Lecture 22: Blood drugs Flashcards
1
Q
DRUGS USED IN DISORDERS OF COAGULATION
A
- DRUGSUSEDTOREDUCECLOTTING
- Platelet Aggregation Inhibitors
- Anticoagulants
- Thrombolytics
- DRUGSUSEDINBLEEDINGDISORDERS
- Plasminogen Activation Inhibitors
- Protamine Sulfate
- Vitamin K
Plasma Fractions
2
Q
PLATELET AGGREGATION INHIBITORS
A
- CYCLOOXYGENASE INHIBITORS
- ADP RECEPTOR BLOCKERS
- PHOSPHODIESTERASE INHIBITORS
- BLOCKERS OF PLATELET GP IIb/IIIA RECEPTORS
3
Q
ADP RECEPTOR BLOCKERS
A
- CLOPIDOGREL & TICLOPIDINE
- Irreversible inhibitors of P2Y12, one of the two
- subtypes of ADP receptor on the platelet surface.
- Clopidogrel has fewer adverse effects than ticlopidine.
- Clopidogrel is preferred over ticlopidine.
4
Q
CLOPIDOGREL
A
- Clopidogrel is a prodrug converted to an active metabolite, mainly by CYP2C19.
- Patients who are CYP2C19 poor metabolizers have lower plasma levels of the active metabolite -> at risk of cardiovascular events.
- The concomitant use of clopidogrel and CYP2C19 inhibitors should be avoided.
- Omeprazole, a CYP2C19 inhibitor, reduces plasma levels of the active metabolite of clopidogrel.
- Concurrent use of clopidogrel and omeprazole should be avoided.
Uses: Indicated to reduce the rate of stroke, MI, and death in patients with recent MI or stroke or acute coronary syndrome.
5
Q
DIPYRIDAMOLE
A
- PHOSPHODIESTERASE INHIBITORS
- Coronary vasodilator.
- Used to prophylactically treat angina pectoris.
Uses
- Dipyridamole by itself has little beneficial effect.
- Used in combination with warfarin or aspirin.
6
Q
BLOCKERS OF PLATELET GP IIb/IIIA RECEPTORS
A
- Activation of this receptor is the final common pathway for platelet aggregation.
- ABCIXIMAB: Monoclonal antibody against the GPIIb/IIIareceptor.
- EPTIFIBATIDE: Cyclicpeptide reversible antagonist of the GPIIb/IIIa receptor.
- TIROFIBAN: Nonpeptide reversible antagonist oft he GPIIb/IIIa receptor.
Uses
- To reduce thrombotic cardiovascular events in patients with non-ST elevation acute coronary syndrome (NSTE-ACS)
- Adjuncts to PCI for the prevention of cardiac ischemic complications.
7
Q
ANTICOAGULANTS
A
- Indirect Thrombin and Factor Xa inhibitors
- Direct Thrombin Inhibitors
- Direct Factor Xa Inhibitors
- Coumarin Anticoagulants.
8
Q
Indirect Thrombin and Factor Xa inhibitors
A
- Unfractionated heparin (UFH)
- Low-molecular-weight heparins (LMWH)
- Fondaparinux
9
Q
UNFRACTIONATED & LOW-MOLECULAR-WEIGHT HEPARINS
A
- Mixture of straight-chain,sulfated mucopolysaccharides.
- Isolated from bovine lung or porcine intestinal mucosa.
- Unfractionated heparin (UFH) has a MW range of 5,000 - 30,000.
- Low-Molecular-Weight Heparins are produced by depolymerization of UFH; MW range from 1,000 – 5,000.
- 3 LMWH: enoxaparin, dalteparin, tinzaparin.
MOA
- Heparins of different molecular weights have different anticoagulant activities.
- UFH efficiently inactivates both thrombin and factor Xa due to ternary complex
- **LMWH efficently inhibit Xa but have less effect on thrombin. **
10
Q
MONITORING OF HEPARIN LEVELS
A
- aPTT assay (not accurate for small MW heparin)
- aPTT is a test of the integrity of the intrinsic and common pathways of coagulation.
- Dosing of LMWH results in predictable plasma levels.
- It is not usually necessary to monitor LMWH blood levels.
- The potency of LMWH can be assessed with anti-factor Xa assays.
Uses
- DVT
- Pulmonary embolism
- MI
- DOC during pregnancy
Adverse
- Bleeding
- Hypersensitivity reactions
- Heparin-induced Thrombocytopenia (HIT): Antibodies recognize complexes of heparin and a platelet protein, Platelet Factor 4.
- Rx: ARgatroban
11
Q
HEPARIN-INDUCED THROMBOCYTOPENIA TYPE II
A
- This can result in thrombocytopenia and thrombosis that can be life-threatening.
- Therapy: Discontinuance of heparin and administration of a DTI or fondaparinux.
12
Q
REVERSAL OF HEPARIN ACTION
A
- Excessive anticoagulant action of heparin is treated by discontinuance of the drug.
- If bleeding occurs protamine sulfate is given.
13
Q
FONDAPARINUX
A
- Synthetic pentasaccharide.
- Sequence of five carbohydrates that bind to antithrombin III.
- Specific inhibitor of Xa.
- Negligible antithrombin activity.
- Approved for prevention and treatment of DVT.
14
Q
DIRECT THROMBIN INHIBITORS (DTIs)
A
- exert their anticoagulant effect by directly binding to the active site of thrombin.
- PARENTERAL DTIs
- LEPIRUDIN
- BIVALIRUDIN
- ARGATROBAN
- ORAL DTIs
15
Q
LEPIRUDIN
A
- PARENTERAL DTIs
- Its action is independent from antithrombin III, therefore lepirudin can inactivate fibrin-bound thrombin in thrombi.
- Given parenterally.
- Monitored by the aPTT.
- No antidote exists.
20
Q
COUMARIN ANTICOAGULANTS
A
WARFARIN
Called oral anticoagulants
MOA
- Warfarin inhibits vitamin K epoxide reductase.
- Treatment with warfarin results in the production of inactive clotting factors, because they lack the gamma-carboxyglutamyl side chains.
- Anticoagulant effect is apparent within 24h of warfarin administration, peak @ 72 to 96 h
- Duration of action: 2 to 5 days
- Monitored by PT & expressed by INR
- anticoagulant effects of warfarin can be overcome by the administration of vitamin K.
Adverse
- Warfarin has a narrow TI and participates in many drug–drug interactions.
- Monitoring is performed with the prothrombin time (PT).
- Test of extrinsic and common pathways of coagulation.
- The results are expressed as (International Ratio) INR
- Hemorrhage
- Cutaneous necrosis due to Protein C deficiency
- Teratogenic
