POISONING

Paracetamol-Normal Metabolism

Paracetamol converted to:
N-Acetyl-p-benzoquinonamine (TOXIC)
This is conjugated with Glutathione
Glutathione stored in the body
Produces a NON TOXIC metabolite.
Glutathione stores are used up by the excess Paracetamol
Toxic Metabolite build up
Binds IRREVERSIBLY to Hepatic Cell membranes
Resulting in LIVER NECROSIS

Clinical features of Paracetamol Overdose

Stage I (0.5 to 24 hours)
No symptoms; N&V Malaise
Stage II (24 to 72 hours)
Subclinical elevations of hepatic aminotransferases (AST, ALT)
right upper quadrant pain, with liver enlargement and tenderness. Elevations of prothrombin time (PT), total bilirubin, and oliguria and renal function abnormalities may become evident
Stage III (72 to 96 hours)
Jaundice, confusion (hepatic encephalopathy), a marked elevation in hepatic enzymes, hyperammonemia, and a bleeding diathesis hypoglycemia, lactic acidosis, renal failure 25%, death
Stage IV (4 days to 2 weeks)
Recovery phase that usually begins by day 4 and is complete by 7 days after overdose


Paracetamol Overdose-management
Initial ABC ( usually well systemically)
Get a good history
TIME TAKEN, AMOUNT
Any other medication
History of Liver disease
N-Acetylcysteine. Shown to be advantageous if given in the first 10 hours.

Paracetamol Overdose-management

N - Acetylcysteine
Specific antidote used for Paracetamol
Provides the Sulphydryl groups needed to increase the availability of Glutathione
So that Body can turn the TOXIC metabolite into the non toxic form and prevent Liver Cell Damage and NECROSIS
(Not shown to be effective after 15 hours)

Paracetamol Overdose-management

Able to measure levels of Paracetamol in the blood.
Helps to guide whether amount taken is enough to be Hepatotoxic
IF IN DOUBT start treatment before the Paracetamol levels get back to save time

Fluoride Toxicity

Excessive ingestion / short time
Acute toxic effects
A- Gastric disturbance
B- Nausea, vomiting
C-Death
Excessive ingestion / long period during tooth development
Dental fluorosis;
The effect of long term fluoride exposure on bone is still controversial


Historical perspective of fluoride toxicity
Fluoride was used as a pesticide
Mistaken for powder milk, salt, baking soda, flour
1933-1955: 607 fatal cases in the US.
Pittsburgh 1940:
Salvation Army service center.Mistaken NaF for flour in pancake
40 poisoning cases & 12 deaths .
Oregon 1943:
State hospital,Mistaken roach powder for powder milk.10 gallons of scrambled eggs + 17 lbs NaF 263 poisoning cases & 47 deaths

Current incidences of F toxicity

USA poison control centers ;>20,000 reports/year of over-ingestion of fluoride.
Sources of fluoride
Vitamins, dietary supplements, dental products (fluoridated toothpastes or mouthwashes).
90% are young children, ~5% had minor symptom, ~2% were treated in healthcare facility.
A few cases with life-threatening symptoms and DEATH

Symptoms of fluoride toxicity

Low Dosage
Nausea,Vomiting,Abdominal pain,Diarrhea,
Hypocalcemia and Hyperkalemia
Hypersalivation,Tears,Discharge from nose and mouth and Headache.
High Dosage; Convulsion,Spasm of the extremitie,Generalized weakness,Blood pressure drop. Cardiac arrhythmias ,Respiratory acidosis ,Extreme disorientation
Coma and Death May occur within
the first few hours


Treatment of Fluoride Toxicity


Reduce absorption; Induce vomiting immediately (providing no risk of aspiration)


Reduce bioavailability : 1% CaCl2 or calcium gluconate, milk .


Additional washing of stomach with lime water .


IV fluid replacement,add calcium gluconate .


Blood calcium level ,Plus sodium bicarbonate : urine flow rate & urinary pH


Other monitoring and supportive therapies
Generally, if death has not occurred in 1-2 days the prognosis is good.
Exception: 2 year-old boy died 5 days after ingesting 100 tablets 0.5 mg Fuoride.

Salicylate overdose

Aspirin (acetylsalicylic acid)
Methyl salicylate (Oil of Wintergreen)
5 ml = 7g salicylic acid
Herbal remedies
Fatal intoxication can occur after the ingestion of 10 to 30 g by adults and as little as 3 g by children

Salicylate levels

Rapidly absorbed; peak blood levels usually occur within one hour but delayed in overdose 6-35 hrs
Measure 4 hrs post ingestion & every 2 hrs until they are clearly falling
Most patients show signs of intoxication when the plasma level exceeds 40 to 50 mg/dL (2.9 to 3.6 mmol/L)

Salicylate overdose

Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes
Stimulation of the chemoreceptor trigger zone in the medulla causes nausea and vomiting
Direct toxicity of salicylate species in the CNS, cerebral edema, and neuroglycopenia
Activation of the respiratory center of the medulla results in tachypnea, hyperventilation, respiratory alkalosis
Uncoupled oxidative phosphorylation in the mitochondria generates heat and may increase body temperature
Interference with cellular metabolism leads to metabolic acidosis


Clinical features of Salicylate overdose
Early symptoms of aspirin toxicity include tinnitus, fever, vertigo, nausea, hyperventilation, vomiting, diarrhoea
More severe intoxication can cause altered mental status, coma, non-cardiac pulmonary oedema and death

Metabolic abnormalities Salicylate overdose

Stimulate the respiratory center directly, early fall in the PCO2 and respiratory alkalosis
An anion-gap metabolic acidosis then follows, due to the accumulation of organic acids, including lactic acid and ketoacids
Mixed respiratory alkalosis and metabolic acidosis with ↑ anion gap
Arterial Ph variable depending on severity

Metabolic abnormalities

Metabolic acidosis increases the plasma concentration of protonated salicylate

thus worsening toxicity by allowing easy diffusion of the drug across cell membranes

Salicylate overdose - treatment
Directed toward increasing systemic pH by the administration of sodium bicarbonate .
IV fluids +/- vasopressors
Avoid intubation if at all possible (↑ acidosis)
Supplemental glucose (100 mL of 50 percent dextrose in adults) to patients with altered mental status regardless of serum glucose concentration to overcome neuroglycopaenia

Hemodialysis


Alkalinization of plasma and urine
Alkalemia from a respiratory alkalosis is not a contraindication to sodium bicarbonate therapy.
A urine pH of 7.5 to 8.0 is desirable
Blood gas analysis every two hours
Avoid severe alkalemia (arterial pH >7.60)

Haemodialysis - indications

Altered mental status

Pulmonary or cerebral edema

Renal insufficiency that interferes with salicylate excretion

Fluid overload that prevents the administration of sodium bicarbonate .

A plasma salicylate concentration >100 mg/dL (7.2 mmol/L)

Clinical deterioration despite aggressive and appropriate supportive care

Antidotes
Acetaminophen N-acetylcysteine
Organophosphates Atropine, pralidoxime
Anticholinergic physostigmine
Arsenic, mercury, gold dimercaprol
Benzodiazepines flumazenil
Beta blockers glucagon
Calcium channel block calcium
Carboxyhemoglobin 100% O2
Cyanide nitrite, Na thiosulfate
Digoxin digoxin antibodies


Antidotes
Ethylene glycol fomepizole, HD
Heparin protamine
Iron deferoxamine
Isoniazid pyridoxime
Methanol fomepizole, HD
Methemoglobin methylene blue
Opioids naloxone
Salicylate alkalinization, HD
TCA’s sodium bicarbonate
Warfarin FFP, vitamin K

Decontamination

Skin
Protect yourself and other HC workers
Remove clothing
Flush with water or normal saline
Use soap and water if oily substance
Chemical neutralization can potentiate injury
Corrosive agents injure skin and can have systemic effects