elimination of poisoning and antidotes mechanism of action

1. Elimination of poisoning
and
Antidote administration
Dr.Sunanda Nandikol
Clinical Pharmacy Practice,
BLDEA’s SSM College of
Pharmacy & Research
Centre,Vijayapura

2.  The various methods of Elimination of absorbed poisons from the body include
the following:
 Forced Diuresis
 Extracorporeal techniques:
1. Haemodialysis
2. Heamoperfusion
3. Peritoneal dialysis
4. Hemofiltration
5. Plasmaphersis
6. Plasma perfusion
7. Cardiopulmonary bypass.

3. Forced Diuresis
 (Increased urine formation by diuretics and fluid) Forced Diuresis may
enhance the excretion of drugs in urine and is used to treat drug overdose or
Poisoning.
 Most drugs taken in overdose are extensively detoxified by the liver to produce
inactive metabolites which are voided in the urine.

4.  Principle: Most of the drugs are either weak acids or weak bases. When urine is
made alkaline, elimination of acidic drugs in the urine is increased. The converse applies
for alkaline drugs. This method is only of therapeutic significance where the drug is
excreted in active form in urine and where the pH of urine can be adjusted to levels above
or below the pK value of the active form of drug. For acidic drugs, urine pH should be
above the pK value of that drug, and converse for the basic drugs
Forced alkaline Diuresis:
 This is most useful procedure in the case of Phenobarbitone,lithium,and salicylates.
 Administer 1500ml of fluid IV, in the first hr as follows:
500ml of 5% Dextrose, 500ml of 1.2or 1.4% Sodium carbonate , 500ml of 5% Dextrose.
Forced Acidic Diuresis:
 It is No longer recommended for any drug or poison.

5. EXTRACORPOREAL TECHNIQUES:
Haemodialysis: is a process of purifying the blood of a patient whose kidneys are not
functioning normally.Heamodialysis 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.
All drugs are not dialyzable, 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 significance proportion of the substance should be present in plasma water or be
capable of rapid equilibration with it.
 The Pharmacological effects should be directly related to the blood concentration.
COMPLICATIONS: Infections, Thrombosis, Hypotension, air embolism, bleeding

6. Procedure:
The 3 basic components of haemodialysis are:
 Blood delivery system
 The dialyser
 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 the one catheter is pumped to the dialyser
through lines that contains equipment to measure flow and pressure within the system.
Blood returns through the second catherter.Dialysis begins at a blood flow rate of 50 to
100ml/min, and is gradually increased to 250 to 300 ml/min to give maximal
clearance.

8. Indications for Heamodialysis:
 1. Best indications:
Dialysis should be initiated regardless of clinical conditions, in the following situations,
after heavy metal chelation in patients with renal failure patients, ethylene glycol or
methanol ingestion cases.
 2.Very good indications:
usually effective in patients with severe intoxications with the following agent: Lithium,
Phenobarbitone, Salicylates, and Theophylline
 3.Fairly good indication:
dialysis can be initiated based on the exposure of the following agents, if clinical
condition deems the procedure is necessary e.g. Alcohols, Amphetamine, Anilines,
Antibiotics, Barbiturates, chlorates, iodides, INH, Quinidine, Fluorides.
 Poor indications:
Dialysis can be considered as a supportive measure in the presence of renal failure e.g.
PCT, Antidepressants, antihistamines, Benzodiazepines, Digitalis, opiates, etc.

9. 2. HEAMOPERFUSION:
 This technique 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 patient’s vascular tree. The Heamoperfusion saline in accordance with the
manufacture’s instructions are 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 administrating an infusion of heparinised saline.
 Toxins removed by Heamoperfusion are: Barbiturates, carbon tetrachloride's,
chlorpromazine, Dapsone, Diazepam, Digoxin, Organophosphate, phenols,
promethazine, quinidine, anti depressants, etc..
 Complications: Bleeding, Air embolism ,Infection, Thrombocytopenia, Hypocalcaemia,
Hypotension.

10. 3. PERITONEAL DIALYSIS:
 Although is widely available, this type of dialysis today is almost never recommended,
for detoxification. In general, it is only 10-25% as effective as haemodialysis and often
only slightly more effective than forced diuresis. It is also time consuming, requiring
24hrs for successful completion as compared to 2 to 4 hr cycles of haemodialysis and
Heamoperfusion. The only advantages are that it doesn’t 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.
 COMPLICATION: Pain, Haemorrhage , perforation of viscus, Bacterial peritonitis,
Volume depletion, Pneumonia, Pleural effusion, Hyperglycaemia, Electrolyte imbalance

11. HAEMOFILTRATION:
 Hemofiltration is performed similar to haemodialysis except that the
blood is pumped through a haemofilter.This procedure 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 ultra-filtrate rates of upto 6 litres/hr. or
continuously at rate of 100ml/hr.
 The main advantage of hemofiltration is that it can remove compounds
of large relative molecular weight (4500-40,000) ,Such compounds
include aminoglycosides antibiotics and metal chelates. This can be
useful in treating the lithium, ethanol, methanol, ethylene glycol
poisoning.

12. Haemodiafiltration:
 This is a combination of hemofiltration with haemodialysis. It has
been undertaken very rarely.

13. Plasmaphersis:
 It is technique of separating cellular blood components from plasma. The cells are re-suspended in either
colloids, albumin or fresh frozen plasma, and then re-infused .It is very effective in eliminating toxic
substances but exacts a heavy toll: a part of the patient’s plasma proteins are scarified in the process.
Plasmaphersis has been used in cases of overdose with theophylline, carbamazepine, amanita, mercury,
hemlock, etc.. But serious complications greatly limits its utility:
COMPLICATIONS:
 Bleeding disorders: Thrombocytopenia
 Hyper coagulation: Cerebral thrombosis, pulmonary embolism, myocardial infiltration.
 Anaphylaxis
 Fluid overload: Hypertension,CCF
 Infection
 Vessels perfusion. Air embolism
 Disequilibrium syndrome: Vomiting,tetany(muscle spasm ), chills, arrhythmias,
 Convulsions
 Metabolic alkalosis.

14. PLASMA PERFUSION:
 This is a combination of Plasmaphersis and
Heamoperfusion and has rarely been used in poisoning

15. 8.CARDIOPULMANRY 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.

16. ANTIDOTES

17. ANTIDOTE ADMINISTRATION
 In majority of cases of acute poisoning ,all that is required is intensive supportive
therapy with attention.
 Antidotes can change the chemical nature of a poison by rendering it less toxic or
preventing its absorption.
 Antidotes work in any one of the following common modes of action are:
1. Insert complex formation
2. Accelerated detoxification
3. Reduced toxic conversion
4. Receptor site competition
5. Receptor site blockade
6. Toxic effect by pass

18. Inert Complex Formation
 Some antidotes interact with the poison to form an inert complex which is
then excreted from the body , eg: chelating agents for heavy metals .
Prussian blue for thallium, specific antibody fragments for digoxin,
Dicobalt edeate for cyanide etc.

19. Accelerated detoxification
 Some antidotes accelerate the detoxification of a poison,
eg; thiosulfate the conversion of cyanide to non-toxic , acetyl cysteine acts as a
glutathione substitute which combines with hepatotoxic paracetamol metabolites and
detoxifies.

20. Reduced toxic conversion
 The best examples of this mode of action is provided by
ethanol which inhibits the metabolism of methanol to toxic
metabolites by competing for the same enzyme.

21. Receptor site competition
 Some antidotes displace the poison from specific receptor sites there by
antagonising the effects completely .The best example is provided by
Naloxone, which antagonises the effect of opiates at stereo-specific opioid
receptor sites.

22. Receptor site blockade
 This mode of action is best exemplified by atropine which blocks the effects of
anticholinesterase agents such as organophosphates at muscarinic receptor
sites.

23. Toxic effect bypass
 An example of this type of antidotal action is provided by the use of 100%
oxygen in cyanide poisoning.

24. Examples
 Acetylcysteine for Acetaminophen poisoning
 Oxygen for Carbon monoxide poisoning
 Atropine for Anticholinesterases, organophosphates, carbamates
 sodium Bicarbonate for Membrane-depressant cardiotoxic drugs (tricyclic
antidepressants, quinidine, etc
 Calcium for Fluoride; calcium channel blockers
 Deferoxamine for Iron salts
 Digoxin antibodies for Digoxin and related cardiac glycosides
 Esmolol for Theophylline, caffeine, metaproterenol
 Ethanol for Methanol, ethylene glycol posioning

25. NURSING CARE AND PSYCHIATRIC CARE
Nursing care:
 This is especially imp in comatose patients and involves the following
measures:
 Attention to pressure points to prevent development of decubitus ulcer (injury
to skin and underlying tissue resulting from prolonged pressure on the skin)
 In the absence of spontaneous blinking of eye , avoid exposure keratitis
(inflammation of cornea) by methyl cellulose eye drops
 Inhalation of gastric contents is a frequent problem which can lead to
pneumonitis, it should be treated.
 Passive physiotherapy may be advisable to prevent stiffness and muscle
atrophy.
 Prophylactic antibiotics keratitis is caused because of infection by viruses,
bacterial etc…if necessary.

26. PSYCHIATRIC CARE
 A significant proportion of overdose cases comprise suicide attempts. After
medical stabilization, the most imp aspect of management consists of
psychiatric counselling in order to prevent reoccurrence of suicidal ideation
once the patients has been discharged.
 Careful analysing the patients psychological state will allow for a realistic
appraisal of the psychosocial alternatives w.r.t immediate and long term
treatment ,disposition, and continued follow-up or outpatient care.
 Today psychosocial assessment has become an important component in the
comprehensive evaluation of toxicological emergencies.

27.  END