Interacting drug	Effect	Mechanism	Management
Diazoxide, salicylates, probenecid	Hypotension	Pharmacokinetic. Competition with barbiturates for plasma protein binding sites	Reduce dose of barbiturate. Treat hypotension with IV fluids
ß-Blockers (alprenolol,† metoprolol)	Reduced serum ß-blocker concentrations	Pharmacokinetic. Enhanced metabolism by barbiturates	Close monitoring
Monoamine oxidase inhibitors	Hypotension, CNS and respiratory depression	Pharmacokinetic. Interference with biotransformation of barbiturates	Supportive treatment. Consider using regional blocks with local anaesthetics. Titrate dose of barbiturate
Opioids, propofol, benzodiazepines	Potentiation of hypnotic effects and respiratory depression	Pharmacodynamic. Additive or synergistic interaction	Clinically useful. Titrate dose of barbiturate. monitor respiratory function and consider using mechanical ventilation when indicated
Opioids	Reduction in the incidence of excitatory phenomena with methohexital	Pharmacodynamic (unknown mechanism)	Clinically useful combination
Ketamine (subhypnotic doses)	Antagonism of thiopental sodium	Pharmacodynamic	Increase dose of thiopental sodium
Metoclopramide	Decreases thiopental sodium dose requirements	Pharmacodynamic. Dopamine receptor antagonism	May be clinically useful
Adrenergic drugs	Dysrhythmias	Pharmacodynamic	Treat ventricular dysrhythmia with lidocaine (lignocaine)
Promethazine, scopolamine (hyoscine)	Increased muscular movements caused by methohexital	Pharmacodynamic (unknown mechanism)	Avoid combination
Suxamethonium chloride (succinylcholine)	Aggregate formation resulting in disseminated intravascular coagulation	Pharmacodynamic	Administer drugs into large veins. Flush tubing with saline between administration of each drug

^†Methohexital and alprenolol are not available in Spain.
Abbreviation: IV = intravenous.

Interacting drug	Effect	Mechanism	Management
Halothane	Increased serum concentrations of propofol (may cause CNS and respiratory depression)	Pharmacokinetic. Altered plasma protein binding of propofol	Titrate propofol dosage
Alfentanil, propranolol	Increased plasma concentrations of alfentanil and propranolol can cause respiratory depression, hypotension, bradycardia	Pharmacokinetic. Altered plasma protein binding of alfentanil and propranolol	Titrate dosage of propofol. Treat hypotension and bradycardia in conventional manner
Monoamine oxidase inhibitors (MAOIs)	Hypotension, CNS and respiratory depression	Pharmacokinetic. Interference with biotransformation	Supportive treatment. Consider using regional blocks with local anaesthetics in patients taking MAOIs
Thiopental sodium (thiopentone sodium), benzodiazepines	Potentiation of hypnotic effects and respiratory depression	Pharmacodynamic. Synergistic interaction	Reduce doses of propofol, thiopental sodium and benzodiazepines. Monitor respiratory function and consider using mechanical ventilation when indicated
ACE inhibitors (enalapril)	Hypotension and bradycardia	Pharmacodynamic	Treat hypotension with IV fluids and small doses of direct alpha-adrenergic vasopressors. Treat bradycardia with atropine
Enflurane,† pethidine (meperidine)	Epileptic seizures, CNS and respiratory depression	Pharmacodynamic. Propofol can induce epileptiform activity	Drugs lowering the seizure threshold should be avoided
Epinephrine (adrenaline)	Dysrhythmias	Pharmacodynamic. Decreased threshold for dysrhythmias	Limit the dose of epinephrine to 2 µg/kg. Consider coadministration of lidocaine (lignocaine) and epinephrine. Treat ventricular dysrhythmias with lidocaine
Aminophylline	Decreased effectiveness of propofol	Pharmacodynamic. Antagonism	Monitor (evidence is not conclusive for type of management required)
Suxamethonium chloride (succinylcholine)	Bradycardia	Pharmacodynamic	Treat with atropine
Atracurium besilate	Anaphylactoid reaction (possible aggregate anaphylaxis)	Pharmacodynamic. Histamine release	Flush the tubing with saline between administration of each drug

^† Enflurane is not available in Spain.
Abbreviation: IV = intravenous.

Interacting drug	Effect	Mechanism	Management
Fentanyl	Cardiovascular depression	Pharmacokinetic. Reduced clearance of etomidate	Decrease the dose of etomidate
Diazepam	Reduction in the excitatory effects of etomidate	Pharmacodynamic	Clinically useful
Vecuronium bromide	Bradycardia	Pharmacodynamic. Lack of vagolytic action	Treat with atropine, or consider substitution of vecuronium bromide with an alternative neuromuscular blocking agent
Pancuronium bromide	Prolongation of the neuromuscular block	Pharmacodynamic	Monitor neuromuscular function and titrate doses of pancuronium bromide. Consider using a short- or intermediate-acting neuromuscular blocking agent instead of pancuronium bromide

Interacting drug	Effect	Mechanism	Management
Halothane, diazepam	Prolonged recovery due to increased plasma concentration and prolongation of elimination half-life of ketamine	Pharmacokinetic. Decreased hepatic clearance of ketamine	Reduce dosages of ketamine and other drugs
Volatile anaesthetics	Reduced cardiac output, hypotension	Pharmacodynamic. Blockade of the indirect cardiovascular stimulant effects of ketamine	Careful monitoring
Thyroxine	Hypertension and supraventricular tachycardia (in 2 reported cases)	Pharmacodynamic	Ketamine should be used cautiously. Treat hypertension if present
Theophylline	Extensor-type seizures (in 4 reported cases)	Pharmacodynamic. Possible reduction in seizure threshold	Maintain theophylline concentration within the therapeutic range
Metrizamide†	Seizures	Pharmacodynamic	Ketamine should be avoided
Thiopental sodium (thiopentone sodium)	Subhypnotic doses of ketamine	Pharmacodynamic antagonises thiopental sodium	Higher doses of thiopental sodium may be required
Tubocurarine,† atracurium besilate	Prolongation of the neuromuscular block	Pharmacodynamic	Monitor neuromuscular function and titrate doses of neuromuscular blocking drugs

^†Metrizamide is not available in France, Germany and Spain; tubocurarine is not available in Spain.