptor antagonists MOA

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

What are examples of prostacyclin analogues and receptor agonists?

Epoprostenol (Flolan, Veletri) Treprostinil (Remodulin (continuous SC or IV), Tyvaso (inhalation), Orenitram (PO ER tab)) Iloprost (Ventavis (inhalation)) Selexipag (Uptravi (tab))

Boxed warnings for endothelin receptor antagonists

Teratogenic - must have neg pregnancy test prior to initiation of therapy and monthly thereafter Bosentan - hepatotoxicity Requires REMS program

Endothelin receptor antagonist examples

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

Contraindications for endothelin receptor antagonist

Pregnancy

Warnings for endothelin receptor antagonists

Hepatotoxicity Decrease Hgb/Hct Fluid retention (e.g. pulmonary edema, peripheral edema) Decreased sperm counts Bosentan: hypersensitivity reactions

Side effects for endothelin receptor antagonists

HA, URTI, flushing, hypotension

Bosentan is contraindicated in use with ___ or ___. Bosentan can decrease effectiveness of ____.

cylcosporine and glyburide hormonal contraceptives

Besentan is a substrate and inducer of CYP____ and___

3A4, 2C9

PDE-5i MOA

PDE-5 is responsible for the degradation of cGMP. Increased cGMP concentrations lead to pulmonary vasculature relaxation and vasodilation

Contraindications for PDE5i

Nitrates or riociguat Sildenafil (Revatio) - avoid taking with protease inhibitors (e.g. atazanavir, ritonavir, others)

Sildenafil brand for pulmonary HTN vs erectile dysfunction

Pulmonary HTN - Revatio ED - Viagra

Tadalafil brand for pulmonary HTN vs erectile dysfunction

Pulmonary HTN - Adcirca, Alyq, Tadliq ED - Cialis

Warnings for PDE-5i

Hearing loss, vision loss (NAION), hypotension, priapism (seek emergency medical care if erection > 4hrs), pulmonary edema

Side effects for PDE-5i

HA, epistaxis, flushing, dyspepsia, extremity/back pain, N/D

Use caution with concurrent use of ___ or other antihypertensives as PDE-5i increase risk of hypotension

Alpha-1 blockers

Soluble guanylate cyclase stimulator examples

Riociguat (Adempas)

Soluble guanylate cyclase stimulator (sGCs) MOA

SGC is a receptor for endogenous nitric oxide Riociguat (Adempas) sensitizes sGC to endogenous nitric oxide and directly stimulates the receptor at a different binding site >> increases cGMP, leading to relaxation

Riociguat is approved for use in both PAH and ___

CTEPH

Boxed warnings for riociguat (Adempas)

Teratogenic, must have negative pregnancy test prior to initiation and monthly REMS program only

Contraindications for riociguat (Adempas)

Pregnancy, use of PDE-5i or nitrates

Warnings for riociguat (Adempas)

Hypotension, bleeding, pulmonary edema

Side effects for riociguat (Adempas)

HA, dyspepsia, dizziness, N/V/D

Riociguat should be separated from antacids by ___

>1hr

Riociguate should not be administered within ___ hrs of sildenafil or within ___ hrs before or ___ after tadalafil

within 24 hrs of sildenafil 24hrs before or 48 hrs after tadalafil

Smoking (increases/decreases) riociguat clearance; dose may need to be (increased/decreased) with smoking cessation

increases decreased

Define pulmonary fibrosis (PF)

scarred and damaged lung tissue

S/sx pulmonary fibrosis

External dyspnea with a nonproductive cough As condition worsens, breathing becomes more labored

Drugs that can cause pulmonary fibrosis

Amiodarone/dronedarone Bleomycin Busulfan Carmustine Lomustine Other: nitrofurantoin, sulfasalazine

Often the contributing factor for pulmonary fibrosis is not identified and it is called idiopathic pulmonary fibrosis (IPF). What are the 2 drugs no available for IPF?

Pirfenidone (Esbriet) and nintedanib (Ofev) - slows the rate of decline in lung function

Which meds for PAH require monthly pregnancy tests + REMS?

ERAs - Bosentan, ambrisentan, macitentan sGC stimulator - Riociguat

Patient failed on diltiazem treatment for PAH but is currently on a nitrate. Which meds can they NOT use?

Riociguat and PDE-5i