Pharmacology for Anaesthesia and Intensive Care

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Section IBasic principles

and 3A4. Food and drink can also influence the activity of the cytochrome system;

grapefruit juice inhibits CYP3A4, broccoli induces 1A2 and ethanol induces 2E1.

Excretion

Sodium bicarbonate will make the urine more alkaline, which enhances the excretion

of weak acids such as aspirin or barbiturates. Thus, aspirin overdose has been treated

with infusions of fluid to produce a diuresis, together with sodium bicarbonate, to

alkalinize the urine and to promote its renal excretion.

Pharmacodynamic

Pharmacodynamic interactions may be direct (same receptor system) or indirect

(different mechanisms, same end-effect).

Direct interactions

Flumazenil is used therapeutically to reverse the effects of benzodiazepines and

naloxone to reverse the effects of opioids. This competitive antagonism is useful in

treating drug overdose from these agents.

Indirect interactions

The use of neostigmine in the presence of non-depolarizing muscle relaxants

(NDMRs) is an example of an indirect interaction that is used therapeutically.

Neostigmine inhibits acetylcholinesterase and so increases acetylcholine concentra-

tion in the synaptic cleft that can then compete for nicotinic receptors and displace

the NDMR.

Both enoximone and adrenaline are positive inotropic agents with different mech-

anisms of action that can interact indirectly to improve contractility. Adrenaline

works via a GPCR whereas enoximone acts intracellularly by inhibiting phosphodi-

esterase but both actions result in an increase in intracellular cAMP levels. Captopril

andβ-blockers act additively to lower blood pressure by an indirect interaction; one

via the renin-angiotensin system and the other via adrenoceptors.

Diuretics through their action on the levels of potassium may indirectly cause

digoxin toxicity.

Summation

Summation refers to the action of the two drugs being additive, with each drug having

an independent action in the absence of the other. Therefore, the co-administration

of midazolam and propofol at the induction of anaesthesia reduces the amount of

propofol necessary for the same anaesthetic effect.