Management of Toxicity PDF

Management of Toxicity Dr Amany Said Sallam Lecturer of pharmacology & Toxicology Menoufia university  D) GIT decontamination: (Applied within 4-6 hours after ingestion/ postingestional) It is used only for orally ingested poisons. Methods of gut decontamina...

Management of Toxicity Dr Amany Said Sallam Lecturer of pharmacology & Toxicology Menoufia university  D) GIT decontamination: (Applied within 4-6 hours after ingestion/ postingestional) It is used only for orally ingested poisons. Methods of gut decontamination: a) Emesis b) Gastric lavage c) Activated charcoal d) Cathartics e) Whole Bowel Irrigation  1-EMESIS Indication: Conscious and alert poisoned patient within 4-6 hours after ingestion. Previously, emesis was performed by applying several popular methods (fingertip stimulation, salt water, apomorphine) but are ineffective and dangerous.  Syrup of ipecac is the emetic of choice in both children over the age of 6 months and in adults. Ipecac is the dried root of Cephaelis ipecaquanha plant. that contains two main active ingredients alkaloids, emetine and cephaeline Mechanism of action: Early vomiting: Local activation of peripheral sensory receptors in the gastrointestinal tract. Late vomiting: Central stimulation of the chemoreceptor trigger zone (CTZ) with subsequent activation of the central vomiting center. Dose:  In children 6-9 months: 5 ml ipeca syrup +120 ml water  In children 9-12 months : 10 ml ipeca syrup + 120 ml water.  1-12 years : 15 ml ipeca + 120 ml water.  12 years :30 ml ipeca + 250-350 ml water.  The dose can be repeated once if emesis has not occurred in 30 minutes.  If vomiting failed gastric lavage is done immediately. Contraindication:  Children up to 6 months of age.  Comatose patient because of increased risk of aspiration.  Convulsions (due to risk of aspiration of gastric contents).  Certain toxins: Hydrocarbons & volatile substances. Corrosives (Caustics). Ingestion of sharp objects. 2- Gastric lavage  Method: The patient should be placed on his left lateral decubitus position, as this position causes the liver (on the right side) to compress and block the junction between stomach and intestine to keep toxicant in the stomach for lavage and prevent its transfer to intestine.  It is performed by introducing Warm water alternating with warm saline in small aliquots, as using warm solution is to avoid hypothermic shock and using water alone may lead to hyponatremia.  The removal of stomach contents is carried out by suction and it is advisable to hold back the first aliquot of washing for chemical analysis.  Endpoint: no further particulate matter is seen or simply clear efferent lavage solution.  G.L can be performed in comatose patients with concurrent insertion of cuffed endotracheal intubation.  Contraindications: A) Relative contraindications B) Absolute contraindications 1- Patients with unprotected airway; 1- Patients with risk of obtunded, comatosed, or convulsing patients (Control of convulsions and perforation (due to pathology intubation with a cuffed endotracheal or recent operation) or tube should be performed first to hemorrhage. protect the airway). 2- Chronic poisoning. 2- Poisoning with mineral 3- Poisoning since more than 6 acids and alkalis corrosives. hours except salicylate and drugs 3- Froth producing substances which decrease gastric motility. e.g. liquid soap or shampoo.  Complications:  Perforation of the esophagus or stomach.  Epistaxis: Nose bleeds from nasal trauma during passage of the tube.  Vomiting resulting in pulmonary aspiration of gastric contents in an obtunded patient without airway protection.  Local antidotes Local antidotes: are classified into physical antidotes and chemical antidotes(Obsolete now). Physical antidotes: These agents interfere with the ingested poisons through physical means only and do not change the chemical nature. They include: 1- Demulcents: They coat the gastric mucosa e.g. milk, egg white, and olive oil.  2- Diluents: They include water which dilutes some poisons. Dilution and neutralization are contraindicated in acid and alkali corrosives because they may aggravate the chemical burn by heat resulting from the reaction, powdered ice is preferred.  3- Adsorbent Activated Charcoal: It is a highly adsorbent powdered material, made from distillation of organic materials such as wood, bone…etc. then it is activated through superheating (600-900C) in the presence of (oxygen + steam + acids) and in absence of air. The activation process cleans and increases surface area of activated charcoal. It is highly effective in adsorbing most toxins  It is highly effective in adsorbing most toxins Only few toxins are poorly adsorbed to charcoal (e.g. HICAL; hydrocarbons, heavy metals, iron, inorganic corrosives, cyanide, alcohols, lithium). Studies suggest that activated charcoal given alone without prior gastric emptying is as effective as emesis and gastric lavage in reducing drug absorption.  Indications: 1- Used after toxic ingestion to limit drug absorption from the gastrointestinal tract in a reasonable time period after the ingestion. 2- Charcoal is often given even if the toxic substance may not be well adsorbed to charcoal if other substances have been co-ingested. 3- Repeated oral doses may be used to enhance elimination of some drugs from the bloodstream.  Contraindications: 1- Depressed mental status without airway protection (risk of aspiration). 2- Hydrocarbon ingestion (increased risk of aspiration). 3- Toxins poorly adsorbed by activated charcoal (AC). 4- Intestinal obstruction (absolute contraindication) or decreased peristalsis (relative contraindication).  )Multiple doses activated charcoal (MDAC) Repeated doses of activated charcoal slurry along the intestinal tract will allow large surface area for.adsorbing ingested drugs in acute poisoning Dose: 1gm/Kg/4hr OR 0.5gm/kg/2hr (oral)  2) Preventing absorption (Gut Decontamination) Cathertics Types Salt: (Magnesium Citrate & Sodium sulphate) and Saccharide( Sorbitol). Complications: Abdominal distention & cramps.  Prolonged diarrhea.  Electrolyte disturbances.  2) Preventing absorption (Gut Decontamination) Cathertics Contraindications: Magnesium cathartics should be avoided in patients with renal failure &/or C.N.S problems. (Renal failure Magnesium excretion Magnesium accumulationElectrolyte disturbance and C.N.S depression).  Sodium salts should be avoided in patients with renal failure, heart failure, &/or hypertension.  Pre-existing electrolyte disturbance  Intestinal obstruction  GI-Bleeding , perforation , peritonitis  Poisoning with corrosive  Whole Bowel Irrigation  Principle: It is the complete irrigation of the bowel by PEG (non absorbable and does not cause electrolyte and water imbalance) to fasten removal of poisons and prevent its absorption which induces a liquid stool.  It involves the instillation of large volumes of PEG (Colyte®) into the stomach in a nasogastric tube over a period of 2 to 6 hours producing voluminous (huge/large) diarrhea.  The patient receives PEG until clear effluent is attained.  Of particular value in poisons that does not adsorb on activated charcoal and in slow release preparations. 3- ENHANCED ELIMINATION It means increasing rate of removal of poison from the blood after absorption.  Elimination Enhancement Patient Poison 3- Ingestion of 1- Critically ill patient known lethal dose despite maximal or lethal blood supportive care level of drug. 2- The normal or usual route of elimination is impaired.  Forced Diuresis: It is done by changing the urinary pH according to whether the poison is alkaline or acidic. It includes urine alkalinization and acidification (urine acidification is obsolete now). It is used in moderate and severe cases of poisoning. It may enhance elimination of polar drugs by ion trapping.  REQUIREMENTS:  Low protein binding.  Low volume of distribution.  High renal clearance (normal kidney functions)  Alkalinization of urine Principle: Altering the acidic urine pH to alkaline (using sodium bicarbonate) which converts a lipid-soluble acidic drug in the tubular lumen into the charged lipid-insoluble salt that cannot easily move back across the renal epithelium. This leads to a marked increase in  Precautions: Check the following: 1- Renal function tests (blood urea nitrogen and serum creatinine to be normal) 2- Urine pH and maintain at 7-8. 3- Urine volume and maintain at 300-500 ml/hour. 4- Blood pH (no higher than 7.55 - 7.60) and correct if elevated 5- Electrolytes and correct any abnormality (e.g. hypokalemia).  Adverse effects: 1. Fluid overload. 2. Acid-base abnormalities (alkalosis). 3. Electrolyte abnormalities (e.g. hypokalemia, hypernatremia). Contraindications: 1- The poison is not excreted in urine in active form, has large volume of distribution, highly plasma protein bound. 2- Renal dysfunction. 3-Lack facilities to monitor pH and electrolytes levels.  Dialysis Principle: The poison moves along concentration gradient across semipermeable membranes through using physiologic membrane (peritoneum; peritoneal dialysis) or artificial membrane (hemodialysis).  1- HEMODIALYSIS Principle and technique: Blood is taken from a large vein (e.g. femoral vein) with a double-lumen catheter and is pumped through the hemodialysis system. The patient must be anticoagulated to prevent clotting of blood in the dialyzer. Drugs and toxins flow passively across the semipermeable membrane down a concentration gradient into a dialysate solution. Fluid and electrolyte abnormalities can be corrected concurrently. 3) Elimination Enhancement Hemodialysis  Requirements:  Low volume of distribution  Low plasma protein binding..  The drug molecular weight should be less than 500 Dalton so can pass easily across the dialysis membrane.  high water solubility.  Heparin should be administered before dialysis to avoid blood coagulation.  Indications:  Severely intoxicated patients who don't respond to early supportive management.  Renal failure (where forced diuresis can't be applied).  Prolonged coma.  If lethal amounts of drug was absorbed despite gut decontamination. Complications: Hypotension, Electrolyte disturbance, Bleeding, Thrombocytopenia, Infection.  2. Hemoperfusion Principle and technique: During hemoperfusion, blood is derived from the radial artery to pass through a cartridge coated with activated charcoal to which toxic agents in the blood will be adsorbed. The blood is then returned to the patient through the radial vein. Anticoagulation with heparin is necessary. Close monitoring of glucose, calcium and other electrolytes should be done as they may be adsorbed to the charcoal. Indications: 1- Adsorbed by activated charcoal. 2- Low volume of distribution. Hemoperfusion (unlike hemodialysis) is not limited by protein binding, molecular weight or water solubility. Contraindication & Complications: The same as hemodialysis.  Exchange transfusion  It is infrequently used.  It is the removal of quantity of the patient's blood & replacement with fresh whole blood.