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Pharmacokinetics in anaesthesia
The loading dose depends on the volume of distribution, the maintenance rate on clearance, and the duration of action after an infusion is set by the "context-sensitive half-time" — which grows with infusion length for most drugs but hardly changes for remifentanil.
Why it matters in the exam
The exam asks what the context-sensitive half-time is and which drug has a short, constant one, why waking from a single dose comes from redistribution, the difference between first-order and zero-order kinetics, how many half-lives are needed to reach steady state, and what sets the hepatic clearance of a high versus a low extraction drug. It also asks about protein binding and enzyme induction and inhibition.
The context-sensitive half-time is how long plasma levels take to halve once an infusion of a given length is stopped. For fentanyl it lengthens greatly after an infusion of a few hours, because the drug has accumulated in tissues; for propofol it rises moderately; and for remifentanil it is about 3–4 minutes almost regardless of duration, because blood esterases break it down. Steady state is reached after 4–5 half-lives, and the half-life equals 0.693 times the volume of distribution divided by clearance.
When the liver extracts a drug efficiently (high extraction ratio: propofol, lidocaine, morphine, fentanyl), its clearance follows hepatic blood flow — so a fall in cardiac output slows it. For drugs with a low ratio (warfarin, phenytoin, diazepam) clearance depends on enzyme activity and the free fraction. Acidic drugs bind to albumin, and basic drugs to alpha-1 acid glycoprotein, which rises in stress states. With phenytoin and alcohol at high doses kinetics become zero-order — a fixed amount is cleared each hour.
Key points
- Volume of distribution sets loading; clearance sets maintenance.
- Half-life = 0.693 × volume of distribution ÷ clearance.
- Remifentanil: context-sensitive half-time about 3–4 minutes, constant.
- Steady state after 4–5 half-lives.
- High hepatic extraction — flow-dependent; low — enzyme-dependent.
Summary table
| Concept | Definition | Exam example |
|---|---|---|
| Volume of distribution | How far the drug "spreads" outside the blood; sets the loading dose | Larger with fat and ascites |
| Clearance | Plasma volume cleared per unit time; sets the maintenance dose | Falls in liver and kidney failure |
| Context-sensitive half-time | Time to fall by half after an infusion of a given duration | Remifentanil short and constant; fentanyl lengthens |
| First order versus zero order | A constant fraction versus a constant amount per unit time | Phenytoin and alcohol at high doses — zero order |
| Hepatic extraction ratio | High — flow-dependent; low — dependent on enzymes and binding | Propofol, lidocaine versus warfarin, phenytoin |
A free exam question
למטופל אישון קטן מימין (miosis) , העפעף נופל באותו צד (ptosis) , והוא גם אינו מזיע בצד ימין (anhidrosis) . נוירולוג נותן למטופל טיפות של hydroxyl amphetamine בעיניים ללא תגובה. הוא מכריז שהמקור האנטומי של הפגיעה ב ”3rd order neuron” . איזה אבחנה יכולה להסביר את כל הקליניקה של המטופל? (the question as examined, in Hebrew)
- א. הרדמה אפידורלית
- ב. אירוע מוחי
- ג. Carotid dissection
- ד. ניתוח Cataract
In the full version for subscribers
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Sources
- Miller's Anesthesia, 9th edition (2020) — Basic Principles of Pharmacology
- Morgan & Mikhail's Clinical Anesthesiology, 7th edition (2022) — Pharmacological Principles
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-02. The text may contain errors; when in doubt, check the source.