Biochemical Targets and Mechanisms of Action
The pharmacological effects of antiplatelet agents are mediated through several key targets within platelets:
- Elimination of mediators: blocking the effects of thromboxane $A_2$ and adenosine diphosphate (ADP).
- Intracellular messengers: increasing the concentration of cyclic adenosine monophosphate (cAMP), which leads to a decrease in cytoplasmic calcium ($Ca^{2+}$) levels and prevents glycoprotein activation.
- Final stage of aggregation: direct blockade of glycoprotein receptors, preventing fibrinogen binding.
Classification by Mechanism of Action
Drugs are divided into several groups depending on their sites of action:
- Agents eliminating the effect of thromboxane $A_2$: cyclooxygenase inhibitors (acetylsalicylic acid, indobufen).
- Agents increasing cAMP levels: prostacyclin receptor stimulators (epoprostenol), phosphodiesterase inhibitors (dipyridamole, pentoxifylline).
- Receptor antagonists and activation blockers: ADP inhibitors ($P2Y_{12}$ receptor blockers such as clopidogrel and ticagrelor).
- Glycoprotein IIb/IIIa blockers: monoclonal antibodies (abciximab), synthetic peptides (eptifibatide), and non-peptide mimetics (tirofiban).
Thromboxane Synthesis Inhibitors and Aspirin
The main representative of drugs eliminating the effects of thromboxane $A_2$ is acetylsalicylic acid.
- Mechanism: binds to cyclooxygenase-1 (COX-1) in platelets.
- Type of bond: causes irreversible acetylation of the enzyme's active center due to the presence of an acetyl group.
- Result: interrupts the conversion of arachidonic acid into cyclic endoperoxides, disrupting thromboxane $A_2$ synthesis and reducing platelet aggregation.
Glycoprotein IIb/IIIa Receptor Blockers
These drugs disrupt the final stage of platelet aggregation by preventing fibrinogen from binding to receptors on the cell membrane.
Depending on chemical structure, they include:
- Monoclonal antibodies: abciximab (non-competitive inhibition).
- Synthetic peptides: eptifibatide (cyclic heptapeptide).
- Non-peptide mimetics: tirofiban (competitive antagonist).