Antiplatelet drug

An antiplatelet drug (antiaggregant) is a member of a class of pharmaceuticals that decrease platelet aggregation ^[1] and inhibit thrombus formation. They are effective in the arterial circulation, where anticoagulants have little effect.

They are widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease.

Choice of antiplatelet drug

A 2006 review ^[2] states: "...low-dose aspirin increases the risk of major bleeding 2-fold compared with placebo. However, the annual incidence of major bleeding due to low-dose aspirin is modest—only 1.3 patients per thousand higher than what is observed with placebo treatment. Treatment of approximately 800 patients with low-dose aspirin annually for cardiovascular prophylaxis will result in only 1 additional major bleeding episode."

Classification

The class of antiplatelet drugs include:

• Irreversible cyclooxygenase inhibitors
  • Aspirin
  • Triflusal (Disgren)
• Adenosine diphosphate (ADP) receptor inhibitors
  • Clopidogrel (Plavix)
  • Prasugrel (Effient)
  • Ticagrelor (Brilinta)
  • Ticlopidine (Ticlid)
• Phosphodiesterase inhibitors
  • Cilostazol (Pletal)
• Protease-activated receptor-1 (PAR-1) antagonists
  • Vorapaxar (Zontivity)
• Glycoprotein IIB/IIIA inhibitors (intravenous use only)
  • Abciximab (ReoPro)
  • Eptifibatide (Integrilin)
  • Tirofiban (Aggrastat)
• Adenosine reuptake inhibitors
  • Dipyridamole (Persantine)
• Thromboxane inhibitors
  • Thromboxane synthase inhibitors
  • Thromboxane receptor antagonists
    • Terutroban

Usage

In dental implantation procedures

Dental implant procedures can be safely performed in patients on long-term antiplatelet medication, with no interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding.^[3]

Prevention and treatment of arterial thrombosis

Treatment of established arterial thrombosis includes the use of antiplatelet drugs and thrombolytic therapy. Antiplatelet drugs alter the platelet activation at the site of vascular damage crucial to the development of arterial thrombosis.

• Aspirin and Triflusal irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA₂ (thromboxane - powerful vasoconstrictor that lowers cyclic AMP and initiates the platelet release reaction).
• Dipyridamole inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI₂ – opposes actions of TXA₂
• Clopidogrel affects the ADP-dependent activation of IIb/IIIa complex
• Glycoprotein IIb/IIIa receptor antagonists block a receptor on the platelet for fibrinogen and von Willebrand factor. 3 classes:
  • Murine-human chimeric antibodies (e.g., abciximab)
  • Synthetic peptides (e.g., eptifibatide)
  • Synthetic non-peptides (e.g., tirofiban)
• Epoprostenol is a prostacyclin that is used to inhibit platelet aggregation during renal dialysis (with or without heparin) and is also used in primary pulmonary hypertension.

Thrombolytic therapy is used in myocardial infarction, cerebral infarction, and, on occasion, in massive pulmonary embolism. The main risk is bleeding. Treatment should not be given to patients having had recent bleeding, uncontrolled hypertension or a hemorrhagic stroke, or surgery or other invasive procedures within the previous 10 days.

• Streptokinase forms a complex with plasminogen, resulting in a conformational change that activates other plasminogen molecules to form plasmin.
• Plasminogen activators (PA), tissue-type plasminogen activators (alteplase, tenecteplase) are produced by recombinant technology.

Drug toxicity

Drug toxicity may be increased when multiple antiplatelet drugs are used. Gastrointestinal bleeding is a common adverse event seen in many patients.^[4]

See also

• Anticoagulant drug
• Thrombolytic drug
• Nitrophorin

References