Intravenous Anaesthetics These agents belongs to the category of General Anesthetics. Intravenous anaesthetics usually cause unconsciousnes...
Intravenous Anaesthetics
These agents belongs to the category of General Anesthetics. Intravenous anaesthetics usually cause unconsciousness when administered parenterally. However, the duration of action can be safely monitored depending on the amount of drug administered. Intravenous (i.v.) anesthetics include etomidate, midazolam, propofol, thiopental, ketamine, and opioid agonists. The first four agents act by enhancing the activity of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the CNS. Ketamine antagonizes the effect of the excitatory neurotransmitter N-methyl-D-aspartate (NMDA) on NMDA receptors, and opioid agonists stimulate opioid receptors.
Medicinal Chemistry of some important Intravenous Anesthetics
These agents belongs to the category of General Anesthetics. Intravenous anaesthetics usually cause unconsciousness when administered parenterally. However, the duration of action can be safely monitored depending on the amount of drug administered. Intravenous (i.v.) anesthetics include etomidate, midazolam, propofol, thiopental, ketamine, and opioid agonists. The first four agents act by enhancing the activity of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the CNS. Ketamine antagonizes the effect of the excitatory neurotransmitter N-methyl-D-aspartate (NMDA) on NMDA receptors, and opioid agonists stimulate opioid receptors.
Explanation
Parenteral anesthetics are small, hydrophobic, substituted aromatic or heterocyclic compounds Hydrophobicity is the key factor governing their pharmacokinetics (Shafer and Stanski, 1992). After a single intravenous bolus, these drugs preferentially partition into the highly perfused and lipophilic tissues of the brain and spinal cord where they produce anesthesia within a single circulation time. Subsequently blood levels fall rapidly, resulting in drug redistribution out of the CNS back into the blood. The anesthetic then diffuses into less perfused tissues such as muscle and viscera, and at a slower rate into the poorly perfused but very hydrophobic adipose tissue. Termination of anesthesia after single boluses of parenteral anesthetics primarily reflects redistribution out of the CNS rather than metabolism. After redistribution, anesthetic blood levels fall according to a complex interaction between the metabolic rate and the amount and lipophilicity of the drug stored in the peripheral compartments (Hughes et al., 1992; Shafer and Stanski, 1992). Thus, parenteral anesthetic half-lives are "context-sensitive," and the degree to which a half-life is contextual varies greatly from drug to drug, as might be predicted based on their differing hydrophobicities and metabolic clearances . For example, after a single bolus of thiopental, patients usually emerge from anesthesia within 10 minutes; however, a patient may require more than a day to awaken from a prolonged thiopental infusion. Most individual variability in sensitivity to parenteral anesthetics can be accounted for by pharmacokinetic factors (Wada et al., 1997). For example, in patients with lower cardiac output, the relative perfusion of and fraction of anesthetic dose delivered to the brain is higher; thus, patients in septic shock or with cardiomyopathy usually require lower doses of anesthetic. The elderly also typically require a smaller anesthetic dose, primarily because of a smaller initial volume of distribution (Homer and Stanski, 1985). As described below, similar principles govern the pharmacokinetics of the hydrophobic inhalational anesthetics, with the added complexity of drug uptake by inhalation.
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Medicinal Chemistry of some important Intravenous Anesthetics
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