Anticonvulsants and Antiplatelets Overview

Primidone is an anticonvulsant of the pyrimidinedione class.

Primidone is a prodrug requiring an oxidative metabolic activation to the major active metabolite phenobarbital.

N-Oxidation prodrug activation reaction is represented by the reversible redox drug delivery strategy for getting drugs into the brain.

In case of N-Methylpyridinium-2-carbaldoxime chloride (2-PAM = Pralidoxime) is used as an antidote to poisoning with cholinesterase inhibitors.

Because of its charge and hydrophilicity, it does not penetrate the BBB.

Pro-2-PAM, the reduced dihydropyridine form of 2-PAM, readily enters the CNS.

There, it is oxidized to form 2-PAM, which remains trapped in the CNS since its charge reduces its rate of transfer from the brain back into the blood.

Clopidogrel and Prasugrel (thienopyridine derivatives), inhibits platelet aggregation -> prolong bleeding time and delay clot retraction.

They are irreversible antagonists of P2Y12 purinergic receptor -> selective inhibition of ADP-induced platelet aggregation (last for 7-10 days after discontinuation of the medications).

They are pro drugs requiring cytochrome P450 activation.

The thiol binds irreversibly to P2Y12 by forming a disulfide bridge to a cysteine in P2Y12.

Primidone

Primidone is an anticonvulsant in the pyrimidinedione class
It's a prodrug, requiring oxidative metabolic activation to become its active form, phenobarbital
N-oxidation is the prodrug activation reaction, achieved via a reversible redox drug delivery strategy
In cases of N-methylpyridinium-2-carbaldoxime chloride poisoning, 2-PAM is used as an antidote to cholinesterase inhibitors
Primidone does not penetrate the blood-brain barrier (BBB) due to its charge and hydrophilicity
The reduced dihydropyridine form of 2-PAM (pro-2-PAM) readily enters the central nervous system (CNS)
Pro-2-PAM is oxidized to 2-PAM in the CNS, which remains trapped there due to its charge, slowing its transfer back into the blood.

Clopidogrel and Prasugrel

Clopidogrel and Prasugrel are thienopyridine derivatives, acting as antiplatelet drugs
They prolong bleeding time and delay clot retraction by inhibiting platelet aggregation
They are irreversible antagonists of the P2Y12 purinergic receptor, inhibiting ADP-induced platelet aggregation
They are prodrugs requiring cytochrome P450 activation
The active metabolites remain active for 7-10 days after discontinuation
The thiol group binds irreversibly to P2Y12 receptors, forming a disulfide bridge with cysteine residues.

This quiz covers the pharmacology of Primidone, an anticonvulsant, and compares it with Clopidogrel and Prasugrel, two antiplatelet agents. Explore their mechanisms of action, metabolic pathways, and clinical implications in treating resistance to clot formation. Test your knowledge of drug interactions and the role of prodrugs in therapeutic contexts.