Drugs for Pulmonary Hypertension and DVT/PE (Wolff) Flashcards
What are the 5 drug classes used to treat Pulmonary Hypertension? (P/EA/PI/GCS/C)
prostanoids, endothelin antagonists, PDE 5 inhibitors, Guanylate cyclase sensitizers, CCBs
What are the 4 Prostanoids used for Pulmonary Hypertension? (E/T/I/S)
epoprostenol
treprostinil
iloprost
selexipag
What are the 3 Endothelin antagonists used for Pulmonary Hypertension? (B/A/M)
bosentan
ambrisentan
macicentan
What are the 2 PDE 5 inhibitors (S/T) and what is the 1 guanylate cyclase sensitizer (R) used for Pulmonary Hypertension?
PDE 5 –> sildenafil and tadalafil
GCS –> riociguat
What is a known genetic mutation that is linked to PAH and what are two drugs that can cause PAH? (Fen/Phen)
Genetics: BMPR2 (bone morphogenic protein receptor 2)
- seen in < 25% of idiopathic PAH
Drugs: fenfluramine/phentermine
- weight loss pills
What is the difference between these WHO FC for PAH:
Class 1
Class 2
Class 3
Class 4
- pulmonary HTN without resulting limitation of physical activity
- pulmonary HTN with SLIGHT limitation of physical activity; ordinary activity causes symptoms
- pulmonary HTN with MARKED limitation of physical activity; less than ordinary activity causes symptoms; still comfortable at rest
- pulmonary HTN with INABILITY to carry out physical activity without symptoms; manifest signs of RIGHT HEART FAILURE
What is the Vasopressor Test and what are positive findings?
- recommended that Group 1 PAH undergo vasopressor testing; administration of short-acting vasodilators
(+) = PAP dec. > 10 mmHg, MPAP < 40 mmHg, or CO is unchanged or increased
- see more response from idiopathic, familial, or anorexigen-induced PAH
50% of these patients benefit from treatment with CALCIUM CHANNEL BLOCKERS - nifedipine, diltiazem, amlodipine
Epoprostenol
What is its MOA, what is it used for, how is it administered, and what is its major serious adverse effect?
MOA: mimics endogenous prostacyclin –> vascular relaxation/inhib. platelet agg. and exerts effects by binding to G-protein on cell membrane to generate cAMP; used for PAH
- administered as continuous IV due to 6 minute half-life; used with pump that can keep the drug COLD
AE: sepsis due to chronic catheter
Treprostinil
What is its MOA, what is it used for, how is it administered, and what is its major adverse effect?
MOA: mimics endogenous prostacyclin –> vascular relaxation/inhib. platelet agg. and exerts effects by binding to G-protein on cell membrane to generate cAMP; used for PAH
- administered with pump IV in dilution 1:2 and DOESN’T require refrigeration; has 4 hour half-life
- used to be SubQ but was too painful
AE: sepsis due to chronic catheter
Iloprost
What is its MOA, what is it used for, how is it administered, and what is its major adverse effect?
MOA: mimics endogenous prostacyclin –> vascular relaxation/inhib. platelet agg. and exerts effects by binding to G-protein on cell membrane to generate cAMP; used for PAH
- administered by INHALATION 6-9x day
AE: fainting due to hypotension (especially if SBP < 85 mmHg)
Selexipag
What is its MOA, what is it used for, and how is it administered?
Who benefits from this medication?
MOA: mimics endogenous prostacyclin –> vascular relaxation/inhib. platelet agg. and exerts effects by binding to G-protein on cell membrane to generate cAMP; used for PAH
- administered ORALLY twice daily, but is EXPENSIVE
kids with PAH and/or their caregivers often refuse central line for IV, so this is a good alternative
Bosentan
What is its MOA, what is it used for, how is it administered, and what are its two serious adverse effects?
What are two drug interactions this drug has?
MOA: nonspecific ETa and ETb endothelin receptor blocker used for PAH
- administered ORALLY
AE: hepatotoxicity and teratogenesis
DI: accelerates metabolism of WARFARIN and ORAL CONTRACEPTIVES
- all patients MUST use 2 forms of birth control
Ambrisentan
What is its MOA, what is it used for, how is it administered, what is its serious adverse effect?
What are its drug interactions?
MOA: selective ETa receptor blocker used for PAH
- administered ORALLY
AE: teratogenesis (does NOT DAMAGE LIVER)
DI: does NOT accelerate Warfarin or oral contraceptive metabolism, but pts should STILL USE 2 forms of contraception
Macitentan
What is it and what is its half-life?
- non-selective Endothelin Antagonist
- half-life of 18 hrs allows for one/day dosing
Sildenafil
What is its MOA, what is it used for, how is it administered, and what are its 3 most common complications (H/F/D)?
What is Tadalafil?
MOA: selectively blocks phosphodiesterase Type 5, an enzyme that breaks down cGMP, and is used to treat PAH
- administered ORALLY with a 4 hr half-life
AE: headache, flushing, dyspepsia
- mild hypotension when used alone
- inc. hypotension with alpha-blockers/nitrates
Tadalafil = LONGER half-life than Sildenafil
Riociguat
What is its MOA, what is it used for, how is it administered, and what are its two major adverse effects?
MOA: sensitizes soluble guanylate cyclase to NO by stabilizing NO-sGC binding AND directly stimulates sGC independent of NO; used to treat PAH and type 4 PH
- administered ORALLY with half-life of 12 hours
AE: may cause fetal harm and should NOT be administered with NO donors or Type 5 PDE inhibitors
What is a very common PAH drug combination used to PAH patients?
tadalafil + ambrisentan
What are 3 Tissue-type Plasminogen Activator Drugs that can be used for thrombus busting? (A/R/T)
How do these drugs work?
TpD = Alteplase, Reteplase, Tenecteplase
- all end in suffix “-teplase”
- activate plasminogen in thrombus ONLY
What are the 5 Parenteral indirect thrombin/Xa inhibitors that can be used for DVT and PE? (H/E/D/T/F)
heparin
enoxaparin, dalteparin, tinzaparin
fondaparinux
What are the 2 Parenteral direct thrombin inhibitors that can be used for DVT and PE? (B/A)
bivalirudin, argatroban
DVT and PE Drug Treatment
What is the Oral coumarin derivative?
What are the 3 Oral direct Factor Xa inhibitors? (R/A/E)
What is the Oral direct thrombin inhibitor?
CD: warfarin
XaI: ribaroxaban, apixaban, endoxaban
TI: dabigatran
Heparin
What is its MOA, what does it block, and what is its antidote?
How does it affect pregnancy?
MOA: binds to/activates antithrombin III to inhibit Factor Xa and thrombin (blocks generation and inactivates thrombin)
- large negative charge, cannot cross membranes
Antidote: Protamine
Pregnancy: doesn’t cross placenta, so CAN use in pregnancy
Heparin
What are 3 major contraindications to use? (T/B/S)
What is Heparin-induced Thrombocytopenia?
- thrombocytopenia
- uncontrollable bleeding
- surgery involving brain, eye, spinal cord
Heparin-induced Thrombocytopenia
- reduced platelet counts w/paradoxical inc. in thrombotic events
- Abs to heparin-platelet complexes
LMW heparins can also cause thrombocytopenia and severe bleeding
Enoxaparin, Dalteparin, Tinzaparin
What is their MOA, what are they used for, and what is their antidote?
How do they affect pregnancy?
MOA: shorter length heparin molecules that selectively block Factor Xa but NOT thrombin; used for DVT and red thrombus prevention
- FIRST CHOICE TREATMENTS FOR DVT
- easier to use (can be used at home; long 1/2 lives)
Antidote: protamine
Pregnancy: SAFE
Fondaparinux
What is its MOA, what is it used for, and what is its antidote?
How is it administered and what does it NOT potentially cause in patients?
MOA: synthetic pentasaccharide that selectively inhibits Factor Xa and prevents DVT
- more effective than Enoxaparin, but inc. bleeding risk
- can be used in conjunction with Warfarin
- administered SubQ with 17-21 hr 1/2 life
Antidote: NONE (not affected by protamine)
- does NOT cause Heparin-induced Thrombocytopenia
Bivalirudin (Hirudin-analog)
What is its MOA, what drug is it commonly used with, and how is it administered?
What is its antidote?
MOA: synthetic peptide that directly (reversibly) inhibits thrombin; given w/GP IIb/IIIa antagonists in pts. undergoing coronary angioplasty
- must be given IV like heparin (expensive though!!)
Antidote: NONE
Argatroban
What is its MOA, what is it used for, and how is it administered?
What patient population is it used in?
MOA: directly binds to catalytic site of thrombin and reduced new thrombus development, specifically pts. with Heparin-induced thrombocytopenia
- treatment monitored with aPTT
- given IV (short half-life)
Warfarin
What is its MOA, what is it used for, and what is it NOT useful for?
What is a consideration when using this drug?
MOA: vitamin K antagonist that dec. production of active forms of calcium-dependent clotting factors (2, 7, 9, 10) and protein C/S (anti-clotting factors)
- for long-term thrombosis prophylaxis
- for mechanical heart valves and atrial fibrillation
- NOT useful for emergencies (delayed effects)
remember: slow onset and slow offset, monitor frequently when other drugs are added/subtracted
Warfarin
What is a major complication of use and how can it be corrected?
What is its effect in pregnancy?
MC: BLEEDING; if occurs, discontinue immediately
- effects can be reversed with Vitamin K (12-24 hrs)
- give fresh blood for quick change
- can cause cutaneous necrosis (loss of Protein C causes procoagulant state)
Pregnancy: DO NOT USE ON PREGNANT PTS
- crosses the placenta
has greatest affects on Factor VII and Protein C
Rivaroxaban (Apixaban, Endoxaban)
What is its MOA, what are its 2 uses, and what is its antidote?
How does it affect pregnancy?
MOA: direct inhibitor of Factor X (binds in active center); used for DVT prevention and stroke prevention in pts with nonvalvular A Fib (not as good w/mechanical valve)
Antidote: andexanet alfa
Pregnancy: appears UNSAFE
- do NOT use with other anticoagulants
- avoid in pts. with renal/hepatic involvement
Dabigatran
What is its MOA, what is it used for, and what is it contraindicated in?
What is its antidote?
MOA: reversible direct thrombin inhibitor that has advantages over Warfarin (no monitor, lower bleeding risk, same dosing)
- used for stroke and systemic embolism prevention
- in pts. with nonvalvular Atrial Fibrillation
CI: pts. with MECHANICAL HEART VALVES
- also pills are unstable (bleeding major concern)
Antidote: idarucizumab
What is definitive imaging used to diagnose PE?
CT Pulmonary Angiography
What are two surgical preventative measures for DVT and PE?
- IVC filter used to break apart thrombi
2. stent placement in common iliac veins to help keep them open
What is the treatment for PE due to air?
- position patient in left later decubitus position with head down OR use Trendelenburg machine to avoid further venous embolization
- immediately administer high flow oxygen/mechanical ventilation –> inc. rate with which the embolized air is resorbed
- secure access for administration of IV fluids and/or vasopressors to restore adequate tissue perfusion
What is the treatment for PE due to fat?
- no definitive treatments available; treatment is largely supportive while fat emboli resolve spontaneously
- can give fluid resuscitation, oxygenation, rare use of vasopressors +/- noninvasive/invasive mechanical support
- corticosteroids and heparin are NOT commonly used
