Pharm: Anticoagulants and Thrombolytics

Question 1

Heparin

Answer 1

Large, anionic, acidic polymer.
Binds antithrombin III –> v activity of thrombin (factor II) and factor Xa.
Administer parenteral (IV, SC)
Short half-life.
Site of action is blood.
Rapid onset of action (seconds)
Use: immediate anticoagulation from PE, acute coronary syndrome, MI, DVT
Pregnancy
Follow PTT (intrinsic pathway)
Side effects: bleeding, HIT, osteoporosis, drug-drug interactions
Antidote: protamine sulfate

Question 2

HIT

Answer 2

Heparin-induced thrombocytopenia
Development of IgG antibodies against heparin-bound platelet factor 4
Ab-heparin-PF4 complex activates platelets –> thrombosis and thrombocytopenia

Question 3

Low-molecular weight heparins (enoxaparin, dalteparin), and fondaparinux

Answer 3

Act more on factor Xa, less effect on thrombin
Better bioavailability
2-4x longer half-life
Can be administered subcutaneously w/o monitoring
Not easily reversible (too small for antidote)
Really eliminated

Question 4

Bivalirudin, argatroban, dabigatran

Answer 4

Direct thrombin inhibitors
Related to anticoagulant of leeches
Directly inhibits activity of free and clot-associated thrombin
Use: venous thromboembolism, a-fib, HIT
Does not require lab monitoring
Side effects: bleeding, no specific reversal agent

Question 5

Warfarin

Answer 5

Small, amphipathic molecule
Interferes w gamma-carboxylation of vit K-dependent clotting factors (II, VII, IX, X, proteins C and S).
Vit K is necessary co-factor to get these clotting factors to active form.
Warfarin inhibits reduction of vit K-epoxide back to its active form, therefore clotting factors won’t be activated.
Use: chronic anticoagulation (venous thromboembolism prophylaxis, prevent stroke in a-fib)
Do NOT use in pregnant women.
Oral admin.
Acts in liver.
Slow onset of action (have to wait for active coagulation factors to leave - just inhibits their synthesis)
Increases PT (extrinsic pathway) - monitor PT/INR
Chronic use - duration of action long (days)
Side effects: bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions (Warfarin is cytochrome P-450 substrate)
Early hypercoagulability could occur bc C and S are anti-coagulant factors and have shorter half-lives, so they will be inhibited first, leaving clotting factors II, VI, IX, X still around.
Prevent this with heparin bridging - use heparin when first starting warfarin (heparin is fast-acting anti-coag)
Antidote: vit K, fresh frozen plasma (faster bc provides coagulation factors)

Question 6

Apixaban, rivaroxaban

Answer 6

Direct factor Xa inhibitors - binds to Xa directly
Use: treatment and prophylaxis for DVT and PE, stroke prophylaxis in patients w a-fib
Oral agents - don’t need to monitor
Side effects: bleeding (no antidote!)

Question 7

Aspirin

Answer 7

NSAID that irreversibly inhibits COX-1 and COX-2 by covalent acetylation –> v synthesis of TXA2 and PGEs
^ bleeding time
- PT, PTT
Effects last until new platelets produced (about 1 week)
Use: low dose - v platelet aggregation; intermediate - antipyretic and analgesic; high - anti-inflammatory
Side effects: gastric ulcers, tinnitus; chronic use - acute renal failure, interstitial nephritis, GI bleeding, Reye syndrome in kids, alkalosis

Question 8

Clopidogrel, prasugrel, ticagrelor (reversible), ticlopidine

Answer 8

ADP (aggregate da platelets) receptor inhibitors
Inhibit platelet aggregation by irreversibly blocking ADP receptors; prevent expression of glycoproteins IIb/IIIa on platelet surface
Use: acute coronary syndrome, coronary stunting, v incidence of thrombotic stroke
Side effects: neutropenia (ticlodipine), TTP

Question 9

Cilostazol, dipyridamole

Answer 9

Phosphodiesterase III inhibitors
^ cAMP in platelets –> inhibition of platelet aggregation
vasodilators
Use: intermitten claudication, coronary vasodilation, prevent stroke or TIAs (w aspirin), angina prophylaxis
Side effects: nausea, headache, facial flushing, hypotension, abdominal pain

Question 10

Abciximab, eptifibatide, tirofiban

Answer 10

Glycoprotein IIb/IIIa inhibitors
Bind to GIIb/IIIa receptor on activated platelets –> prevents aggregation
Abcimixab made from monoclonal antibody Fab fragments
Use: unstable angina, percutaneous transluminal coronary angioplasty

Question 11

Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA)

Answer 11

Thrombolytics - clot blasters!
tPA = tissue plasminogen activator
Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots.
^PT, ^PTT, -no change in platelet count
Use: early MI, early ischemic stroke, direct thrombolysis of severe PE
Side Effects: bleeding
Contraindications: patients w active bleeding, hx of intracranial bleeding, recent surgery, known bleeding diatheses, severe HTN
Treat: aminocaproic acid (fibrinolysis inhibitor), fresh frozen plasma and cryoprecipitate (correct factor deficiencies)