Clopidogrel is a relatively new agent that acts as an antiplatelet agent to influence blood clotting. As an anticoagulant, clopidogrel is used in the presence of certain conditions in competition with the much less expensive conventional anticoagulants such as ASA (acetylsalicylic acid, aspirin) for the prevention of myocardial infarction, stroke, stent implantation, and the treatment of peripheral occlusive disease, among other uses. Clopidogrel acts principally as an ADP receptor blocker, inhibiting ADP-dependent platelet activation and thus platelet aggregation.
What is clopidogrel?
Clopidogrel is a relatively new drug that acts as an antiplatelet agent to influence blood clotting. Platelets, also known as thrombocytes, are equipped with adenosine diphosphate receptors that are used to control platelet aggregation when needed, for example, to close injured blood vessels. The drug clopidogrel inhibits the platelet receptors so that no or only limited platelet aggregation can occur. Clopidogrel is a thienopyridine derivative and in its role as an anticoagulant belongs to the group of platelet aggregation inhibitors. The drug is administered in a metabolically inactive form and, after oral uptake, must first be converted by the body into the bioactive form through several steps of oxidation and hydrolysis. Bioavailability after absorption in the digestive tract is about 50%. About 30% of Central Europeans are carriers of a mutated gene that reduces or completely prevents the conversion of the active substance into the bioactive form. If a rapid anticoagulant effect is to be achieved, a It The inactivation of platelet adenosine diphosphate receptors is irreversible, so that the effect of clopidogrel persists for several days after discontinuation of the drug until the “old” platelets are replaced by newly formed ones, which occurs after about a week.
Pharmacologic effect
In the presence of certain conditions or diseases, such as stroke, myocardial infarction, narrowing of the coronary arteries, or peripheral arterial occlusive disease (PAVD), the resulting repair mechanism in the form of platelet aggregation can lead to occlusion of the blood vessels with sometimes serious consequences. In these cases, anticoagulants – also known as anticoagulants or blood thinners – are intended to reduce the tendency of platelets to coagulate in order to prevent the formation of so-called thrombi (aggregation clots) in the veins or to dissolve existing thrombi. Since platelet aggregation is controlled by adenosine diphosphate receptors (ADP receptors), there is an opportunity for intervention here. Clopidogrel, which has been converted into its bioactive form, renders the ADP receptor P2Y12 inactive by inhibition. The goal of reducing the tendency to form thrombi, some of which are life-threatening, is thus achieved. It must be borne in mind that the process of inactivation or inhibition of the P2Y12 receptors is irreversible. This means that the platelets cannot regain their ability to aggregate even after the active substance clopidogrel has been broken down in the liver. The ability to coagulate is only restored via the process of natural platelet renewal. The platelet life cycle in humans is approximately 7 to 10 days, so that 10 days after clopidogrel degradation, complete platelet renewal has occurred and full coagulation ability has been restored, which may be important, for example, in upcoming surgery.
Medical application and use
Clopidogrel is incorporated into a variety of drugs from different manufacturers-including generic drugs-in the form of certain salts. Monopreparations containing only clopidogrel as the active ingredient are available, as are combination preparations with at least one other active ingredient. Combination preparations usually contain ASA (aspirin) as a second active ingredient, which also helps to inhibit clotting but acts at a different point in the clotting process. To achieve a rapid anticoagulant effect, a so-called loading dose of 300 to 600 milligrams is required once, while the normal daily maintenance dose is 75 milligrams.If the loading dose is observed, the full effect is achieved after only two to six hours, whereas full anticoagulation protection is not achieved until after five to seven days if the loading dose is not taken. As a special feature, interactions with other anticoagulants, with certain painkillers and with so-called proton inhibitors to reduce gastric acid must be taken into account.
Risks and side effects
The greatest dangers associated with the use of drugs containing the active ingredient clopidogrel lie, on the one hand, in the fact that the active ingredient is not or only insufficiently converted into the bioactive form in so-called non-responders due to a known gene mutation. As a result, the intended anticoagulant effect is not achieved or not achieved completely. If it is not known whether the patient belongs to the group of non-responders, regular use of clopidogrel may be virtually ineffective. After all, about 30% of people in Central Europe are affected by the mutation. Interactions with other drugs must also be taken into account. If other anticoagulants are also taken, the anticoagulant effect is usually enhanced. Interactions with antidepressants and proton inhibitors used to treat reflux consist of a reduction in anticoagulation. At the other extreme, there is an overdose of the drug. There is no known antidote that could reverse or reduce the effect of clopidogrel in the event of an accidental overdose. The only option is to infuse platelet-containing fluids, but it must be noted that the platelets added will also be altered while clopidogrel is present in the blood. The half-life for clopidogrel degradation is 7 to 8 hours. Adverse reactions during the treatment period may include gastrointestinal bleeding, increased nosebleeds, hematomas, diarrhea, and skin rash. In the event of injury by accident or the need for emergency surgery, the problem may arise that the anticoagulation achieved by clopidogrel cannot be reversed in the short term and may result in bleeding that is difficult to stop.
