Elimination

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ELIMINATION
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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 A substantial proportion of the
drug is excreted unchanged. The drug is
distributed mainly in the extracellular fluid.
The drug is minimally protein-bound
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• Principle Most drugs are weak electrolytes and
  exist partly as undissociated molecules at
  physiological pH. 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.

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• Forced alkaline diuresis This is most useful
  in the case of phenobarbitone, lithium, and
  salicylates. Y 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.
• Forced acid diuresis Forced acid diuresis is no
  longer recommended for any drug or poison,
  including amphetamines, strychnine, quinine or
  phencyclidine.

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• Extracorporeal Techniques
• 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

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• 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.
• Extensive plasma protein binding, insolubility in
  water, and high molecular weight are the three
  most important factors in making haemodialysis
  ineffective.

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• 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.

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• 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.

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Best indications Dialysis should be
initiated, regardless of clinical condition, in
the following situations after heavy metal
chelation in patients with renal failure, and
following significant ethylene glycol or methanol
ingestion. Very good indications Dialysis is
usually effective in patients with severe
intoxications with the following agents -
Lithium - Phenobarbitone - Salicylates -
Theophylline. Fairly good indications Dialysis
may be initiated following exposure to the
following agents, if clinical condition deems the
procedure necessary (patient deteriorating
despite intense supportive care) - Alcohols -
Amphetamines Anilines
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Poor indications Dialysis can be considered as a
supportive measure in the presence of renal
failure, following exposure to - Paracetamol -
Antidepressants Antihistamines Complications
Infection (especially AIDS, hepatitis B),
Thrombosis, Hypotension, Air embolism, Bleeding
(due to use of heparin as a systemic
anticoagulant).
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Haemoperfusion This is a technique that is
increasingly becoming popular since it is capable
of removing many of the toxins that are not
removed well by haemodialysis. Procedure An
arteriovenous shunt or a double-lumen venous
catheter is inserted into the patients vascular
tree. The haemoperfusion column and lines are
primed with heparinised saline in accordance with
the manufacturers instructions and connected to
the shunt or catheter. On commencement of
perfusion, a bolus of heparin is injected into
the arterial line and heparinisation is continued
by administering an infusion of heparinised saline
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Complications Bleeding (because of
heparinisation), Air embolism, Infection,
Thrombocytopenia Hypocalcaemia, Hypotension
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• The latter is preferred in the treatment of
  poisoning.
• The main advantage of haemofiltration is that it
  can remove compounds of large relative molecular
  weight (4,50040,000).
• Such compounds include aminoglycoside
  antibiotics and metal chelates (such as
  iron-desferrioxamine). CAVH is also useful in
  poisoning with lithium, methanol, ethanol, and
  ethylene glycol.

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• Haemofiltration
• Haemofiltration is performed similar to
  haemodialysis except that the blood is pumped
  through a haemofilter. An arteriovenous pressure
  difference induces a convective transport of
  solutes through a hollow fibre flat sheet
  membrane.
• This allows a substantial flow of plasma water,
  and a high permeability to compounds with
  molecular weight less than 40,000.
• The procedure can be done intermittently at high
  ultrafiltrate rates of upto 6 litres/hour, or
  continuously at rates of 100 ml/hour (Continuous
  Arteriovenous Haemofiltration, or CAVH).

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• Haemodiafiltration
• This is a combination of haemofiltration with
  haemodialysis.
• It has been undertaken very rarely, and nothing
  much is known as to its actual advantages, if
  any.
• Plasmapheresis
• Plasmapheresis is a technique of separating
  cellular blood components from plasma. The cells
  are resuspended in either colloids, albumin, or
  fresh frozen plasma, and then reinfused.
• It is very effective in eliminating toxic
  substances but exacts a heavy toll a part of the
  patients plasma proteins are sacrificed in the
  process.
• Plasmapheresis has been used in cases of overdose
  with theophylline, carbamazepine, amanita,
  mercury, hemlock, etc., but serious complications
  greatly limit its utility

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• Complications
• Bleeding disorders DIC, thrombocytopenia,
• Hypercoagulation Cerebral thrombosis, pulmonary
  embolism, myocardial infarction. Anaphylaxis.
• Fluid overload Hypertension, congestive heart
  failure.
• Infection, Vessel perforation, air embolism,
• Dysequilibrium syndrome Vomiting, hypovolaemia.
• Citrate toxicity Paraesthesias, tetany, chills,
  arrhythmias.
• Convulsions, Metabolic alkalosis

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Peritoneal Dialysis Although widely available,
peritoneal dialysis today is almost never
recommended for detoxification. In general, it is
only 10 to 25 as effective as haemodialysis, and
often only slightly more effective than forced
diuresis. It is also time consuming, requiring 24
hours for successful completion as compared to
the 2 to 4 hour cycles of haemodialysis and
haemoperfusion. The only advantages are that it
does not require anticoagulation and uses minimal
equipment. Procedure Peritoneal dialysis
works on the same principle as haemodialysis,
allowing the diffusion of toxins from mesenteric
capillaries across the peritoneal membrane into
the dialysate dwelling in the peritoneal cavity.
It involves the placing of a stylet catheter at
the bedside under local anaesthesia, or the
surgical insertion of a Tenckhoff catheter in the
abdomen. Dialysate fluid is instilled, and 1 to 2
litres is exchanged each hour.
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Complications Pain, Haemorrhage (from vascular
laceration), Perforation of viscus, Bacterial
peritonitis, Arrhythmias, Volume
depletion/overload, Pneumonia, Pleural effusion,
Hyperglycaemia, Electrolyte imbalance.
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Plasma Perfusion This is a combination of
plasmapheresis and haemoperfusion, and has rarely
been used in poisoning. Cardiopulmonary Bypass
This is another rarely used experimental
procedure in the treatment of poisoning, and has
been shown to be useful in certain cases of
overdose involving cardiac depressants such as
verapamil and lidocaine.