Title 5. ELIMINATION ENHANCEMENT.pdf ✅

PHARMD GURU Page 1 The various methods of eliminating absorbed poisons from the body include the following: 1) Forced Diuresis 2) Extracorporeal techniques Extracorporeal techniques include:  Haemodialysis  Haemoperfusion  Peritoneal dialysis  Haemofiltration  Plasmapheresis  Plasma perfusion  Cardiopulmonary bypass 1) FORCED DIURESIS: Most drugs taken in overdose are extensively detoxified by the liver to produce inactive metabolites which are voided in the urine. Sometimes hepatic degradation produces active metabolites, but the secondary compounds are then converted to non-toxic derivatives. Under these circumstances, forced diuresis is inappropriate. The procedure should be undertaken only if the following conditions are satisfied: 1) A substantial proportion of the drug is excreted unchanged. 2) The drug is distributed mainly in the extracellular fluid. 3) The drug is minimally protein-bound. 4) Principle:  Most drugs are weak electrolytes and exist partly as undissociated molecules at physiological pH. ELIMINATION ENHANCEMENT
PHARMD GURU Page 2  The extent of ionisation is a function of the ionisation constant of the drug (Ka for both acids and bases), and the pH of the medium in which it is dissolved.  Ionisation constants are usually expressed in the form of their negative logarithm, pKa.  Hence the pKa scale is analogous to the pH notation: the stronger an acid the lower its pKa, and the stronger a base the higher its pKa.  Thus when pKa = pH, the concentrations of ionised and non-ionised drugs are equal.  Cell membranes are most permeable to substances that are lipid soluble and in the non-ionised, rather than the ionised form.  Thus the rate of diffusion from the renal tubular lumen back into the circulation is decreased when a drug is maximally ionised. Because ionisation of acidic drugs is increased in an alkaline environment, and that of basic drugs is increased in an acid solution, manipulation of the urinary pH enhances renal excretion. 5) Forced alkaline diuresis:  This is most useful in the case of phenobarbitone, lithium, and salicylates.  Administer 1500 ml of fluid IV, in the first hour as follows:  500 ml of 5% dextrose  500 ml of 1.2 or 1.4% sodium bicarbonate  500 ml of 5% dextrose. 6) Forced acid diuresis :  Forced acid diuresis is no longer recommended for any drug or poison, including amphetamines, strychnine, quinine or phencyclidine.
PHARMD GURU Page 3 2) EXTRACORPOREAL TECHNIQUES: 1. HAEMODIALYSIS:  Haemodialysis was first used in 1913 in experimental poisoning, but was not applied clinically until 1950, when it was used for the treatment of salicylate overdose. It was widely employed in the subsequent two decades accompanied by much adulatory reportage of its efficacy in medical journals. However, the popularity of haemodialysis has declined since then owing to authentic observation of its lack of utility in several types of poisoning, and the high incidence of complications such as infection, thrombosis, and air embolism.  All drugs are not dialysable, and so it must be ensured before embarking on this procedure that the following conditions are satisfied:  The substance should be such that it can diffuse easily through a dialysis membrane.  A significant proportion of the substance should be present in plasma water or be capable of rapid equilibration with it.  The pharmacological effect should be directly related to the blood concentration.  Table 3.19 outlines the various factors in a toxin which can affect the outcome of haemodialysis. Extensive plasma protein binding, insolubility in water, and high
PHARMD GURU Page 4 molecular weight are the three most important factors in making haemodialysis ineffective.  PROCEDURE:  The three basic components of haemodialysis are the blood delivery system, the dialyser itself, and the composition and method of delivery of the dialysate. For acute haemodialysis, catheters are usually placed in the femoral vein and passed into the inferior venacava. Blood from one is pumped to the dialyser (usually by a roller pump) through lines that contain equipment to measure flow and pressure within the system. Blood returns through the second catheter. Dialysis begins at a blood flow rate of 50 to 100 ml/min, and is gradually increased to 250 to 300 ml/min, to give maximal clearance.  INDICATIONS FOR HAEMODIALYSIS:  Haemodialysis may be considered in those patients not responding to standard therapeutic measures while treating a dialysable toxicant (vide infra). It may also be considered a part of supportive care whether the toxicant is dialysable or not in the following situations: Stage 3 or 4 coma, or hyperactivity caused by a dialysable agent which cannot be treated by conservative means, marked hyperosmolality which is not due to easily corrected fluid problems, severe acid-base disturbance not responding to therapy, or severe electrolyte disturbance not responding to therapy.