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Therapeutics II > Pulmonary Arterial HTN > Flashcards

Pulmonary Arterial HTN Flashcards

1
Q

For PAH tx, ___________

A

there are medications specifically for tx of PAH

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2
Q

AMBITION trial

A
  • 500 tx naive pts
  • in combo group, AE were more common than in monotherapy groups
  • rates of hypotension were similar
  • rates of discontinuation and serious ADRs were similar across all groups
  • thus, reasonable to combine tadalafil + ambrisentan as 1st line therapy
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3
Q

If pts do not improve to functional class I or II after CCB initiation…

A

start additional or alternative PAH therapy

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4
Q

When start intervening for PH?

A

Class II (slight limitation of physical activity - ordinary activity may cause symptoms. Comfortable at rest)

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5
Q

Prostacyclins reserved for WHO…

A

class III and IV pts

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6
Q

Adverse effects of ERA

A
  • HA
  • anemia
  • UTI
  • nasopharyngitis
  • pharyngitis
  • bronchitis
  • peripheral edema
  • increased LFTs (esp bosentan)
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7
Q

What is PAH?

A

progressive disease involving endothelial dysfunction –> elevated pulmonary arterial pressure and pulmonary vascular resistance

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8
Q

Therapeutic pathways for PAH: NO

A
  • PDE5 inhibitors: sildenafil, tadalafil

- sGC: riociguat

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9
Q

Therapeutic pathways for PAH: Prostacyclin

A
  • prostacyclins: epoprostenol (IV), iloprost (inh), treprostinil (IV, SQ, inh, oral)
  • IP prostacyclin receptor agonist: selexipag
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10
Q

Therapeutic pathways for PAH: Endothelin

A

-Endothelin receptor antagonists = bosentan, macitentan, ambrisentan

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11
Q

riociguat cannot be used in combination with ____________

A

tadalafil or sildenafil due to risk of hypotension

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12
Q

How to diagnose PAH

A
  • echocardiogram
  • right heart catheterization (confirms diagnosis)
  • exercise testing (distance walked in 6 minutes)
  • biomarkers (BNP and NTproBNP)
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13
Q

What is riociguat?

A

soluble guanylate cyclase stimulator

alternative to PDE-5i

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14
Q

Guideline recommendation for WHO FC III:

WHO FC III w/ rapid progression or poor prognosis

A
  1. Candidate for parenteral prostanoids
    2a. Yes –> SC treprostinil, IV treprostinil, IV epoprostenol
    2b. No –> Consider inhaled or oral prostanoid (likely in combo w/ ERA + PDE-5i)
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15
Q

What is an acute vasoreactivity test (AVT)?

A

Acute response to pulmonary-specific vasodilators predicts response to CCBs

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16
Q

Prostacyclins are first line if

A

class IV or rapidly progressing class III

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17
Q

Agents during AVT include:

A
  • inhaled NO
  • IV epoprostenol
  • IV adenosine
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18
Q

PAH is _____ and _____

A

fatal ; rare

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19
Q

PH is _____ than PAH

A

more common

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20
Q

When to consider CCBs in PAH pts that have undergone AVT?

A

In positive responders WITHOUT right-sided failure or other contra to CCB (do NOT use w/out positive AVT)

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21
Q

ADRs of prostacyclins

A
  • HA
  • jaw pain
  • thrombocytopenia (more in epoprostenol)*
  • hypotension*
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22
Q

Sildenafil/ERA drug interactions

A
  • sildenafil increases bosentan
  • bosentan decreases sildenafil
  • mechanism: CYP 3A4 interaction
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23
Q

Most common prostacyclin medication errors

A
  • flushing of the line (33%)

- calculation or concentration error (31%)

24
Q

Effects of PAH

A
  • pulmonary arterial wall and its smaller vessels become damaged, restricting blood flow to lungs
  • left heart becomes smaller
  • right heart becomes larger
  • heart wall muscle becomes enlarged
25
Q

Shorthand for pulmonary HTN

A

PH

26
Q

for prostacyclins, do not use….

A

oral, inhaled and parenteral concurrently

27
Q

PAH more prevalent in ________

A

women

28
Q

Recommended CCBs in PAH pts that have undergone AVT

A
  • long acting nifedipine
  • long acting diltiazem*
  • amlodipine*

NO VERAPAMIL due to negative inotropic effects

29
Q

Causes of PAH

A
  • unknown (idiopathic)
  • genetics
  • drug and toxin exposure
  • disease associated w/ PAH: CHD, HIV, connective tissue disorders
30
Q

Key information regarding PGI2 analogs

A
  • prostacyclins require significant education
  • $$$
  • pts should have their own pumps and supplies
  • interview pt, may need to call specialty pharmacy to confirm info
31
Q

Pulmonary HTN is higher than normal BP ___________

A

IN THE LUNGS

not the same as HTN

32
Q

PAH is considered group __ under WHO classification

A

1

33
Q

Prostacyclins may be used in combo with

A

ERA plus PDE-5 or riociguat

34
Q

Bosentan is the __________ but ambrisentan is __________. Bosentan must be ___________

A

original ; studied more ; monitored monthly

35
Q

Prostacyclins available in

A

parenteral (IV, subQ), oral or inhaled formulations

36
Q

What do prostacyclins so

A
  • prostacyclins stimulate cAMP pathway to increase pulmonary vasodilation
  • inhibits platelet aggregation
  • parenteral prostacyclins = standard for severe PH with RV failure (subQ treprostinil is becoming most common)
37
Q

Shorthand for pulmonary arterial HTN

A

PAH

38
Q

Negative predictors of PAH

A
  • advanced functional class
  • poor exercise capacity
  • high right atrial pressure
  • right ventricular dysfunction
  • low cardiac output
  • underlying scleroderma
39
Q

Endothelin Receptor Antagonists

A
  • ET receptors on vascular smooth muscle mediate vasoconstriction
  • blocking ET –> vasodilation
40
Q

prostacyclins (oral) contraindicated with

A

strong CYP2C8 inhibitors (i.e. gemfibrozil)

41
Q

PAH FC I pts ___________ require immediate drug therapy; consider CCB if responder

A

do not necessarily

42
Q

Sildenafil (revatio) more so for __________

A

kids (20mg TID - might see 40 - 80 TID)

43
Q

signs and symptoms of PAH

A
  • fatigue
  • fainting; light-headedness
  • chest pain
  • reported SOB
  • reported palpitations
  • edema
44
Q

PDE inhibition

A
  • decreases conversion of cGMP to GMP
  • increased levels of cGMP –> pulmonary vasodilation
  • can be monotherapy or combo, $$$
  • often considered 1st line*
45
Q

PAH prognosis

A

15% mortality in a year

46
Q

Avoid using Endothelin Receptor Antagonists in

A

hepatically impaired pts

do not initiate if LFT > 3x ULN

47
Q

Pharmacotherapy for PAH

A
  • CCB
  • iNO (inhaled NO)
  • PDE-5 inhibitors
  • Endothelin Receptor Antagonists (ERAs)
  • Prostacyclins (oral, inhaled, parenteral)
  • riociguat
48
Q

All endothelin receptor antagonists are in

A

REMs program

49
Q

prostacyclins (inhaled) [good for IV but don’t want to give IV i.e. can’t manage] examples

A
  • iloprost (ventavis): requires up to 9 doses daily

- treprostinil (tyvaso): 1 ampule = 24 hrs of therapy

50
Q

IV sildenafil

A
  • rare, $$$
  • restricted for pts who are strictly NPO
  • dosing diff from oral
  • must be given as slow infusion
51
Q

must be in the __________ to use prostacyclins

A

hospital

52
Q

Tyvaso more common due to ____________

A
  • less frequent dosing
  • new device can be charged
  • assembling device is hard; done once every day
  • txs throughout the day are 2 - 3 minutes
53
Q

Guideline recommendation for WHO FC IV:

WHO FC IV

A
  1. Candidate for parenteral prostanoids
    2a. Yes –> SC treprostinil, IV treprostinil, IV epoprostenol
    2b. No –> Inhaled prostanoid + ERA + PDE-5i
54
Q

Tadalafil (adcirca) more so for _________

A

adults (40mg QD)

55
Q

Goals of PAH Tx therapy

A
  • alleviate symptoms
  • improve QOL
  • prevent or delay disease progression
  • reduce hospitalization
  • improve survival
56
Q

Guideline recommendation for AVT (acute vasoreactivity testing)

A
  1. Suggest acute vasoreactivity testing
    2a. Positive responder –> Consider CCB (not for kids or infants)
    2b. Negative responder, RV failure, or CCB contraindication –> Do not use CCB
57
Q

PDE-5 Inhibitor ADRs

A
  • flushing
  • HA
  • dyspepsia
  • visual disturbances (blueish vision)
  • tinnitus/hearing loss, sudden vision loss, hypotension*

Therapeutics II (12 decks)

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