Pharmacological Principles


Most anesthetic drugs are lipophilic, resulting in a Vd that exceeds total body water (∼ 40 L). For example the Vd of fentanyl is about 350 L in adults, and the Vd for propofol may exceed 5000 L.



 

Biotransformation: The chemical alteration of the drug molecule. Also referred to as metabolism.


The liver is the primary organ of metabolism. The end products are usually—but not necessarily—inactive and water soluble. The latter property allows excretion by the kidney.


Can be divided into phase I and phase II reactions.



° Phase I reactions convert drug into more polar metabolites through oxidation, reduction, or hydrolysis.


° Phase II reactions couple (conjugate) a parent drug or a phase I metabolite with an endogenous substrate (e.g., glucuronic acid) to form water-soluble metabolites that are eliminated in the urine or stool.


Phase I metabolites may be excreted without undergoing phase II biotransformation, and a phase II reaction can precede or occur without a phase I reaction.


Hepatic clearance: Volume of plasma or blood cleared of drug per unit of time


The hepatic clearance is liver blood flow times the hepatic extraction ratio (which is the fraction of drug entering the liver that is metabolized.)


Example: If the extraction ratio is 50%, then hepatic clearance is half of liver blood flow.


Excretion


The kidneys are the principal organ of excretion. The nonionized fraction of drug is reabsorbed in the renal tubules, and the ionized portion is excreted in urine.


Renal clearance is the rate of elimination of a drug from kidney excretion and can be calculated by renal blood flow times the renal extraction ratio.


Enterohepatic recirculation: drug excreted into the bile and then reabsorbed in the intestine.


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Jan 28, 2017 | Posted by in ANESTHESIA | Comments Off on Pharmacological Principles

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