Medications for Pulmonary Hypertension & Artificial Surfactants

what are the three primary therapies for pulmonary hypertension?

1. diuretics

2. oxygen therapy

3. anticoagulation

what are the five advanced therapies that is directed at the pulmonary hypertension itself?

1. Prostacyclin pathway agonists.

2.Endothelin receptor antagonists.

3. PDE5 inhibitors.

4. Guanylate cyclase stimulants.

5. Calcium channel blockers, used rarely.

what do all of these drugs have in common?

1.Prostacyclin pathway agonists.

2.Endothelin receptor antagonists.

3. PDE5 inhibitors.

4. Guanylate cyclase stimulants.

5. Calcium channel blockers, used rarely.

VASODILATORS

What are the two physiological effects of Prostacyclin?

strong vasodilator & inhibition of platelet aggregation

T/F: Prostacyclin is a natural endogenous prostaglandin

true

what are examples of prostacyclin pathway agonist?

-epoprostenol= IV

-Treprostinil= IV or SQ

-Remodulin= inhalation

-Tyvaso= oral

-Iliprost= oral

-Selexipag= oral

what are the adverse effects of prostacyclin pathway agonist?

-HA/D/Flushing= related to vasodilation

-muscle aches & jaw pain

T/F: edothelin-1 is a potent vasoconstrictor; high concentrations of ET-1 have been found in the lungs of many pt with idiopathic PAH

true

what are the two types of receptors for ET-1?

endothelian receptor A & B

What are two oral medications the block both endothelin receptor A & B?

bosentan & macitentan

what is an oral medication that is selective for endothelin receptor A?

ambrisentan

what is the name of the drug that was withdrawn from the EU due to several fatal cases of hepatoxicity?

sitaxsentan

what are the main adverse effects for endothelin receptor antagonist?

-hepatoxicity

-peripheral edema

T/F: AMBRISENTAN is the least hepatoxic ERA:; Bosentan is the most hepatotoxic ERA

true

T/F: Macitentan is the least likely to cause edema

true

if a pt has mild swelling what type of drugs can it be treated with?

diuretics

if a pt has severe cases of edema what should you advise your pt to do?

discontinue medication

T/F: all ERAs are also potent teratogens

true

what is the box warning for ERA's?

-Exclude pregnancy before treatment.

-Test monthly during treatment.

-Continue pregnancy testing for one month after stopping.

-Use reliable contraception during treatment and for one month afterward.

T/F: when taking ERA's medication must use two reliable methods of contraception

true

T/F: Pt's that have undergone tubal ligation, IUD, or contraceptive implant do not require contraceptive measures

true

What are examples of PDE-5 inhibitors?

sildenafil, vardenafil, tadalafil, avanafil

what do PDE-5 inhibitors treat?

erectile dysfunction

T/F: tadalafil a PDE-5 inhibitors has a longer duration of action (36 hrs)

true

T/F: avanafil a PDE-5 inhibitors has a rapid onset of action (15 min)

true

what are the three parallel musculature structures of the penis?

-2 corpora cavernosa

-1 corpus spongiosum

T/F: PDE-5 Inhibitors act to increase intracavernosal cyclic GMP levels which leads to continued relaxation of smooth muscle of the corpora cavernosa & corpus spongiosum, thereby maintaining elevated blood flow of penis

true

What are the two PDE-5 inhibitors approved by the FDA treatment for idiopathic PAH?

Sildenafil & tadalafil

what is a contraindication for PDE-5 inhibitors?

hypotension, reflex tachycardia, and worsening angina

what are the common adverse effects for PDE-5 inhibitors?

flushing, headache, dyspepsia

What is the name of the drug that is a GC stimulant?

riociguat

what are the common adverse effects for riociguat a GC stimulant?

syncope, headache, dizziness, NVD, bleeding

T/F: Riociguat GC stimulant should not be used in conjunction w/ PDE-5 inhibitor

true

T/F: Riociguat GC stimulant should be used w/ caution in those patient w/ hepatic and/or renal impairment

true

T/F: Prior to starting Riociguat GC stimulant should have a negative pregnancy test and should continue monthly during treatment and one month after discontinuing therapy. Should not become pregnant after one month d/c.

true

What do calcium channel blockers do (CCBs)?

dialate peripheral arterioles and can exert cardiac depressant activity

MOA for calcium channel blockers do (CCBs)?

inhibit calcium influx into arterial smooth muscle ( to produce vasodilation) and/or cardiac muscle and nodal cells (to decrease stroke volume and heart rate)

what are the two basic types of calcium channel blockers do (CCBs)?

non-dihydropyridines & dihydropyridines

what do non-dihydropyridines do?

block calcium channels in vascular smooth muscle and cardiac muscle

what are the two medications that are non-dihydropyridines do?

diltiazem & verapamil

what do dihydropyridines drugs do?

greater affinity for blocking vascular calcium channels in the heart, more selective and potent vasodilators and less cardiac effect

what is an example of first generation dihydropyridines drug?

Nifedipine

what are examples of 2nd Gen dihydropyridines drug?

amlodipine, felodipine, isradipine "-dipine drugs"

what are the most common frequently used drugs for calcium channel blockers do (CCBs)?

diltiazem & nifedipine; amlodipine as an alternative

what are the most common side effects for calcium channel blockers (CCBs)?

-vasodilation, headaches, dizziness, facial flushing, peripheral edema (occur less w/ slow release)

what other side effects occur at higher dose of calcium channel blockers drugs (CCBs)?

constipation & nausea, gingival hyperplasia

what are artificial surfactants mainly composed of?

phospholipid suspensions

what are artificial surfactants used for?

prevention and treatment of respiratory distress syndrome in premature infants

what are three examples of artificial surfactants?

beractant, poractant alfa, calfactant