PHARM Pulmonary HTN (Wolff)

Question 1

Who is the common demographic for pulmonary arterial HTN?

Answer 1

young women

Question 2

What is the definition of pulmonary arterial HTN?

Answer 2

sustained elevation of mean pulmonary arterial pressure >25mmHg at rest

Question 3

Major causes of PAH?

Answer 3

Vasoconstriction

Inflammation

Localized thrombosis formation

Obstructive remodelling of pulm vessel walls

Question 4

Complications of progressively increasing pulmonary vascular resistance (PVR)?

Answer 4

RV overload –> RVF –> death

mean survival without treatment is less than 3yrs

Question 5

What are some characteristic histopathological features associated with PAH?

Answer 5

Plexiform lesions

intimal and medial thickening

medial and smooth muscle hypertrophy

Question 6

What are the common s/s of pHTN?

Answer 6

EARLY:

DOE, fatigue, chest pain, tachycardia, anorexia, URQ pain

PROGRESSIVE:

syncope/near-syncope, edema, cyanosis

Question 7

What is the first gene linked to pHTN?

Answer 7

BMPR2

Question 8

What common drug causes weight loss and pHTN?

Answer 8

fen/phen

Question 9

What is the vasopressor test?

Answer 9

short acting vasodilator is administered

test is positive if PAP falls >10

MPAP <40

CO is unchanged or increased

Question 10

Some positive responders to the vasopressore test will achieve sustained functional improvement and prolonged suvival with what drug?

Answer 10

CCB: nifedipine, amlodipine, diltiazem

will be deleterious in non-responders

Question 11

What drugs do not help pHTN?

Answer 11

anticoagulants

diuretics

O2 therapy

Question 12

What is the MOA of prostanoids (or prostacyclin analogs)?

Answer 12

promotes vascular relaxation

increases cAMP

ROA: continous IV or intermitten nebulizer

Question 13

What are the effects of prostanoids?

Answer 13

lowers pulmonary arterial resistance

decreases pulmonary arerial pressure

increases exercise tolerance

improves survival

Question 14

Epoprostenol has a (short or long) half life?

Answer 14

short half life

must be given by IV continuously and kept cold

Question 15

What are some serious adverse effects of epoprostenol?

Answer 15

sepsis

life-threatening if pump problems ensue

Question 16

What are the pharmokokinetics of treprostinil?

Answer 16

given SUBQ but caused too much pain, so given with IV pump

longer half life, no refrigeration

can do QID inhalation

extended release oral form avaialble

Question 17

What are the adverse effects for treprostinil?

Answer 17

sepsis

jaw pain

cough/throat irritation

Question 18

How is iloprost administered?

What are some adverse effects?

Answer 18

inhalation 6-9x per day

fainting from hyptension, jaw pain

Question 19

Selexipag is a prostanoid that can be administered (oral or IV)?

common adverse effect?

Answer 19

Orally, BID

$$$

typically given when Pt/caregiver refuses IV

Jaw pain

Question 20

Bosentan is an endothelin antagonist that blocks what?

Answer 20

blocks nonspecifically ETa and ETb receptors

Question 21

What are some toxicities of bosentan?

Answer 21

hepatotoxicity

teratogenesis (Preg Cat X)

accelerates warfarin metabolism and oral contraception

Question 22

Ambrisentan is an endothelin antagonist that blocks what?

What are the main adverse reactions?

Answer 22

Eta selectively

teratogenesis, no liver damage, does not interfere with warfarin, but still must use 2 forms of birth control (due to teratogenesis)

Question 23

Macitentan is an endothelin antagonist that has what benefit?

Answer 23

18hr half life allowing for once/day dosing

Question 24

Silidenafil blocks what?

what can it cause if combined with a-blockers or nitrates?

Answer 24

selectively blocks PDE 5

can cuase significant hypotension

Question 25

What is the MOA of riociguat?

Answer 25

sensistizes sGC to endogenous NO by stabilizing the NO-sGC

increases cGMP to increase vasodilation

Question 26

In patient with naive PHTN with WHO FC II and patient is able to tolerate combination therapy, treat with what?

If they are unable to tolerate combo therapy, treat with what?

Answer 26

ambristentan and tadalafil

Monotherapy with macitentan, ambrisentan, riocguat, sildenafil, or tadalafil

Question 27

In pt with naive PAH with WHO FC III w/o evidence of rapid dz progression who is able to take combo theraoy, treat with what?

If unable to take combo therapy?

Answer 27

ambrisentan and tadalfil

Monotherapy with macitentan, ambisentan, riociguat, sildenafil, or tadalafil

Question 28

In pt with naive PHTN with WHO FC III with evidence of rapid dz progression and able to take parenteral prostanoids, treat with

IF unable to take parental prostanoids, take

Answer 28

IV epoprosteonol, IV treprostinil, or SC treprostinil

inhaled or oral prostanoid

Question 29

In pt with pHTN with WHO FC IV and able to take parenteral prostanoids, treat with waht?

If unable to take parentarel prostenoids, tx with?

Answer 29

IV epoprostenol, IV treprostinil, or SC treprostinil

inhaled prostanoid + oral PDE5 inhibitor and oral ET antagonist

Question 30

What is the strategy for pts with unacceptable clinical status desptie established PAH-specific monotherapy?

What if they are deteriorating on established PAH-specific therapy with two classes?

Answer 30

Add a second class

Add a third class

Question 31

What is the most common pHTN drug combo?

Answer 31

tadalafil + ambrisentan

Question 32

What are the prostanoids?

Answer 32

P for prostanoids

epoprostenol

treprostinil

iloprost

selexipag (haha!)

Question 33

What are the PDE5 inhibitors

Answer 33

sildenafil

tadalafil

Question 34

what are the endothelin antagonists?

Answer 34

E for endothelin

bosentan

ambrisentan

macicentan

Question 35

What is the guanylate cyclase sensitizer

Answer 35

riociguat