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ProdrugsA drug that is inactive until the body converts it into its active form.Read more → and active metabolitesA breakdown product of a drug that is itself still able to produce an effect in the body.Read more → matter because a drug's effect does not always come from the molecule that was actually swallowed, and knowing which is which explains otherwise puzzling clinical patterns. A prodrug is an inactive form that needs metabolism to become active. Lisdexamfetamine, for example, is converted by the body to active dexamfetamine, and codeine is converted by CYP2D6A cytochrome P450 liver enzyme that breaks down many antidepressants and antipsychotics, with wide genetic variation between people.Read more → (a liver enzyme) to morphine. An active metabolite, by contrast, is a breakdown product of an already-active drug that itself remains active, sometimes for much longer than the parent drug. For example, imagine a patient taking fluoxetine who stops the tablets abruptly: because its active metabolite, norfluoxetine, has a very long half-lifeThe time it takes for the amount of a drug in the body to fall by half.Read more →, withdrawal symptoms are minimal compared with stopping a short-acting SSRISelective serotonin reuptake inhibitor, a common type of antidepressant.Read more → (selective serotonin reuptake inhibitor). In practice, telling the two apart matters because they have opposite implications for how a drug's effect appears and fades.

ProdrugsA drug that is inactive until the body converts it into its active form.Read more → require enzymatic conversion before they become active at all. Lisdexamfetamine needs cleavage to release dexamfetamine, giving a smoother, slower onset with lower misuse potential than immediate-release amphetamine. Codeine needs CYP2D6A cytochrome P450 liver enzyme that breaks down many antidepressants and antipsychotics, with wide genetic variation between people.Read more →, a liver enzyme, to convert it to morphine, so patients who are CYP2D6 poor metabolisers get little pain relief from codeine. Active metabolitesA breakdown product of a drug that is itself still able to produce an effect in the body.Read more →, by contrast, extend a drug's action beyond its parent compound. Diazepam is broken down to desmethyldiazepam, a long-acting active metabolite that explains diazepam's prolonged effect and gentle withdrawal profile. Fluoxetine's active metabolite norfluoxetine has a similarly long half-lifeThe time it takes for the amount of a drug in the body to fall by half.Read more → and allows fluoxetine to be 'self-tapering' when stopped. Venlafaxine converts to desvenlafaxine, and risperidone converts to paliperidone, both active metabolites available as separate licensed drugs in their own right. For example, imagine a patient on codeine for pain who reports no benefit at any dose: testing might reveal they are a CYP2D6 poor metaboliser, unable to convert codeine to its active form, morphine. In practice, this means an apparently 'resistant' response to codeine can reflect genetics rather than needing an ever-higher dose.

• Why was lisdexamfetamine designed as an inactive compound requiring conversion in the body?
• Why does stopping fluoxetine abruptly rarely cause discontinuation symptoms?
• A woman gets no pain relief from tramadol despite adequate dosing. Which explanation is most likely?

• Prodrug (lisdexamfetamine, codeine), inactive until enzymatically converted, unlike an active metaboliteA breakdown product of a drug that is itself still able to produce an effect in the body.Read more →, which is a breakdown product of an already-active parent drug.
• Active metaboliteA breakdown product of a drug that is itself still able to produce an effect in the body.Read more → (norfluoxetine, desmethyldiazepam): extends the parent drug's action and softens withdrawal, rather than being required before any effect occurs at all.
• CYP2D6 poor metabolisers, convert codeine to morphine poorly and get little analgesia, whereas ultrarapid metabolisers convert it excessively and risk opioid toxicity.
• Paliperidone, risperidone's active metaboliteA breakdown product of a drug that is itself still able to produce an effect in the body.Read more →, available as its own licensed drug, unlike a prodrugA drug that is inactive until the body converts it into its active form.Read more → such as lisdexamfetamine which has no independently active parent form.

• Conversion is not hepatic, and the onset is gradual rather than immediate.
• The kidney is not the site of activation.
• Fluoxetine is well absorbed orally.
• Binding to the serotonin transporter is reversible.
• It is a potent serotonin reuptake inhibitor.

• Identify the drug, receptor, enzyme or pharmacokinetic change named in the stem.
• Translate it into the immediate mechanism before looking at the options.
• Use timing and the adverse-effect pattern to separate the nearest alternatives.
• Check whether the question asks for mechanism, clinical consequence, monitoring or management.