Pharmacology for Anaesthesia and Intensive Care

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17 Central nervous system

Closed

CH 3

CH 2 NH 3

CH 3

N

N

N

N

CO

F

C

CI CI

F

N

Open

Figure 17.1.Structures of midazolam.

Benzodiazepines (BDZs)

Uses

BDZs are used commonly in anaesthesia as premedication and to sedate patients

during minor procedures. They are also used more widely as anxiolytics, hypnotics

and anticonvulsants.

Structure

Atits core BDZ have two ring structures. The first is a benzene ring (p93); the second

has seven members (5 carbon and 2 nitrogen) and is called a di-azepine ring. How-

ever, for pharmacological activity, BDZs also have a carbonyl group at position 2 on

the di-azepine ring, another benzene ring and a halogen on the first benzene ring.

Midazolam

Presentation

Midazolam is presented as a clear solution at pH 3.5. It is unique among the BDZs in

that its structure is dependent on the surrounding pH. At pH 3.5 its di-azepine ring

structure is open resulting in an ionized molecule, which is therefore water-soluble.

However, when its surrounding pH is greater than 4 its di-azepine ring structure

closes so that it is no longer ionized and therefore becomes lipid-soluble (Figure

17.1). Its pKais 6.5, so that at physiological pH 89% is present in an unionized form

and available to cross lipid membranes.

As it is water-soluble it does not cause pain on injection.