Presentation on theme: "Toxicology Dr Dunia Alhashimi Consultant pediatrician."— Presentation transcript:
Toxicology Dr Dunia Alhashimi Consultant pediatrician
Important areas to be covered Activated charcoal, mechanism of action, indications, contraindications Carbon monoxide Poisoning, signs and management Ethylene glycol, common forms, signs and symptoms, Hydrocarbons, types, Mgt
Q1 A 10kg 14 month old boy is brought to the A&E by his parents. His parents claim that he possibly ingested paracetamol, as six 500mg tablets were found to be missing from the family’s paracetamol container. This possible ingestion occurred within a 60-min window efore their presentation to the Emergency department. Which of th following is the most appropriate management action? a.Measure plasma paracetamol levels b.Administer ipecauanha to induce emesis c.Perform a gastric lavage d.Adminster N-acetyl cysteine e.Administer activated charcoal
Q1 Ans E: Administer activated charcoal The most appropriate management in this instance would be to administer activated charcoal, to limit further absorption of paracetamol, Inducing emesis with ipecuanha is now generally contraindicated. Measurement of plasma paracetmol level is useful only after 4 hours of ingestion. A gastric lavage maybe beneficial, but when you are given these five choices it would not be the first choice of treatment. N-acetylcysteine would not be the first line of treatment either.
Q2 The nomogram is used to determine when a patient is give N-acetyl cysteine is administered in patients even if their levels are below the nomogram line. Which one of the following is not a risk factor? a.Alcoholism b. patient on isoniazide c.pt on cimetidine d.fasting e.malnutrition
Q2 Ans: C If the serum level falls between the two nomogram lines, consider giving NAC if the patient is at increased risk for toxicity; e.g. the patient is alcoholic, malnourished or fasting or is taking drugs that induce P-450 2E1 activity (e.g. isoniazide INH); after multiple or subacute overdoses; or the patient is considered uncertain or unreliable.
Q3 A 3 year old boy was found with a empty packet of extended-release paracetamol tablet. The parents claim that he took 8 500mg tablet. You are called in the emergency and decide to do a drug level. When is the best time to do a paracetamol drug level in the patients a.Immediately as the dose is very high b.A level stat and one after 4 hours c.A level 4 hours after ingestion d.A level 8 hours after ingestion e.A level 8 hours and another after 12 hours
Q3 Ans:E After ingestion of extended release tablets, which are designed for prolonged absorption, there may be a delay before the peak paracetamol level is reached. This can also occur after co-ingestion of drugs is reached. In such circumstances, repeat the serum paracetamol level at 8 hours and possible after 12 hours.
Q4 Which statement is true regarding liver toxicity from paracetamol overdose? a.It is likely because paracetamol plasma half-life is approximately 2 to 3 hours. b.It usually is evident 12 to 24 hours after ingestion c.For a given toxic plasma level, children have a higher incidence of hepatic aminotransferase elevation than adults have. d.Hepatic toxicity results from N-acetyl-p- benzoquinonemime (NAPQ1) e.Diet, nutritional status, and age are not related to liver toxicity.
Q4 Ans: D Liver toxicity results when NAPQ1, a reactive intermediary, is formed by cytochrome P-450 activity. Glutathione conjugates NAPQ1 to nontoxic conjugates. In an overdose, glutathione is depleted, and NAPQ1 binds covalently with hepatocytes to produce hepatic necrosis.
N-acetylcysteine Most effective within 8 hours Precursor for glutathione production Can cause anaphylactoid reactions Consider starting before paracetamol result if: – Presenting > 8 hrs & >150mg/kg taken – Staggered overdose
Patient X 15 year old girl who presents after taking 24 paracetamol over a period of 24 hours No drug history Fit and well Blood level 20mg/l
In patients who have taken several overdoses of paracetamol over a short period of time, the plasma paracetamol concentration will be more difficult to interpret as the treatment graph relates to a single acute ingestion. Such patients should be considered as at serious risk and considered for treatment with N-acetylcysteine (NAC). They can be discharged after NAC treatment or 24 hours from the last paracetamol dose provided they are asymptomatic and the International Normalised Ratio (INR), plasma creatinine and ALT are normal. Staggered overdose. (www.pharmweb.net)
PARACETAMOL DEADLY PITFALLS The Prescott Nomogram High Risk Line Staggered Overdoses Management of late presentation Recheck U&E, LFT, INR after N-acetylcysteine
Q5 A mother brings in her 1-year-old after he drank from a Dettol bottle. What is the most common cause of mortality after Dettol ingestion? a.Neurological depression b.Aspiration pneumonia c.Gastric strictures d.Uncontrolled seizures e.Hypoglycemia
Q5 Ans: B Dettol liquid (chloroxylenol 4.8%, pine oil and isopropyl alcohol) is a commonly used household disinfectant. Labeled nonpoisonous, Serious complications were reported in up to 8% of cases of ingestion – included aspirations with gastric content resulting in pneumonia, – cardiopulmonary arrest, bronchospasm, adult respiratory distress syndrome – severe laryngeal edema with upper airways obstruction. "Burning" in the mouth and throat with nausea and vomiting. Later contaminated skin becomes erythematous and there is redness, swelling and superﬁcial ulceration in the mouth and upper alimentary tract. The larynx may also be involved leading to breathlessness and stridor.
Q6 Which of the following ingestions could be seen with an increased anion gap? a.Paracetamol b.Isopropanol c.Ethylene glycol d.Ethylene dibromide e.Methane
Q6 Ans: C The etiologies of metabolic acidosis with elevated anion gap can be recalled with the mnemonic MUD-PILES: Methanol, Uremia,Diabetic ketoacidois, paraldehyde, Iron, Isoniazid or Inhlaants, Lactic Acidosis, Ethylene glycol or chronic Ethanol abuse, Salicylates or Solvents. In paracetamol poisoning metabolic acidois is uncommon. Isopropyl alcohol results in high srum keones with little or no acidosis
Q7 Ethylene glycol poisoning is characterized by all of the following except: a.Metabolic acidosis b.Increased anion gap c.Hypocalemia d.Hypomagnesemia e.Hypokalemia
Q7 Ans: E Metabolic acidosis with increased anion gap is suggestive of methanol and ethylene glycol ingestion. Ethylene glycol toxicity results from its metabolite oxalate, which chelates calcium ion to form insoluble calcium oxalate crystals and results in hypocalcaemia. Hyopmagmasemia usually occurs with hypocalcemia. However, hyperkalemia results from muscle necrosis, the development of acute tubular necrosis and renal failure, and metabolic acidosis.
Q8 A 13-year-old girl comes to the A&E with a history of ingesting a bottle of diphenhydramine (Benadryl) tablets. Which of the following signs and symptoms would be expected on examining the patient? a.Sweating, lacrimation, salivation, miosis, an blurred vision. b.Lethargy, slow respiration, hypotension, and lured vision. c.Agitation, tachycardia, sweating, and mydriasis d.Flushed face, agitation, dry mucous membrane, and dilated pupils e.Headache, tachycardia, tachypnoea, cherry red mucous membrane, and dim vision.
Q8 Ans: D Benadryl (diphenhydramine) is an anticholinergic agent. Toxidrome: Hot as a hare, Blind as a bat, Dry as a bone, Red as a beet, and Mad as a hatter A: anticholinesterase inhibitors or cholinergic agents (organophoshates) B: narcotic overdose C: sympathomimetic agents (amphetamines) E: carbon monoxide poisoning
Common causes Antidepressants-Tricyclics Antihistamines Atropine Antipsychotics Antispasmodics
Q9 A 2-year old is brought to the A&E by his mother, who says her son may have ingested a few CBZ (Tegretol) chewable tablets used by his sibling. Which of the following clinical findings would best support the possibility of an ingestion? a.Vomiting b.Confusion and excitation c.Tachycardia d.Hyperreflexia e.Nystagmus
Q9 Ans: E Dizziness, ataxia, and nystagmus with deviating pupils are the classic triad seen in CBZ toxicity. Although vomiting, confusion and excitement, tachycardia, and hyperreflexia are all possible signs of toxicity, the are nonspecific.
Q10 A grandmother brings in her 15-month-old toddler who may have swallowed one clonidine tablet (0.1mg) about 30minutes ago. The child is sitting quietly on her lap with heart rate (HR) 80 beats per minute, her blood pressure (BP) 130/80 mm Hg, and respiratory rate (RR) 20 breaths per minute. Which of the following would be the most appropriate management of this patient? a. The patient can be discharged afte initial assessment b.Look for other ingestants because hypertension is unlikely with a clonidine overdose c.Nalaxone 0.1mg/kg IV boluis should be given because the patient is bradycardiac d.Emesis should be immediately attempted with syrup of ipecac e.Only supportive care and monitoring are needed because most patients recover in 12 to 24 hours
Q10 Ans: E All children who are symptomatic after clonidine ingestion require admission, monitoring, and supportive care because symptoms may persist for up to 24 hours. Although the toxic dose of clonidine is not known, significant toxicity has resulted with as little as 0.1mg 30 minutes after ingestion. The central effects of clonidine predominate and cause tachycardia and hypotension, but initially there maybe peripheral α 2 stimulation and reduced uptake of epinephrine, resulting in benign, transient paradoxic hypertension.
Q11 A 2-year old who swallowed digoxin tablets is found to have bradycardia. An electrocardiogram (ECG) shows ventricular bigeminy. Which of the following is true? a.ECG findings of T wave depression and scooped ST segment correlate with significant digoxin toxicity b.Digoxin immune FAB (Digibind) is indicated for life- threatening dysrhythmias c.There is a wide margin between therapeutic and toxic doses d.Hyperkalemia is not affected by digoxin immune FAB (Digibind) therapy e.Forced alkaline diuresis may increase renal excretion
Q11 Ans: B Digoxin immune FAB (Digibind) is indicated for use in treating life-threatening digoxin- induced dysrhythmias and for hyperkalemia. The ECG finding of T wave depression and scooped ST segemnts ar known as digitalis effect but do not indicate toxicity. Alkaline diuresis is not useful in digitalis elimination.
Q12 Which of the following regarding caustic injury to the esophagus is true? a.Acid burns are usually deeper than alkali burns in the esophagus and thus cause greater long-term complications b.If there are no orophayngeal lesions, esophagoscopy is not required because esophageal burns are unlikely c.Patients who ingest caustics appear to have an increased risk of esophageal carcinoma d.Only 50% of all stricture formation results within 2 months of ingestion e.About 10% of first-degree burns results in esophageal strictures
Q12 Ans: C Drain pipe cleaners usually contain sodium hydroxide as their principal components. Patients who ingest caustics have an increased risk of developing esophageal carcinoma. In the esophagus, acid burns usually cause a superficial coagulation necrosis with eschar formation of the mucosa, which limits penetration of the injury. However, bases causes liquefaction necrosis of the fat and protein involving the mucosa, submucosa, and muscle and penetrate deeply, causing the potential for greater tissue damage. Oropharyngeal lesions do not predict esophageal burns as only a third of patients with oral lesions develop esophageal burns, and about 10% to 15% of those with esophageal burns have no oral lesions. First degree burns do not develop strictures; 15% to 30% of second- degree do; and almost 100% of third-degree burns do
Q13 A frantic mother calls you saying that her 2-year-old child just swallowed some household bleach. She gave him milk, which he drank without any drooling or vomiting. Which of the following is the most appropriate action to take? a.Tell the mother to give her son syrup of ipecac immediately b.Tell the mother to bring her child to the A&E for endoscopy to rule out esophageal strictures c.Reassure the mother that it is a mild irritant and that her son will do fine as he has been drinking without problems d.Warn the mother that because household bleach is an alkali, it can cause esophageal strictures even if oral lesions are not seen e.Tell the mother to give her son antacid to buffer the effect of the bleach
Q13 Ans: C Household bleach contains chlorine or sodium hypochlorin, which is a mild irritant and usually causes no tissue destruction. Immediate dilution with water or milk is all that is required.
Salicylate DEADLY PITFALL Salicylate levels can continue to rise following admission (10% of cases) – Repeat levels every until peaked
Q14 Which statement most accurately describes the effects of insecticides? a.Carbamates create an irreversible bond with cholinesterase b.Organophosphates stimulate the release of excessive amounts of acetylcholine at the synaptic junction c.Insecticide poisoning can be confirmed by a rise in cholinesterase level in the blood d.Humans have no biotransformation mechanism for metabolizinig (detoxifying) insecticides e.Organophosphates inhibit the degradation of acetylcholine
Organophosphates exert their effect by interfering with the enzyme cholinesterase, which degrades acetylcholine but rather cause its accumulation by preventing degradation. Insecticide poisoning causes cholinesterase levels to fall, and this test can be used to confirm the clinical impression of insecticide poisoning. Humans are, in fact able to detoxify organophosphates by conjugation in the liver. Carbamates form a reversible bond with cholinesterase. In contrast, organophosphates irreversibly bind to cholinesterase via phosphorylation. Q14 Ans: E
Q15 Which statement most accurately characterizes the differences between organophosphate and carbamate poisoning? a.Carbamate exposure is more common than organophosphate exposure b.Carbamate poisoning is usually of shorter duration c.Pralidoxime must be started sooner to be effective in carbamate poisoning d.Only organophosphates are absorbed through the skim e.Both answers B and C are correct.
Q15 Ans: B
Q16 Which of the following statements concerning cholinergic poisoning treatment is most correct? a.Pralidoxime is used to prevent irreversible deactivation of cholinesterase b.Atropine restores the biologic activity of cholinesterase c.The dose of atropine should not exceed 2 mg d.Pralidoxime is more useful as a treatment for Carbamate exposure than for organophosphate exposure e.Bronchorrhea must be treated by loop diuretics because atropine is ineffective for this
Q16 Ans: A Pralidoxime reactivates cholinesterase by competing for the phosphate moiety of the organophosphate compound, thus releasing if from the cholinesterase enzyme. Atropine counteracts the effects of acetylcholine excess but has no effect on the biological activity of cholinesterase. There is no maximum dose of atropine in insecticide poisoning. Rather, the dose is titrated to the patient’s clinical response. Loop diuretics such as frusemide should be avoided in insecticide poisoning because they exacerbate already excessive urinary output. Bronchorrhea generally is controlled with ventilation and atropine.
Q17 A 22-month-old, 15-kg girl is found with an empty bottle of chewable vitamin tablets (15 mg of elemental iron per tablet). Although originally 100 tablets were in the bottle, the mother believes that at least 75 tables are found on the floor in the house. The child is asymptomatic when she comes to the ED 90minutes after the ingestion. Which of the following is the next most appropriate action? a.Administer an immediate dose of activated charcoal and observe for 6 hours b.Obtain a serum iron level, complete blood count, serum electrolytes, and liver function test and observe the patient for 6 hours in the ED c.Obtain an abdominal radiograph, and if no iron tablets are seen, discharge the patient. d.Administer syrup of ipecac and observe for 6 hours in the ED e.Administer a desferoxamine challenge of 50mg/kg intramuscularly
Q17 Ans: B
Q18 Which of the following regarding Naloxone (Narcan) is most correct? a.It can be administered intravenously, intramuscularly, and endotracheally, but not intraosseously b.It is often effective in reversing miosis associated with barbiturate overdose c.It can reverse the respiratory depression of a clonidine overdose d.It is effective with natural and semisynthetic opioids and is ineffective with synthetic opioid e.It has agonist as well as antagonist effects at higher doses
Q18 Ans: C
Q18 Naloxone has been shown to be effective antidote in narcotic and clonidine overdose, although its effect with clonidine is less consistent. Naloxone can be safely administered via all routes, including all intraosseous infusion. It is effective against all forms of opiods, including synthetic ones, but has no effect on barbiturate reversal. Naloxone is a pure antagonist with no agonist effects.
Q19 A 13-year old boy comes in 3 hours after ingestion of salicylate. The maximal amount ingested is 35g of salicylate. He is complaining of tinnitus, nausea, and vomiting. At the time he arrives in the A&E his vital signs are BP 108/68 mmHg, P 124 beats per minute, and RR 26 breaths per minute. An arterial blood gas reveals a pH of 7.44, and his serum salicylate level is 44 mg/dl. Which of the following would not be expected in this patient? a.Normal anion gap metabolic acidosis b.Elevateion of prothrombin time (PT) c.Lsctic acidosis d.Hypoglycemia e.Decreased serum ionized calcium
Q19 Ans :A A quick calculation indicates that the child in the scenario ingested approximately 20mg of elemental iron per kilogram. This is the lower range at which toxicity can occur. However, this child is currently asymptomatic. Because we cannot base our management approach on history alone, it is best to observe the child in the ED for symptoms while we wait for laboratory tests. Iron does not bind to activated charcoal, and its administration will not be helpful. An abdominal radiograph is useful when it is positive, but a negative abdominal radiograph is more commonly seen with chewable tablet ingestions. The use of ipecac is questionable in this case. A desferoxamine challenge test would be overly aggressive in this asymptomatic child with an estimated ingestion of 20 mg/kg.
Q20 Which of the following statements concerning the patient described is most accurate? a.Activated charcoal is unlikely to be of value in this patient’s management because of the length of time since ingestion b.The patient should not receive IV dextrose and NAHCO3 concomitantly because of the risk of cerebral edema c.Alkalinization of the urine is unnecessary into his case because the salicylate level places the patient in the “mild” category d. Effective alkalinization of the urine will require adequate replacement of potassium e.NaHCO3 therapy should be avoided because the patient’s serum is already alkaline
Q20 Ans: D
Q21 Which of the following statements concerning the patient described is correct? a.Hemodialysis and hemoperfusion would be about equally effective in removing salicylate from this patient b.The serum salicylate level indicates that dialysis will not be needed c.An acute ingestion of salicylates is more likely to require dialysis than a chronic ingestion d.Hypothermia, seizures, and renal failure are indications for dialysis e.If pulmonary edema develops, dialysis should be avoided
Q21 Ans: A
Q22 Which of the following statements concerning the patient described is correct? a.Hemodialysis and hemoperfusion would be about equally effective in removing salicylate from this patient b.The serum salicylate level indicates that dialysis will not be needed c.An acute ingestion of salicylates is more likely to require dialysis than a chronic ingestion d.Hypothermia, seizures, and renal failure are indications for dialysis e.If pulmonary edema develops, dialysis should be avoided
Q22 Ans: B
Q23 Which of the following metabolic complications is most likely to occur in the setting of both therapeutic use and overdose of valproic acid? A.Elevated ammonia B.Elevated calcium C.Elevated carnitine D.Low sodium E.Metabolic alkalosis
Q23 Ans:A Disruption of urea cycle Metabolic acidosis, hypernatremia, hypocalcemia, low carnitine, elevated ammonia (complication of therapeutic use) Hyperammonia: MS changes Sometimes hepatitis with bumps in AST/ALT. Carnitine may be beneficial. Very rarely renal failure, urea elevation
Q24 Activated Charcoal will adsorb all the following meds except: a.Phenobarbital b.Theophylline c.Ferrous sulfate d.Verapamil e.Salicylates
Activated Charcoal will adsorb all the following meds except: a.Phenobarbital b.Theophylline c.Ferrous sulfate d.Verapamil e.Salicylates Q24
Q25 A 10-month boy is brought in by his parents after he turned blue at home. The mother says he has been fussy recently, which she presumed to be caused by teething; she has been treating him with a topical teething gel. On exam, the boy has marked cyanosis, including the perioral area and nail beds, mild tachypnea and tachycardia, room air O 2 sat 88% does not improve with oxygen. Lungs are clear; work of breathing and heart sounds are normal.
Which treatment is most likely to be successful in treating the cyanosis? A.Botulinum antitoxin B.Deferoxamine C.Methylene blue D.Prostaglandin E 1 E.Sodium bicarbonate Q25
Q25 Ans: C
MetHb Cyanosis: increased deoxygenated Hb or abnormal pigments, e.g. silver (argyria) Oxidation of Fe in Hb from ferrous 2+ to ferric 3+: cannot bind O 2, impairs 02 release from remaining normal Hb, shifting curve left Overdose: benzocaine (teething gels), amyl nitrate, pyridium, sulfonamides Chocolate-brown blood Methylene blue accelerates NADPH- methemoglobin reductase, contraindicated in G6PD, need exchange transfusion
Common Non toxic ingestions A variety of product commonly found around the home are completely nontoxic or have little or no toxicity after typical accidental ingestion Treatment is rarely required because the ingredients are non toxic or potentially harmful material is present in minimal doses
Confirm ingredients In all cases, attempt to confirm the identity and/or ingredients of the product Ensue no other toxic product was involved Advise parents that mild GI upset may occur Water or other liquid may be given to reduce the taste and texture of the product
Non toxic products Crayons Clay Silica gel Supergle Wax Zinc oxide ointment
Non toxic products with minimal gastrointestinal irritation Antibiotic ointment Baby soap Bar soap Bleach ( household, less than 6% hypochlorite) Hair shampoo Prednisolone Toothpaste
Other low toxicity products Oral contraceptives: – In excessive amounts may cause GI upset – in females even prepubertal my cause vaginal spotting Thermometer: – Household thermometers contain less than 0.5ml liquid mercury which is harmless if swallowed. Clean cautiously to avoid dispersing mercury as mist or vapor (i.e. Do not vacuum)
Whole bowel irrigation is recommended in all of the following ingestions except: a.Lead paint chips b.Cocaine packets c.Button batteries d.Hydrocarbons e.Sustained-release lithium tablets Q26
Whole bowel irrigation is recommended in all of the following ingestions except: a.Lead paint chips b.Cocaine packets c.Button batteries d.Hydrocarbons e.Sustained-release lithium tablets Q26 Ans:D
Q27 A 14-year-old girl comes to the ED I hour after ingesting 36g of sustained release-enteric coated aspirin tablets. Which of the following statements concerning this patient’s condition is true? a.It is unlikely that any aspirin remains in the stomach at the time the patients arrives b.Peak serum levels of aspirin will occur at approximately 6 hours c.The pills should be visible on a plain radiograph of the abdomen d.Management should be withheld until a serum drug level confirms the overdose or the patient becomes symptomatic e.Arrangements should be initiated to perform hemoperfusion for the patient.
Q27 Ans: A
Q27 Enteric-coated tablets are often visible on plain x-ray films, especially enteric –coated salicylate tablets. Salicylate induces pyloric spasm and forms concretions that adhere to the gastric mucosa, thereby making it probable that some aspirin remains in the stomach. Although the Done nomogram uses 6 hours for the peak level in salicylate overdoses, this is an overdose of enteric-coated tablets, and the nomogram is therefore unreliable because it is unlikely that the peak level will achieved in 6 hours. Because this is a potentially serious overdose, management should begin as soon as possible pending the results of the drug level. The definitive treatment of choice for salicylate poisoning is hemodialysis, not hemoperfusion. Arrangements need not be instituted until the levels are obtained from this patient because it is early in the poisoning and hemodialysis might not be necessary.
Salicylate Metabolic and acid-base disturbance Complex Respiratory alkalosis – direct stimulation to over breathe Metabolic acidosis- acid, impaired normal metabolism, production of lactic acid Check ABG / VBG
Q28 Which of the following household substance, if ingested by a toddler, should cause the most concern? a.Silica gel (dehumidifying packets) b.Pencil lead c.Eye make up d.Mercury from a broken thermometer e.A whole cigarette
Q28 Ans: E
Q28 A whole cigarette can produce symptomatic nicotine poisoning in a small child. Pencil lead, of course is not lead but carbon. Silica gel and eye make up are nontoxic The amount of mercury ingested from a broken thermometer would also be non toxic, especially because its absorption would be minimal.