Moderate and deep sedation can be provided using various classes of drugs, each having unique mechanisms of action. While drugs within a given classification share similar mechanisms and effects, certain classes demonstrate superior efficacy but added concern regarding safety. This continuing education article will highlight essential principles of pharmacodynamics and apply these to drugs commonly used to produce moderate and deep sedation.
Drug potency versus efficacy. This dose-response curve compares 3 drugs that can be used to increase heart rate. Drug A has the greatest potency because it produces effects at the lowest dose. However, it has the least efficacy because it can increase heart rate only 80%. In contrast, Drug C has the least potency but demonstrates the greatest efficacy. Notice that Drug A 10 mg, Drug B 20 mg, and Drug C 30 mg will increase heart rate 80%. These are regarded as “equipotent” doses.
The GABAA receptor complex. The GABAA receptor complex consists of several protein subunits, with each comprised further of subunit families. These subunits provide myriad sites or receptors at which drugs may bind. While GABA and its precise receptor is the normal “commander” of the chloride channel, benzodiazepines can potentiate its influence. Additional drugs such as propofol and barbiturates not only potentiate the influence of GABA but are able to open the channel directly.
Biotransformation of various benzodiazepines. Parent drugs and their active metabolites vary in their elimination half-lives: L, >24 hours; I, 6–24 hours; and S, <6 hours (derived from Mihic and Harris7).
Midazolam configurations. The midazolam molecule exists in an open ring, water soluble state while in formulated solutions for parenteral injection. When subjected to physiologic pH upon administration, the ring closes, rendering the molecule highly lipid soluble.
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