Pulmonary Arterial HTN Flashcards
What is Pulm HTN and how do we diagnose
High BP in the pulmonary arteries
Dx using right heart catheterization if mPAP> 25 mmHg in a pt with normal fluid status (normally 8-20 mmHg)
very hard to manage and drugs have a lot of SE
There are 5 groups of PAH, what is group 1
Group 1 is the standard PAH we might see. it includes idiopathic, heritable, drug and toxin induced, disease associated (ex: connective tissue disease, HIV infection, portal HTN), and persistent pulmonary HTN of a newborn
What drugs cause PAH
cocaine and methamphetamines
SSRIs used during pregnancy (increase risk of persistent PAH in newborn)
Weight loss drugs (ex: phentermine)
most common cause of death in PAH patients
right heart failure - develops when the PAH causes thickened walls, challenges pumping blood from right ventricle and then right ventricle enlargement -> failure
symptoms of PAH
fatigue, dyspnea, chest pain, syncope, edema, raynauds phenomenon (numbness/tingling fingers because of decreased oxygenation from blood)
Pathophysiology of PAH
imbalance of vasoconstrictors (increased endothelin1 and thromboxane A2) and vasodilators (decreased prostacyclins), which leads to increased pressure in the pulmonary artery
also imbalance of proliferation and apoptosis leads to arteries thickening and scar tissue forming . both of these contribute to the increase pressure.
The right ventricle has trouble pumping blood, so it becomes englarged and then that leads to right heart failure and death because the right side is the first place where deoxygenated blood comes into heart from the lungs
PAH patients are at higher risk of thrombosis because of the way increased vasoconstriction and decreased vasodilation is so we need to put most patients on
warfarin w an INR goal of 1.5 -2.5
non drug tx in PAH
- not very effective
- use sodium restricted diet (< 2.4 g/day) to help manage volume status. esp. if they have right heart failure
- immunizations (pneumonia and flu)
- O2 used if O2 sat < 90%
what drugs should be avoided in PAH
NSAIDS because they increase sodium and water retention
there is no cure, without treatment life expectancy is
3 years. Heart or lung transplant is an option for younger patients
How do we determine what treatment to use
Their response to the right heart catheterization vasoreactivity test:
(short acting vasodilators: IV epoprostenol or IV adenosine)
will tell us which vasodilator too use:
if mPAP falls by at least 10 mmHg to an absolute value < 40 mmHg, the patient is a RESPONDER to CCBs (nifedipine, diltiazem, or amlodipine (verapamil is not recommended cause its more negative ionotropic and we want to avoid that in HF pts)
* if pt stops responding to CCB, give them the non responder treatment
NONRESPONDERS:
Treat with more potent vasodilators like
***prostacyclin analogues (IV endothelin receptors can reduce mortality)/receptor agonists –> great for severe pts
endothelin receptor antagonists (ERAs)
phosphodiesterase-5 (PDE-5) inhibitors
and/or soluble guanylate cyclase inhibitors
IF they don’t respond, try an additional medication or titrate the current regimen, or do a completely different drug
Supportive therapy for PAH
loop diuretics for volume overload
digoxin to improve cardiac output or control heart rate in afib.
warfarin because of the decreased vasodilator and increased vasoconstrictor.
SE of prostacyclin analogues and warnings
- they are platelet inhibitors and potent vasodilators of the pulmonary and systemic system
- dizziness, flushing, HA, hypotension
- GI
- Anxiety, chest palpitations
- edema
- jaw pain
- neuropathy
- inj site pain with SC treprostinil (remodulin)
- coughing with inhaled products (iloprost, tyvaso)
Warning:
-vasodilation, rebound PH with interruptions to infusions or large decrease in doses
- increased risk of bleeding bc they are platelet inhibitors
- Chronic infusion can lead to blood stream infection
- The effects of antiHTN, anticoags, and antiplatelets can be enhanced
Epoprostanil (Flolan, Veletri akak “prostacyclin”) dose and counseling
2 ng / kg/min increase by 1-2 ng/kg/min in 15 min intervals (usually dosed 25-40 ng/kg/min)
- super short half life (5 min), when we give IV via central venous catheter, we need to start slow and increase slowly AND NEVER MAKE ABRUPT STOPS. IF they run out of drug we will see rapid spiraling, acute HF, flash pulm edema. usually pulm HTN pts cary around this for life.
- doses should only be changed under a physician or pharmacist supervision
-educate pts who compound their own parenteral administration doses, make sure to use central line or change the IV cassette or SC syringe q1-3days depending on the product or route - pts should always have access to a back up pump
MUST BE PROTECTED FROM LIGHT during infusion and before reconstituting
Contraindicated in HF with decreased left ventricular ejection fraction
Treprostinil dosage forms and brand names, strengths, and CI
Remodulin - the continuous SC or IV 1.25 ng/kg/min
Tyvaso - the inhalation 18 mcg (3 inhal.) 4x/day and increase q2wks up to 54 mcg (9 inhalations) 4 times/day (coug/mouth throat irritation expected)
Orenitram (oral, ER tablet) 0.25 mg BID
prostacyclin analogues
Contraindicated in severe hepatic impairment (Child- Pugh class C)
Warning: the oral tablet shell doesn’t dissolve (ghost tablet) and can lodge in diverticulum
- levels are increased with CYP 28C inhibitors and decreased with inducers
Iloprost (Ventavis)
Inhalation 2.5 - 5 mcg/ inhalation 6-9 x/day no more than once q2hrs
prostacyclin analogue
Selexipag (Uptravi)
Tablet 200 mcg BID
avoid with strong CYP28C inhibitor
Endothelin receptor antagonists (ERA’s)
they block endothelin, a vasoconstrictor with proliferative effects. all tablets
Bosentan (Tracleer)
Bosentan decreases effectiveness of hormonal contraceptives
CYP2C9 and CYP 3A4 inhibitors increases levels of bosentan because its a substrate and inducer - most drug interactions of all ERAs. boxed warning for serious hepatotoxicity
Ambrisentan (Letairis)
cyclosporine increases serum conc. of this, so limit dose to 5 mg daily
Macitentan (Opsumit) - substrate of cyp3a4, avoid with srtong inhibitors/inducers
Boxed warning - teratogenic (REMS) requires negative pregnancy test. and Bosentan can cause SERIOUS HEPATOTOXICITY
SE: HA, edema, Hypotension, flushing
PDE’S
cause pulmonary vasculature relaxation and vasodilation
SE: dizziness, hypotension, and HA
CI: nitrates
Sildenafil (Revatio) 20 mg TID 4-6 hours apart
Tadalafil (Adcirca) 40 mg daily, avoid if Crcl < 30 ml/min
Soluble guanylate cyclase stimulato
Riociguat (adempas)
- SO MANY DRUG INTERACTIONS (pdes, pregnancy, Nitrates)
pulmonary fibrosis and what drugs cause it and what treats it
- dyspnea on exertion with non productive cough. poor prognosis (5 year survival is 20-30 %)
drugs that cause:
- amiodarone/dronedarone
- bleomycin
- methotrexate
- nitrofurantoin
- sulfasalazine
drugs that treat it:
chronic oxygen supplementation
Pirfenidone (esbriet)
Nintedanib (ofev)
these slow the rate of decline in lung fx
sometimes sildenafil could work
