Basic Principles of Clinical Toxicology PDF

Basic principles of Clinical Toxicology DR. RIHARDS PĒTERIS ROČĀNS Definitions Toxicology is the study of harmful effects of agents on people, animals, and other living organisms. Analytical Toxicology deals with the evaluation of toxic substances present in biological specimen as well as in raw fo...

Basic principles of Clinical Toxicology DR. RIHARDS PĒTERIS ROČĀNS Definitions Toxicology is the study of harmful effects of agents on people, animals, and other living organisms. Analytical Toxicology deals with the evaluation of toxic substances present in biological specimen as well as in raw form or crude form. Clinical Toxicology in the study of adverse effects of agents and drugs in human beings, and the study of how to treat, ameliorate, modify, or prevent the adverse effects. Definitions Toxicant – any toxic substance (man made or naturally occuring) Poison - a substance that is capable of causing the illness or death of a living organism when introduced or absorbed. Toxin - a substance (commonly protein) that is synthesised by a plant species, an animal, or by micro-organisms, that is harmful to another organism. Venom – a poisonous substance secreted by animals for active or offensive transmission (bite, sting). Definitions The presence of adverse effects of agents and drugs in humans is defined as Poisioning. Poisioning can be acute or chronic. Toxicokinetics refers to the study of absorption, distribution, metabolism/biotransformation, and excretion of toxicants in relation to time. Toxicodynamics - the quantitative description of the effects of a toxicant on a biological system. Syndrome is a group of symptoms that occur together and characterize a specific condition. Narcology: The study of alcohol and drug abuse. Studies the causes, diagnosis and treatment of substance abuse. Toxydrome - a group of symptoms and/or characteristic effects associated with exposure to a particular substance or class of substances. Acute posioning classification By mechanism: Deliberate self poisioning Accidental Household toxins Occupational Pharmaceuticals Envenoming Ingestion of biological toxins Substance misuse Iatrogenic Most common types of poisoning Addictive substances: Mushrooms; Alcohol; Household products Opioids; ◦ Pesticides Medications: ◦ Concentrated vinegar ◦ Bleach Benzodiazepines; Miscellaneus: Paracetamol; ◦ Carbon monoxide Antidepressants; ◦ Ethylene glycol Antipsychotics; ◦ Corrosives NSAIDs; Occasionaly taken in combinations. The concept ofantidotes Antidotes disrupt the distribution or metabolism of toxicants via: Distribution: Blocking access to receptors (e.g. blockers, antagonists) Chelation (binding of toxic substances to form molecules that are easily excreted) Metabolism: Enhance metabolism into non-toxic forms; Prevent metabolism to avoid production of toxic metabolites. T1 - Kind and Estimated Stocking Amount of Antidotes for Initial Treatment for Acute Poisoning at Emergency Medical Centers in Korea VL - 29 DO - 10.3346/jkms.2014.29.11.1562 - Journal of Korean medical science Universal principles in managementof acute poisoning General approach to acutepoisoning Treat the patient instead of the poision! ◦ The agent is rarely known at time of clinical presentation. The history may be incomplete, unreliable, or unobtainable; ◦ Multiple toxicants may be involved; ◦ No specific antidotes and interventions are available for most types of poisioning. ◦ Focus on support of vital functions is key for survival in the acute phase of any poisioning. ◦ Overdose must be differentiated from a drug reaction. Examples are allergic or idiosyncratic reaction, or a drug–drug interaction. General approach to acutepoisoning Thim, Troels & Krarup, Niels & Grove, Erik & Rohde, Claus & Løfgren, Bo. (2012). Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. International journal of general medicine. 5. 117-21. 10.2147/IJGM.S28478. Emergency management ofacute poisioning Airway, Breathing, Circulation, Disability, Exposure! Disability is in the context of toxicology is checking the presence or absence of altered mental status (AMS). For example: -Loss of Conciosness -Confusion -Psychosis -Agitation Universal treatment of poisoningwith AMS High-flow oxygen (8–10 L/min) to treat a variety of toxicant induced hypoxic conditions. Hypertonic dextrose 0.5–1.0 g/kg of 40% glucose for an adult or a more dilute glucose solution for a child; the glucose is administered as an IV bolus to diagnose and treat or exclude hypoglycemia. Thiamine (100 mg to 480 mg IV for an adult; usually unnecessary for a child) to prevent or treat Wernicke encephalopathy. Naloxone (0.04 mg IV with upward titration towards 0.4 mg) for an adult or child with opioid-induced respiratory compromise. Management ofspecific routes of exposure Initial management of inhalationexposure 1. Consider your own safety, avoid exposure. 2. Use the ABCD approach 3. Use oxygen treatment, bronchodilators. 4. In severe cases the airway must be secured by intubation and subsequent mechanical ventilation. Inhalants can cause severe disruption of vital functions in two ways: 1. Local airway and respiratory epithelium damage 2. Systemic absorption from lung tissue Initial management of cutaneousexposure 1. Consider your own safety. Some secondary exposures can be avoided by wearing protective (rubber or plastic) gowns, gloves, etc. 2. Remove the patient’s clothing, place it in plastic bags, and then seal the bags. 3. Wash the patient with soap and copious amounts of water twice regardless of how much time has elapsed since the exposure. 4. Make no attempt to neutralize an acid with a base or a base with an acid. Further tissue damage may result from the heat generated by this reaction. 5. Avoid using any greases or creams because they will only keep the toxicant in close contact with the skin and ultimately make removal more difficult.  Initial management of ophtalmicexposure The eyes should be irrigated with the eyelids fully retracted for no less than 20 minutes. Lukewarm tap water can also be used. To facilitate irrigation, a drop of an anesthetic in each eye can be used, and the eyelids should be kept open with an eyelid retractor. An adequate irrigation stream may be obtained by running 1 L of normal saline through regular IV tubing held a few inches from the eye. Management ofingestion First response: 1. Use the ABCDE approach 2. If the patient is vomiting, prevent inhalation or repeated swallowing of vomit; 3. Do not encourage or otherwise cause vomiting. Emergency management: 4. General poisoning management principles are used 5. Specific interventions for toxic ingestion 1. Gastric lavage 2. Activated charcoal Management ofingestion Gastric lavage is performed by placing a large-bore orogastric tube (30–40 F); It is done by instilling and re-aspirating several litres of water to wash out the stomach contents. This is continued until no more pill fragments or other signs of a given toxicant are identified in gastric contents. Management ofingestion General properties of Gastric lavage: Drug absorption is not reduced if lavage is commenced 1 h or more after drug ingestion. Gastric lavage may promote post-pyloric transfer of poison into the small intestine where it is more rapidly absorbed. Complications include: aspiration pneumonia, charcoal aspiration, laryngospasm, inadvertent tracheal intubation, bradycardia, gastrointestinal perforation. Management ofingestion Indications of gastric lavage: 1. Given the time of ingestion, a significant amount of the toxicant might still be present in the stomach. 2. The toxicant is not adsorbed by activated charcoal or activated charcoal is unavailable. 3. The toxicant exceeds the activated charcoal-to-toxicant ratio of 10:1 even when using high doses. 4. No highly effective specific antidote exists or alternative therapies or other interventions pose a significant risk to the patient. Management ofingestion General principles in use of Activated charcoal: It is an adsorbent that creates weak van der Waals forces that bind with the substance in the gastrointestinal tract – adsorbs most drugs and chemichals. Its structure provides a large surface area to prevent absorption. Management ofingestion General principles in use of Activated charcoal: It is not recommended in poisoning with lithium, iron, alcohol, methanol, ethylene glycol, petroleum distillates, corrosives, acids, or alkalis. A rare adverse effect from is acute bowel obstruction from charcoal concretions - likely in the presence of an anticholinergic ileus. Management ofingestion Dosage of activated charcoal: 1 g/kg of body weight or a 10:1 ratio of activated charcoal to toxicant, whichever is greater. After massive ingestions 2 g/kg of body weight might be indicated if such a large dose can be easily administered and tolerated. Clinical aspects of use: It is administered orally or nasogastrically via a 16 F tube. The dose should be given within 1 h of poison ingestion. Its efficacy is time-dependent, with nearly 90% reduction in absorption 30 min after drug ingestion decreasing to 30% at 1 h. It is unpalatable, can cause vomiting and black stools. Mushroom poisoning Mushroom poisoning - Overview Of the approximately 5000 kinds of fungi known worldwide, about 20 are excellent eaters, a few hundred are edible. In Europe around 150 are known to be poisonous—including a few that are potentially deadly. Poisonous mushrooms are ingested due to: Ignorance; Confusing with other, edible species; Misuse as intoxicating drugs. Mushroom poisoning - Overview All mushroom poisoning can be broadly grouped in four categories: Gastrointestinal irritant (30 min to 6 hours) – usually self limiting diarrhoea and vomiting. Treated symptomatically. Muscarinic syndrome (3 min to 2 hours) – vomiting, diarrhea, miosis, sweating, bradycardia, hypotension. Treated with atropine. Psilocibin syndrome (15 min to 1h) - Euphoria, hallucinations, nausea, mydriasis, headache. Treated with sedatives and antipsychotics. Amatoxin syndrome (90% of poisioning cases) is caused by amatoxin, a RNA polymerase II inhibitor which prevents transcription of DNA to mRNA, thus blocking the biosynthesis of cell proteins. Syndrome is reviewed in later slides. Mushroom poisoning – Amatoxin syndrome 1. A gastrointestinal stage with 6 to 24 hour latency: severe stomach pains, nausea, vomiting, cholera-like diarrhoea 2. A hepatic stage with 12 to 48 hour latency: cytolytic hepatitis with a rise in liver enzyme values, apparent clinical improvement 3. Progressive acute liver and kidney failure after 24 to 72 h latency: coagulopathy, encephalopathy, nephropathy, seizures, hepatic coma, brain oedema, possibly a fatal outcome. Amatoxin syndrome - Management Treatment for amatoxin poisoning rests on four pillars: 1. Gastrointenstinal decontamination with activated charcoal 2. Volume replacement therapy. This is required due to extensive dehydration seen in profuse vomiting. 3. Antidotes: penicillin G, silibinin, and N-acetylcysteine (NAC). 4. Supportive treatment for liver failure. Severe cases need liver transplantation. References and furtherreading L. Nelson, N. Lewin, M. Howland, R. Hoffman, L. Goldfrank and N. Flomenbaum, ed., Goldfrank's Toxicologic Emergencies, 10th ed. (2015). Continuing Education in Anaesthesia Critical Care & Pain, Volume 10, Issue 1, February 2010 Poisoning & Drug Overdose. Kent R. Olson, Lange Medical Books/McGraw-Hill, 2004 Al-Jelaify M, AlHomidah S. The Individualized Management Approach for Acute Poisoning. Adv Pharmacol Pharm Sci. 2021;2021:9926682. Published 2021 May 12. doi:10.1155/2021/9926682 Emergency Management of Poisoning. Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose. 2007;13-61. doi:10.1016/B978-0-7216-0693-4.50007-4