Anesthetics Lecture-2

ELIMINATION The time to recovery from inhalation anesthesia depends on the rate of elimination from the brain after the inspired concentration of the anesthetics has been decreased.

A. Blood gas partition coefficient: Inhaled anesthetics that are relatively insoluble in blood (low blood:gas partition coefficient) and brain are eliminated at faster rates than more soluble anesthetics. The “washout” of nitrogen oxide, which leads to rapid recovery from there anesthetic effects. Halothane is almost twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide; its elimination therefore takes place more slowly, and recovery from halothane anesthesia is less rapid.

B. The duration of exposure: D uration of exposure to the anesthetic can have a marked effect on the time of recovery, especially in the case of more soluble anesthetics such as methoxyflurane. Accumulation of anesthetics in tissues, including muscle, skin, and fat increases with continuous inhalation. And blood tension may decline slowly during recovery as the anesthetic gradually leaves such tissues. Thus if the exposure of anesthetic is short recovery may be rapid, and vice versa.

C. The magnitude of ventilation: Clearance of inhaled anesthetics by the lungs into the expired is the major route of elimination from the body. However metabolism by enzymes of the liver or other tissues may also contribute to the elimination of anesthetics. Example: 40% of inhaled halothane is metabolized during an average anesthetic procedure.

MECHANISM OF ACTION

A. ANATIMIC SITES OF ANESTHETIC ACTION General anesthetics interrupt nervous system function at myriad levels, including peripheral sensory neurons, the spinal cord, the Brian stems, and the cerebral cortex. Although the sites at which the intravenous anesthetics and inhaled anesthetics produce unconsciousness have not been identified, inhalational anesthetics have been shown recently to depress the excitability of thalamic neurons.

Finally both intravenous and inhalational anesthetics depress hippocampal neurotransmitter, this provides a probable locus for the amnesic effects of anesthetics.

B. PHYSIOLOGIC MECHANISM OF ANESTHESIC ACTION General anesthetics produce two important physiologic effects at the cellular lever. First. The inhalational anesthetics may or can HYPERPOLARIZE ( an inhibitory action) neurons. It also may be important in synaptic communication, since reduced excitivity in a postsynaptic neuron may reduce the chance of that an potential will be initiated in response to neurotransmitter release.

Second, both inhalational and intravenous anesthetics have substantial effect on synaptic function. The inhaled anesthetics have been shown to inhibit excitatory synapses and enhance inhibitory synapses. Intravenous anesthetics have a profound but specific effect on the post synaptic response to released neurotransmitters, they enhance inhibitory neurotransmission.

C. MOLECULAR ACTION OF GENERAL ANESTHETICS The electrophysiological effects of general anesthetics at the cellular level suggested several potential molecular targets for anesthetics action. Chloride channel gated by the inhibitory neurotransmitter gamma-aminobutyric acid are sensitive to clinical concentration of a wide variety of anesthetics. At clinical concentrations, general anesthetics increase the sensitivity of GABA A receptor to GABA, thus enhancing inhibitory neurotransmission and depressing nervous system activity.

Closely related to GABA A receptors are other ligand -gated ion channels including glycine receptors and neuronal nicotinic acetylcholine receptors. Clinical concentration of inhaled anesthetics enhance the ability of glycine to activate glycine-gated chloride channels ( glycinereceptors), which play an important role in inhibitory neurotransmission in the spinal cord and brain stem.

Current evidence supports the view that most of the intravenous general anesthetics act predominately through GABA A receptors and perhaps through some interaction with other ligand-gated ion channels. Nitrous oxide, Ketamine and Xenon constitute a third category of general anesthetics that are likely to produce unconsciousness via inhibition of the NMDA ( N-methyl D- aspartate) receptor.

ORGAN SYSTEM EFFECTS OF INHALED ANESTHETICS

Effects on cardiovascular system: Inhaled anesthetics change heart rate either by directly altering the rate of sinus node depolarization or by shifting the balance of autonomic nervous system activity. Bradycardia offen seen in case of Halothane inhalation probably happens through vegal nerve stimulation. All inhaled anesthetics tend to increase right arterial pressure in a dose-related fashion, which reflects depression of myocardial function.

Effects on Respiratory System: All inhaled anesthetics(except NO 2 ) cause decrease in tidal volume and an increase in respiratory rate. However the increase in reate is insufficient to compensate for the decrease in volume, resulting in decrease in minute ventilation. Inhaled anesthetics also depress mucociliary function in the airway. Thus prolonged anesthesia may lead to pooling of mucus and then result in atelectasis and respiratory infection.

Effects on Brain: Inhaled anesthetics decrease the metabolic rate of brain. Most of them increase cerebral blood flow because they decrease cerebral vascular resistance.

Effects on the Kidney: To varying degrees, all inhaled anesthetics decrease glomerular filtration rate and effective renal plasma flow and increase filtration fraction. All the anesthetics tend to increase renal vascular resistance. Possible nephrotoxicity occurs.

Effects on the liver: All inhaled anesthetics causes a decrease in hepatic blood flow, ranging from 15% to 45% of the preanesthetic flow. Rarely permanent damage occurs in liver function for the use of these agents.

Effects of Uterine Smooth Muscle: The halogenated hydrocarbon anesthetics are potent uterine muscle relaxants. This pharmacologic effects can be used to advantage when profound uterine relaxation is required for intrauterine fetal manipulation during delivery.