Thromboembolic Drugs Flashcards
1
Q
- long polysaccharide chain
- blocks generation of thrombin
- used in need of rapid onset anticoagulant effects (pulmonary embolism, stroke, massive DVT)
- given parenterally
- highly variable plasma levels requires intensive monitoring via aPTT assay
A
heparin
2
Q
When is heparin contraindicated?
A
thrombocytopenia
3
Q
- short polysaccharide
- cannot form tertiary complex with antithrombin III and thrombin
- selectively inhibits factor Xa
- prevents DVT after abdominal surgery, hip/knee replacement
- longer half life than heparin, more expensive
- bleeding is major adverse effect
A
enoxaparin
4
Q
What is the antidote for bleeding caused by enoxaparin?
A
protamine
5
Q
- synthetic pentasaccharide
- selectively inhibits factor Xa
- prevents conversion of prothrombin to thrombin
- slightly more effective than enoxaparin, but has increased risk of bleeding
- administered subQ with fixed daily dose
- NOT reversible with protamine***
- does NOT cause heparin-induced thrombocytopenia***
A
fondaparinux
6
Q
- synthetic 20aa peptide, given IV
- directly blocks thrombin (reversible inhibits)
- can be given in combination to patients undergoing angioplasty
- doesn’t require antithrombin, causes less bleeding
- NO antidote
A
bivalirudin (parenteral anticoagulant)
7
Q
What is the classic drug given for hepatin-induced thrombocytopenia?
A
argatroban
8
Q
- directly binds catalytic site of thrombin
- prophylaxis/tx of thrombosis
- efficacy monitored by aPTT
- short half life, given IV
A
argatroban
9
Q
- vitamin K agonist (inhibits vitK epoxide reductase-1, enzyme that converts K epoxide back to reduced form)
- oldest oral anticoagulant
- decreases production of factors 2, 7, 9, 10, protein C and S
- prevents thromboembolism in patients with mechanical heart valves
- prevents thrombosis in patients with A-fib
- delayed effects (not useful in emergency)
- monitored with prothrombin time ratio (INR)
A
warfarin
10
Q
What is the most widely used long-term prophylaxis of thrombosis?
A
warfarin
11
Q
What are the contraindications of warfarin?
A
- severe thrombocytopenia
- any surgery/procedure
- patients at high risk of bleeding
- PREGNANCY**
12
Q
Why can warfarin cause cutaneous necrosis?
A
Protein C has a shorter half-life than several other clotting factors, so warfarin can initially cause a pro-coagulant state
13
Q
- direct inhibitor of activated factor X (inhibiting thrombin production)
- rapid onset
- fixed dosage (oral administration)
- lower bleeding risk and fewer drug interactions than warfarin, no INR monitoring needed
- used to prevent DVT and pulmonary embolism after hip/knee replacement
A
rivaroxaban
14
Q
What are the contraindications of rivaroxaban? adverse effects?
A
pregnancy! also should not be combined with any other anticoagulants
- epidural hematoma
- major intracranial/retinal bleeds
- GI bleeds
- adrenal bleeds
- interact with CYP3A4
15
Q
- reversible direct thrombin inhibitor
- used in prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrilation
- rapid onset, few drug/food interactions, low risk of bleeding, same dose for all patients (pills are unstable**)
A
dabigatran
16
Q
What is the antidote for dabigatran?
A
idarucizumab (Ab fragment that binds dabigatran with high affinity)
17
Q
What are the contraindications for dabigatran?
A
- for patients with mechanical heart valves (since more likely to experience strokes/MI)
18
Q
- irreversible blockade of P2Y receptors on platelets (that mediate ADP-induced aggregation)
- prevent Gi pathway (decreasing cAMP)
- inhibits platelet aggregation
- is a prodrug*** that must be converted to active form
- generally well tolerated
- risk of bleeding (lower for GI bleeds and intracranial heorrhage than for aspirin)
- often given with proton-pump inhibitors to relieve GI effects
A
clopidogrel
** the drug to start with**
19
Q
What patient demographics have CPY2C19 variant enzyme that cannot activate clopidogrel?
A
- 50% of Chinese
- 34% of African Americans
- 25% of Caucasians
- 19% of Mexican Americans
20
Q
- suppresses platelet aggregation by unknown mech
- used in fixed-dose combination with aspirin to prevent recurrent ischemic stroke in patients with past stroke or TIA***
A
dipyridamole (PDE inhibitor)
21
Q
What are the adverse effects of PDE inhibitors?
A
- headache
- dizziness
- nausea
- vomiting
- dyspepsia
- diarrhea
22
Q
- type 3 PDE inhibitor (prolongs life of cAMP in platelets and cells)
- platelet aggregation inhibitor
- vasodilator
- causes claudication (leg cramping/pain induced by exercise)
- oral table 2x/day
- metabolized by CYP3A4
A
cilostazol
23
Q
- purified Fab fragment of monoclonal Ab, reversibly binds GP11b/111a receptors, preventing binding to fibrinogen
- blocks final common pathway of platelet aggregation (inhibiting aggregation cause by all factors)
- used to treat acute coronary syndromes (unstable angina), and percutaneous coronary intervention
- IV administration
A
abciximab
24
Q
What is the most effective antiplatelet drug?
A
abciximab
25
- purified glycoprotein of 527 amino acids, with sequence identical to human tissue plasminogen activator
- catalyzes the conversion of clot-bound plasminogen to plasmin
- administered by continuous IV infusion, has a very short half life
- major indications: ***AMI, acute ischemic stroke, acute massive pulmonary embolism***
alteplase (tPA)
** clot buster!
26
What is the most serious concern of tPA?
intracranial hemorrhage, occurs for 2 reasons:
- destroying preexisting clots
- degrades clotting factors, interfering with clot formation
27
What is the clinical application of urokinase (uPA)?
pulmonary embolism
NOTE: is second plasminogen activator, recently back on market
28
What are the complications of uPA?
potentially fatal hemorrhage, easy bruising, nosebleeds, red/pink urine
- anaphylactic shock**
