General Toxicology PDF

General Toxicology Toxicology: Literally, it means a study of poisons on living organisms. The term is derived from Greek and Latin origins (L. toxicum = poison; G. toxikom = arrow poison; L. logia = science or study). Toxicology deals with: a) Source b) Kinetics c) Action d) Diagnosis [c...

General Toxicology Toxicology: Literally, it means a study of poisons on living organisms. The term is derived from Greek and Latin origins (L. toxicum = poison; G. toxikom = arrow poison; L. logia = science or study). Toxicology deals with: a) Source b) Kinetics c) Action d) Diagnosis [clinical effects, DD and laboratory investigations] e) Prevention and Treatment of poisoning. N.B. All substances known to man are poisons, and only the dose determines the effect. [e.g. Therapeutics are considered poisons if given in large doses]. Classification of poisons: Poisons are classified according to the followings: 1- Nature: solid, liquid and gaseous poisons. 2- Site of action: a) local [Inorganic corrosives] b) Remote [Alkaloids and most Therapeutics] c) Local & Remote [Metals and Organic Corrosives] 3- Target organ:  Central Nervous System (CNS) CNS stimulants e.g. Amphetamines, cocaine, strychnine. CNS depressants e.g. Hypnotics, narcotics, alcohol and anesthetics. Classification of poisons: 3- Target organs  GIT: e.g. Metals and Corrosives.  Kidneys: Mercury, phenol and Cadmium  Liver: Paracetamol, Iron and carbon tetrachloride.  CVS: Digitalis and aconitine  Lungs: Metal fumes  Factors Modifying Toxic effects  Factors related to the poison [Pharmacokinetic factors]: The state of the toxic agent: The dose: Route of administration: The descending order of toxicity of the other routes includes; inhalation > IV > intraperitoneal > subcutaneous > intramuscular > intradermal> oral >topical. Cumulation: i.e. the rate of intake exceeds the rate of elimination e.g. digitalis. Chemical interaction: Addition i.e. he chemicals involved added to the effects of each others (1+1=2) e.g. Aspirin + paracetamel (doubled analgesic effect) Synergism: when one chemical increases or markedly exaggerates the effect of another (1+1= 3) e.g. Alcohol + Barbiturate (severe CNS depression) Antagonism: when one chemical diminishes or completely abolishes the effect of another. e.g. BAL +Lead Metabolism of toxic agent: Unfortunately, some poisons are metabolized to equally active or even more active compounds e.g. methanol gives rise to formaldehyde and formic acid which are more toxic compounds.  Factors Modifying Toxic effects  Factors related to the patient [Host factors]:  G.I.T: pH of stomach : increased gastric acidity enhances acid poison toxicity (e.g. aspirin). While, achlorhydria decreases toxicity of potassium cyanide. Amount of food Type of food  Age  State of health  Toxicogenetics [Idiosyncrasy] Abnormal response to drugs. Hereditary basis e.g. favism & sulphonamide in G 6-P D patients lead to hemolytic anemia hypersensitivity = Allergy Exaggerated response to the drug e.g. Aspirin or penicillin. It is an antigen- antibody reaction.  Tolerance Diagnosis of poisoning  History  Clinical examination  Laboratory investigations Diagnosis of poisoning History Sudden appearance of symptoms in a healthy person. Symptoms appearing in a group of persons taking the same food. History of recent purchase of a poison or the presence of syringe, drug or empty bottle nearby the patient. History of failure, financial or emotional troubles or presence of suicidal note. Diagnosis of poisoning Clinical examination Vital signs [BP, pulse, Resp, Temp]. Neurological examination + pupil’s state. Chest + Abdomen. Skin + smell of breath. N.B. Toxidromes:. (Toxic Finger prints) are signs & symptoms that are observed after an exposure to a substance which are helpful to establish a diagnosis. Diagnosis of poisoning Laboratory investigations A) In living + dead persons: Qualitative and Quantitative analysis of the poison from: [Blood, urine, vomitus, stool, hair, nail] and organs from dead only B) In living only ECG+EEG. Electrolytes and arterial blood gases (ABG) Liver+ Kidney Functions, etc. Diagnosis of poisoning Postmortem picture Search for:  Stomach: Smell (phenol, opium, organophosphorus and cyanide) Ulcers ( corrosives) Seeds or tablets  Skin: Smell Eschars [colored ulcers] (black in sulphuric acid, yellow in nitric, white turns brown in phenol) Site of injections [In addicts] Diagnosis of poisoning Postmortem picture Search for: Brain: For edema or congestion (CO)  Respiratory system: For signs of asphyxia (barbiturates, opium, CO and HCN)  Postmortem changes: Hypostasis Rigor Mortis (earlier in convulsants e.g. amphetamines and strychnine) Putrefaction ‘( delayed in dehydration as in arsenic poisoning) Coma & the poisoning N.B. Causes of coma: Toxic (CNS depressants, anticholinergics and toxin causing cellular hypoxia e.g. HCN & CO) Pathologic (hepatic failure, renal failure, metabolic e.g. hypoglycemia, hypertensive encephiopathy, etc.) Traumatic (head injuries). Coma & the poisoning Coma scales: I- Rapid evaluation of the level of consciousness AVPU system: it is a rapid mean of documenting the level of consciousness (A=alert, V=verbal response, P= response to pain and U = unresponsive). II- Definitive monitoring of toxic coma: In definitive monitoring of toxic coma some prefer to use Reed’s coma scale, as Glasgow coma scale overestimates the degree of impairment. Coma & the poisoning Reed’s coma scale Scale 0 1 2 3 4 Deep Conscious level Sleep Stupor Coma Coma coma Answer questions Painful stimuli Reflexes No respiratory or circulatory depression Treatment of poisoning I- Supportive therapy II- Gastrointestinal Decontamination III- Elimination of the poison from the blood IV- Antidotes Treatment of poisoning Treat the patient not the poison Treatment of poisoning I- Supportive therapy = [Treat the patient not the poison] = [Support the ABCs]  Airway [keep it patent] by: 1- Head: extended 2- Tongue: prevent from [falling back against the pharynx by using oropharyngeal tube 3- Dentures or foreign bodies: Must be removed 4- Tubes for: Suction of secretions Endo tracheal tube in case of prolonged coma Tracheostomy tube in upper airway obstruction. Treatment of poisoning I- Supportive therapy  Breathing [O2 therapy] by: Simple Face mask Nasal cannula Mechanical ventilation Treatment of poisoning I- Supportive therapy Circulation: - Hypotension mast be treated by IV fluids. Drugs. - Vasopressors [Dopamine] - Inotropics [Digitalis] - Arrhythmia must be treated by : Antiarrhythmic Drugs. [lidocaine. phenytion etc..] Treatment of poisoning I- Supportive therapy  CNS : [Altered Mental status] Coma cocktail should be used as diagnostic or therapeutic agents. 1) Dextrose : All comatosed patients should receive concentrated dextrose unless hypoglycemia is excluded by an immediate bedside test. 50m1 of a 50% solution I.V. 2) Thiamine :100mg I.V. for possible Wernick’ s encephalopathy in alcoholics. 3) Naloxone [Narcan] : 2mg IV. For adult & 0.03mg/kg IV for children [To exclude opiate overdose]. Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] The three general methods of G.I.T decontamination Involve: Gastric emptying by [emesis or gastric lavage). Activated charcoal (AC) [adsorbs the poison & prevents its absorption]. Cathartics & whole bowel irrigation (WBI) [they enhance excretion of poisons from the GIT]. Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] Emesis Definition: Removal of the stomach contents by inducing vomiting. Indication: Recent ingestion of substances [within 3 hours post ingestion]. Methods of emesis: A - Mechanical B- Chemical: Peripherally acting. Centrally acting. Mixed [Peripherally + centrally]  Contraindications of emesis Patient Poison CNS. Problems: a) Coma: fear of asphyxia & aspiration pneumonia. b) Convulsions: as it may induce new attack of convulsion. * Chronic poisoning Serious CVS diseases: [as it will cause electrolyte * Corrosives [Inorganic]:- fear of perforation imbalance and effort on heart] * Volatile hydrocarbons [kerosene] :-fear of * GIT problems: aspiration pneumonia. * Poisons result in rapid onset of CNS depression -Varices [as it will cause bleeding] [phenol]:- - Recent gastric operation. absent gag reflex and fear of aspiration pneumonia. Infants under 6 months ( poor gag and air way protective reflexes) or neurologically impaired patients: (poor air way protective reflexes) Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] Gastric Lavage Definition: Removal of the stomach contents by washing using a tube. Indication: Recent ingestion of substances. [Within 3 hrs post ingestion & emesis failed]. But it may be useful as long as 12 hrs post ingestion in some poisons as: Poisons which stick to stomach [Salicylates make aspirin cake]. Poisons which slow down motility of stomach [Barbiturate]. Poisons which secreted in stomach [Morphine]. Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] Contraindications of gastric lavage [are the same as for emesis] except: Coma & volatile hydrocarbons - Lavage is allowable after inserting a cuffed endotracheal tube to prevent aspiration pneumonia. Convulsions - Lavage can be performed under general anesthesia. Cardiac dysrhythmias must be controlled before gastric lavage is initiated, as insertion of the tube may create vagal response - cardiac arrest Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] Procedure of gastric lavage The tube: Rounded with multiple holes on the sides of its tip 1.5rnetre in length, 1.5cm in diameter It has a mark at a distance of 50cm from its lower end, which is the distance between the front of teeth & epigastrium. Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] To be sure that the tube is in the stomach and not entered the trachea must be assessed by: 1) No cough, dyspnea or cyanosis. 2) Aspiration brings up gastric contents. 3 ) Absence of bubbling when the end of the tube is immersed in water during expiration, but present only during inspiration. 4) No Breath sounds can be heard from the end of the tube. Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] Activated charcoal - Can be used alone. after emesis and with or after gastric lavage. Source: it is manufactured by pyrolysis of wood or other carbonaceous material which is then oxidized at high temperature using steam, air, Co2 or o2 to enhance pore development. The final product has surface area of 950-2000 m2/g. Action: The charcoal particles have many pores& holes [One molecule of A.C adsorb 10 molecules of poisons] which adsorb (bind) poisons in GIT and hence decrease their absorption. Dose: 50gm — 100gm in adults [orally, mixed with H2o] 15gm — 30gm in children. Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] N.B. Poisons poorly adsorbed by Activated Charcoal: C--Cyanide and Corrosives. H--Heavy metals (Iron, Lead, Arsenic, Lithium and Mercury). A--Alcohols. R--Rapid onset or absorption (Cyanide and Strychnine). C--Chlorine and iodine. O--Others insoluble in water (substances in tablet form). A--Aliphatic and poorly adsorbed hydrocarbons (petroleum distillates). L--Laxatives (sodium, magnesium and potassium) Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] Cathartics [Purgatives] The commonly used cathartics are magnesium sulphate, magnesium citrate and sorbitol (some commercial preparations of A.C. come premix with sorbitol). Types: Osmotic cathartics: MgSO4 30gm in adult 250 mg/kg in children or Sorbitol 1g/kg only once. Oil cathartics: Castor oil. Treatment of poisoning II) Gastrointestinal Decontamination [i.e Removal of the poison from GIT& prevention of absorption] Whole bowel irrigation Definition: Irrigation of the entire GIT non absorbable isotonic electrolyte solution containing Polyethylene Glycol through nasogastric tube until the bowel has been cleansed rapidly of the poison. Indications: Poorly adsorbed drugs by Activated Charcoal [see before] Preparations which are slow release e.g. Salicylates and Calcium channel blockers Packets of illicit drugs (e.g. Cocaine or Heroin). Treatment of poisoning III- Elimination of the poison from the blood (enhanced elimination)  Forced diuresis and alteration of the urine pH (ion trapping):  Extracorporeal methods which include:  Dialysis: Hemo [Artificial kidney] or Peritoneal.  Haemoperfusion.  Plasmapheresis.  Treatment of poisoning III- Elimination of the poison from the blood (enhanced elimination) a) Forced dieresis Definition: Removal of the poison from the blood through increasing the glomerular filtration rate. Types: Osmotic: Mannitol (20%) Fluid: DNS The objective is to maintain a urine output of 300-500ml/hr or 8-14 L/day.  Treatment of poisoning III- Elimination of the poison from the blood (enhanced elimination) b) Alteration of the urine pH (ion trapping) Definition: Changing PH of urine making the poison ionized “ion trapping” [i.e. poison can’t be reabsorbed through the cells of the renal tubule as ionized drugs are poorly absorbable through cell membranes] this will lead to increase Excretion. Principles of ion trapping: Alkalinization of urine in acidic drugs e.g. salicylates and barbiturates. Solution: [NaHCo3] 1-2 mg/ kg/ in 5% dextrose Keep urine pH 7.5-8.0 Acidification of urine in alkaline drugs e.g. Amphetamine, Quindine and PCP. Treatment of poisoning III- Elimination of the poison from the blood (enhanced elimination) Dialysis (hemo- & peritoneal) Indications: 1) Renal failure and the poison is excreted by kidneys 2) Liver failure and the poison is metabolized by the liver 3) Prolonged coma Contraindications: 1) Non - dialyzable drugs or poisons 2) Presence of coagulopathy. 3) Pregnancy in case of peritoneal dialysis. Treatment of poisoning III- Elimination of the poison from the blood (enhanced elimination) Hemoperfusion Indications: For clearing toxic substances that are poorly eliminated by dialysis [Non dialyzable substances] i.e. High molecular weight. High lipid solubility. High protein binding. Low water solubility. Contraindications: If the toxic agent cannot effectively be absorbable to charcoal. Treatment of poisoning III- Elimination of the poison from the blood (enhanced elimination) Plasma pharesis Mechanism: A volume of blood is removed, and all blood components except the plasma are returned to the circulation. The plasma is replaced with a crystalloid solution. Indications: Toxins which are poorly dialyzed or filtered. Contraindications: Bleeding disorders. Treatment of poisoning IV- Antidotes (I) Local (II) Physiological [systemic] A) Physicomechanical e.g. Chelators B) Chemical * EDTA * BAL * DMSA & DMPS * Penicillamine * Deferoxamine Treatment of poisoning IV- Antidotes Physicomechanical Adsorbents Delmulcents Entanglers Dissolvents Protect the Dissolve the Used to adsorb stomach Catch the poisons. the toxic agents mucosa by solid objects e.g. Ethanol 10% coating it e.g. Activated e.g. cotton used to dissolve e.g. Milk & egg charcoal for pins phenol white Treatment of poisoning IV- Antidotes (chemical) (1) Neutralization (2) precipitation (3) Reduction (4) Oxidation * Weak alkalis used to neutralize acidic corrosives. [obsolete] Mercuric chloride *Weak acids used to [divalent, toxic] *Ca ppt. Oxalic acid neutralize alkaline *MgSo4 ppt Lead Is reduced Oxidation by H2O2 or corrosives. [obsolete] by Na Due to:- KmnO4 1/5000 formaldhy de (1) Exothermic heat used for: *Skimmed milk ppt sulfoxylate reaction increase mercury *Plants destructive effect Mercurous *Cyanide * Tannic acid (strong (2) Co2 formation chloride tea) ppt plants [Monovalent, non when NaHCo3 is used, toxic) gastric perforation occurs. Thank y u