Biochemical targets and mechanisms of action
The pharmacological effects of antiplatelet agents are mediated through action on several key targets in platelets:
- Elimination of mediators: blocking the action 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 aggregation link: 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 that eliminate the action of thromboxane $A_2$: cyclooxygenase inhibitors (acetylsalicylic acid, indobufen).
- Agents that increase cAMP levels: prostacyclin receptor stimulants (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 primary representative of agents that eliminate the effects of thromboxane $A_2$ is acetylsalicylic acid.
- Mechanism: binds to the cyclooxygenase-1 (COX-1) enzyme in platelets.
- Type of bond: causes irreversible acetylation of the enzyme's active site due to the presence of an acetyl group.
- Result: interrupts the conversion of arachidonic acid into cyclic endoperoxides, which impairs thromboxane $A_2$ synthesis and reduces platelet aggregation.
Glycoprotein IIb/IIIa receptor blockers
These medications disrupt the final stage of platelet aggregation, preventing fibrinogen from binding to receptors on the cell membrane.
Depending on their chemical structure, they are classified into:
- Monoclonal antibodies: abciximab (non-competitive inhibition).
- Synthetic peptides: eptifibatide (cyclic heptapeptide).
- Non-peptide mimetics: tirofiban (competitive antagonist).
Briefly: answers to topical questions
Which drugs belong to $P2Y_{12}$ receptor blockers?
- Ticlopidine (Ticlopidinum) — an ADP receptor blocker.
- Clopidogrel (Clopidogrelum) — an ADP receptor blocker.
- Prasugrel (Prasugrelum) — a $P2Y_{12}$ receptor blocker.
- Ticagrelor (Ticagrelorum) — a $P2Y_{12}$ receptor blocker.
- Cangrelor (Cangrelorum) — a $P2Y_{12}$ receptor blocker.
These medications block adenosine diphosphate receptors on the platelet membrane, eliminating its stimulating effect and preventing platelet activation, which disrupts the binding of glycoproteins IIb/IIIa to fibrinogen and impedes the formation of platelet aggregates.
cAMP increased — calcium dropped — the platelet froze and did not aggregate.
Class and exam questions
What type of inhibition is characteristic of acetylsalicylic acid regarding COX?
Acetylsalicylic acid causes irreversible inhibition of the cyclooxygenase (COX-1) enzyme by acetylating its active site.
What is the function of glycoprotein IIb/IIIa receptors?
These receptors serve as binding sites for fibrinogen, which forms "bridges" between activated platelets during the final stage of aggregation.
How does an increase in cAMP levels affect platelet aggregation?
An increase in cAMP concentration leads to a decrease in intracellular calcium ($Ca^{2+}$) concentration, which prevents glycoprotein activation and inhibits aggregation.
What else to study on this topic
- The role of phosphodiesterase in cAMP metabolism
- Comparison of competitive and non-competitive inhibition of GP IIb/IIIa
- Arachidonic acid metabolism and thromboxane synthase
- Characteristics of ADP $P2Y_{12}$ receptor blockers
- Pharmacological differences between dipyridamole and pentoxifylline
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