Anesthetics Drug Pharmacodynamics

Dr. A. Alisher MD PhD AL SABAH & ZAIN HOSPITALS, MOH, KUWAIT

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Anesthetics drug PhDs

Anesthesia cannot be defined in an unambiguous manner.
The essential components of GA are absence of consciousness and pain.

Anesthetics drug PhDs

This translates into two particular qualities: (1) Sedation and Hypnosis, i.e., mental blockade and (2) Analgesia / Antinociception, i.e., sensory blockade.

Anesthetics drug PhDs

Anesthetic actions on these two subcomponents are difficult to separate.

Anesthetics drug PhDs

On the one hand, very few anesthetics act exclusively on one of these components. On the other hand, these components are closely related to each other.

Anesthetics drug PhDs

Unconsciousness prevents (conscious) perception of pain, and nociception may serve as an arousal stimulus and change the level of sedation and hypnosis.

Anesthetics drug PhDs

The art of anesthesia lies in adequate dosing of drugs to reach both mental and sensory blockade.
Drug administration can be based on PhK considerations.

Anesthetics drug PhDs

PhK models allow an estimation of what happens to the administered drug in the body.
Models with an effect site compartment may facilitate a tailored administration of anesthetic drugs.
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Anesthetics drug PhDs

Finally, the quantification of PhD effects allows a precise titration of drugs.
Clinical assessment of mental blockade is often dichotomous, and therefore not very helpful to guide drug administration.

Anesthetics drug PhDs

Several scoring systems exist, but once consciousness is lost they become less reliable, in particular because reaction to stimuli is assessed, which mixes assessment of mental blockade with assessment of sensory blockade.

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Anesthetics drug PhDs

Clinical assessment of analgesia requires a conscious patient, so antinociception is difficult to measure. Several methods of objective quantification on the basis of electrical brain activity are discussed including EEG and evoked potentials.
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Anesthetics drug PhDs

Despite numerous indexes of the hypnotic component of anesthesia, there is no parameter that unambiguously quantifies the level of mental or sensory blockade.

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Anesthetics drug PhDs

Bischoff P, Schneider G, Kochs E. Anesthetics drug pharmacodynamics. Handb Exp Pharmacol. 2008;(182):379408. Klinik und Poliklinik fr Ansthesiologie, Universittsklinikum Hamburg-Eppendorf, Gebude O50, Martinistrasse 52, 20246, Hamburg, Germany. bischoff@uke.unihamburg.de 13

PhK-PhD modeling in anesthesia, intensive care and pain medicine

Sadean MR, Glass PS. Pharmacokineticpharmacodynamic modeling in anesthesia, intensive care and pain medicine. Curr Opin Anaesthesiol. 2009 Aug;22(4):463-8. Department of Anesthesiology, SUNY at Stony Brook, Stony Brook, New York, USA. msadean@notes.cc.sunysb.edu
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PhK-PhD modeling in anesthesia, intensive care and pain medicine

The most important developments in the field of PhK - PhD modeling.

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PhK-PhD modeling in anesthesia, intensive care and pain medicine

The PhK models focused on incorporating covariate, especially age for pediatricgeriatric use, and altered physiological states.

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PhK-PhD modeling in anesthesia, intensive care and pain medicine

The PhD models studied the effect of rate of anesthetic administration, age, experimental conditions, and delay within the monitor on estimation of drug concentration in the biophase.

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 Models for the surrogate measure of the components of GA: Hypnosis (bispectral index scale, entropy), Immobility (limb tetanic stimulus-induced withdrawal reflex); And antinociception (surgical stress index, skin conductance algesimeter) were developed and validated.

PhK-PhD modeling in anesthesia, intensive care and pain medicine

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 Response surface models were used to study drug interactions for important endpoints during surgery and also to optimize dosing of anesthetic agents to maximize the desired/undesired effect ratio.

PhK-PhD modeling in anesthesia, intensive care and pain medicine

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PhK-PhD modeling in anesthesia, intensive care and pain medicine

The models for TCIs were improved by incorporating more covariates, and the closed-loop system was refined by using adaptive controllers that individualize the PhK/PhD parameters to the particular patient by using Bayesian, Kalman filters, fuzzy logic or neural networks.
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PhK-PhD modeling in anesthesia, intensive care and pain medicine

Progress was made by improving population PhK / PhD models, developing new indexes to measure drug effect and using them in an adaptive delivery system to the individual patient.

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