Pharmacology Of Anticoagulants Flashcards
Steps in hemostasis (4)
- Vessel injury
- Vessel spasm
- Platelets adhere to injury site and aggregate to form plug
- Formation of insoluble fibrin strands and coagulation
General MOA of antiplatelet agents, anticoagulants, thrombolytics/fibrinolytics
Antiplatelet agents: prevent platelet aggregation
Anticoagulants: interfere with the clotting cascade
Thrombolytics/fibrinolytics: clot-dissolving agents
What are the 2 substances that are responsible for platelet aggregation?
- Thromboxane (TxA2)
2. ADP
Steps of platelet activation (3)
- Attached platelets activate
- Release substances to stimulate the attachment of other platelets
- Platelets attach to one another using the GPIIb-IIIa receptors
Platelet inhibitor agents and their general MOA (3)
- Aspirin: blocks formation of TxA2
- ADP receptor antagonists: Blocks ADP receptors on platelets
- Glycoprotein IIb-IIIa receptor antagonists (GP IIb/IIIa): Blocks the receptors used for platelet aggregation
Aspirin (MOA, PK, Pregnancy category, Indications)
MOA: Irreversibly inhibits COX-1 and COX-2 in platelets and inhibits the production of TxA2, a potent platelets aggregator
PK: Half-life of 20-30 minutes for aspirin and 6 hours for salicylic acid (active metabolite)
Pregnancy category: D
Indications: Thromboembolic disorder, OA, RA, fever, pain, prophylaxis of stroke and MI
Aspirin (ADRs [2 common/3 serious] and Considerations)
Common ADRs:
- GI disturbance
- Tinnitus
Serious ADRs:
- GI ulcer
- Hemorrhage
- Reye’s syndrome (rare progressive encephalopathy usually seen in children recovering from a viral infection that was treated with aspirin)
Considerations: 81 mg minimum but no more than 325 mg to prevent thrombi, MI, or stroke. Avoid use with other anticoagulants unless provider-approved. Irreversible effects means platelet inhibition may last up to 1 week. Allergic reactions/hypersensitivity. Possible Reye’s syndrome in children/teens with chickenpox or flu symptoms.
ADP Receptor Antagonists [Clopidogrel, Prasugrel, Ticagrelor] (MOA, PK, Pregnancy category, Indications)
MOA: Irreversibly inhibits the ADP receptor on the surface of platelets that is necessary for platelet aggregation. Used to prevent thrombotic events. Ticagrelor has a reversible agent.
PK: Prasugrel - half-life of 7-8 hours
Pregnancy category: B
Indications: Used to prevent thrombotic events in patients with acute coronary syndromes (unstable angina), and those at high risk for stroke, clots, and MI
ADP Receptor Antagonists [Clopidogrel, Prasugrel, Ticagrelor] (ADRs [2 common/1 serious] and Considerations)
Common ADRs:
- Hemorrhage
- Easy bruising
Serious ADRs:
1. GI hemorrhage
Considerations: Reversal agent for Ticagrelor in clinical trials. Currently no reversal agent and resultant platelet inhibition lasts for the lifespan of the platelet (7-9 days). Clopidogrel and Prasugrel are prodrugs that must be activated by 2 liver reactions, including CYP2C19. Omeprazole is a potent CYP2C19 inhibitor.
Advantage of using Ticagrelor over Clopidogrel?
Ticagrelor is not metabolized in the liver and is much less likely to have DDIs. Clopidogrel is metabolized in the liver by CYP2C19, which can be inhibited by omeprazole, a common PPI used for GERD.
GP IIb/IIIa Receptor Antagonists [Abciximab, Eptifibatide, Tirofiban] (MOA, PK, Pregnancy category, Indications)
MOA: Blocks the GP IIb/IIIa receptor that is necessary for platelet aggregation. Most potent platelet inhibitors.
PK: All administered IV
Pregnancy category: B
Indications: Used for patients with recent MI, stroke, or PCI
GP IIb/IIIa Receptor Antagonists [Abciximab, Eptifibatide, Tirofiban] (ADRs [1 common/1 serious/ and Considerations)
Common ADRs:
1. Hemorrhage
Serious ADRs:
1. Thrombocytopenia
Considerations: Major and minor events have occured; increased risk with a history of bleeding disorders, and concomitant use with drugs that increase the risk of bleeding (thrombolytics, oral anticoagulants, NSAIDs)
Why are GP IIb/IIIa Receptor Antagonists so efficacious?
Platelets have multiple GP IIb/IIIa receptors along their surface and creating an agent that blocks them all produces a very strong inhibitory effect against aggregation; prevents bridging between adjacent platelet since fibrinogen is not able to bind.
Anticoagulant agents [Inhibitors of the blood clotting cascade] (4)
- Heparin
- Factor Xa Inhibitors
- Direct thrombin inhibitors
- Warfarin
Primary use of anticoagulants?
To prevent formation of clots in veins to treat thromboembolic disorders