40. Pulmonary Arterial Hypertension Flashcards
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)
Pulmonary HTN is characterized by mPAP ≥____ (normal range is ___)
≥25mmHg
Normal range 8-20 mmHg
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
____ is the most common cause of death in pts who have PAH
HF
S/sx of PAH
Fatigue, dyspnea
Others: chest pain syncope edema, tachycardia and/or Raynaud’s phenomenon
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
Non-drug treatments for PAH
Sodium restriction (<2.4 grams/day)
Avoid meds that increase sodium/water retention (NSAIDs)
Influenza and pneumococcal vaccines recommended
____ is performed to confirm the diagnosis of PAH
Right heart catheterization
During a right heart catheterization, what meds are administered for vasoreactivity testing?
short-acting vasodilators (e.g. inhaled nitric oxide, IV epoprostenol, IV adenosine)
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
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
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
Parenteral prostacyclin analogues, specifically ___, have shown to decrease mortality
IV epoprostenol
Supportive therapies for PAH may include ___ (for volume overload) and ___ (to improve cardiac output or control HR in Afib)
Loop diuretics
Diogxin
T/F: PAH leads to a higher risk of bleeding
False - leads to a pro-thrombic state and increased risk of blood clots
What is the preferred anticoagulation if needed in PAH pts?
Warfarin
MOA of prostacycline analogues
Potent vasodilators and inhibitors of platelet aggregation
Which prostacyclin analogues can be administered by continuous IV at home using an ambulatory infusion pump?
Epoprostenol and treprostinil
Treprostrinil (Remodulin) starting dose
1.25ng/kg/min, titrate
Epoprostenol (Flolan) starting dose
2ng/kg/min, titrate
CI with epoprostenol
HF with decreased LVEJ
CI with treprostinil (oral)
severe hepatic impairment (Child-Pugh C)
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
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»_space; 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
