acute poisoning
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Acute Poisoning. Michael Eddleston NPIS Edinburgh SpR in Clinical Toxicology, RIE. NPIS Edinburgh. THE IMPORTANCE OF PHARMACOLOGY. - PowerPoint PPT PresentationTRANSCRIPT
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Acute PoisoningMichael Eddleston
NPIS EdinburghSpR in Clinical Toxicology, RIE
NPIS
Edinburgh
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THE IMPORTANCE OF PHARMACOLOGYYou 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.What to do in cases of poisoning, William Murrell, 1925
NPIS
Edinburgh
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EPIDEMIOLOGYmost 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
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APPRAISAL OF THE POISONED PATIENThistory from patienttablets / circumstances foundclinical features (TOXIDROMES)Opiateanticholinergicstimulantmetabolic acidosis
NPIS
Edinburgh
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Gastric lavageWard 3, Royal Infirmary of Edinburgh, 1973(courtesy of Alex Proudfoot)
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PREVENTION OF ABSORPTION
activated charcoalbinds non-specificallybinds about 1/10 of charcoal weight(charcoal dose 50 g in an adult)Slow release products
NPIS
Edinburgh
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Christophersen et al, Br J Clin Pharmacol 2002; 53: 312-7.
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ACTIVATED CHARCOAL
timing - use within 1 hourairway - dont if problemsagent - eg iron, lithium, hydrocarbons NOT bound
NPIS
Edinburgh
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PARACETAMOLNPIS
EdinburghPROBLEMSIndications for treatmentStaggered overdoseLate presentationsReactions to antidoteInterpretation of results in poisoning
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NPIS
Edinburgh
ParacetamolQuantity Activity Quantity RISK FACTORS IN PARACETAMOL OD
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PARACETAMOL: RISK FACTORSNPIS
EdinburghNutritional deficiencyEating disordersAlcoholism Malabsorption syndromesAIDS?? Acute starvation(CLUE: Blood urea)
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PARACETAMOL: RISK FACTORSNPIS
EdinburghEnzyme inducers: carbamazepinephenytoinbarbituratesrifampicinSt Johns wortchronic ethanol
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PARACETAMOL: RISK FACTORSNPIS
EdinburghEnzyme inducers: carbamazepinephenytoinbarbituratesrifampicinSt Johns wortchronic ethanol
CLUE: Gamma GT
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Schmidt et al Hepatol 2002; 35: 876-882.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 Coxs F test)
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NPIS
Edinburgh
ParacetamolQuantity Activity Quantity RISK FACTORS IN PARACETAMOL OD
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NPIS
Edinburgh
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Outcome ALT >1000 related to original plasma level and time of ingestion- ORAL NACRumack 2002 Clin Toxicol 40: 3-20.
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Current use of AcetylcysteineNPIS
Edinburgh Before 4 hours- WAIT until 4 hours4-8 Hours- Blood sample and wait **8- 24 Hours- Treat on history, do bloodsAfter 24 hours- Do bloods unless toxic
STAGGERED INGESTION use first dose time for treatment decisions**ASSUMES RESULT SOON
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What to do if patient presents >20h post ingesionNPIS
EdinburghDo 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
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PARACETAMOL: ANTIDOTENPIS
EdinburghAcetylcysteine IV
Adverse effects Vomiting flushinghypotensionbronchospasm Anaphylactoid reaction - treat with antihistamines
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Intravenous acetylcysteineNPIS
Edinburghadverse reactions common Treatment is symptomatic: antihistamine and beta agonists. NOT ANAPHYLAXISfatalities 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.
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Risk factors for ADRs to acetylcysteine NPIS
Edinburghasthmatics 2.9 (95% CI 2.1, 4.7) more likely to develop ADR allergy to other medicines not a risk factor
Schmidt and Dalhoff. BJCP 2001:51; 87-91)
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What to do after 20 hours antidote?? NPIS
EdinburghTransaminase, sensitive. If normal or less than 2x elevated risk of hepatotoxicity is low
INR more specific, if above 1.3
ALWAYS also check creatinine
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STIMULANTS amphetamine ecstasy cocaine LSD psilocybe mushrooms phencyclidine NPIS
Edinburgh
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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
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CALCIUM ANTAGONIST POISONINGcardiac effects - diltiazem, verapamil
peripheral effects - dihydropyridines (eg nifedipine, amlodipine)
Both seen in overdoseBeware bradycardic hypotensive patient
NPIS
Edinburgh
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MANAGEMENT OF CALCIUM ANTAGONIST POISONINGCNS effects often seen late
hypotension and rhythm disturbance
hyperglycaemia and lactic acidosis
beware slow release preparations
NPIS
Edinburgh
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TREATMENT OF CALCIUM ANTAGONIST POISONINGatropinecalciumglucagoncatecholaminescardiac pacinginsulin and glucose
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Edinburgh
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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 verapamil1 amlodipine and atenolol
Yuan et al. Clin Tox 1999; 37, 463-74 NPIS
Edinburgh
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ANTIDEPRESSANTSTricyclicsamitriptyline dosulepinSNRIvenlafaxineSSRIsparoxetinefluoxetinesertralinecitalopramNRIreboxetine
Presynaptic -2 antgstmirtazepine
MAOIphenelzineSMAOImoclobemide
NPIS
Edinburgh
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TRICYCLICSACTIONSAmine reuptake inhibitorsAnticholinergicsMembrane effects (Na channel blockade)AntihistamineTOXICITYArrythmias and fits
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Edinburgh
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ANTIDEPRESSANTSECG of patient at risk:QRS > 100ms possible arrythmia (higher risk for fits) > 160ms definite arrythmia
Dosulepin (Dothiepin ) most toxic
NPIS
Edinburgh
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ANTIDEPRESSANTSTreatment of patient at risk:Monitor using serial 12 lead ECGsConsider Bicarbonate IV if risk factors (QRS >100, and decreased conscious level) are present
Magnesium additionally if torsade
NPIS
Edinburgh
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Metabolic acidosisDefinition: process that lowers serum HCO3-Occurs when H+ ion production exceeds bodys ability to compensate adequately via buffering or ventilation
Mechanisms of metabolic acidosis in poisoningIncreased acid productionImpaired acid elimination
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Mechanisms of increased acid productionPoisons 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)
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Mechanisms of impaired acid eliminationToxic metabolites damage kidneys (ethylene glycol)Poison causes distal RTA (eg toluene)
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CalculationsNote 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] andrequest a measured osmolality on a blood sample
Osmol Gap = measured osmolality calculated osmolality
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AG & metabolic acidosisHigh AGOccurs when an acid is paired with an unmeasured anion (eg lactate, formate)
Normal AGOccurs 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
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Use of the osmol gap in patients with a high AG metabolic acidosisOsmol 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/LHowever, normal range has problems due to wide variability between people and assays
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Toxins associated with a high osmol gapMannitolAlcohols: ethanol, etylene glycol, isopropanol, methanol, propylene glycolDiatrizoate (amidothizoate)GlycerolAcetoneSorbitol
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Metabolism of toxic alcoholsEthylene glycol
Glyceraldehyde
Glycolate
Glyoxylate
Oxalate
Methanol
Formaldehyde
Formate
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The mountainMycyk & Aks, 2003
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METHANOL & ETHYLENE GLYCOL
action - CNS depressantsmetabolic toxicity secondary to metabolites- formic acid, aldehydes- renal failure, blindnessTreatment - block metabolic production- ethanol- fomepizoleincrease removal- dialysis
NPIS
Edinburgh
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Metabolism of toxic alcoholsEthylene glycol
Glyceraldehyde
Glycolate
Glyoxylate
Oxalate
Methanol
Formaldehyde
Formate
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DELIBERATE RELEASE
Irritant gases- ChlorineToxic chemicals- CyanideNerve agents- sarin, VX
Infective agents-anthrax
NPIS
Edinburgh
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NERVE AGENTS
Cholinesterase inhibitorsBronchorrhoeaIncreased gut motilitySmall pupilsCNS activity, Fits
AtropineOximes
NPIS
Edinburgh
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CARE AFTER RECOVERYNPIS
Edinburgh1. psycho-social assessment 2. approximately 15% of patients have psychiatric illness3. most never re-attend with self harm
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