Toxicology

By Group 4 2018/2019
Tan Geok Eng
Reena Dewi
 Toxidromes
A term that combines 2 Greek roots
•Toxikon = bow, as arrows shot from bow, commonly have
poison on their tips
•Dromos = race course
•Defined as the course that specific poison runs on in
toxicological terms
•A syndrome that results from a specific toxin

•Anticholinergic •Serotonin
•Cholinergic •Sedatives/hypnotics
•Opiods •Neuroleptic malignant syndrome
•Sympathomimetics
Anticholinergic

•A class of drug that block the neurotransmitter

acetylcholine in the central and peripheral nervous system
•Used to treat a wide variety of conditions associated with
activation of the parasympathetic nervous system
•Also known as anti-muscarinic

•Example – antihistamines, cyclic antidepressants,

homatropine, scopolamine

•Treatment: Physostigmine (short-acting cholinesterase

inhibitor)
Cholinergic

•Results of increased acetylcholine activity at both

central and peripheral nicotinic and muscarinic
receptors
•Dominant parasympathetic effects
Rest, digest & wet
•Can arise from either:
Cholinesterase inhibitors
Cholinomimetics
•Treatment: Atropine (anti-cholinergic)
 Acetylcholinesterase Acetylcholine agonists
inhibitors
Organophosphates Muscarinic agents:
Acetylcholine, carbachol,
pilocarpine

Carbamate insecticides Nicotinic agents:

Nicotine
Chemical warfare nerve
agents
Agents used in dementia:
Donepezil, galantamine,
rivastigmine, tacrine

Agents used in myasthenia

gravis: edrophonium,
neostigmine, physostigmine,
pyridostigmine
 Opiods
•Produce profound analgesia, mood
changes, physical dependence, tolerance
and a hedonic ('rewarding') effect which
may lead to compulsive drug use
•Act in both the central and peripheral
nervous systems
•Within the central nervous system, opioids
have effects in many areas, including the
spinal cord
•Naturally found in opium poppy plant

•Treatment: Naloxone
• Short term effects:
• drowsiness, slowed breathing, constipation, unconsciousness, nausea, coma
• Long term effects:
• physical dependence and addiction, restlessness, muscle and bone pain, insomnia, diarrhea,
vomiting
Sympathomimetics
•Drugs that have an activating effect on the sympathetic
nervous system through the direct or indirect effect on
catecholamines

•Direct acting: alpha-agonists, dopaminergic agents

•Indirect acting agents: cause increased catecholamine
release, inhibition of enzymatic breakdown, or delayed
reuptake (e.g., pseudoephedrine, amphetamines, cocaine)

•Treatment: Benzodiazepine
Serotonin syndrome

• A serious and life-threatening reaction caused by

excess serotonin in the CNS
• Treatment – Cyproheptadine
Sedative hypnotics
• Modulate activity of GABA neutrotrasmitter complex
• Clinical presentation:
• Unpredictable pupillary changes
• Confusion/coma
• Respiratory depression
• Hypothermia
• Vesicles/bullae (‘barb burns’)
• Example: benzodiazepines, barbiturates, zolpidem, zopliclone,
baclofen
• Treatment: Flumazenil
Neuroleptic malignant
syndrome
• Rare and potentially lethal, due to the use of neuroleptic
medications
• May be due to deficiency/blockade of dopaminergic
neurotransmission in nigrostriatal, mesolimbic, and
hypothalamic-pituitary pathways
• Example: Haloperidol
Central Nervous System Autonomic Instability Neuromuscular

• Confusion • Hyperthermia • Lead-pipe rigidity

• Delirium • Tachycardia • Generalised
• Stupor • Hypertension, bradykinesia or akinesia
• Coma Respiratory • Mutism and staring
irregularities • Dystonia and abnormal
• Cardiac postures
dysrhythmias • Abnormal involuntary
movements
• Incontinence

• Treatment: bromocriptine, dantrolene, lorazepam

General approach

for a poisoned person

 Principles
Patient with altered mental status/haemodynamic
instability – managed at critical care area, otherwise,
most cases can be managed at intermediate care
area

•First priority to airway, prepare for equipment and

resuscitation drugs
•Supplemental oxygen to maintain oxygen saturation
level of at least 95%
•Monitoring ECG, vital signs (5-15min), pulse
oximetry
•Establish large bore cannula and take blood for
investigations
•Consider placement of CBD
•Manage seizure/dysrhythmia accordingly
History
• Patient is in definite drug overdose/questionable drug overdose
• Always consider chemicals/toxins available to the patient in
question
• Always obtain a collaborative history from all available sources
• Ask when, what, how much, how, where and why
• How many types of drugs consumed
• Any symptoms from exposure
• Any suicidal risk
• Ask about psychiatric and past medical history including the
medications
• Any previous similar presentation/suicidal attempts
 Physical examination

•Level of consciousness
(coma/stupor/delirium)
•Blood pressure
•Fits
•Pulse rate and rhythm
•Respiratory rate
•Temperature

•Diaphoretic skin
•Dry skin
•Blistering
•Colour (red/blue) •Presence
•Needle tracks •Absence
Investigations

• Full blood count – elevated TWBC may indicate presence of infection,

iron/theophylline/hydrocarbon toxicity
• Serum electrolytes – anion gap (Na+K)-(HCO3-Cl) •Glycols (Ethylene, propylene glycol)
• Serum urea and creatinine – determine any •Oxoproline
•Lactate
pre-existing renal dysfunction •Methanol
• CBS – determine any hypoglycaemia •Aspirin
•Renal failure
• Toxicology screening – determine the drug level •Ketoacidosis
(Paracetamol, salicylates, iron, lithium,
theophylline, carbon monoxide) selective screening
• ECG – prolonged PR, QTc, QRS in cyclic antidepressants overdose, bradycardia and
heart blocks in CCB/beta-blocker overdose
 Imaging

Chest x-ray Abdominal x-ray

Radioopaque
•Chloral hydrate
•Heavy metals
•Iron
•Phenothiazines
•Enteric coated
•Pulmonary toxic agent (hydrocarbon, paraquat) preps
•Non-cardiogenic pulmonary oedema (opiates, •Sustained release
phenobarbitone, salicylates, carbon monoxide) products
 Specific treatment
• Done when patient is stabilized
Decontamination

Surface Gastrointestinal
•Required when toxic exposures affecting large
dermal areas •Not a routine part of poisoned-patient
•Healthcare providers need to wear PPE, management non-pleasant
undressing, washing patient using copious •May be considered after 3 questions analysis – Is
amounts of water the exposure likely to cause significant toxicity, is
•Contaminated clothing is collected, bagged and this likely to change the clinical outcome, is it going
properly disposed usually done outside hospital, to cause more harm than good
during ambulance call, with paramedics
 Gastrointestinal
decontamination
• Is achieved via removal of the toxin from the stomach,
binding toxin within the GI tract, or enhancing transit
time through the gut

• 4 types

Emesis – traditionally, Ipecac syrup was administered to

induce vomiting, theoretically emptying the stomach
from poisons, no studies shown it improves outcome,
routine use should be abondoned
Orogastric lavage
Single dose activated charcoal
Whole bowel irrigation
 Was once a widely practiced intervention, attempted removal of ingested
Orogastric lavage
toxin from stomach by aspiration of fluid placed via orogastric tube
Patient positioned left lateral at mild Tredelenburg position
•Now rarely indicated, no evidence published that it changes outcome and
it has numerous complications
 Single – dose
activated charcoal
Super-heating
carbonaceous material

•Not effectively absorb metals, corrosives,

Toxins within GIT lumen alcohols
Highly porous,
absorbed onto it, carried •Decision of giving it require individual risk
suspended in solution
thorough GIT, limiting assessment and not considered as routine
and given per orally
absorption management
Drugs absorbed by AC Dugs not absorbed by AC

• Acetaminophen • Heavy metal ( arsenic, lead, mercury, iron,

• Amphetamine zinc, cadmium)
• Antihistamine • Inorganic ions (Li, Na, Ca, K, Mg, Fl, Iodide)
• Aspirin • Boric acid
• Barbiturates • Corrosives (acids, alkali)
• Benzodiazepine • Hydrocarbons (alkanes, alkenes, alkyl halides,
• Beta blocker aromatic hydrocarbons)
• Calcium channel blocker • Alcohol (acetone, ethanol, ethylene glycol.
Isopropanol. Methanol)
• Cocaine
• Opioid usually preferred naloxone • Essential oils
• Phenytoin
• Theophylline
• Valproic acid
 Whole bowel irrigation
PEG is osmotically balanced electrolyte solution, administration in large quantities mechanically forces substances
through GIT, limiting toxic absorption
Commonly used in asymptomatic body drug packers, endpoint of treatment is clear and good
Enhancement of elimination

• minimizing toxin accumulation or promoting its removal to facilitate

endogenous excretion through

- Multi-dose activated charcoal

- Urinary alkalinization
- Extracorporeal removal
Multi-dose activated charcoal
 Multi-dose activated charcoal
•Increases elimination of toxins with enteroenteric,
enterohepatic or enterogastric recirculation
Interruption of enterohepatic circulation
For drugs with low volume distribution, to be excreted from
the bile and reabsorbed from distal ileum
Gastrointestinal dialysis
Small molecule, lipid soluble, low volume of distribution, low
protein binding
Charcoal will set up the gradient, the drugs will flow freely
across the gut mucosa from the intravascular compartment
down the concentration gradient

•May also absorb residual intraluminal toxins (substances

slowing gastric motility or forming bezoars)
•May be administered by an orogastric or nasogastric tube to
intubated patients
•Regular aspiration of stomach contents helps avoid gastric
distension
 Urinary alkalinization
•Alkaline urine favors ionization of acidotic drugs within renal tubules, preventing resorption of the ionized drug
back across the renal tubular epithelium, enhancing elimination of drugs through the urine
•Most effective for weak acids primarily eliminated by renal tract and readily filtered at glomerulus, small in volumes
of distribution
Technique
• Correct any existing hypokalaemia
• Given 1-2 mmol/kg IV sodium bicarbonate bolus
• Commence infusion of 100 mmol sodium bicarbonate in 1000 mL 5% dextrose at 250
mL/hr
• 20 mmol of potassium chloride may be added to infusion to maintain
normokalaemia
• Monitor serum bicarbonate and potassium every 2 to 4 hours to detect
hypokalaemia or escessive serum alkalinization
• Check urine pH regularly (every 15 to 30min), aiming pH 7.5-8.5
• A further IV bolus of 1 mmol/kg of sodium bicarbonate may be necessary if sufficient
alkalinization of the urine not achieved
• Continue until clinical and laboratory evidence of toxicity is resolving
Extracorporeal removal
• Including hemodialysis, hemoperfusion and continuous renal replacement
therapies
• Limited indications in poisoned patients
• Required critical care setting, expensive, invasive, not always available and have
complications
• Must improve endogenous clearance rate by >30% to be clinically beneficial
•Low volume of distribution (<1 L/kg)
•Low molecular weight (<500 Da)
•Relatively low protein binding
•Low endogenous clearance

•A patient who requires extracorporeal

removal should undergo hemodialysis or
hemoperfusion if available. Continuous renal
replacement therapy can be used if the
former unavailable or will not be tolerated
due to hypotension
Complications

• Fluid/metabolic disruption
• Removal of antidotes
• Limited availability
• Limited by hypotension (except continuous renal replacement
therapy)
• Infection/bleeding at the catheter site
• Intracranial hemorrhage secondary to anticoagulation
Team management

• Admission is indicated if patient has persistent and / severe toxic effects / will
require a prolonged course of treatment
• Most cases, 6 hours of observation period is sufficient to exclude the
development of serious toxicity
• A period of extended observation is indicated for some drugs due to the onset of
the clinical toxicity can be delayed after a number of exposures (modified release
CCB, selective norepinephrine reuptake inhibitor such as tramadol, venlafaxine,
amilsupride
• Patients who have deliberately self-poisoned require appropriate mental health
assessment before discharge