It is indicated to reduce the risk of myocardial infarction for patients with non-ST elevated acute coronary syndrome (ACS), patients with stroke or established peripheral arterial disease.
Aspirin is a commonly used drug for the treatment of pain and fever due to various causes. It has both anti-inflammatory and antipyretic effects. This drug also inhibits platelet aggregation and is used in the prevention of blood clots stroke, and myocardial infarction.
Indications:
Clopidogrel is also used with aspirin to treat new/worsening chest pain heart attack, unstable angina and to keep blood vessels open and prevent blood clots after certain procedures such as cardiac stent.
Indicated for Pain, fever, and inflammation. Reduces the risk of cardiovascular death in suspected cases of myocardial infarction.
Mechanism of action:
Clopidogrel inhibits adenosine diphosphate (ADP) from binding to its receptor sites on the platelets and subsequent activation of glycoprotein GP IIb/IIIa complex thus preventing fibrinogen binding, platelet adhesion and aggregation. Clopidogrel is metabolized to its active form by carboxylesterase-1. The active form is a platelet inhibitor that irreversibly binds to P2Y12 ADP receptors on platelets. This binding prevents ADP binding to P2Y12 receptors, activation of the glycoprotein GPIIb/IIIa complex, and platelet aggregation Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for COX-1 and COX-2 enzymes 9,10,11. Inhibition of COX-1 results in the inhibition of platelet aggregation for about 7-10 days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds with a serine residue of the cyclooxygenase-1 (COX-1) enzyme, leading to irreversible inhibition. This prevents the production of pain-causing prostaglandins.
Pharmacodynamics:
Clopidogrel is a prodrug of a platelet inhibitor used to reduce the risk of myocardial infarction and stroke. It has a long duration of action as it is taken once daily and a large therapeutic window as it is given in doses of 75-300mg daily.
Acetylsalicylic acid disrupts the production of prostaglandins throughout the body by targeting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) . Prostaglandins are potent, irritating substances that have been shown to cause headaches and pain upon injection into humans. Through the disruption of the production and prevention of release of prostaglandins in inflammation, this drug may stop their action at pain receptors, preventing symptoms of pain. Acetylsalicylic acid is considered an antipyretic agent because of its ability to interfere with the production of brain prostaglandin E1.
Pharmacokinetics:
clopidogrel:A 75mg oral dose of clopidogrel is 50% absorbed from the intestine.Clopidogrel can be taken with or without food. A meal decreases the AUC of the active metabolite by 57%.The active metabolite of clopidogrel reaches a maximum concentration after 30-60 minutes.Clopidogrel reached a Cmax of 2.04±2.0ng/mL in 1.40±1.07h.
The AUC for a 300mg oral dose of clopidogrel was 45.1±16.2ng*h/mL for poor metabolizers, 65.6±19.1ng*h/mL for intermediate metabolizers.The Cmax was 31.3±13ng/mL for poor metabolizers, 43.9±14ng/mL for intermediate metabolizers, and 60.8±34.3ng/mL for extensive metabolizers. Both the active and inactive metabolites of clopidogrel are 98% protein bound in plasma.
85-90% of an oral dose undergoes first pass metabolism by carboxylesterase 1 in the liver to an inactive carboxylic acid metabolite about 2% of clopidogrel is oxidized to 2-oxoclopidogrel. 2-oxoclopidogrel is further metabolized to the active metabolite. This conversion is 32.9% by CYP2B6, 6.79% by CYP2C9, 20.6% by CYP2C19, and 39.8% by CYP3A4 An oral dose of radiolabelled clopidogrel is excreted 50% in the urine and 46% in the feces over 5 days. The remainder of clopidogrel is irreversibly bound to platelets for their lifetime, or approximately 8-11 days.
Asprin: Aspirin is available in oral forms. When taken, it is absorbed in the gastrointestinal tract. It is distributed to all tissues of the body. In pregnant women, it does cross the placenta to the fetus. It is also passed through breastmilk to a nursing infant. In the body, it quickly breaks down into salicylic acid, and the liver changes it into metabolites. It is then excreted by the kidneys.
The half-life of aspirin is only 15 to 20 minutes. Half-life is the amount of time it takes to decrease the concentration of the drug in your body by half. Once the aspirin is broken down into salicylic acid, the salicylic acid has a half-life of six hours. In higher doses, the half-life increases, and in toxic doses it may exceed 20 hours.
Side Effects:
● Dyspepsia
● abdominal pain
● nausea, vomiting,
● flatulence, constipation
● gastritis, gastric and duodenal ulcers.
● GI upset, diarrhoea, paraesthesia, vertigo, headache, dizziness, pruritus and rashes.
● Potentially Fatal: Bleeding disorders including GI and intracranial haemorrhage
Contraindications:
This combination is contraindicated in:
● Hypersensitivity
● Active pathological bleeding. admin within 7 days after MI and ischaemic stroke, coagulation disorders. Lactation
Special warnings and precautions for use:
Patients at risk of increased bleeding from trauma, surgery, or other pathological conditions; ulcer; renal and hepatic impairment; history of bleeding or haemostatic disorders.
Pregnancy and Lactation:Contact your doctor before using the drug.