Clinical Psychopharmacology · Paper A
Alcohol pharmacokinetics
This pattern matters because it explains why blood alcohol level cannot simply be scaled by how much a person drank. Alcohol is broken down by the body at a fixed rate per hour, regardless of how much is in the blood, which is unusual compared with most other drugs. For example, imagine two people who drink very different amounts: both clear roughly the same fixed number of units per hour. In practice, this fixed clearanceThe rate at which the body removes a drug from the blood.Read more → rate is why blood alcohol level falls in a straight line over time, not a curve.
Ethanol is broken down mainly by the enzyme alcohol dehydrogenase into acetaldehyde, then by aldehyde dehydrogenase into acetate. Because these enzymes become saturated even at low alcohol concentrations, ethanol shows zero-order kinetics at usual drinking levels: a constant amount, roughly one unit per hour, is cleared regardless of blood level. This differs from the first-order kinetics of most other drugs, where a constant fraction, not a constant amount, is cleared. Disulfiram, a drug used to support abstinence, blocks aldehyde dehydrogenase, causing acetaldehyde to build up and produce flushing and nausea if alcohol is then consumed. Chronic heavy drinking induces a separate enzyme system, CYP2E1, contributing to toleranceNeeding a larger dose of a drug over time to get the same effect.Read more →. For example, imagine a patient on disulfiram who has a single alcoholic drink at a party, the resulting flushing and nausea are severe enough to reliably deter further drinking. In practice, this means disulfiram works by making drinking unpleasant, not by reducing craving directly.
Most drugs are cleared from the body by first-order kinetics, meaning a constant fraction of the drug is removed per hour, so higher blood levels are cleared faster in absolute terms. Alcohol behaves differently, and that difference is not a trivia point: it is what lets a clinician predict roughly when a patient will be sober, explains why chronic drinkers tolerate sedatives differently, and underpins how withdrawal is recognised and treated.
At typical drinking levels, alcohol follows zero-order kinetics (a fixed amount cleared per hour regardless of how much is in the blood), roughly one standard unit per hour in an average adult. This matters clinically because it means blood alcohol level falls in a straight line over time rather than a curve, making the time to sobriety somewhat predictable from a single starting measurement.
It is tempting to assume alcohol scales with how much was drunk, the way it does for most drugs. It does not, and the reason is that the enzymes responsible are already saturated (working at maximum ) even at low alcohol concentrations. For example, imagine two people who drink very different quantities in one evening; both will clear roughly the same fixed number of units per hour, because the rate-limiting enzymes cannot go any faster no matter how much substrate is available, which is exactly what produces zero-order behaviour and makes alcohol the classic teaching example of it.
Ethanol is broken down mainly through two sequential enzyme steps. First, alcohol dehydrogenase (ADH), an enzyme found largely in the liver, converts ethanol into acetaldehyde, a toxic intermediate responsible for many hangover-like symptoms. Second, aldehyde dehydrogenase (ALDH) converts acetaldehyde into acetate, a relatively harmless compound the body can use for energy. Alongside ADH, a hepatic (liver-based) enzyme called CYP2E1, part of the family, also metabolises alcohol, and it becomes more active with chronic heavy drinking, a process called . This is one contributor to the seen in long-term heavy drinkers, since more enzyme activity means alcohol is cleared somewhat faster, though the primary ADH/ALDH route still dominates at typical drinking levels.
Disulfiram is a treatment used to support abstinence in alcohol dependence by deliberately blocking aldehyde dehydrogenase. When a patient taking disulfiram drinks alcohol, acetaldehyde builds up rather than being converted to acetate, producing a strong flushing reaction, nausea, palpitations, and headache. Suppose a patient stable on disulfiram has a single drink at a social event; the resulting reaction is typically unpleasant enough to reliably deter further drinking that evening, working by making drinking itself aversive rather than by reducing craving directly, a different mechanism from other pharmacological treatments for alcohol dependence such as acamprosate or naltrexone. Because alcohol is fairly predictable, clinicians can also use a starting blood alcohol concentration to estimate roughly when a patient will be sober enough for a procedure requiring assessment, or to interpret a reading in a forensic or occupational health context.
A level far higher than expected for the reported history, or a level that stays high with minimal apparent intoxication, is a clue to from chronic heavy drinking rather than simple acute intoxication, and prompts further investigation into dependence. Acute intoxication itself must be distinguished from alcohol withdrawal, which can look superficially similar (tremor, agitation, autonomic symptoms) but occurs as the level falls or after stopping, not while it is rising, and from Wernicke's encephalopathy, a distinct thiamine-deficiency complication of chronic alcohol use presenting with confusion, (unsteady gait), and eye movement abnormalities rather than a simple intoxication or withdrawal picture. Confusing these three matters because their management is completely different: observation for intoxication, a reducing benzodiazepine regimen for withdrawal, and urgent thiamine replacement for suspected Wernicke's.
Alcohol use disorder is identified through structured screening instruments and diagnostic criteria described in ICD-11 and DSM-5, alongside biomarkers such as gamma-glutamyl transferase (GGT) and mean corpuscular volume (MCV), which can suggest chronic heavy use even before a patient discloses their drinking history. These tools complement, rather than replace, a direct clinical history, and they are most useful when a patient's laboratory picture is inconsistent with what they report. Withdrawal itself is assessed using a structured screening tool to grade severity and guide the reducing regimen, since symptom severity, not blood alcohol level, drives the withdrawal treatment decision.
When a dependent drinker stops suddenly, the system, which alcohol enhances chronically, becomes under-stimulated, and glutamate activity, normally suppressed, rebounds. This produces the withdrawal syndrome: tremor, anxiety, autonomic instability, and, in severe cases, seizures or delirium tremens. NICE (National Institute for Health and Care Excellence) guidance recommends assessment tools and a symptom-triggered or fixed-dose benzodiazepine reducing regimen, most commonly chlordiazepoxide, as first-line management, alongside thiamine (vitamin B1) replacement to prevent . Longer-term relapse-prevention management adds acamprosate, naltrexone, or disulfiram depending on patient goals and suitability.
The high-yield trap is order of kinetics: examiners love asking what happens to as dose rises, and the answer for alcohol, uniquely among commonly tested drugs, is nothing, because it is already zero-order at ordinary drinking levels. The second classic trap is timing thiamine before glucose in a malnourished heavy drinker, since giving glucose first can precipitate or worsen by consuming the little thiamine that remains.
Alcohol's zero-order kinetics, roughly a fixed one unit per hour cleared via saturated hepatic ADH and ALDH, make blood alcohol level predictable over time and distinguish it from the first-order kinetics of most drugs, while chronic use induces CYP2E1 and underlies , and disulfiram exploits the ALDH step therapeutically to support abstinence.