Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PH > PH Meds > Flashcards

PH Meds Flashcards

1
Q

Differentiate dosing of the PDE5i

A

Tadalafil (adcirca) 20-40mg daily
t1/2 15-17 hours

Sildenafil 20-80mg TID
t1/2 4 hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which classes of PH drugs work on NO pathway

(a) Mechanism of vasodilation

A

iNO pathway drugs

-PDE5 present in pulmonary vasculature to breakdown cGMP. So PDE5i reduce breakdown of cGMP => more cGMP => smooth muscle relaxation = vasodilation
-sGC agonist (riociguat) works slightly up-stream of PDE5i. Sensitizes soluble guanylate cyclate to NO and activates sGC (independently of NO) to increase cGMP production => smooth muscle relaxation = vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Drug-drug interactions to consider with PDE5i

A

PDE5i
-contraindicated with riociguat due to hypotension = category X
-consider not using with protease inhibitors (HIV patients) = category D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Adverse effects of PDE5i

A

Both sildenafil and tadalafil:

Common: headache, flushing, hypotension
Uncommon: hearing/vision loss (can be unilateral and irreversible)m epistaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which PDE5i requires renal dose adjustment

A

Tadalafil requires renal dose adjustment, sildenafil does not

CrCl < 50 consider maxing out dose of tadalafil at 20mg daily or 40mg q48h

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Compare PDEi onset of action and half-life

A

Both sildenafil and tadalafil onset of action ~60 minutes

Sildenafil t1/2- 4 hours
Tadalafil t1/2- 15-17 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Riociguat starting dose

A

Riociguat: starting dose generally 1 mg TID (or 0.5mg TID if c/f hypotension)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Riociguat max dose

(a) Uptitration schedule

A

Riociguat: starting dose generally 1 mg TID (or 0.5mg TID if c/f hypotension)

(a) Uptitrate by 0.5mg q2-4 weeks as BP tolerates to max 2.5mg TID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Contraindications to riociguat

A

Riociguat contraindications
-pregnancy
-concomitant use of PDE5i due to hypotension
-ILD-PH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

2 FDA-approved indications for riociguat

A

Riociguat FDA-approved indications

  1. CTEPH
  2. Group I (idiopathic) PAH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How to cross-titrate PDE5i to riocguat for CTEPH

A

Riociguat is a better drug for CTEPH- so if on PDE5i then consider transition

Sildenafil stop 24 hrs, tadalafil stop 48 hrs before initiating riociguat (1 mg TID generally starting dose unless c/f hypotension 0.5mg TID)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Exact mechanism of adempas

A

Adempas = riociguat
soluble guanylate cyclase agonist

  1. stabilizes No-sGC binding to sensitize soluble guanylate cyclase to soluble NO
  2. independent of NO, directly stimulates soluble guanylate cyclase to make more cGMP

More cGMP => vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Compare mechanism of adempas and adcirca

A

iNO pathway drugs

-PDE5 present in pulmonary vasculature to breakdown cGMP. So PDE5i reduce breakdown of cGMP => more cGMP => smooth muscle relaxation = vasodilation
-sGC agonist (riociguat) works slightly up-stream of PDE5i. Sensitizes soluble guanylate cyclate to NO and activates sGC (independently of NO) to increase cGMP production => smooth muscle relaxation = vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Dosing algorithm for sildenafil

A

Initiate at 20mg TID, then increase (as BP tolerates) by 20mg q month to maximum 80mg TID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Side effects of ERAs

A

ERAs side effects (ambristentan, macitentan, bosentan)
-fluid retention = edema, swelling
-transaminitis: worst with bosentan so bosentan requires monthly LFTs
-anemia (~1 point drop in Hgb)
-upper respiratory infections: bronchitis, naso/pharyngitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Compare dosing regimens for the 3 ERAs

A

ERA dosing

Ambrisentan- start 5mg daily, after a month increase to 10mg daily
Macitentan- 10mg daily
Bosentan- start 62.5mg BID, after a month increase to 125mg BID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which ERAs has the most drug-drug interactions

A

Bosentan has the most DDIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

ERAs require what baseline bloodwork?

A

All ERAs require baseline hCG
Bosentan has highest hepatotoxicity risk => requires monthly LFTs

19
Q

Off-label use for bosentan

A

Bosentan off-label used for Raynaud’s and digital ulceration in systemic sclerosis

20
Q

Differentiate mechanism of the ERAs

A

Endothelin receptor antagonists

Bosentan and macitenan inhibit endothelin receptor A and B (nonselective)
Ambrisentan more selective, inhibits only endothelin receptor A (ETa)

21
Q

Match class of PH drug with side effect

(a) Anemia
(b) Hearing loss
(c) Bleeding
(d) Jaw pain

A

PH drug side effects

(a) 1 point drop in Hb expected from ERAs
(b) Hearing loss can be seen in PDE5i
(c) Bleeding in prostacyclin analogues because inhibits platelet aggregation
(d) Jaw pain in prostacyclin analogues

22
Q

Explain mechanism of ERAs

A

Endothelin receptor antagonist- blocks endothelin receptors A and B on vascular smooth muscle to block smooth muscle proliferation and vasoconstriction

23
Q

Mechanism of uptravi

A

Uptravi- selective IP receptor agonist to activate intracellular adenylyl cylase to make more cAMP => vasodilation

24
Q

Mechanism by which selexipag can increase bleeding

A

Activates prostacyclin receptor which => vasodilation and inhibits platelet aggregation

25
Q

Main side effects of selexipag

A

Selexipag side effects, same as other prostacyclins

-flushing, headache, jaw pain
-GI: nausea, vomiting, diarrhea

26
Q

Dosing regimen for selexipag

A

Selexipag (uptravi) start at 200mcg BID, increase by 200mcg BID weekly to goal dose 1,600mcg BID

-monitor for GI intolerance

27
Q

DDI to be aware of for uptravi

A

Uptravi and plavix (clopidogrel): for pts on plavix dose reduce uptravi to daily (insteaad of BID) due to reduced hepatic clearance of uptravi’s activate metabolites

28
Q

Describe mechanism of 3 drugs that work on NO pathway

A

NO activates soluble guanylate cyclase (sGC) to generate more cGMP. cGMP –> arteriole smooth muscle relaxation

  1. iNO
  2. sGC stimulator = riociguat
  3. PDE5i reduces degradation of cGMP
29
Q

Differentiate mechanism of the three ERAs

A

Endothelin receptor antagonists b/c endothelin is a potent vasoconstrictor and smooth muscle mitogen
(PH pts overexpress endothelin in lung and plasma)

-both bosentan (tracleer) and macitentan (opsumit) block both endothelin A and B receptors
While
Ambristentan (letairis) blocks endothelin A selectively

30
Q

Mechanism of prostacyclin pathway medications

A

Prostacyclins bind IP receptors to increase cAMP => pulmonary vasodilation

31
Q

Half life of flolan vs. remodulin

A

Flolan (IV epoprostinil) half life < 5 mins

While remodulin (IV treprostinil) has a half life of ~3 hrs

32
Q

Mechanism of vision changes 2/2 tadalafil

A

PDE6 inhibition in the retina => vision changes

33
Q

RESPITE ERJ 2017

(a) Main outcomes

A

RESPITE- ERJ 2017

Switching from PDE5i to riociguat in pts who don’t reach treatment goals with PDE5i
51 patients completed, most on concomittant ERAs

(a) improved 6MWT by 31m, proBNP decreased by 347, WHO FC improved in half

34
Q

Timeline to switch PDE5i to ERA (how long should the transition take)

A

in RESPITE (ERJ 2017, trial that showed benefit in 6MWT, reduction in BNP, improved FC in half): 1-3 day PDEi free period then riociguat adjusted to 2.5mg TID max

35
Q

Name of selexipag trial

A

Phase 3 GRIPHON trial (PGI receptor agonist in pulmonary hypertension) NEJM 2015

36
Q

GRIPHON trial for selexipag primary outcome

A

GRIPHON trial (PGI receptor agonist in pulmonary hypertension)- NEJM 2015

Primary outcome = composite of death from any cause or complication related to PAH (admission to hospital, progression of disease, need for lung txp listing, requirement of parenteral prostacyclin)
-lower in selexipag group

37
Q

Options for escalation in pts taking ERA/PDE5i

A
  1. Switch NO pathway drug from PDE5i to riociguat based on REPLACE trial (Lancet 2021) that showed clinical improvement in PAH pts (not group II or III) with intermediate risk of 1-yr mortality already on ERA/PDE5i
    -IIb recommendation in ESC/ERS guidelines
  2. Add prostacyclin pathway drug
    -IIa recommendation
38
Q

REPLACE trial (PDE5i to Riociguat)

(a) Pt selection
(b) Primary outcome
(c) Clinical takeaway

A

REPLACE trial- Lancet 2021

(a) 225 adults with PAH (excluded if significant lung or L heart disease) already on ERA/PDE5i with intermediate risk of 1-year mortality

(b) Primary outcome- clinical improvement based on 6MWD, WHO FC, NT pro-BNP
-better in riociguat
-fewer adverse events in riociguat

(c) Strategy for escalation of therapy in PAH pts on ERA/PDE5i is to switch NO pathway agent from PDE5i to riociguat

39
Q

Which ERA has the best tolerability profile? In what 3 adverse events?

A

Macitentan better tolerated than both ambrisentan and bosentan (bosentan the worst) in
- LE edema
- LFT abnormality
- equal Hb drop

40
Q

Differentiate ETA and ETB receptors- which is impacted by which ERAs?

A

ETA (endothelin receptor A) is on vascular smooth muscle and mediates vasoconstriction
- hence why ambrisentan (made 2nd) was made ETA selective but that didn’t pan out to be better

ETB on endothelial cells regulates endothelin clearance and NO/PGE release

Macitentan and bosentan both ETA/ETB, while ambrisentan is ETA selective

41
Q

Differentiate half life of flolan and IV remodulin

A

Half life

IV flolan (epoprostenol) < 6 mins
IV treprostinil (remodulin): 34 minutes
(vs. 85 minutes of subQ remodulin)

42
Q

Differentiate half life of IV and subQ remodulin

A

Half life

IV flolan (epoprostenol) < 6 mins
IV treprostinil (remodulin): 34 minutes
(vs. 85 minutes of subQ remodulin)

43
Q

Risk of interruption or withdrawal of IV prostanoids

A
44
Q

How to minimize infusion site pain/reaction of subq mode of administration

A

Not dose dependent! So answer isn’t to lower the dose of remodulin

Instead manage with local, topical, or systemic analgesics

PH (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions