Answer by Jens Mowatt:

It completely depends on the drug, its mechanism of action, the amount of drug they were exposed to, and the person’s genetics.

Unfortunately I can’t give you an example of an irreversible antagonist on a receptor, but I can give you an example of one that affects an enzyme. One such substance is Sarin gas, an irreversible antagonist of acetylcholine esterase, the enzyme that breaks down acetylcholine in the synapse. As a result, ACh can’t bind to the active site, and there is an excess of this neurotransmitter in the synapse. Victims have extreme activation of their muscles.

You can prevent Sarin from binding to the active site if you quickly administer phylostigmine, a temporary antagonist of acetylcholine esterase. During the First Gulf War soldiers were given phylostigmine to administer in case they were attacked by gas because once Sarin has bound to that enzyme, it won’t let go.

Assuming you survive a Sarin gas attack, it will take time for your body to synthesize new acetylcholine esterase proteins. Even with anticholinergic drugs, full recovery from acetylecholine esterase inhibitors could take between three to six weeks [1 & 2]. There are a lot of variables at play here, including the degree of exposure and whether or not the person got rapid treatment.

The body can’t replace enzymes immediately, thats for certain. The same applies for receptors when they are bound by an irreversible antagonist. It takes time and valuable resources for cells to make new proteins. If your body can’t replace essential proteins fast enough, death is a likely scenario.

[1] Nerve Agents
[2] Facts You Should Know about the Chemical Weapon Sarin 

For how long do irreversible antagonists affect the brain?

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