DRUG INTERACTIONS(June 2006)

INTRODUCTION ->Modern anesthesiologist tries to balance the anaesthesia technique and he relies on polypharmacy.Interactions of drugs invariably occur, as many drugs are used which are having varied actions and metabolic pathways. Elderly patients are at the greatest risk for adverse drug interactions. ->An anaesthesiologist is more likely to face the problems of drug interactions because he i)uses large number of drugs in a shorter time ii)frequently relies on drug antagonism iii)titrates the doses(or concentration )of drugs for the desired effects. iv)measures the clinical response to drugs. ->Pharmacokinetic factors that influence plasma concentration of drugs i)Tissue uptake ii)Renal excretion iii)Hepatic metabolism ->Types of drug interactions i) Additive effect(summation)(2+2=4):-the combined effect of two drugs equals the sum of the effects of the individual drugs e.g 70 Nitrous Oxide 0.3 MAC Halothane achieves the same effect as 1.0 MAC Halothane ii)Potentiation(2+0=>2):-Enhancement of action of a drug by a second drug,which has no action of its own.

e.g Aminoglycoside antibiotics enhance the action of non-depolarising type of muscle relaxants.Antibiotics administered alone in ususal doses to an awake patient do not have any effect at neuro muscular junction iii)Synergism(2+2=>4):-The effect of the combination is greater than the combined effect of the two drugs e.g Pethidine 1mg/Kg IV produces deep sedation(or coma) in patient on MAO Inhibitors used in the management of endogenous depression iv)Antagonism(2+2=<4):-Action of one drug is opposed by another e.g use of an anticholinesterase for reversing the residual effects of a nondepolarising muscle relaxants. CLASSIFICATION OF DRUG INTERACTIONS i)In Vitro interactions ii)Pharmacokinetic interactions iii)Pharamacodynamic interaction i)In Vitro interactions ->This type of reaction occurs before the drugs enter the body. ->Insulin,Diazepam adheres to the glass or plastic container and IV infusion sets.All the drug will not reach the patients circulation. ->Orally given drugs are adsorbed by previously given activated charcoal,aluminium silicate and reduce the potency. ->High alkaline pH drug;Thiopentone reacts with acidic drugs(e.g Scoline,Morphine,Lignocaine,Pethidine,Ketamine,Pentazocine,Pancuronium)formi ng a white precipitate. ->The following drugs should not be injected into the side port when the blood is flowing through a blood administration set.

a)Calcium-antagonism of the anticoagulant citrate b)Mannitol-crenating of blood cells c)Sodium bicarbonate-antagonism of acid in the anticoagulant d)Dextrose-clumping of cells. e)5% Dextrose,0.9% NaCl are acidic. f)Aminophylline INFUSION ON FLOW Dopamine Dobutamine Lignocaine Mannitol Aminophylline Pethidine Sodium Bicarbonate Thiopentone Potassium Chloride INADVISABLE TO INJECT Aminophylline,Sodium Bicarbonate Aminophylline,Sodium Bicarbonate Frusemide,Sodium Bicarbonate Frusemide,Potassium Iodide Adrenaline,Mannitol,Thiopentone Morphine,Thiopentone,Succinyl choline Pethidine,Morphine,Thiopentone Atracurium Adrenaline,Mannitol,Thiopentone

ii)Pharmacokinetic interactions ->Best known pharmacokinetic interaction is hastening of induction of Halothane by addition of Nitrous Oxide to the inhaled mixture(second gas effect). ->Broncho-dilators given to a patient with COPD improves the ventilation as well as v/q match and thus hasten the induction of anaetshesia. iii)Pharmacodynamic interactions -There are many possibilities for pharmacodynamic interactions at all the levels of anaesthesia.They are depicted in the form of tables:-

1. Lithium carbonate 2. -blockers

Muscle relaxant Inhalational agents

Potentiation Additive or synergistic effect Synergistic Synergism Additive effect

3. Nifedipine

Profound Hypotension 4. Digoxin Inotropy not affected -blockers ,Chronotropy and dromotropy enhanced 5. Cimetidine Diazepam,Lignocaine Cimetidine binds to Warfarin,Propranolol p450 enzyme Theophylline,Phenytoin, system,decreases the Phenobarbitone metabolism of these drugs 6. MAO Pethidine Deep Inhibitors and coma,Hyper/hypo TCA tension,respiratory arrest,hyperpyrexia 7. Levodopa Droperidol Precipitates parkinsonism 8. Isoniazid Enflurane Induces defluorination 9. Erythromycin- Midazolam Inhibits the 7 day course metabolism,prolongs the action of Midazolam

Neostigmine Pyridotigmine -blockers

Sever e bradycardia

Potentiation

Marked potentiation

Antagonism Antagonism Potentaition

CONCLUSION As the drug interactions are very common,the anaesthetist must be aware of the actions and interactions of every drug he is using and be prepared for known and unknown complications.