Drug Interactions(June 2006)

7/28/2019 Drug Interactions(June 2006)

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DRUG INTERACTIONS(June 2006)

INTRODUCTION

->Modern anesthesiologist tries to balance the anaesthesia technique and herelies 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.


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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 thecombined 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=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.


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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 INADVISABLE TO INJECT

Dopamine Aminophylline,Sodium Bicarbonate

Dobutamine Aminophylline,Sodium Bicarbonate

Lignocaine Frusemide,Sodium Bicarbonate

Mannitol Frusemide,Potassium Iodide

Aminophylline Adrenaline,Mannitol,Thiopentone

Pethidine Morphine,Thiopentone,Succinyl choline

Sodium Bicarbonate Pethidine,Morphine,Thiopentone

Thiopentone Atracurium

Potassium Chloride 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:-


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1. Lithium

carbonate

Muscle relaxant Potentiation

2. -blockers Inhalational agents Additive or

synergistic

effectNeostigmine

Pyridotigmine

Sever e bradycardia Synergistic

3. Nifedipine -blockers Profound

Hypotension

Synergism

4. Digoxin -blockers Inotropy not affected

,Chronotropy and

dromotropy

enhanced

Additive

effect

5. Cimetidine Diazepam,LignocaineWarfarin,Propranolol

Theophylline,Phenytoin,

Phenobarbitone

Cimetidine binds top450 enzyme

system,decreases the

metabolism of these

drugs

Potentiation

6. MAO

Inhibitors and

TCA

Pethidine Deep

coma,Hyper/hypo

tension,respiratory

arrest,hyperpyrexia

Marked

potentiation

7. Levodopa Droperidol Precipitatesparkinsonism

Antagonism

8. Isoniazid Enflurane Induces

defluorination

Antagonism

9. Erythromycin-

7 day course

Midazolam Inhibits the

metabolism,prolongs

the action of

Midazolam

Potentaition


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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.

Drug Interactions(June 2006)

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