Pulmonary Arterial Hypertension Flashcards
class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
(PH) Pulmonary Hypertension:
is characterized by continuous high blood pressure in the pulmonary arteries.
A normal pulmonary artery pressure (PAP) ranges from:
8 - 20 mmHg when resting
PH is defined as a mean PAP (mPAP) of ____________
> or equal to 25 mmHg in the setting of normal fluid status
The WHO classifies pulmonary hypertension into 5 groups:
Group 1-
Group 2-
Group 3-
Group 4-
Group 5-
*Group 1- pulmonary arterial hypertension (PAH) with No identifiable cause
Group 2- pulmonary hypertension due to Left Heart Disease
Group 3- pulmonary hypertension due to lung diseases (COPD, pulmonary fibrosis, emphysema) and/or hypoxia
Group 4- (CTEPH) Chronic Thromboembolic Pulmonary Hypertension, which occurs in a minority of pulmonary embolism survivors. (Warfarin, with an INR goal of 2-3 is recommended for CTEPH)
Group 5- pulmonary hypertension with unclear or multifactorial mechanisms that DO NOT fit in the other group categories (ex sarcoidosis)
When there is no identifiable cause, it is called _________
primary or idiopathic
Hypoxia -
an absence of enough oxygen in the tissues to sustain bodily functions.
How is PAH diagnosed? How do we know the mPAP is elevated?
we have to do a right heart catheterization
During the right heart catheterization, short acting vasodilators (________) are administered for __________
If the mPAP falls by at least ___________ to an absolute value ______________, then the patient is considered a responder, and should be initially treated with __________.
(inhaled nitric oxide, IV epoprostenol, or IV adenosine)
vasoreactivity testing
10 mmHg
less than 40 mmHg
oral calcium channel blocker
-
-
- cocaine & methamphetamines
- SSRI use during pregnancy, can lead to PH in the newborn
- Weight loss drugs (phentermine, phendimetrazine, dithylpropion and others)
Pulmonary Arterial Hypertension stems from the imbalance in __________ and __________.
__________ are increased
_________ are decreased
There is also an imbalance of _________ and _________.
This leads to __________
This results in _________
vasoconstrictors
vasodilator substances
vasoconstrictors
vasodilator substances
-proliferation & apoptosis
-Arteries thicken and scar tissue forms. As the walls thicken and scar, the arteries become increasingly narrower. With these changes it makes it more difficult for the right ventricle to pump blood.
- increased pressure in pulmonary vasculature. Which makes it difficult for the right ventricle to pump blood through the pulmonary arteries and into the lungs due to this increased pressure. As a result of the right ventricle working harder, it becomes enlarged and right heart failure develops.
“if right ventricle is failing, blood backs up behind it, stretching things out”
Vasoconstrictor substances include:
endothelin-1
thromboxane A2 (TXA2)
which are increased in PAH
Vasodilator substances include
prostacyclins
which are decreased in PAH
__________ 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
-
-
-
-
- sodium restricted diet of < 2.4 grams per day to help manage volume status
-Avoid certain medications like NSAIDs (which increase sodium and water retention) - routine immunizations against annual influenza and pneumococcal pneumonia
Drug treatment algorithm:
Drug Treatment for PAH: what are the classes of medications approved for PAH?
warfarin +/- loop diuretics +/- oxygen +/- digoxin
(loop diuretics for volume overload)
(digoxin to improve cardiac output or control heart rate in afib)
right heart catheterization AND acute vasoactive testing (when MD gives patient vasodilator)
*cause remember the vasoconstriction is predominating in pulmonary vasculature of PAH”
if patient is a responder (+) ——> Oral CCB (nifedipine ER, diltiazem, amlodipine), verapamil NOT recommended
if patient not a responder (-) ——> Initiate a PAH-approved drug
- prostacyclins
- endothelin receptor antagonists
- PDE-5 inhibitors
- soluble guanylate cyclase stimulator
Pulmonary Arterial Hypertension creates a _________.
pro-thrombotic state and increased risk for blood clots.
If warfarin is used for PAH, it should be titrated to an INR goal of
1.5 - 2.5
Digoxin is a positive inotrope. Meaning ________
Increases Force of Ventricular Contraction
Verapamil is a negative inotrope. Meaning ________
Decreases Force of Ventricular Contraction
Negative chronotropes =
Decrease Heart Rate
exs. beta blockers
Positive chronotropes =
Increase Heart Rate
patients who are unable to be physically active and with signs of right heart failure, which may be present at rest.
First line treatment for PAH is an ____________
IV prostacyclin analogue
Prostacyclin analogues:
- are started at a small dose and then slowly increased as patient tolerates
- dose only changed under physician supervision
- Life threatening if stopped suddenly. AVOID interruptions
- parenteral administration
- sterile compounding technique critical
- central line needed for home IV use
- IV cassette or SC syringe changed every 1-3 days dependent upon product and route
- if suddenly stopped, will led to pulmonary edema, serious rapid downward spiral, acute heart failure
Flolan
class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
epoprostenol
aka prostacyclin
class: prostacyclin receptor agonists/prostacyclin analogues
Indications: Pulmonary arterial hypertension
MOA: is a potent vasodilator (of both pulmonary and systemic vasculature) and inhibitor of platelet aggregation.
Dosage forms: Continuous IV infusion via central venous catheter
Dosing:
Start at 2ng/kg/min and increase by 1-2 ng/kg/min in 15 minute intervals based on clinical response; usual dose is 25-40 ng/kg/min (can be higher)
Max dose:
Contraindications:
- (epoprostenol): heart failure with decreased left ventricular ejection fraction
Warnings:
- vasodilation reactions (hypotension, flushing. HA)
- Rebound Pulmonary Hypertension (with interruption of large decrease in dose), which can be fatal
- increased risk of bleeding
- Chronic IV infusions: sepsis and bloodstream infections
Side Effects:
- hypotension, flushing, jaw pain, headache, N/V/D, dizziness, edema
- infusion-site pain
- anxiety, chest pain, palpitations
Monitoring:
Pearls/Notes:
- Must be Protected from light before reconstitution and during infusion
- parenteral agents (Flolan, Veletri, Remodulin) are very potent vasodilators; AVOID interruptions and sudden, large dose reductions
- Flolan requires use of ICE packs for stability
- t1/2 half-life = ~5min
- Due to short half-lives, it is essential to have immediate access to a backup pump, infusion sets and medication
- can be administered by continuous IV infusion at home using an ambulatory infusion pump
- IV cassette or SC syringe changed every 1-3 days depending upon the product and route patient uses
Drug-Drug/Food interactions:
Veletril
class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
epoprostenol
class: prostacyclin receptor agonists/prostacyclin analogues
Indications: Pulmonary arterial hypertension
MOA: is a potent vasodilator (of both pulmonary and systemic vasculature) and inhibitor of platelet aggregation.
Dosage forms: Continuous IV infusion via central venous catheter
Dosing:
Start at 2ng/kg/min and increase by 1-2 ng/kg/min in 15 minute intervals based on clinical response; usual dose is 25-40 ng/kg/min (can be higher)
Max dose:
Contraindications:
- (epoprostenol): heart failure with decreased left ventricular ejection fraction
Warnings:
- vasodilation reactions (hypotension, flushing. HA)
- Rebound Pulmonary Hypertension (with interruption of large decrease in dose), which can be fatal
- increased risk of bleeding
- Chronic IV infusions: sepsis and bloodstream infections
Side Effects:
- hypotension, flushing, jaw pain, headache, N/V/D, dizziness, edema
- infusion-site pain
- anxiety, chest pain, palpitations
Monitoring:
Pearls/Notes:
- **Must be Protected from light before reconstitution and during infusion
- parenteral agents (Flolan, Veletri, Remodulin) are very potent vasodilators; AVOID interruptions and sudden, large dose reductions
- t1/2 half-life = ~5min
- Due to short half-lives, it is essential to have immediate access to a backup pump, infusion sets and medication
- patient can mix product and using clean technique administer at home
- IV cassette or SC syringe changed every 1-3 days depending upon the product and route patient uses. “cassette’s get changed every day”
Drug-Drug/Food interactions:
Remodulin
treprostinil
class: prostacyclin receptor agonists/prostacyclin analogues
Indications: Pulmonary arterial hypertension
MOA: is a potent vasodilator (of both pulmonary and systemic vasculature) and inhibitor of platelet aggregation.
Dosage forms: given via continuous SC pump or IV via central venous catheter infusion.
Dosing: start at 1.25ng/kg/min and increase at weekly intervals, up to 40ng/kg/min (and possibly more)
Max dose:
Contraindications:
- (epoprostenol): heart failure with decreased left ventricular ejection fraction
Warnings:
- vasodilation reactions (hypotension, flushing. HA)
- Rebound Pulmonary Hypertension (with interruption of large decrease in dose), which can be fatal
- increased risk of bleeding
- Chronic IV infusions: sepsis and bloodstream infections
Side Effects:
- hypotension, flushing, jaw pain, headache, N/V/D, dizziness, edema
- infusion-site pain
- anxiety, chest pain, palpitations
Monitoring:
Pearls/Notes:
- parenteral agents (Flolan, Veletri, Remodulin) are very potent vasodilators; AVOID interruptions and sudden, large dose reductions
- t1/2 half-life = ~4 hours
- Due to short half-lives, it is essential to have immediate access to a backup pump, infusion sets and medication
Drug-Drug/Food interactions:
treprostinil levels are increased by CYP2C8 inhibitors (ex. gemfibrozil) AND decreased by CYP2C8 inducers (rifampin).
Tyvaso
treprostinil
class: prostacyclin receptor agonists/prostacyclin analogues
Indications: Pulmonary arterial hypertension
MOA: is a potent vasodilator (of both pulmonary and systemic vasculature) and inhibitor of platelet aggregation.
Dosage forms: inhalation
Dosing:
Max dose:
Contraindications:
- (epoprostenol): heart failure with decreased left ventricular ejection fraction
Warnings:
- vasodilation reactions (hypotension, flushing. HA)
- Rebound Pulmonary Hypertension (with interruption of large decrease in dose), which can be fatal
- increased risk of bleeding
- Chronic IV infusions: sepsis and bloodstream infections
Side Effects:
- hypotension, flushing, jaw pain, headache, N/V/D, dizziness, edema
- infusion-site pain
- anxiety, chest pain, palpitations
- cough with inhaled products
Monitoring:
Pearls/Notes:
- parenteral agents (Flolan, Veletri, Remodulin) are very potent vasodilators; AVOID interruptions and sudden, large dose reductions
- t1/2 half-life = ~4 hours
-
Drug-Drug/Food interactions:
treprostinil levels are increased by CYP2C8 inhibitors (ex. gemfibrozil) AND decreased by CYP2C8 inducers (rifampin).
Orenitram
treprostinil
class: prostacyclin receptor agonists/prostacyclin analogues
Indications: Pulmonary arterial hypertension
MOA: is a potent vasodilator (of both pulmonary and systemic vasculature) and inhibitor of platelet aggregation.
Dosage forms: oral ER tablet
Dosing:
Max dose:
Contraindications:
- (epoprostenol): heart failure with decreased left ventricular ejection fraction
Warnings:
- vasodilation reactions (hypotension, flushing. HA)
- Rebound Pulmonary Hypertension (with interruption of large decrease in dose), which can be fatal
- increased risk of bleeding
- Chronic IV infusions: sepsis and bloodstream infections
Side Effects:
- hypotension, flushing, jaw pain, headache, N/V/D, dizziness, edema
- infusion-site pain
- anxiety, chest pain, palpitations
Monitoring:
Pearls/Notes:
- parenteral agents (Flolan, Veletri, Remodulin) are very potent vasodilators; AVOID interruptions and sudden, large dose reductions
- oral tablet shell does not dissolve (ghost tablet)
-
Drug-Drug/Food interactions:
Ventavis
iloprost
class: prostacyclin receptor agonists/prostacyclin analogues
Indications: Pulmonary arterial hypertension
MOA: is a potent vasodilator (of both pulmonary and systemic vasculature) and inhibitor of platelet aggregation.
Dosage forms: inhalation
Dosing:
Max dose:
Contraindications:
- (epoprostenol): heart failure with decreased left ventricular ejection fraction
Warnings:
- vasodilation reactions (hypotension, flushing. HA)
- Rebound Pulmonary Hypertension (with interruption of large decrease in dose), which can be fatal
- increased risk of bleeding
- Chronic IV infusions: sepsis and bloodstream infections
Side Effects:
- hypotension, flushing, jaw pain, headache, N/V/D, dizziness, edema
- infusion-site pain
- anxiety, chest pain, palpitations
- cough with inhaled products
Monitoring:
Pearls/Notes:
- parenteral agents (Flolan, Veletri, Remodulin) are very potent vasodilators; AVOID interruptions and sudden, large dose reductions
Drug-Drug/Food interactions:
