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TOXICOLOGY. Presented by Seelan Pillay. Toxicology. General Approach Psychiatric Drugs TCA’s SSRI’s MAOI’s Neuroleptic Malignant Syndrome Lithium. General Approach. ABCD’s Remember hypoglycemia! Decontamination

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TOXICOLOGY


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    1. TOXICOLOGY Presented by Seelan Pillay

    2. Toxicology • General Approach • Psychiatric Drugs • TCA’s • SSRI’s • MAOI’s • Neuroleptic Malignant Syndrome • Lithium

    3. General Approach • ABCD’s • Remember hypoglycemia! • Decontamination • Consider a specific antidote while a detailed history and physical examination are performed • Investigations

    4. Detailed History Time of ingestion ?? Obtain and identify all bottles and pills and perform a pill count Accessibility of medication Search for drugs and drug paraphernalia Look for tract marks + bites Consider body packing and body stuffing

    5. Physical Examination • Vital Signs + Pulse Oximetry • Unusual odours of breath, skin, clothes + NG aspirate • Neurological Exam • Pupils + reflexes • ? CVA in a comatose patient • Respiratory • Aspiration + Pulmonary Oedema • Abdomen • Bowel sounds + PR

    6. Toxidromes Modified from Kulig K: Initial management of ingestions of toxic substances, N Engl J Med 326:1677, 1992

    7. Decontamination • Removal of clothing + Skin irrigation • Gastric Lavage • Indicated less than 1hr of ingestion • has been shown not to improve the outcome of patients • Activated Charcoal • ? Risk of aspiration, must be given careful consideration • Given to anticholinergic effects, opioids, sustained release drugs and drug packets • Acids, Alkalies, Li, Borates, Bromides, Hydrocarbons, Metals (Fe) and Ethanol do not absorb charcoal

    8. Investigations • Toxic Screen • Blood, urine, gastric contents • Full screen is rarely indicated • Alternatives are : • Discrete drug levels • Urine screen for drugs of abuse • Check Electrolytes + ABG • Remember Rhabdomyolysis (Urine dipstick + Blood Myoglobin) • 12 – Lead ECG • X-rays • Cxr – Aspiration + ? Pulmonary Oedema • Axr – Radiopaque drugs – Heavy metals, Ca and Phenothiazides + Smuggled Packets

    9. Key Concepts • Thorough history • Remember polypharmacy OD • Drug interactions • Common toxidromes should guide in the use of antidotes • Good supportive care is the key to Mx • Call poison centre !

    10. TCA’s • Absorbed in GIT reach peak plasma levels between 2 to 4 hours • A dose >10mg/kg is life threatening • Pharmacodynamic effects include : • Na channel blockade – increased QRS complex >100msec • Alpha1 adrenoreceptor blockade – vasodilation, widened pulse pressure, decrease pupillary size • K efflux blockade prolongs myocardial action potential repolarisation – increased QT interval • Anticholinergic & antihistaminic effects

    11. Clinically • Deteriorate rapidly • Incr PR + decr BP (Vasodilation) • Decr GCS – 13% may have seizures • Hypereflexia, hyperthermia • ECG changes – QRS >100, Incr QT

    12. Management • Activated charcoal • IV fluids for hypotension – NaCl • If QRS >100 then NaHCO3 bolus until serum Ph 7.5 – 7.55 • IV infusion NaHCO3 in 1L 5% Dextrose saline • Refractory hypotension – consider inotropes • Beware of fluid overload + excess NaHCO3

    13. Management • 6hrs of observation • Ventilatory insufficiency • Decr Sats • QRS >100 • PR >120 • Dysrhythmias • Hypotension • Decreased GCS • Seizures • Abnormal / Inactive bowel sounds • ICU

    14. SSRI’s • Absorbed GIT peak plasma 3–8hrs • Lipophilic & have long half lives (4-9 days) – Serotonin Syndrome – Serotonin Toxicity • A serotoninergic agent is added (Cocaine or amphetamine incr release + Tegretol decr uptake) • Dose of agent is incr • High but therapeutic dose is used • Sternbach diagnostic criteria

    15. Clinically • Decreased GCS, Ataxia, Hyperreflexia, Hyperthermia • Hypertension, ventricular tachycardia or bradycardia

    16. Management • Activated charcoal • IV fluids for hypotension • Ventricular dysrythmias – ACLS Protocols • Benzodiazapines for CNS manifestations • Haemodialysis is not indicated • 24hr observation

    17. MAOI’s • Absorb the GIT with peak concentration 0.5-2.5hrs • Life threatening dose >2mg/kg • Presentations • MAOI’s overdose • 4 Phases – latent, CVS/CNS Excitation, CNS/CVS Depression, Secondary complications • 6-12hr onset typically but up to 24hrs • MAOI’s food/beverage interactions • Onset of symptoms minutes to hours • Tyramine containing foods, eg. Aged cheeses, bananas, ginseng, etc. • MAOI’s drug interactions • Serotonin syndromes after ingesting incompatible drugs • Onset of symptoms minutes to hours

    18. Clinically • Agitation, decr GCS • Tachycardia, hyperthermia • Eye changes (Nystagmus, Mydriasis, Papilloedema)

    19. Management • No antidote – Supportive management • Activated charcoal • Hypertension – only treat if life threatening • IV fluids to treat Hypotension • Hypotension + Bradycardia = Atropine • No response – Consider pacing • Lignocaine for dysrhythmias • Dialysis is not indicated • OD observe for 24hrs even if asymptomatic

    20. Neuroleptic Malignant Syndrome • Life threatening idiosyncratic reaction to neuroleptic medication – haloperidol • Other drugs like Maxalon + Li • Secondary to decr dopamine activity in CNS • Incidence of 0.1-0.2% + Mortality of 5-11% • Males > Females 2:1 • Onset within hours but typically 4-14 days • Risk factors • Incr ambient temp • Dehydration • Rapid initiation / dose escalation of neuroleptic • Concomitant use of predisposing drugs

    21. Clinically • Incr temp > 38 C, Incr PR, Incr RR • Lead pipe rigidity • Decr GCS • Investigations • ABG – Metabolic Acidosis • Incr WCC • Incr CPK + Urine Myoglobin

    22. Management • Cornerstone is prompt recognition + withdrawal of neuroleptic • Cooling interventions + antipyretics • IVF • Bromocryptine >15yrs – Reverses Dopamine D2 blockade • Dantrolene • Rhabdomyolysis – NaHCO3 • Rule out other causes • ECT & ICU

    23. Lithium • Peak levels 2-4hrs after ingestion • Half life 12-27hrs • Narrow theurapeutic index • Re-absorbed in proximal tubule & GFR dependant • Aminophylline inhibits reabsorption • Vol depleted / hypo-Na (diuretics) decr excretion

    24. Clinically • Decr GCS • hyperreflexia,fasciculations ,tremor • CVS collapse • ECG changes • ST depression Chronically • T-wave inversion • Dysrhythmias – complete heart block

    25. Management • Gastric lavage <1hr post ingestion • Activated charcoal does not bind Li • Consider whole bowel irrigation – Golytely • IV fluids –NaCL • ? NaHCO3 • Kayaxalate binds Li • Haemodialysis in unstable chronic patients & Li level >2.5