Toxidromes

Toxic-
Syndromes

BUGS DRUGS
SLUGS

Adapted from source

 Classifying Toxicity....
Bugs:
Snake Venom
Jellyfish
Conefish, Ticks
Drugs:
Stimulants:
 Cocaine, Amphetamines
Depressants:
 Opiates, Alcohols, Benzodiazepines, GHB
Hallucinogens
 Ketamine, Cannabis
Prescription:
 TCA, Metformin, Paracetamol
Slugs:
Cyanide
 Bugs: Snakes
 Venoms:
 Species dependent.
 Myotoxins, Cardiotoxins, Haemolysins,
anticoagulants, procoagulants.
 Symptoms of neurotoxin envenomation:
Ptosis, Respiratory distress, Voice changes->
global paralysis. Mx: Intubation, ventillation,
antivenom.
 Antivenom: Specific, Polyvalent. Often ellicits
anaphylactic/anaphylactoid reaction.
 Snake venom toxicity measured in LD50
(mice). King Cobra 1.91mg/kg. (15000). Inland
Taipan (0.01mg/kg = 500,000).

 Brazilian pit viper Bothrops jararaca – Origin of

the ACE inhibitors.
 Bugs: Jellyfish
 Irukandji Syndrome:
 Carukia barnesi
 1964, Dr. Jack stung himself, his son, and
a local lifeguard, and observed the
symptoms.[
 catecholamine excess
 Tips of the nematocysts inject venom
into lymphatics.
 Symptoms: severe headache, backache,
muscle pains, chest and abdominal pain,
nausea and vomiting, sweating, anxiety,
hypertension, tachycardia and
pulmonary edema. “impending doom".
 Treatment: Vinegar, Opioids, ?
Magnesium..... ?Clonidine.
 Bugs: Conefish, Ticks
 Coneshell:
 Predatory sea snails.
 Radular tooth (harpoon like hollow barb) attached to throat and
which is fired at prey. Conotoxin is injected through tooth from the
poison glands in the throat.
 Tooth can be fired in any direction (even backwards).
 Conotoxin (Neurotoxins): Similar to tetrodoxins. (Na+ channel
blockers).
 Symptoms: Vary according to species. Pain at site, agitation,
numbness/tingling... Cardiac arrhythmia...
 ?The future of pain relief: 1000x more potent then morphine. Trials
show efficacy in post surgical and neuropathic pain. First drugs
Ziconotide recently approved by FDA (2004) ‘Prialt’.

 Ticks: Shellback tick (paralysis tick)

 Symptoms: Itch, coughing, a change in voice, vomiting, progressing to
weakness and staggering in the hind legs, eventually leading to full
paralysis, respiratory failure.
 Treatment: Antivenom
 Drugs : Stimulants
 Cocaine
 Mechanisms of action: Blocks the Reuptake of Dopamine,
Serotonin, Nor-Adrenaline.
 Symptoms: Euphoria, Agitation, Paranoia, Hyperreflexia,
drowsiness, convulsions.
 Signs: Tachycardia, malignant hypertension (intracranial
haemorrhage), Coronary artery spasm (MI, VF), Hyperthermia
(Rhabdomyolysis, Acute Renal Failure, Myocaridal Infarction).
 Treatment: Toxic dose dependent upon tolerance, presence
of other drugs and route of administration. >1gram usually
fatal (smuggling).
 Vitals monitoring (NIBP, SpO2, ECG); Activated charcoal if
ingestion within the hour.
 Specific: Benzodiazipines for agitation/psychosis, a2-agonists
(clonidine , dexmedetomidine), Labetaolol (a1 blocker) or
direct vasodilators. Caution with beta blockers due to
unopposed alpha stimulation. Cooling. Convulsions....
Intubation, Ventillation, Sedation/Paralysis.
 Amphetamines
 Mechanisms of action: Indirect acting sympathomimetic
amine. Enters presynaptic nerve terminal via NorAd
Reuptake. Enters vesicles via VMAT and displaces NorAd
which enters cytosol and synaptic cleft via escape through
NorAd transporter.
 Symptoms: Sweating, Dry Mouth, Anxiety, Dehydration....
Hyponatraemia from excess H2O consumption. Mx: As per
cocaine. Hypertonic Saline if Hyponatraemia is severe.
 Drugs: Depressants
 Opiates
 Mechanisms of action: Mu, Kappa, Lambda (Cell Hyperpolarisation).
 Syndrome: Miosis, Sedation, Respiratory Depression.
 Treatment: Naloxone: .1-.4mg Q15mins. ½ life important. I+V if
naloxone insufficient.
 Alcohols (Methanol, Ethylene Glycol)
 Agents non-toxic, metabolites (formic acid, glycolic acid) extremely
toxic.
 Metabolic acidosis, Optic Nerve Toxicity, Renal Failure...
 Signs: Increase in osmolar and anion gaps.
 Activated charcoal of no benefit. EtOH treatment of choice in the
past (competitive metabolism). New Rx = Fomepizole. Folinic Acid for
metabolism of formic acid. Haemodialysis if severe acidosis.
 Benzodiasepines
 Act on GABA receptor.
 Commonly seen, uncommonly severe.
 Symptoms: Sedation, Dysarthria, Ataxia, Nystagmus, Confusion.
 Treatment: AC if within 1 hr; Flumazenil as diagnostic aid only, note
contraindications before administration.
 GHB
 Syndrome: Coma, Convulsions, Bradycardia, Hypotension,
Respiratory depression.
 Rx: Supportive care for most, Benzodiazepines for convulsions.
 Hallucinogens
 Ketamine
 NMDA receptor antagonist.
 Synthesised in 1962 and first utilised on
US soldiers during the vietnam war.
 Anesthesia, Analgesia, Amnesia,
Immobility + Pyschological reactions....
Dissociative state.
 Treatment: Supportive, benzodiazepines,
I+V if near anaesthetic state.
 Cannabis
 Acts on endogenous cannabinoid
receptors. High incidence of psychogenic
reactions.
 Potential symptoms of OD: Paranoid
pscyhosis, ataxia, nystagmus, tachycardia,
confusion.
 Potential role as future analgesic (when
non-CNS acting agents isolated).
 Drugs: Prescription Medicine
 TCA
 Syndrome: Anti cholinergic effects – Warm dry skin,
tachycardia, blurred vision, mydriasis, urinary
retention. Severe: Respiratory depression, CNS
depression, Cardiac Arrhythmias, Convulsions.
Arrhythmias likely if QRS >100ms; QRS >160ms...
Seizures. Cardiac arrhythmias due to slowing of Phase
0 depolarisation.
 Rx: AC, Continuous cardiac monitoring, intentional
alkalinisation of blood to pH >7.45 (reduces
availability of free/active drug) – achieved via
hyperventilation and NaHCO3). Arrythmia
Managment: Everything except class 1a.
 Metformin
 Mechanisms of action: Increases glucose transport
into glucose utilizing cells and decreases hepatic
gluconeogenisis. Biguanide therapy decreases the
activity of the enzyme pyruvate dehydrogenase and
the transport of mitochondrial reducing agents, and
thus enhances anaerobic metabolism.
 Toxicity: Can result in Type B (non-hypoxic) lactic
acidosis. Metformin’s propensity to shift cells into
anaerobic metabolism is not dependant on a lack of
oxygen and, in the presence of reduced insulin,
increases production of precursors for the
tricarboxylic acid cycle. The inhibition of pyruvate
dehydrogenase leads to a decreased ability to channel
these precursors into aerobic metabolism which
causes increased metabolism of pyruvate to lactate
and an increase in lactic acid production.
 Treatment: Haemodialysis.
 Paracetamol
 Doses >10grams (adults) have the potential to
exceed hepatic glutathione conjugation with
the resultant toxic metabolites. Plasma
concentrations > 200mg/L at 4hrs or >50mg/L
at 12hrs usually result in hepatic damage.
 Symptoms: N/V may be only symptoms
initially.
 Treatment: Drug levels, follow the
nomogram. Administer AC. N-Acetylcysteine
150mg/kg followed by 50mg/kg over 4 hrs.
Seek expert opinion from transplantation
centre if ongoing deterioration...
 N-Acetylcystein: augments glutathione
reserves in the body and, together with
glutathione, directly bind to toxic metabolites.
 Slugs - Cyanide
 Any compound containing the carbon---nitrogen
group. CN- is extremely toxic...
 Uses: Malignant Hypertension (Na Nitroprusside),
Colouring (Pottasium ferrocyanide), Gold and Silver
Mining, Fumigation, Illegal Fishing, Genocide.
 Hydrogen Cyanide: Librates the cyanide anion
which inhibits the enzyme cytochrome C oxidase
(4th complex of electron transport chain in
mitochondria). Results in switch from aerobic to
anaerobic metabolism.
 Syndrome: Rapidly fatal, if however one survives
then: hypotension, metabolic acidosis, respiratory
depression, coma.
 Rx: Inhaled amyl nitrate and 100% oxygen. Dicobalt
edetate. Sodium Thiosulphate. Hydroxocobalamin.
NaHCO3 to treat metabolic acidosis.