Transcript Toxicology (10 Oct 2006)

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
 Consider a specific antidote while a detailed history
and physical examination are performed
 Investigations
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
 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
Toxidromes
Modified from Kulig K: Initial management of ingestions of
toxic substances, N Engl J Med 326:1677, 1992
Anticholinergic
Common signs
Delirium with mumbling speech, tachycardia, dry flushed skin, dilated pupils, myoclonus, slightly elevated
temperature, urinary retention, decreased bowel sounds. Seizures and dysrhythmias may occur in severe cases
Common causes
Antihistamines, antiparkinsonians, atropine, scopolamine, amantadine, antipsychotics, antidepressants,
antispasmodics, mydriatics, muscle relaxants, many plants (e.g., jimson weed, Amanita muscaria)
Sympathomimetic
Common signs
Delusions, paranoia, tachycardia (or bradycardia with pure α-agonists), hypertension, hyperpyrexia, diaphoresis,
piloerection, mydriasis, hyperreflexia. Seizures, hypotension, and dysrhythmias may occur in severe cases
Common causes
Cocaine, amphetamine, methamphetamine and its derivatives, over-the-counter decongestants
(phenylpropanolamine, ephedrine, pseudoephedrine). In caffeine and theophylline overdoses, similar findings, except
for the organic psychiatric signs, result from catecholamine release
Opioid/Sedative/ Ethanol
Common signs
Coma, respiratory depression, miosis, hypotension, bradycardia, hypothermia, pulmonary edema, decreased bowel
sounds, hyporeflexia, needle marks. Seizures may occur after overdoses of some narcotics (e.g., propoxyphene)
Common causes
Narcotics, barbiturates, benzodiazepines, ethchlorvynol, glutethimide, methyprylon, methaqualone, meprobamate,
ethanol, clonidine, guanabenz
Cholinergic
Common signs
Confusion, central nervous system depression, weakness, salivation, lacrimation, urinary/fecal incontinence,
gastrointestinal cramping, emesis, diaphoresis, muscle fasciculations, pulmonary edema, miosis,
bradycardia/tachycardia, seizures
Common causes
Organophosphate and carbamate insecticides, physostigmine, edrophonium, some mushrooms
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
 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
 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
 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
 Deteriorate rapidly
 Incr PR + decr BP (Vasodilation)
 Decr GCS – 13% may have seizures
 Hypereflexia, hyperthermia
 ECG changes – QRS >100, Incr QT
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
Management
 6hrs of observation
1.
2.
3.
4.
5.
6.
7.
8.
9.
Ventilatory insufficiency
Decr Sats
QRS >100
PR >120
Dysrhythmias
Hypotension
Decreased GCS
Seizures
Abnormal / Inactive bowel sounds
 ICU
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
Clinically
 Decreased GCS, Ataxia, Hyperreflexia,
Hyperthermia
 Hypertension, ventricular tachycardia or bradycardia
Management
 Activated charcoal
 IV fluids for hypotension
 Ventricular dysrythmias – ACLS Protocols
 Benzodiazapines for CNS manifestations
 Haemodialysis is not indicated
 24hr observation
MAOI’s



Absorb the GIT with peak concentration 0.5-2.5hrs
Life threatening dose >2mg/kg
Presentations
1.
MAOI’s overdose
•
•
2.
MAOI’s food/beverage interactions
•
•
3.
4 Phases – latent, CVS/CNS Excitation, CNS/CVS Depression,
Secondary complications
6-12hr onset typically but up to 24hrs
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
Clinically
 Agitation, decr GCS
 Tachycardia, hyperthermia
 Eye changes (Nystagmus, Mydriasis, Papilloedema)
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
 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
Clinically
 Incr temp > 38 C, Incr PR, Incr RR
 Lead pipe rigidity
 Decr GCS
 Investigations
• ABG – Metabolic Acidosis
• Incr WCC
• Incr CPK + Urine Myoglobin
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
 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
Clinically
 Decr GCS
 hyperreflexia,fasciculations ,tremor
 CVS collapse
 ECG changes
• ST depression
Chronically
• T-wave inversion
• Dysrhythmias – complete heart block
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