Analgesic and Antipyretic Poisoning

Analgesic cont….
 Common Preparations:
1. Tablets:
• Aspirin (acetyl salicylic acid).
• Integrated in various cold preparations.
2. Vials:
• Aspegic.
3. Topical preparations:
• Methyl salicylate
• Salicylic acid - (Keratolytic)
 Salicylates
• Salicylates are a type of drug found in many over-the-counter and prescription
medicines. Aspirin is the most common type of salicylate.
Clinical use:
• Anti-inflammatory , antipyretic and analgesic drug
• Platelet aggregation inhibitor.
Conditions of poisoning:
1. Accidental
• In children: intoxication may occur during treatment because pyrexia due to aspirin
overdose may be mistaken for fever of infection with further administration of
aspirin.
• Co-administration of more than one salicylate-containing medication.
• Elderly patient may suffer chronic toxicity due to gradual alteration of patient’s
metabolic elimination process.
2. Suicidal By young adolescents

Toxic dose:
Acute overdose:>150 mg/Kg (Single dose)
Chronic overdose:>100 mg/Kg over 2days.

Fatal dose : 400mg /Kg

 Mechanism of action
At therapeutic dose:
• Antipyretic, anti-inflammatory and analgesic effect primarily
through inhibition of prostaglandin biosynthesis
at toxic dose:
• Salicylates impair cellular respiration by uncoupling oxidative
phosphorylation resulting in fever, acid-base, fluid and electrolyte
abnormalities that are observed in the following phases:
1. Respiratory alkalosis
2. Renal compensation
3. Metabolic acidosis
 Clinical presentation
1.Gastrointestinal(GIT) side effects are due to gastric irritation and
simulation of chemoreceptor trigger zone and include
 Nausea, vomiting and abdominal pain.
 GIT bleeding & ulceration.
2.Neurologic effects include irritability, agitation, and confusion
Coma, seizures, and cerebral edema are late signs of severe toxicity and these
symptoms result from accumulation of CO2 in brain, decreased brain
glucose concentration, and direct toxic effect
3.Cardiovascular symptoms include tachycardia in mild toxicity, hypotension
and dysrythmias in severe toxicity.
4. Fluid and electrlyte disturbance due to dehydration
 Clinical Presentation cont…
5. Respiratory system: Non-cardiogenic pulmonary edema resulting from
adrenergic over activity leading to the shift of blood from systemic to the
pulmonary circulation causing pulmonary hypertension and edema.
6. Urinary system:
 Direct nephrotoxicity leading renal tubular necrosis that result renal
failure.
 Indirect effect due decreased renal blood flow caused by dehydration,
inhibition of prostaglandins necessary to maintain renal blood flow,
and Rhabdomyolysis.
 Clinical Presentation cont…
6. Hepatic: Chronic toxicity and Reye’s syndrome in children
(acute brain damage and liver dysfunction when aspirin is
given during exposure to chickenpox or flu infections).
7. Others like bleeding tendency, hyperthermia, hypersensitivity,
and salicylism (tinnitus, vertigo, deafness due to 8 th cranial
nerve involvement are also reported.
Cause of death:
 Earlier: due to central respiratory failure, pulmonary edema and/or
cardiac arrhythmias (acidosis).
 Delayed (few days): renal failure and hemorrhage
 Investigation
1. Routine lab investigations:
• ABG: Respiratory alkalosis metabolic acidosis
• Serum electrolyte: Hypokalaemia
• Serum glucose: hyperglycaemia
• Hepatic function test
2. Coagulation profile
3. Serum salicylate level
4. Abdominal and chest X-ray
5. Brain CT/MRI
 Treatment
1. Supportive measure
2. GIT decontamination
3. Elimination of the poison from the blood
4. Symptomatic treatment
• Dehydration: normal saline
• Hypokalaemia: Potassium
• Hypoglycaemia: glucose
• Seizure: diazepam
• Pulmonary edema: oxygen and haemodialysis
 Acetaminophen(paracetamol)
Paracetamol, also known as acetaminophen is a medication used to
treat fever and mild to moderate pain
Common preparation:
• Tablet :Paracetamol, panadol, paramol,and pyral
• Vials: anadol, calpol, Tylenol
Pharmacokinetics:
1. Rapidly absorbed from GIT
2. Peak plasma level usually occur within 4hours
3. 5-20% bounds to plasma protein
 Metabolism
Thereputic dose:
• 95% of paracetamol is metabolized in the liver through conjugation with
glucuronide(42%) and sulfate(52%)
• 2% is excreted unchanged in the urine
• The remaining 4% is metabolized via the cytochrome p450 to atoxic metabolite,
N-actyle-p-bezoquinone amini(NAPQI) and it’s rapidly conjugated with hepatic
glutathione forming a nontoxic Compounds that’s excreted in the urine
At toxic dose:
The sulfate pathway becomes saturated, resulting in increased fraction of the
toxic metabolite (NPQI) depletion glutathione storage
 Conditions of poisoning
Accidental: most common specially in children
1. Suicidal: common
Toxic dose:
• Acute toxicity(single dose) : Adults >150mg/kg and >200mg/kg
in children
• Chronic toxicity: >150mg/kg over 2days
• Children appear to be more resistance to paracetamol toxicity
due to more ability of sulphation than adults
 Mechanism of action
Therapeutic action:
• Potent Inhibitory effect on synthesis of central prostaglandin
(PG), however the anti-inflammatory action is very weak due to
it’s weak inhibitory Action on synthesis of peripheral
prostaglandin
Toxic action:
• The toxic metabolite N-actyle-p-bezoquinone imine (NPQI) will
bind to (-SH) group of hepatocellular protein leading to centri-
lobular necrosis.
 Investigation
1. Routine lab investigations
2. Coagulation profile: prothrombin time
3. Serum paracetamol level(4hrs post ingestion)
Treatment
1.Supportive measure: ABCs
2.GIT decontamination:
• gastric lavage is not recommended due to it’s rapid absorption in GIT
• Activated charcoal is not recommended to be administrated in conjunction
with N-acetyle-cysteine(NAC) as charcoal may adsorption NAC
 3.Elimination of the poison from the blood
4.Specific antidote: N-acetyl-cysteine
Mechanism
• It’s metabolized by the hepatocytes to a glutathione precursor that provides protective
level of glutathione to detoxify the hepatotoxic metabolite NPQI by providing(-SH) group
• Enhances sulphating conjugation by providing sulphur
Forms of NAC
• Oral(Mucomyst) 140mg/kg
• Intravenous(Parvolex) it’s preferable in two situations which are:
1. Fulminant hepatic failure
2. Inability to tolerate oral NAC
Oral Hypoglycaemic Agents
Common preparation:
• Sulfonylurea: Tolazsmide and chlorpromide
• Biguanides: Metformin
Mechanism of action
1.sulfonylureas:
• Increase Insulin level through stimulation of beta receptor in
pancreas
2.Biguanide:
• Decrease amount of glucose produced by liver
• Decrease intestinal absorption of glucose
• Decrease the body need to insulin and improve insulin
sensitivity by increasing peripheral glucose uptake and
utilization
Conditions of poisoning
1.Accidental overdose
2.Suicidal
3.Homicidal
 Clinical presentations:
• General symptoms and signs of hypoglycaemia
• CNS manifestation: mental status ranged from normal to coma
• Respiratory manifestation: rapid shallow respiration and rapid
deep respiration
 Investigation
 Routine lab investigations:
• ABG: metabolic Acidosis may occur
• Serum glucose: hypoglycaemia
 Treatment:
1. Supportive measures: ABC
2. GIT decontamination
3. Enhance elimination
4. Specific antidote
5. Symptomatic
 Lithium
Lithium is a monovalent cat-ion chemically similar to Na+ and k+
Uses of lithium:
Lithium metal: Manufacture of storage of batteries
Lithium salts: Treatment of manic-depressive disorder
Mechanism of action:
Lithium competes with Na+ and k+ altering their transport at the level of
cell membrane and neural synapses .
Inhibits: Release of dopamine and norepinephrine
Increase: Release of serotonin
Clinical picture of acute toxicity
• GIT: anorexia, vomiting , abdominal pain and diarrhoea
• Respiratory: Acute respiratory distress syndrome
• CNS: mild to moderate toxicity : mental confusion and tremors.
:Severe toxicity: Seizure and coma

• Renal: Acute renal failure and chronic renal failure

• Cardiovascular: conduction disturbance and ECG change
• Fluid electrolyte balance:
Dehydration
Decreased anion gap
 Investigations
 Routine lab investigations
 Toxicological screening for lithium
 ECG and continuous cardiac monitoring
 Treatment
• Supportive measures: ABC
• GIT decontamination
• Elimination of poison from the blood
• Symptomatic:
Dehydration :normal saline
Dysrythia:antiarrhythmic drugs
 Antidote therapy: sodium polystyrene (for hyperkalaemia caused by Li)
Mechanism of action:
SPS acts by exchanging of it’s sodium for potassium in large Intestine,
It may delay but not prevent absorption of lithium
Indications: Hyperkalaemia and Lithium toxicity
Contraindications: Hypersensitivity to SPS and obstructive bowel disease
Dosage:
Adults: 15g orally 1to14 times daily
30 to 50g rectally every 6hours