Clinical Toxicology Lecture Notes PDF

Shared using Xodo PDF Reader and Editor Clinical Toxicology Fifth year pharmacy students Lecturer : Rasool Chaloob Shared using Xodo PDF Reader and Editor Lecture Two 01 Decontamination (Elimination):  A. Eye Exposure...

Shared using Xodo PDF Reader and Editor Clinical Toxicology Fifth year pharmacy students Lecturer : Rasool Chaloob Shared using Xodo PDF Reader and Editor Lecture Two 01 Decontamination (Elimination):  A. Eye Exposure  B. Dermal Exposure:  C. GIT Exposure: 02 Methods of gastric emptying 1- Syrup of Ipecac: II- Gastric Lavage III- Activated Charcoal (AC) IV- Whole Bowel Irrigation (WBI) 03 Enhancement of Excretion I. Multiple doses Activated Charcoal (MDAC): II. Diuresis: III. Manipulation of Urine pH IV. Dialysis 04 Toxidromes and antidotes Emergency Measures Decontamination (Elimination)  Shared using Xodo PDF Reader and Editor II- Decontamination (Elimination): The aim of these procedures is to reduce the absorption of poisons before approaching the systemic circulation. Early intervention is recommended for these methods to be efficient. B. Dermal Exposure: A. Eye Exposure: Many poisons are absorbed through the The eyes should be irrigated with skin & produce systemic toxicity e.g. lids fully retracted for no less than Organophosphates and phenol. Avoid 20 minutes. secondary exposures by wearing Solid corrosives should be protective (rubber or plastic) gowns, removed first by forceps and gloves, and shoe covers. Cases of serious washed with running tap water for secondary poisoning have occurred in at least 20 minutes. emergency personnel after contact with xenobiotics such as organic phosphorus compounds on the victim's skin or clothing.. Indications for gastric emptying: C. GIT Exposure: 1) If the patient had ingested Gut Emptying Methods of gastric potentially highly lethal doses of The aim of gastric emptying is to 1) Induction of emesis. emptying: the poison. remove the poison from the stomach 2) Gastric lavage 2) If the poison is not adsorbed before it gets absorbed to minimize on activated charcoal or if not its toxic effects. However it is amenable to treatment by other described to be aggressive and measures as hemodialysis or multiple studies revealed that effective antidote. patients could be successfully. managed without its use.  Shared using Xodo PDF Reader and Editor Methods of gastric emptying Methods of gastric emptying: 1- Syrup of Ipecac: It causes vomiting through 2 phases: Early phase: within 3 min due to direct GI stimulation Late phase: After 30 min through its central action on chemoreceptor trigger zone. Dose: 30ml for adults and 15ml for children. Water can be offered but not essential for success. Give another dose if emesis does not occur within 30 minutes. For children (6-12 months), syrup of Ipecac should be limited to a single dose of maximum 10ml. If the second dose of Ipecac does not induce vomiting, do not give a third dose and perform gastric lavage. Adverse effects: Syrup of Ipecac should no longer be used as a routine for its adverse effects such as: 1. Aspiration of gastric contents. 2. Vagally mediated bradycardia. 3. Persistent vomiting. 4. Intracerebral hemorrhage.  Shared using Xodo PDF Reader and Editor Methods of gastric emptying Methods of gastric emptying: II- Gastric Lavage The goal of the procedure is to remove poisons by washing the stomach by saline or warmed tap water via a specific tube. Contraindications: 1. In corrosives poisoning for risk of perforation of the esophagus or the stomach (except in carbolic acid). 2. Froth producing substances (liquid soap & shampoo). 3. The patient is at risk of hemorrhage or gastrointestinal perforation if there is an underlying pathology, e.g: recent surgery or other medical condition that could be further compromised by the use of orogastric lavage. 4. Coma or Convulsions (for risk of aspiration). The use of an endotracheal tube (ETT) with inflatable cuff is recommended to avoid aspiration of the gastric wash. 5. Petroleum distillates (as kerosene) except if ETT is used. 6. Time factor. Lavage is less effective if time passed since ingestion of the poison is more than 2 hours. However a delayed lavage may be useful with certain poisons that are eliminated in the GIT (opiates, alcohol), form concretions (salicylates, meprobamate), have delayed gastric emptying as drugs with anticholinergic action (tricyclic antidepressants 'TCA' atropine, and phenothiazines), sedative hypnotics (barbiturates).  Shared using Xodo PDF Reader and Editor Methods of gastric emptying: Methods of gastric emptying III- Activated Charcoal (AC) 1. It is an extremely effective adsorbent of nearly all poisons from the gastrointestinal tract. 2. It is prepared by destructive distillation of wood pulp. 3. It has small particles with large surface area; each particle adsorbs many particles of poison. 4. It is available in the form of tablets or black powder that is mixed with water, and has an inedible taste. 5. It is claimed to be more effective than emesis or gastric lavage, but is usually given after emesis or lavage is performed. 6. Some poisons are not adsorbed by activated charcoal such as iron, alcohols, cyanide, lead and mercury. Dose: 1gm/Kg body weight if the amount of poison is not known. If known, activated charcoal is given 5-10 times the weight of the ingested poison. Multiple Dose Activated Charcoals (MDAC): It is the administration of repeated doses of activated charcoal to enhance poison elimination. Indications: 1. Adsorption of drugs remaining in the gut for long time: Slow release preparations as theophylline Drugs producing concretions e.g. Salicylates, phenobarbitone 2. Adsorption of drugs having enterohepatic circulation e.g. dapsone, quinine, digoxin, TCA, glutethimide. 3. Drugs diffusing passively from the blood to the lower GI lumen as theophylline and salicylate. Dose: 0.5-1gm/kg every 4 hours.  Shared using Xodo PDF Reader and Editor Methods of gastric emptying: Methods of gastric emptying Contraindications of AC: Corrosives: It worsens mediastinitis & peritonitis in case of perforation. It masks the view in endoscopy. It is not effective. Hydrocarbons: It may precipitate vomiting with the high risk of aspiration. Intestinal obstruction, perforation or ileus IV- Whole Bowel Irrigation (WBI) A newer method for decontamination, Effective well tolerated process for evacuating intestinal tract and safe in pregnancy. Adverse effects: Vomiting with rapid PEG administration. Abdominal fullness and cramps and pruiritis.  Shared using Xodo PDF Reader and Editor Enhancement I. Multiple doses Activated III. Manipulation of Urine pH: Definition: It is the change of the urine of Excretion Charcoal (MDAC): II. Diuresis: pH in order to turn the drug to its ionized form. Drugs can be weak acids or bases. If they are rendered ionized, Certain methods are applied to It is a simple method for enhancing they are trapped not reabsorbed easily enhance excretion of the poison from the blood after excretion of some poisons. It is by the renal tubules, so they are readily being absorbed. They include efficient only in poisons with the excreted. the following: following pharmacokinetic properties: A- Alkalinization of urine: 1. The kidney is the main route of Used for weak acidic toxins as their excretion. salicylates and phenobarbitone which 2. Have a small volume of distribution. have greater ionization and better 3. Have low protein binding. excreted at urine pH of 7.5-8. a. Fluid diuresis: Dextrose 5-10% or a Indications: mixture of glucose and normal saline. 1. Overdose of salicylates. 2. Long acting barbiturates overdose as b. Osmotic diuresis: Mannitol 20% is they are excreted mainly through the given in a dose of 1-2 gm/kg. It is kidneys and have low volume of excreted in renal tubules leading to distribution. increase its osmotic pressure and 3. Poisons producing hemolysis and diuresis. It is usually given as a part of rhabdomyolysis. alkaline diuresis. Method: It is produced by repeated. cycles of IV fluids.  Shared using Xodo PDF Reader and Editor Enhancement B. Acidification of urine: Formerly used for basic drugs as B - Hemoperfusion: This method allows blood derived from radial of Excretion amphetamine. Now it is obsolete because it does not significantly enhance removal of xenobiotics and is complicated by artery to pass through a cartridge coated with activated charcoal to adsorb poisons existing in the plasma. It can Certain methods are applied to systemic metabolic acidosis. be done for toxins with high protein binding, or enhance excretion of the for those having big molecular weight, and poison from the blood after also in lipid soluble drugs. The poison must be IV. Dialysis: being absorbed. They include absorbable to charcoal. The principle of dialysis is to allow blood to the following: circulate in contact with a semi-permeable Complications: membrane to remove substances from the 1. Trapping of white blood cells and platelets blood by concentration gradient, i.e. to allow causing a reduction in the platelet count. particles to pass from higher concentration to 2. Reduction in serum calcium, glucose. the lower concentration. Dialysis is of value 3. Hypotension. when renal function becomes impaired. 4. Adsorption of therapeutically administered drugs A. Hemodialysis: A cellulose membrane (semipermeable membrane) in the hemodialysis apparatus is used. Heparinized blood is extravasated and allowed to circulate in the apparatus to pass against the semi-permeable membrane. Exchange of toxic materials from the blood to a special fluid (dialysis fluid) takes place (according to concentration gradient). In addition to removal of toxins, it can correct acid-base and electrolyte disturbances, and extracellular fluid volume overload. Shared using Xodo PDF Reader and Editor  Shared using Xodo PDF Reader and Editor TOXIDROMES Toxidromes are toxic syndromes or the constellation of signs and symptoms associated with a class of poisons. Rapid recognition of a toxidrome, if present, can help determine whether a poison is involved in a patient’s condition and can help determine the class of toxin involved. TOXIDROMES 1.Parasympathetic Toxidromes: Anticholinergic and cholinergic 2.Sympathetic Toxidromes: Sympathomimetic and hypermetabolic 3.CNS Toxidromes: Benzodiazepine and extrapyramidal 4.Opioid Toxidromes: Opioid and withdrawal 1.Parasympathetic Toxidromes: Anticholinergic : Features: Mydriasis, dry skin, dry mucous membranes, decreased bowel sounds, sedation, altered mental status, hallucinations, dysarthria, urinary retention Causes: Belladonna alkaloids, antihistamines, TCAs, antipsychotics, anti-Parkinson drugs, Antidote: Physostigmine Cholinergic: Features: Miosis, lacrimation, diaphoresis, bronchospasm, bronchorrhea, vomiting, diarrhea, bradycardia Causes: OPs, carbamates, and oximes; pilocarpine eye drops, nerve gases, Antidote: Atropine +/− pralidoxime  Shared using Xodo PDF Reader and Editor TOXIDROMES 2.Sympathetic Toxidromes: Sympathomimetic : Features: Agitation, mydriasis, tachycardia, hypertension, hyperthermia, diaphoresis TOXIDROMES Causes: Amphetamines/diet drugs, cocaine, theophylline, caffeine, methylphenidate; over-the- counter (OTC) cold medications, especially phenylpropanolamine (PPA), ephedrine, and pseudoephedrine Antidote: Beta-blockers Hypermetabolic Toxidrome Features: “Uncoupling of oxidative phosphorylation” with high fever, tachycardia, hyperpnea, tachypnea, restlessness, convulsions, combined metabolic acidosis and respiratory alkalosis Causes: Salicylates (ASA), chlorphenoxyacetic acid herbicides (2,4-D and 3,4,5-T), dinitrophenol, phenol, Antidote: Lavage and activated charcoal, supportive  Shared using Xodo PDF Reader and Editor TOXIDROMES 3.CNS Toxidromes: Benzodiazepine Toxidrome Features: “Coma with stable vital signs,” mild sedation-to-complete unresponsiveness, amnesia, respiratory depression, loss of airway protective reflexes, mild hypotension TOXIDROMES Causes: Benzodiazepines, GHB Antidote: Flumazenil > physostigmine Extrapyramidal Toxidrome Features: “Drug-induced Parkinsonism,” tremor, rigidity, opisthotonus, torticollis, oculogyric crisis = tardive dyskinesias Causes: Phenothiazines, butyrophenones (haloperidol, droperidol), metoclopramide, clomipramine Antidote: supportive 4.Opioid Toxidromes: Opioid Toxidrome Features: Pinpoint pupils, CNS depression, respiratory depression, bradycardia, hypotension, hypothermia, decreased GI motility, constipation Causes: All opioids, natural and synthetic, including propoxyphene, tramadol, codeine. Exception: α-2-agonists = clonidine and the imidazolines, oxymetazoline, and tetrahydrolozine Antidote: Naloxone  Shared using Xodo PDF Reader and Editor TOXIDROMES TESTING IN POISONING 4.Opioid Toxidromes: Withdrawal Toxidrome Features: sneezing, runny nose, lacrimation, abdominal cramps, diarrhea, restlessness, hallucinations, tachycardia, and hypertension Causes: Opioid, alcohol, barbiturate, benzodiazepine cessation withdrawal Antidote: antagonists for maintenance (naltrexone) TESTING IN POISONING When used appropriately, diagnostic tests may be of help in the management of the intoxicated patient. When a specific toxin or even class of toxins is suspected, requesting qualitative or quantitative levels may be appropriate. In the suicidal patient whose history is generally unreliable, or in the unresponsive patient where no history is available, the clinician may gain further clues as to the etiology of a poisoning by responsible diagnostic testing.  Shared using Xodo PDF Reader and Editor TESTING IN POISONING TESTING IN POISONING ANION GAP Obtaining a basic metabolic panel from all poisoned patients is generally recommended. When low serum bicarbonate is discovered on a metabolic panel, the clinician should determine if an elevated anion gap exists. The formula most commonly used for the anion gap calculation is: Anion gap = [Na⁺] - [Cl⁻ + HCO₃ ] This equation allows one to determine if serum electroneutrality is being maintained. The primary cation (sodium) and anions (chloride and bicarbonate) are represented in the equation. The normal range for this anion gap is accepted to be 8 to 16 mEq/L. Practically speaking, an increase in the anion gap beyond an accepted normal range, accompanied by a metabolic acidosis, represents an increase in unmeasured endogenous (e.g., lactate) or exogenous (e.g., salicylates) anions. A list of the more common causes of this phenomenon is organized in the classic MUDILES mnemonic: Methanol, Uremia ,Diabetic ketoacidosis, Inhalants (e.g., carbon monoxide, cyanide, toluene), Isoniazid, Ibuprofen , Lactic acidosis ,Ethylene glycol, Ethanol ketoacidosis , Salicylates, Starvation ketoacidosis, Sympathomimetics  Shared using Xodo PDF Reader and Editor TESTING IN POISONING TESTING IN POISONING OSMOL GAP The serum osmol gap is a common laboratory test that may be useful when evaluating poisoned patients. This test is most often discussed in the context of evaluating the patient suspected of toxic alcohol (i.e., ethylene glycol, methanol, isopropanol) intoxication. Though this test may have utility in such situations, it has many pitfalls and limitations. The difference between the measured (Osmm) and calculated (Osmc) is the osmol gap (OG) and is depicted by the equation below: OG = Osmm – Osmc If a significant osmol gap is discovered, the difference in the two values may indicate the presence of foreign substances in the blood. A list of possible causes of an elevated osmol gap is provided in Table The osmol gap should be used with caution as an adjunct to clinical decision making and not as a primary determinant to rule out toxic alcohol ingestion. If the osmol gap obtained is particularly large, it suggests that an agent from Table may be present. A “normal” osmol gap should be interpreted with caution; a negative study may, in fact, not rule out the presence of such an ingestion. As with any test result, this must be interpreted within the context of the clinical presentation.  Shared using Xodo PDF Reader and Editor TESTING IN POISONING TESTING IN POISONING OSMOL GAP Toxins Causing Elevated Osmol Gap Acetone Ethanol Ethyl ether Ethylene glycol Glycerol Isoniazid Isopropanol Mannitol Methanol Osmotic contrast dyes Propylene glycol Trichloroethane  Shared using Xodo PDF Reader and Editor Specific Treatments There are a number of potential antidotes readily available to the emergency physician for the treatment of specific poisonings. Specific Treatments ANTIDOTES number of pharmacologic antagonists or antidotes is quite limited. There are few agents that will rapidly reverse toxic effects and restore a patient to a previously healthy baseline state. As a result, antidotes should be used cautiously and with clearly understood indications and contraindications  Shared using Xodo PDF Reader and Editor THANK YOU