Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Mechanism of action

Flumazenil is a competitive BDZ antagonist. However, it has some agonist activity

as well and its ability to precipitate seizures in certain patients may be a result of

inverse agonist activity.

Effects

These include nausea and vomiting. It may also precipitate anxiety, agitation and

seizures especially in epileptic patients.

Kinetics

Flumazenil is 50% plasma protein bound and undergoes significant hepatic

metabolism to inactive compounds that are excreted in the urine.

Non-benzodiazepine hypnotics (the Z drugs)

Zopiclone, zaleplon and zolpidem are hypnotics that act via the BDZ receptor but

cannot be classified as benzodiazepines structurally. They were developed in order

to try to overcome some of the side effects of the BDZs, namely dependence and

next day sedation.

Zopiclone has the longest elimination half-life of approximately 5 hours while

zaleplon and zolpidem have elimination half-lives of 1 and 2 hours, respectively.

They have not had a major impact in the area of short-term hypnotics as they carry

all the same side effects as the BDZs. Only where there has been a specific intolerance

to a specific BDZ is switching to a Z drug recommended. Where general intolerance

is a problem the patient is just as likely to expereince intolerance to the Z drugs.

Antidepressants

Four groups of drugs are used to treat depression:


Tricyclics


Selective serotonin re-uptake inhibitors


Monoamine oxidase inhibitors


Atypical agents

Tricyclics – TCAs (amitriptyline, nortriptyline, imipramine, dothiepin)

As its name suggests, this group of drugs was originally based on a tricyclic ring

structure, although now many second-generation drugs contain different numbers

of rings.

Uses

TCAs are used to treat depressive illness, nocturnal enuresis and as an adjunct in the

treatment of chronic pain.