Specific poisoning Dr EMAN ISAM Acetaminophenparacetamol Normally metabolized

Specific poisoning Dr. EMAN ISAM

Acetaminophen(paracetamol): • Normally metabolized by liver; saturation of normal pathways leads to breakdown of acetaminophen by p 450 to NAPQI (N-acetyl-p -benzoquinone imine )which combined with hepatic cell causes hepatic necrosis. In therapeutic doses it is known to have very few adverse events.

The maximum daily dose of acetaminophen is 4 g in adults and 90 mg/kg in children. A single ingestion of 7. 5 g in an adult or more than 200 mg/kg in a child is a potentially toxic dose but smaller doses may also cause liver damage.

Clinical manifestations: ● Stage I – (0 -24 hrs) ØEarly symptoms Mild (Nausea, vomiting, malaise and diaphoresis). Serum acetaminophen level 4 hrs post ingestion PLOT ON SPECIFIC NOMOGRAM. No need to repeat levels If > 900 µmol/L ---> Possible risk ØNormal bilirubin Transaminases and PT

Serum level 4 h or more after ingestion can help predict hepatotoxicity Stage II: › 24 -48 hrs after ingestion. Better, less symptoms. Elevated bilirubin, transaminases and PT

Stage III › ( 2 - 4 days) after ingestion: Hepatic dysfunction (Rarely hepatic failure) Peak elevations in: Bilirubin Transaminases may reach > 1000 IU/L Prolonged PT

Stage IV _ (7 -8 days) › Depending on the extent of damage: Clinical improvement LFTs returning to normal or…. . Death

Probable toxicity should be treated with: N-acetylcysteine oral (effective as many as 24 hours after a toxic ingestion). i. v administration NAC is recommended for selected pt. Most pediatric patients can be treated with activated charcoal alone. GIT decontmination limited to patients with recent (within 60 min) and potentially life-threatening toxicity.

Iron Poisoning Five Stages but variable › Stage 1: 30 min to 6 hr after ingestion GIT stage: within several hrs of ingestion: V/D, Hematochezia and abdominal pain significant volume losses leading to potential hypovolemic shock. Patients who do not develop GI symptoms within 6 hr of ingestion are unlikely to develop serious toxicity

Toxic doses occur at 10 -20 mg/Kg of elemental iron. Stage 2: › Quiescent stage: 4 -48 hrs Clinical improvement of GIT signs of hypoperfusion, including tachycardia, pallor, and fatigue Decreased U. O. P.

Stage 3: › Circulatory collapse : 48 -96 hrs Metabolic acidosis, hypotension, Shock Coagulopathy Multi Organ Failure

Stage 4: › Hepatic failure: 96 hrs › Liver transplant can save lives o Stage 5: Bowel obstruction 2 -6 wks Due to scarring

Management: 1. Gastric decontamination: WBI remains the decontamination strategy of choice No activated charcoal to be used!!! 2. Secure good IV 3. Get initial then 4 hrs Iron levels and TIBC 4. Chelate with Deferoxamine if levels> 500 mg/d. L

Hydrocarbons (HC) are composed of large number of organic compounds made up of carbon and hydrogen atoms. e. g kerosene, benzene They cause damage to lung and nervous system.

Ingestion is rarely more than 10 ml but as little as 2 ml entering in to the tracheobronchial tree can cause severe chemical pneumonitis. Pathophysiology: q. Hydrocarbon aspiration primarily affects the CNS and respiratory systems. Volatile hydrocarbons are highly lipid soluble. They enter the circulation through the lungs and rapidly diffuse throughout the body and into the CNS.

Kerosene ingestion: Clinical Presentation Respiratory : › Choking, gagging, and coughing usually begins immediately or within 2– 5 min of the aspiration, and persists. › There may be oral pain. › Vomiting is common. › Signs of significant exposure are continued cough, tachypnea, increased respiratory effort, rib cage retractions, grunting, wheezes, and rales on chest auscultation.

Radiographic findings : often occur before the development of physical findings. They may be seen within 20 minutes or as late as 24 hours after aspiration. CXR abnormalities typically peak between 2 -8 hr after aspiration. CXR findings include perihilar, basal, or lobar densities. Occasionally, pneumatoceles develop after several days and may take weeks to resolve.

CVS — Cardiac arrhythmia may occur after inhalation. GIT — local irritation to the pharynx, esophagus, stomach, and small intestine, with edema and mucosal ulceration which may lead to hematemesis.

CNS — HC ingestion or inhalation may have direct CNS effects as headache, ataxia, dizziness, blurred vision, weakness, stupor, seizures & coma or 2 ry to hypoxia like CNS depression, including drowsiness, tremors, or convulsions. Hematologic — Leukocytosis (with fever) occurs early in the clinical course. Hemolysis, hemoglobinuria, and consumptive coagulopathy also may occur with significant ingestion.

Treatment: › Do not induce vomiting !!!!! › Do not attempt gastric lavage !!!!!! › Bronchospasm treated with selective beta 2 agonists. › If gastric lavage is to be performed, the patient should be intubated with a cuffed ETT to protect the airway from further aspiration. › Activated charcoal also is not useful because it does not bind the common hydrocarbons.

–Corticosteroid should be avoided. –Antibiotcs given if bacterial pneumonia occurs. –Treatment is usually supportive, attention to respiratory and CNS symptoms. –Observe in ER for 6 -8 hrs if no symptoms discharge.

Organophosphorus › Insecticides › Inhibition of Cholinesterase enzymes all over. Muscarinic symptoms are DUMBBELS, which stands for diarrhea/defecation, urination, miosis, bronchorrhea/bronchospasm, bradycardia, emesis, lacrimation, and salivation. Nicotinic signs and symptoms include muscle weakness, fasciculations, tremors, hypoventilation (diaphragm paralysis) CVS hypertension, tachycardia, and dysrhythmias. Severe manifestations include coma, seizures, shock, arrhythmias, and respiratory failure

Weakness from Pesticides

Diagnosis: from hx &physical examination. blood Cholinesterase levels < 50% indicates poisoning. Atropine as test dose Management: A…. B…. C…. . Stabilization Wash hair and body with soap & water Consider Gastric lavage if within 1 hr Atropine sulphate I. V. till pupils are normal size.

Remember…Atropine has no effect on muscle paralysis must support breathing USE Cholinestrase reactivator such as Pralidoxime

Tricyclic Antidepressants e. g amitriptyline Anticholinergic effects cause most of the following presenting symptoms: Dry mouth Flushed skin Blurred vision Urinary retention Constipation Dizziness Emesis

Physical Signs of TCA toxicity include the following: Anticholinergic effects Altered mental status (agitation, confusion, lethargy) Resting sinus tachycardia Dry mucous membranes Mydriasis Fever Cardiac effects Hypertension (early and transient, should not be treated) Tachycardia Orthostasis and hypotension Arrhythmia/ECG changes

CNS effects Coma Seizure Myoclonic twitches/tremor Hyperreflexia Pulmonary effects - Hypoventilation resulting from CNS depression GIT effects - Decreased or absent bowel sounds

Lab Studies: Rapid bedside glucose level determination Serum p. H, electrolytes, calcium, Urine toxicology screening The single most important test to guide therapy and prognosis remains the 12 -lead surface ECG. Important ECG changes include the following: 1. Prolongation of the QRS complex 2. Prolongation of the QT interval 3. Tachycardia and arrhythmia

ECG changes in TCA poisoning

Medical Care: Careful attention to ABC, and neurologic parameters are of most importance because of the risk of rapid deterioration in patients. Decontamination strategies should be used carefully in selected patients(usually charcoal) Sodium bicarbonate given in doses to achieve PH level 7. 45 -7. 55 to treat and prevent dysrhythmias Lidocain is used to treat dysrhythmias that are unresponsive to serum alkalization

Lomotil (enterostop®) Antidiarrheal agent containing both diphenoxylate and atropine. Both agents are absorbed by the GIT and absorption may be delayed in overdose due to inhibitory effects on smooth muscle motility. Diphenoxylate is an opioid

Patients manifest signs and symptoms of opiate toxicity(respiratory depression, altered mental status, and miosis). Respond well to naloxone and supportive care. Current recommendations are for a minimum of 24 hour observation.

Common Antidotes 1. Organophosphate : atropine+pralidoxime 2. Anticholinergic drugs : physostigmine 3. Acetaminophen : N-acetylcystiene 4. Methemoglobinemia : methylene blue+vitamin C 5. Narcotics (opiates) : naloxone 6. Benzodiazepines (valium) : flumazenil 7. Iron : deferoxamine (desferal) 8. Cyanide : amylnitrate 9. Arsenic, mercury, other metals : BAL 10. Lead : DMSA-EDTA 11. Methanol : ethanol 12. Acute dystonic reaction : diphenhydramine