Toxicology
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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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Toxicology

TOXICOLOGY

Presented by Seelan Pillay


Toxicology1

Toxicology

  • General Approach

  • Psychiatric Drugs

    • TCA’s

    • SSRI’s

    • MAOI’s

    • Neuroleptic Malignant Syndrome

    • Lithium


General approach

General Approach

  • ABCD’s

  • Remember hypoglycemia!

  • Decontamination

  • Consider a specific antidote while a detailed history and physical examination are performed

  • Investigations


Detailed history

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


Physical examination

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


Toxicology

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


Decontamination

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


Investigations

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


Key concepts

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 !


Tca s

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


Clinically

Clinically

  • Deteriorate rapidly

  • Incr PR + decr BP (Vasodilation)

  • Decr GCS – 13% may have seizures

  • Hypereflexia, hyperthermia

  • ECG changes – QRS >100, Incr QT


Management

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


Management1

Management

  • 6hrs of observation

    • Ventilatory insufficiency

    • Decr Sats

    • QRS >100

    • PR >120

    • Dysrhythmias

    • Hypotension

    • Decreased GCS

    • Seizures

    • Abnormal / Inactive bowel sounds

  • ICU


Ssri s

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


Clinically1

Clinically

  • Decreased GCS, Ataxia, Hyperreflexia, Hyperthermia

  • Hypertension, ventricular tachycardia or bradycardia


Management2

Management

  • Activated charcoal

  • IV fluids for hypotension

  • Ventricular dysrythmias – ACLS Protocols

  • Benzodiazapines for CNS manifestations

  • Haemodialysis is not indicated

  • 24hr observation


Maoi s

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


Clinically2

Clinically

  • Agitation, decr GCS

  • Tachycardia, hyperthermia

  • Eye changes (Nystagmus, Mydriasis, Papilloedema)


Management3

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


Neuroleptic malignant syndrome

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


Clinically3

Clinically

  • Incr temp > 38 C, Incr PR, Incr RR

  • Lead pipe rigidity

  • Decr GCS

  • Investigations

    • ABG – Metabolic Acidosis

    • Incr WCC

    • Incr CPK + Urine Myoglobin


Management4

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


Lithium

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


Clinically4

Clinically

  • Decr GCS

  • hyperreflexia,fasciculations ,tremor

  • CVS collapse

  • ECG changes

    • ST depression Chronically

    • T-wave inversion

    • Dysrhythmias – complete heart block


Management5

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


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