Acetaminophen toxicity occurs when its metabolism is overwhelmed, producing a toxic metabolite that binds to liver proteins and causes necrosis. N-acetylcysteine is the antidote and helps prevent liver damage. Anticholinergic toxicity from drugs like atropine is treated with physostigmine, which crosses the blood brain barrier to counteract anticholinergic effects in the central nervous system. Benzodiazepine overdose symptoms include sedation, respiratory depression, and hypotension. Flumazenil can reverse benzodiazepine effects, while naloxone may help if opiate co-ingestion is suspected.

2. Acetaminophen Toxicology
• Mechanism of Action:
• In acute overdose or when maximum daily dose is exceeded
over a prolonged period, the normal pathways of metabolism
become saturated
• Excess acetaminophen is then metabolized in the liver via the
mixed function oxidase P450 system to a toxic metabolite
• Under conditions of excessive toxic metabolite formation or
reduced glutathione stores, the reactive metabolite is free to
covalently bind to vital proteins and the lipid bilayer of
hepatocytes; this results in hepatic injury and
subsequent centrilobular liver necrosis.

3. • Antidote/Treatments:
• The antidote for acetaminophen poisoning is N-
acetylcysteine
• Oral activated charcoal avidly adsorbs acetaminophen
& should be given within 1-2 hours after ingestion of
acetaminophen, or if the time of ingestion is unknown.
• Supportive therapy: IV fluids, oxygen, and cardiac
monitor.

4. Anticholinergics (antimuscarinics)
• Source: Atropine-like drugs, H-1blockers
• Mechanism of Action:
• block muscarinic receptors in the CNS and peripheral nervous
system.
• Symptoms:
• flushing, dry skin and mucous
membranes, mydriasis with loss of accommodation, altered
mental status, and fever, respectively.
• Also: tachycardia, urinary retention, decreased bowel sounds.

5. • Antidote/Treatment:
• The antidote for anticholinergic toxicity is physostigmine salicylate.
• Physostigmine is the only reversible acetylcholinesterase inhibitor
capable of directly antagonizing the CNS manifestations of anticholinergic
toxicity;
• it is an uncharged tertiary amine that efficiently crosses the blood brain
barrier.
• GI decontamination with activated charcoal is usually necessary after
anticholinergic poisoning by ingestion.
• Ipecac syrup is contraindicated because of the potential for seizures.
• Manage seizures with benzodiazepines, preferably diazepam or
lorazepam

6. Benzodiazepine Toxicology
• Source: sedative hypnotic, antiepileptic
• Mechanism of Action:
• potentiates the activity of GABA
• results in sedation, striated muscle relaxation, anxiolysis,
and anticonvulsant effects
• stimulation of peripheral nervous system (PNS) GABA
receptors may cause decreased cardiac contractility,
vasodilation, and enhanced perfusion

7. Benzodiazepine Toxicology
• Symptoms:
• drowsiness
• nystagmus
• confusion
• slurred speech
• ataxia
• coma
• weakness
• amnesia
• hypotension
• respiratory depression.

8. • Toxic Dose:
• the therapeutic index (toxic/therapeutic dose ratio) for
benzodiazepines is very high
• oral doses of diazepam that are 15-20 times the normal
therapeutic dose have been reported without serious
depression
• death from overdose with benzodiazepines alone is
rare, however, respiratory arrest has been reported after
rapid iv injection of benzodiazepines
• ingestion of other CNS-depressant drugs (ethanol,
barbiturates, opioids) will produce additive effects

9. • Antidote/Treatment:
• Flumazenil is the drug of choice to reverse effects of
benzodiazepines.
• Naloxone can also be administered at a very low dose if
the diagnosis is unclear and an opiate co-ingestion is
suspected (eg, evidence of severe respiratory depression).
• Single-dose activated charcoal is recommended
• Ipecac syrup is contraindicated for prehospital or hospital
use because of the risk for CNS depression and subsequent
aspiration with emesis.
• Respiratory depression may be treated with assisted
ventilation.

10. Cocaine Toxicology
• Source: Drug of abuse
• Mechanism of Action:
• CNS stimulant
• blocks the reuptake of catecholamines:
dopamine, norepinephrine & serotonin (DAT,
NET & SERT transporters)

11. • Symptoms of toxicity with cocaine:
• CNS:
• Euphoria, which may be followed by anxiety & agitation
• Psychatric symptoms (including paranoia, psychosis & the
sensation of something crawling on the skin or itchy skin)
• Hyperactivity & Seizures
• Coma
• Cardiovascular:
• Chest pain MI, arrhythmias
• Tachycardia & prolonged QT interval
• Hypertension
• Cardiomyopathy (chronic use)

12. • Symptoms of toxicity with cocaine:
• Other:
• Hyperthermia
• Dilated pupils (mydriasis)
• Insomnia, weight loss (with chronic use)
• Sudden Death

13. • Treatment:
• Establish ABC's :"airway, breathing and circulation"
• Provide oxygen & i.v. access
• Monitor vital signs & glucose levels
• Administer benzodiazepines to manage seizures
• Administer sodium bicarbonate to manage acidosis
• Nitroglycerin for cocaine-related MI if present
• Treat hyperthermia with cooling, ice packs or cooling
blankets.

14. Barbiturate Toxicology
• Source: sedative/hypnotic/anesthetic
• Mechanism of Action:
• At low doses barbiturates bind to specific sites on GABA-
sensitive ion channels found in the CNS
• they allow an influx of chloride into cell membranes and,
subsequently, hyperpolarize the postsynaptic neuron

15. Barbiturate Toxicology
• Symptoms:
• Neurologic:
• lethargy & impairment in thinking
• coma
• hypothermia
• decreased pupillary light reflex
• nystagmus
• respiratory depression - the most common cause of
death
• Cardiovascular:
• tachycardia or bradycardia
• hypotension

16. • Treatment of barbiturate toxcity:
• ABC (airway, breathing and circulation).
• Check for hypothermia & if present, warm the patient to
avoid precipitating a fall in blood pressure.
• Perform GI decontamination once the airway is
protected and hemodynamic stabilization addressed.
• Activated charcoal

17. • Treatment of barbiturate toxcity:
• Alkalinization of the urine with sodium bicarbonate to
enhance the elimination of phenobarbital and, likely,
other long-acting barbiturates by ion trapping.
• Aggressively initiate fluid therapy if the patient is
hypotensive or appears to be in hypovolemic shock.
• Hemodialysis and hemoperfusion enhance elimination
of barbiturates.

18. Morphine, Heroin & similar Opioid Narcotics
• Source:
• narcotic analgesic, drug of abuse
• Mechanism of Action:
• opioid receptor agonist

19. Morphine, Heroin & similar Opioid Narcotics
• Symptoms:
• Clinical triad of: 1) CNS depression, 2) respiratory depression,
and 3) pinpoint pupils (miosis) are present.
• Euphoria is frequently seen
• Hypotension & hypothermia
• Death: the leading cause of morbidity and mortality from
pure opioid overdoses is respiratory compromise. Less
commonly, pulmonary edema, status epilepticus, and
cardiotoxicity.

20. Antidote/Treatment:
• Administer naloxone for significant CNS and/or
respiratory depression.
• In patients with opiate addiction, naloxone may
precipitate opiate withdrawal symptoms, so the dose of
naloxone should be titrated carefully in such patients.

21. Organophosphate Toxicology
• Source:
• pesticides, chemical warfare
• Mechanism of Action:
• Organophosphates irreversibly bind to cholinesterase,
causing the phosphorylation and inactivation of
acetylcholinesterase

22. Organophosphate Toxicology
• Symptoms:
• Mild flulike symptoms from minimal exposures
frequently are unreported or untreated.
• Headache
• Mental confusion
• Diffuse muscle cramping and/or fasiculations &
weakness
• Miosis
• Bronchospasm
• Excessive secretions
• Nausea, vomiting, and diarrhea

23. • Severe toxicity:
• Seizures
• Paralysis
• Coma
• Respiratory failure & death
• Delayed or inadequate treatment of organophosphate
poisoning can lead to prolonged (months) or permanent
neurotoxic symptoms.

24. Antidote/Treatment:
• decontamination
• atropine
• oxygen
• Pralidoxime
• benzodiazepines to control seizures

25. Theophylline Toxicology
• Sources:
• bronchodilator for asthma & COPD
• Mechanism of Action:
• Theophylline is methylxanthine (similar to caffeine) & exerts most
of its effects by antagonizing adenosine receptors similar to
caffeine
• It can also inhibit phosphodiesterase at toxic concentrations

26. Theophylline Toxicology
• Hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia,
and acidosis commonly occur after an acute overdose
• Medication, diet, and underlying diseases can alter its narrow
therapeutic window
• Adverse effects can be evident at therapeutic serum levels

27. Theophylline Toxicology
• Symptoms:
• nausea, vomiting, abdominal pain
• mild metabolic acidosis
• hypokalemia, hypophosphatemia, hypomagnesemia
• hyperglycemia
• sinus tachycardia
• seizures (& tremors)
• hypotension
• arrhythmias

28. Treatment of Theophylline toxicity:
1. Aggressive gut decontamination with repeated doses of
activated charcoal & whole bowel irrigation
2. Propranolol or other beta blockers can block a beta-
mediated sinus tachycardia & hypotension
3. Phenobarbital is preferred over phenytoin for treatment of
convulsions; most anticonvulsants are ineffective
4. Hemodialysis is indicated for serum levels >100mg/L and
for intractable seizures

32. Heavy metals Toxicology