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Acute Poisoning

Acute Poisoning. Michael Eddleston NPIS Edinburgh SpR in Clinical Toxicology, RIE. NPIS Edinburgh. THE IMPORTANCE OF PHARMACOLOGY.

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Acute Poisoning

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  1. Acute Poisoning Michael Eddleston NPIS Edinburgh SpR in Clinical Toxicology, RIE NPIS Edinburgh

  2. THE IMPORTANCE OF PHARMACOLOGY “You may experience a difficulty in remembering the antidotes for the various poisons. If so, rest assured that your knowledge of pharmacology is defective. All rational treatment of cases of poisoning is founded on a correct appreciation of the physiological action of drugs.” NPIS Edinburgh What to do in cases of poisoning, William Murrell, 1925

  3. EPIDEMIOLOGY • most common cause of medical presentation accounting for 10-20% of acute medical admissions (RIE 3000 of 15000/annum) • females > males, but male rate rising NPIS Edinburgh

  4. APPRAISAL OF THE POISONED PATIENT • history from patient • tablets / circumstances found • clinical features (“TOXIDROMES”) • Opiate • anticholinergic • stimulant • metabolic acidosis NPIS Edinburgh

  5. Gastric lavage Ward 3, Royal Infirmary of Edinburgh, 1973 (courtesy of Alex Proudfoot)

  6. PREVENTION OF ABSORPTION • activated charcoal • binds non-specifically • binds about 1/10 of charcoal weight • (charcoal dose 50 g in an adult) • Slow release products NPIS Edinburgh

  7. Christophersen et al, Br J Clin Pharmacol 2002; 53: 312-7.

  8. ACTIVATED CHARCOAL • timing - use within 1 hour • airway - don’t if problems • agent - eg iron, lithium, hydrocarbons NOT bound NPIS Edinburgh

  9. PARACETAMOL PROBLEMS • Indications for treatment • Staggered overdose • Late presentations • Reactions to antidote • Interpretation of results in poisoning NPIS Edinburgh

  10. Quantity Paracetamol Activity Quantity NPIS Edinburgh RISK FACTORS IN PARACETAMOL OD

  11. PARACETAMOL: RISK FACTORS Nutritional deficiency Eating disorders Alcoholism Malabsorption syndromes AIDS ?? Acute starvation (CLUE: Blood urea) NPIS Edinburgh

  12. PARACETAMOL: RISK FACTORS Enzyme inducers: carbamazepine phenytoin barbiturates rifampicin St Johns wort chronic ethanol NPIS Edinburgh

  13. PARACETAMOL: RISK FACTORS Enzyme inducers: carbamazepine phenytoin barbiturates rifampicin St Johns wort chronic ethanol CLUE: Gamma GT NPIS Edinburgh

  14. The cumulative survival rates for every time to acetylcysteine for each alcohol subgroup. There was a significant difference between the chronic and other subgroups (p < 0.0001 by Cox’s F test) Schmidt et al Hepatol 2002; 35: 876-882.

  15. Quantity Paracetamol Activity Quantity NPIS Edinburgh RISK FACTORS IN PARACETAMOL OD

  16. NPIS Edinburgh

  17. Outcome – ALT >1000 related to original plasma level and time of ingestion- ORAL NAC Rumack 2002 Clin Toxicol 40: 3-20.

  18. Current use of Acetylcysteine • Before 4 hours - WAIT until 4 hours • 4-8 Hours - Blood sample and wait ** • 8- 24 Hours - Treat on history, do bloods • After 24 hours - Do bloods unless toxic • STAGGERED INGESTION – use first dose time for treatment decisions NPIS Edinburgh **ASSUMES RESULT SOON

  19. What to do if patient presents >20h post ingesion • Do bloods (U&E, LFTs, INR, pcm) • If transaminase less than 2x elevated, INR < 1.4, creatinine normal, and paracetamol is not detected: • The patient has not been poisoned and can be safely discharged home NPIS Edinburgh

  20. PARACETAMOL: ANTIDOTE Acetylcysteine IV Adverse effects Vomiting flushing hypotension bronchospasm Anaphylactoid reaction - treat with antihistamines NPIS Edinburgh

  21. Intravenous acetylcysteine • adverse reactions common • Treatment is symptomatic: antihistamine and beta agonists. NOT ANAPHYLAXIS • fatalities uncommon (usually miscalculation), caution in asthmatics • Patients with a late presentation seem to have a higher incidence of anaphylactoid reactions that relates to lower paracetamol levels. NPIS Edinburgh

  22. Risk factors for ADRs to acetylcysteine • asthmatics 2.9 (95% CI 2.1, 4.7) more likely to develop ADR • allergy to other medicines not a risk factor NPIS Edinburgh Schmidt and Dalhoff. BJCP 2001:51; 87-91)

  23. What to do after 20 hours antidote?? • Transaminase, sensitive. If normal or less than 2x elevated risk of hepatotoxicity is low • INR more specific,if above 1.3 • ALWAYS also check creatinine NPIS Edinburgh

  24. STIMULANTS • amphetamine • ecstasy • cocaine • LSD • psilocybe mushrooms • phencyclidine NPIS Edinburgh

  25. STIMULANTS • Key issue is control of central excitation and hyperthermia • Use of judicious HIGH DOSES of diazepam and cooling • Watch for coronary spasm and infarction • Caution with antipsychotics • and flumazenil NPIS Edinburgh

  26. CALCIUM ANTAGONIST POISONING • cardiac effects - diltiazem, verapamil • peripheral effects - dihydropyridines (eg nifedipine, amlodipine) Both seen in overdose Beware bradycardic hypotensive patient NPIS Edinburgh

  27. MANAGEMENT OF CALCIUM ANTAGONIST POISONING • CNS effects often seen late • hypotension and rhythm disturbance • hyperglycaemia and lactic acidosis • beware slow release preparations NPIS Edinburgh

  28. TREATMENT OF CALCIUM ANTAGONIST POISONING • atropine • calcium • glucagon • catecholamines • cardiac pacing • insulin and glucose NPIS Edinburgh

  29. INSULIN-GLUCOSE AS ADJUNCTIVE THERAPY FOR CALCIUM CHANNEL ANTAGONIST POISONING • insulin 10-30 u/hr with dextrose (mean 0.5 IU/kg/hr) in five patients: 4 verapamil 1 amlodipine and atenolol NPIS Edinburgh Yuan et al. Clin Tox 1999; 37, 463-74

  30. ANTIDEPRESSANTS Tricyclics amitriptyline dosulepin SNRI venlafaxine SSRIs paroxetine fluoxetine sertraline citalopram NRI reboxetine Presynaptic -2 antgst mirtazepine MAOI phenelzine SMAOI moclobemide NPIS Edinburgh

  31. TRICYCLICS ACTIONS Amine reuptake inhibitors Anticholinergics Membrane effects (Na channel blockade) Antihistamine TOXICITY Arrythmias and fits NPIS Edinburgh

  32. ANTIDEPRESSANTS ECG of patient at risk: QRS > 100ms possible arrythmia (higher risk for fits) > 160ms definite arrythmia Dosulepin(Dothiepin ) most toxic NPIS Edinburgh

  33. ANTIDEPRESSANTS Treatment of patient at risk: Monitor using serial 12 lead ECGs Consider Bicarbonate IV if risk factors (QRS >100, and decreased conscious level) are present Magnesium additionally if torsade NPIS Edinburgh

  34. Metabolic acidosis • Definition: process that lowers serum HCO3- • Occurs when H+ ion production exceeds body’s ability to compensate adequately via buffering or ventilation Mechanisms of metabolic acidosis in poisoning • Increased acid production • Impaired acid elimination

  35. Mechanisms of increased acid production • Poisons are acids (eg HCl vs. sulphuric acid) • Poisons have acid metabolites (eg metabolism of alcohols to acids) • Poisons affect ATP consumption/production in mitochondria (eg pcm, valproate, ARVs, metformin, CO, cyanide, formate, +++ adrenergic stimulation) [uncoupling oxidative phosphorylation or inhibiting cytochromes of the electron transport chain] • Poisons create ketoacids (eg ethanol, isoniazid)

  36. Mechanisms of impaired acid elimination • Toxic metabolites damage kidneys (ethylene glycol) • Poison causes distal RTA (eg toluene)

  37. Calculations • Note the low pH (or high H+) • Then calculate Anion Gap (AG) AG = [Na+] – ([Cl-] + [HCO3-]) Usual range = 12 +/- 4 m/Eq/L (more recently 7 +/- 4) • If toxic alcohols suspected, calculate osmolality: 2 x [Na+] + [glucose] + [urea] and request a measured osmolality on a blood sample Osmol Gap = measured osmolality – calculated osmolality

  38. AG & metabolic acidosis • High AG Occurs when an acid is paired with an unmeasured anion (eg lactate, formate) • Normal AG Occurs with gain of both H+ and Cl- ions, or a loss of HCO3- and retention of Cl-, preserving electroneutrality • However, AG can be affected by errors of calculation or assay and by many disease states. So the lack of a high AG does not exclude any particular cause

  39. Use of the osmol gap in patients with a high AG metabolic acidosis • Osmol gap may provide extra information if a toxic alcohol is suspected. • However, be aware that other medical conditions such as ketoacidosis and renal failure also cause a raised OG • Normal osmol gap = less than 10 +/- 6 mOsm/L • However, normal range has problems due to wide variability between people and assays

  40. Toxins associated with a high osmol gap • Mannitol • Alcohols: ethanol, etylene glycol, isopropanol, methanol, propylene glycol • Diatrizoate (amidothizoate) • Glycerol • Acetone • Sorbitol

  41. Ethylene glycol Glyceraldehyde Glycolate Glyoxylate Oxalate Methanol Formaldehyde Formate Metabolism of toxic alcohols

  42. The mountain Mycyk & Aks, 2003

  43. METHANOL & ETHYLENE GLYCOL • action - CNS depressants metabolic toxicity secondary to metabolites - formic acid, aldehydes - renal failure, blindness • Treatment - block metabolic production - ethanol - fomepizole increase removal- dialysis NPIS Edinburgh

  44. Ethylene glycol Glyceraldehyde Glycolate Glyoxylate Oxalate Methanol Formaldehyde Formate Metabolism of toxic alcohols

  45. DELIBERATE RELEASE • Irritant gases- Chlorine • Toxic chemicals- Cyanide • Nerve agents- sarin, VX • Infective agents- anthrax NPIS Edinburgh

  46. NERVE AGENTS • Cholinesterase inhibitors • Bronchorrhoea • Increased gut motility • Small pupils • CNS activity, Fits • Atropine • Oximes NPIS Edinburgh

  47. CARE AFTER RECOVERY 1. psycho-social assessment 2. approximately 15% of patients have psychiatric illness 3. most never re-attend with self harm NPIS Edinburgh

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