3 Clinical psychopharmacology3.4 Therapeutics
3.4.4.1 With substances of abuse
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Written by Resident Doctor Committee · Published
Adaptation to repeated use
Term | Meaning |
|---|---|
Tolerance | A repeated dose produces less effect; it develops at different rates for different effects and does not prevent overdose |
Sensitisation | The opposite of tolerance: an unchanged dose given repeatedly produces a growing effect, as with some stimulant effects |
Physical dependence | Adaptation that produces withdrawal, which can occur with prescribed use and without addiction |
Craving | A strong urge, often triggered by cues, that outlasts acute withdrawal |
Tolerance falls after abstinence, so a previously tolerated opioid dose can cause fatal overdose after detoxification, discharge from hospital or release from prison.
Neuroadaptation and withdrawal
Chronic alcohol exposure alters inhibitory and excitatory signalling, so withdrawal brings tremor, autonomic activation, seizures and delirium.
Opioid withdrawal includes increased noradrenergic activity after the brain adapts to receptor stimulation.
Kindling is the rise in future seizure risk after repeated alcohol withdrawals.
Short-acting drugs often cause earlier withdrawal.
Hours since last drink | Alcohol withdrawal features |
|---|---|
6 to 12 | Tremor, sweating, anxiety, nausea, insomnia |
12 to 24 | Hallucinations with relatively preserved orientation |
24 to 48 | Seizures |
48 to 72 | Delirium tremens |
The times overlap, and seizures and delirium can start earlier or later.
Thiamine deficiency
Alcohol dependence and malnutrition raise the risk of thiamine deficiency.
Thiamine pyrophosphate is the cofactor for transketolase and pyruvate dehydrogenase, and deficiency damages the brain by disabling these enzymes, which links it to Wernicke-Korsakoff syndrome.
Wernicke encephalopathy should be suspected without waiting for the full triad of confusion, ataxia and ophthalmoplegia, and treated with parenteral thiamine.
Thiamine is given alongside glucose when needed, but emergency treatment of hypoglycaemia is never delayed.