Chapter 40: Pulmonary Arterial Hypertension Flashcards
What are common drugs that can cause PAH
- Cocaine
- Methamphetamines/amphetamines
- SSRI use during pregnancy ↑ risk of persistent PH of a newborn
- Weight loss drugs (diethylpropion, lorcaserin, phendimetrazine, phentermine)
PAH stems from an imbalance in vasoconstrictor & vasodilator substances. Vasoconstrictor substances (e.g., ________) are increased and vasodilating substances (e.g., ______) are decreased.
endothelin-1 and TXA2
prostacyclins
_____ is the most common cause of death in people who have PAH
Heart failure
Symptoms of PAH include:
fatigue, dyspnea, chest pain, syncope, edema, tachycardia, and/or Raynaud’s phenomenon
What are some non-drug treatments of PAH
Sodium-restricted diet of < 2.4 grams/day to help manage volume status
NSAIDs, which increase Na and water retention, should be avoided
Routine immunizations against _____ and _____ are advised
influenza, pneumococcal pneumonia
______ is performed to confirm the diagnosis of PAH
Right heart catheterization
If the mPAP falls by at least 10 mmHg to an absolute value less than 40 mmHg during vasoreactivity testing, the patient is considered a ____ and should be initially treated with an oral ____.
responder; CCB (long-acting nifedipine, diltiazem, and amlodipine). Verapamil is not recommended
Non-responders to vasoreactivity testing and positive responders who fail CCB therapy need to be treated with _________
prostacyclin analogues and receptor agonists, endothelin receptor antagonists (ERAs), PDE-5 inhibitors, and/or a soluble guanylate cyclase (sGC) stimulator
Which parenteral prostacyclin analogue has been shown to decrease mortality in PAH
IV esoprostenol
Supportive therapies (similar to systolic HF) include ____ and _____
loop diuretics (for volume overload); digoxin (to improve CO or control HR in AFib)
Biochemical changes (↑ TXA2, ↓ prostacyclin) lead to a pro-thrombotic state and increased risk of blood clots. If warfarin is used for PAH, it should be titrated to a goal INR of:
1.5-2.5
What is the MOA of prostacyclin analogues (prostanoids)
They are potent vasodilators and inhibitors of platelet aggregation
How are epoprostenol and treprostinil administered?
continuous IV infusion at home
What units are epoprostenol and treprostinil dosed in?
ng/kg/min
What are the main warnings of prostaglandin analogues
- vasodilation reactions (hypotension, flushing)
- rebound PH
- Chronic IV influsions: sepsis and blood stream infections
What are the main side effects of prostaglandin analogues
Hypotension
flushing
jaw pain
infusion-site pain with IV/SC infusions
What is the brand name for epoprostenol
Flolan
Since parenteral prostaglandin analogues are very potent vasodilators, what should be avoided
interruptions and sudden, large reductions in dose
Which prostaglandin analogue should be protected from light before reconstitution and during infusion
Epoprostenol
Reconstituted formulations of Flolan require use of ___ for stability
ice packs
Endothelin receptor antagonists such as bosentan, ambrisentan, and macitentan have a boxed warning for:
Teratogenic; women of childbearing potential must have a negative pregnancy test prior to initiation of therapy and monthly thereafter. All are only available through a REMS program
Bosentan has a boxed warning of
hepatotoxicity
Endothelin receptor antagonists are CI in
pregnancy
What are the main warnings of Endothelin receptor antagonists
hepatotoxicity, ↓ Hgb/Hct, fluid retention
Main side effect of Endothelin receptor antagonists
headache
Bosentan can decrease the effectiveness of which drug class
hormonal contraceptives
What is the MOA of PDE5-i
Blocks the degradation of cGMP. Increased cGMP concentrations lead to pulmonary vasculature relaxation and vasodilation
What is the brand name for sildenafil in PAH
Revatio
What is the brand name for tadalafil in PAH
Adcirca
What drug class is CI with PDE5-i
Use with nitrates
What are the main warnings for PDE5-i
Hearing loss, vision loss (NAION), hypotension, priapism
What is the main SE of PDE5-i
Headache
What is the MOA of the soluble guanylate cyclase, Riociguat
sensitizes sGC to endogenous nitric oxide and directly stimulates the receptor at a different binding site. This increases cGMP, leading to relaxation and antiproliferative effects in the pulmonary artery smooth muscle cells
What is a boxed warning for Riociguat (Adempas)
Teratogenic; women of childbearing potential must have a negative pregnancy test prior to initiation of therapy and monthly thereafter. Only available through a REMS program
What is a CI for riociguat
Pregnancy, use of a PDE5-i or nitrates
What is the main warning for Riociguat
Hypotension
What is the main SE for Riociguat
Headache
The common presentation for pulmonary fibrosis is
external dyspnea with a non-productive cough
Common drugs that can cause pulmonary fibrosis
Amiodarone/dronedarone Bleomycin Busulfan Carmustine Lomustine
