Drug Lists — Triggers, Protein Binding, Vd

Malignant hyperthermia

A short list, and the exam wants both halves of it. The defect is in the ryanodine receptor (RYR1), causing uncontrolled calcium release from the sarcoplasmic reticulum.

Triggers	Safe
ALL volatile anaesthetic agents — halothane, isoflurane, sevoflurane, desflurane, enflurane Suxamethonium	Nitrous oxide · propofol · thiopentone · etomidate · ketamine All opioids · benzodiazepines All non-depolarising relaxants Local anaesthetics · neostigmine · atropine

Management

Stop the trigger, call for help, hyperventilate with 100% oxygen at high flows, change to a vapour-free circuit and machine, and abandon or finish surgery quickly.
Dantrolene 2.5 mg/kg IV, repeated as needed up to about 10 mg/kg. It acts on the ryanodine receptor.
Treat the consequences: active cooling, hyperkalaemia, arrhythmias, acidosis, myoglobinuria (forced diuresis), DIC. Monitor core temperature, ABGs, CK and urine output.
Refer for follow-up testing — the in-vitro contracture test on a muscle biopsy remains the gold standard.

Acute porphyria

Anything that induces ALA synthase can precipitate an attack, because it drives the pathway upstream of the enzyme block. Barbiturates are the classic example.

Unsafe / avoid	Generally considered safe
Barbiturates (thiopentone) — the classic trigger Etomidate Amiodarone Phenytoin, carbamazepine, sodium valproate Sulphonamides, erythromycin, rifampicin Diclofenac Ranitidine Prilocaine, ropivacaine Clonidine · nifedipine · pentazocine Oral contraceptives · alcohol	Propofol · ketamine Suxamethonium and all non-depolarising relaxants Nitrous oxide · volatile agents Morphine, fentanyl, alfentanil · paracetamol · aspirin Bupivacaine, procaine Neostigmine · atropine · glycopyrrolate Ondansetron · droperidol Beta blockers · magnesium

Two honest caveats

Lists differ between sources, and some drugs (benzodiazepines, lidocaine, ketamine) appear as "safe" on one list and "use with caution" on another. For a real patient, check a live database such as the Norwegian Porphyria Centre (NAPOS) drug list rather than any textbook table.
Prilocaine is on your page and is widely listed as porphyrinogenic — but bupivacaine is the local anaesthetic to reach for if you need one, and it is consistently listed as safe.
An acute attack presents with abdominal pain, vomiting, neuropsychiatric features, seizures, autonomic instability and hyponatraemia. Treat with carbohydrate loading and haem arginate, plus removal of the trigger.

Protein binding

Only the unbound fraction is pharmacologically active. Acidic drugs bind albumin; basic drugs bind α₁-acid glycoprotein.

Drug	Bound	Why it matters
Warfarin	99%	The highest. A tiny change in binding produces a large change in free drug — the basis of many interactions
Diazepam	~99%
Bupivacaine	~95%	High binding underlies its long duration
Propofol	~98%
Alfentanil	~90%	Despite this, its low pKa gives it the fastest onset of the fentanyl family
Fentanyl	~80%
Thiopentone	~80%	In hypoalbuminaemia the free fraction rises — reduce the induction dose
Lidocaine	~65%
Morphine	~30–35%	The lowest of the group

When binding changes

Free fraction rises in hypoalbuminaemia (liver disease, malnutrition, nephrotic syndrome, pregnancy, the elderly), in uraemia (which displaces acidic drugs), and with displacement by another highly-bound drug.
α₁-acid glycoprotein is an acute phase protein: it rises after surgery, trauma and in malignancy, so basic drugs such as local anaesthetics become more bound and less free.

Volume of distribution

Vd = amount of drug in the body ÷ plasma concentration. It is an apparent volume — a large Vd means extensive tissue binding, not a large body.

Large Vd (>100 L)	Small Vd (<30 L)
Digoxin ~600 L — extensively bound to skeletal and cardiac muscle Fentanyl ~250–350 L — highly lipid soluble Morphine ~200–250 L Thiopentone ~160 L	Alfentanil ~25 L — small Vd explains its rapid offset Gentamicin ~18 L — confined to ECF, hence dosed on lean weight Vecuronium ~15 L Atracurium ~12 L Warfarin ~8 L — nearly all albumin-bound, so it stays in plasma

What Vd predicts

Loading dose = target concentration × Vd. Vd determines the loading dose; clearance determines the maintenance dose.
t½ = 0.693 × Vd / clearance. A large Vd prolongs half-life even when clearance is normal.
Drugs with a small Vd (aminoglycosides, non-depolarising relaxants) are largely confined to ECF, so dose by lean body weight and expect altered kinetics in oedema, ascites and pregnancy.
A large Vd means dialysis and haemofiltration remove the drug poorly — relevant in overdose.

Built from handwritten pages IMG_0976–0978. Protein binding and Vd figures shown are standard reference values; where your page differed slightly (morphine binding and Vd) the standard figure is given here.