CLINICAL PHARMACOLOGY 2003 (PART 9C)

The following mechanisms are involved. Glomerular filtration. The rate at which a drug enters the glomerular filtrate depends on the concentration of free drug in plasma water and on its molecular weight. Substances that have a molecular weight in excess of 50 000 are excluded from the glomerular filtrate while those of molecular weight less than 10 000 (which includes almost all drugs)21 pass easily through the pores of the glomerular membrane. Renal tubular excretion. Cells of the proximal renal tubule actively transfer strongly charged molecules from the plasma to the tubular fluid. There are two such systems, one...
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CLINICAL PHARMACOLOGY 2003 (PART 9C) E LIM I N A T I O N 7RENAL ELIMINATION absorbed from the gut, e.g. neomycin. Drug in the blood may also diffuse passively into the gutThe following mechanisms are involved. lumen, depending on its pKa and the pH difference between blood and gut contents. The effectivenessGlomerular filtration. The rate at which a drug of activated charcoal by mouth for drug overdoseenters the glomerular filtrate depends on the con- depends partly on its adsorption of such diffusedcentration of free drug in plasma water and on its drug, which is then eliminated in the faeces (seemolecular weight. Substances that have a molecular p. 155).weight in excess of 50 000 are excluded from theglomerular filtrate while those of molecular weight Biliary excretion. In the liver there is one activeless than 10 000 (which includes almost all drugs)21 transport system for acids and one for bases, similarpass easily through the pores of the glomerular to those in the proximal renal tubule and, in addition,membrane. there is a system that transports un-ionised molecules, e.g. digoxin, into the bile. Small molecules tend toRenal tubular excretion. Cells of the proximal renal be reabsorbed by the bile canaliculi and in generaltubule actively transfer strongly charged molecules only compounds that have a molecular weightfrom the plasma to the tubular fluid. There are two greater than 300 are excreted in bile. (See also,such systems, one for acids, e.g. penicillin, probenecid, enterohepatic circulation, p. 105)frusemide, and another for bases, e.g. amiloride,amphetamine. PULMONARY ELIMINATIONRenal tubular reabsorption. The glomerular filtratecontains drug at the same concentration as it is free The lungs are the main route of elimination (and ofin the plasma, but the fluid is concentrated uptake) of volatile anaesthetics. Apart from this,progressively as it flows down the nephron so that they play only a trivial role in drug elimination. Thea gradient develops, drug in the tubular fluid route however, acquires notable medicolegal sig-becoming more concentrated than in the blood nificance when ethanol concentration is measured inperfusing the nephron. Since the tubular epithelium the air expired by vehicle drivers involved in roadhas the properties of a lipid membrane, the extent traffic accidents (via the breathalyser).to which a drug diffuses back into the blood willdepend on its lipid solubility, i.e. on its pKa in thecase of an electrolyte, and on the pH of tubular CLEARANCEfluid. If the fluid becomes more alkaline, an acidic Elimination of a drug from the plasma is quantifieddrug ionises, becomes less lipid-soluble and its in terms of its clearance. The term has the samereabsorption diminishes, but a basic drug becomes meaning as the familiar renal creatinine clearance,un-ionised (and therefore more lipid-soluble) and which is a measure of removal of endogenousits reabsorption increases. Manipulation of urine creatinine from the plasma. Clearance values canpH is given useful expression when sodium provide useful information about the biological fatebicarbonate is given to alkalinise the urine to treat ...