Antiplatelet drugs prevent platelets from forming clumps, thus preventing the formation of a clot. They help to prevent strokes and heart attacks. According to their mechanism of action, antiplatelets can be divided into four classes as below -
Cyclooxygenase inhibitors: These drugs inhibit the enzyme cyclooxygenase 1 or COX 1, which reduces the levels of thromboxane A2, decreasing the synthesis of platelet clumps. Examples include aspirin (Ecotrin, Acetylsalicylic acid) and triflusal (Aflen, Disgren). Adverse effects include nausea, heartburn, abdominal pain, and bleeding. Aspirin is typically stopped 72 hours before any planned surgery as it may cause bleeding. Aspirin is available over the counter and in various doses, such as 81 mg and 325 mg. Low dose aspirin is also known as “baby aspirin”. Aspirin is not recommended in children as it can cause potentially fatal Reye’s syndrome, which is associated with liver failure.
ADP P2Y12 inhibitors: These drugs prevent the formation of platelet clumps by inhibiting the ADP receptor. ADP is a chemical produced in the body that is essential for the formation of clots. Examples include clopidogrel (Plavix), prasugrel (Effient), ticlopidine (Ticlid) and ticagrelor (Brilinta). Common side effects include diarrhea and skin rash. Clopidogrel with aspirin is commonly prescribed in patients with coronary, carotid, and coronary stents.
GPIIb/IIIa inhibitors: GPIIb/IIIa plays a pivotal role in blood clotting. Inhibitors of GPIIb/IIIa include abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat). Adverse effects include bleeding and thrombocytopenia.
Phosphodiesterase inhibitors: Phosphodiesterase inhibitors increase the levels of cAMP in the platelets and prevent the formation of platelet clumps. Examples include cilostazol (Pletal) and dipyridamole (Persantine). Adverse effects include headache, nausea, diarrhea, palpitations and bleeding.
Protease activated receptor-1 (PAR -1) antagonists: They are a new type of antiplatelet drugs that inhibit signaling mechanisms within the platelets and prevent platelet activation. They do so by blocking PAR-1 receptors which blocks the action of clotting factor thrombin. Vorapaxar (Zontivity) has been approved by the FDA. Adverse effects include headache, fatigue, nausea and rash.
Anticoagulants prevent blood from clotting. Indications are similar to antiplatelets. Anticoagulants are also used to prevent and treat clots in atrial fibrillation, pulmonary embolisms and peripheral artery disease. They are classified as follows -
Warfarin: Warfarin is a commonly used anticoagulant that prevents the synthesis of Vitamin K-dependent clotting factors by inhibiting the enzyme epoxide reductase. It is sold under the brand names Coumadin and Jantoven. Patients on warfarin need to be monitored by a blood test called PT/INR, which measures the prothrombin time. It should not be used in pregnancy as it is teratogenic. The most common adverse effect is bleeding, especially internal bleeding. Warfarin has a lot of drug and food interactions with antiplatelet drugs, alcohol, NSAIDS, grapefruit juice, green leafy vegetables, etc. Bleeding due to warfarin overdose can be reversed with vitamin K. The full therapeutic effect of warfarin takes three to five days.
Heparin: Heparin enhances the activity of antithrombin III, which in turn inhibits the activity of clotting factors like thrombin, Factor IX, and X. It is available in two separate forms - unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Unfractionated heparin is available as a generic Heparin sodium injection for intravenous or subcutaneous route. There are many types of LMWH, such as enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep). LMWH are derived from UFH, have a longer half-life, and the effect is more predictable than UFH. Heparins are used to prevent and treat blood clots in heart attacks, stroke, pulmonary embolism, and deep vein thrombosis (DVT). The most common adverse effect is bleeding. LMWH dose has to be reduced in patients with renal failure. Heparin may rarely cause thrombocytopenia (low platelets) and decreased bone density or osteopenia. Heparin must be monitored with aPTT or activated partial thromboplastin time and anti-Xa levels. Any bleeding can be potentially reversed by administering protamine which is a heparin antagonist and forms a complex with it.
Factor Xa inhibitors: These anticoagulants either directly or indirectly inhibit the function of clotting factor Xa. Examples include apixaban (Eliquis), rivaroxaban (Xarelto), fondaparinux (Arixtra) and edoxaban (Savaysa). Adverse effects include bleeding and thrombocytopenia.
Direct thrombin inhibitors: These drugs directly inhibit clotting factor thrombin, which plays a key role in the formation of a blood clot. Important ones include argatroban, bivalirudin (Angiomax) and dabigatran (Pradaxa). Dabigatran is the only oral drug in this class. Others are available in injectable form. They can be used as substitutes for heparin. The adverse effect is bleeding.
Warfarin and heparin are traditional anticoagulants. DOACs or direct oral anticoagulants can be taken orally and do not require regular blood testing or special diets like warfarin and have fewer adverse effects. DOACs include the direct thrombin inhibitor dabigatran and the factor Xa inhibitors like rivaroxaban, apixaban and edoxaban.
Thrombolytics are also known as fibrinolytics. They are used to break down blood clots. They do so by activating an enzyme called plasmin, which dissolves clots. Commonly used thrombolytics include alteplase (Activase), reteplase (Retavase,) and tenecteplase (TNKase). They can be used to treat conditions such as heart attacks (myocardial infarction), pulmonary embolism, and stroke. Adverse effects include bleeding and allergic reactions. They are contraindicated in recent surgery, active bleeding, recent brain injury, and severe hypertension.
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