Antiplatelet Drugs
Antiplatelet drugs are a class of medications that prevent blood clots from forming. They work by stopping your platelets from sticking together. Antiplatelet drugs are used to avoid blood clots, which can cause heart attacks and strokes.
• In arterial thrombi, platelets are the main component, and aggregation is promoted by the release of substances such as ADP, TXA2, and serotonin.
• Main antiplatelet drugs include TXA2 synthesis inhibitors (aspirin), ADP antagonists (clopidogrel, ticlopidine), and Gp IIb/IIIa antagonists (abciximab, tirofiban, and eptifibatide).
• Aspirin inhibits the synthesis of TXA2, leading to anti-aggregatory effects. Dipyridamole and ADP antagonists increase platelet survival time by increasing cAMP levels.
• Ticlopidine and clopidogrel are reversible ADP antagonists, and prasugrel is more potent but has a higher risk of fatal bleeding.
• Gp IIb/IIIa antagonists are the strongest antiplatelet drugs and block aggregation induced by all agonists.
• Cilastazole is a phosphodiesterase-3 inhibitor that reduces platelet aggregation and has peripheral vasodilatory effects.
• All antiplatelet drugs have the potential for bleeding as a side effect.
• Antiplatelet drugs are used for the prevention of MI, cerebrovascular disease, and in artificial heart valves.
Newer Antiplatelet Drugs:
- Two groups of newer antiplatelet agents are in the advanced stages of development
- Ticagrelor and cangrelor are direct-acting reversible P2Y12 receptor antagonists. Ticagrelor is orally effective and has a more rapid onset and action offset than clopidogrel. It has been approved by the FDA and has been shown to reduce cardiovascular death more effectively than clopidogrel in patients with acute coronary syndromes. Cangrelor is an intravenous reversible P2Y12 receptor antagonist recently approved as an adjunct to PCI.
- Vorapaxar is an orally active inhibitor of thrombin receptors (PAR-1) on platelets and has been approved as an antiplatelet drug for patients with a history of MI or peripheral artery disease.
Anticoagulants
- Oral Anticoagulants:
- Inhibit activation of vitamin K dependent clotting factors
- Phenindione causes orange urine, liver, and kidney damage
- Warfarin is a mixture of R and S isomers. S-warfarin is more active and metabolized by CYP2C9
- Bleeding is the most common adverse effect
- Prothrombin time is used to adjust the dose of warfarin
- INR is a better test for monitoring oral anticoagulants
- Warfarin interacts with several medications and requires dose adjustment
- New oral anticoagulants include dabigatran etexilate, rivaroxaban, and apixaban
- Indirect Thrombin Inhibitors:
- Include unfractionated heparin, low molecular weight heparin, fondaparinux, and idraparinux
- Act by activating antithrombin III (AT III) in plasma
- Heparin is the strongest organic acid in the body
- Commercially produced from ox lung and pig intestine.
3. Direct Thrombin Inhibitors:
- Direct Thrombin Inhibitors include hirudin, lepirudin, bivalirudin, argatroban, dabigatran, melagatran and ximelagatran
- Dabigatran and Ximelagatran can be given orally; others are parenteral
- These drugs directly inactivate factor IIa (thrombin)
- Anticoagulant of choice for heparin-induced thrombocytopenia
- Bleeding is a major adverse effect
- The effect can be monitored by aPTT
- Except for argatroban, all drugs excreted by the kidney, avoid in renal failure
- Argatroban is secreted in bile and safe in renal failure. Lepirudin can be used in liver disease.
- Idarucizumab is a monoclonal antibody for dabigatran, approved for reversal of its anticoagulant effect.
Uses of Anticoagulants:
- Anticoagulants are used for venous thrombosis and prophylaxis of deep vein thrombosis.
- Warfarin is commonly used for chronic atrial fibrillation to prevent thromboembolism.
- Aspirin and heparin combination are used for unstable angina.
- Heparin is used for disseminated intravascular coagulation.
- Anticoagulants decrease the occurrence of stroke, but antiplatelet drugs are preferred.
- Contraindicated in conditions with increased bleeding risk, bleeding disorders, peptic ulcers, haemorrhoids, severe hypertension, subacute bacterial endocarditis, tuberculosis, and with aspirin and other antiplatelet drugs.
Fibrinolytics
- Fibrin molecules are broken down into soluble fragments with the help of plasmin, which is generated from plasminogen with the help of tissue plasminogen activator (tPA).
- Fibrinolytics are drugs that activate plasminogen to form plasmin and help in the lysis of thrombus. They can cause bleeding as a major adverse effect.
- Streptokinase is the least expensive fibrinolytic drug and is obtained from b-hemolytic streptococci. It activates both fibrin-bound and circulating plasminogen but can lead to allergic reactions and the formation of neutralizing antibodies.
- Anistreplase is a combination of streptokinase and Lys-plasminogen. It is antigenic and not specific for fibrin-bound plasminogen.
- Urokinase is isolated from human urine, is not antigenic, and directly converts plasminogen to plasmin. It is often used for catheter-directed lysis of thrombi, but its availability is limited.
- Alteplase, reteplase, and tenecteplase are recombinant tPA, not antigenic, and more efficacious than streptokinase but have a similar incidence of haemorrhage. Reteplase and tenecteplase are bolus fibrinolytic and do not require a prolonged intravenous infusion.
Disclaimer: This article is for informational purposes only and should not be taken as medical advice. Always consult with a healthcare professional before making any decisions related to medication or treatment.
These drugs play a vital role in treating various medical conditions such as cardiovascular disease, deep vein thrombosis, and stroke. It is crucial for healthcare providers to understand the mechanisms of action, indications, and potential side effects of these medications to provide optimal care for their patients.
To reinforce your understanding of these drugs, I recommend self-assessment through quizzes or tests that do not collect any user data. This will help solidify your knowledge of the important aspects of these medications.
