Pharmacology and Therapeutics-IV

Semester VI

Poisoning and Overdose

Naeem Riaz

Poisoning
The adverse effects of plants, foods, chemicals or pharmaceutical agents on the body

Overdose
Poisoning by excessive dose

Accidental

Deliberate

Two Peak Age Groups

The first group,preschool age when children are exploring there environment The second group is young adult age group, when ingestion is a form or suicidal behavior

General Assessment
Management of poisoning is primarily supportive
Basic Life Support (BLS) Level Of Consciousness (LOC) Airway Breathing Circulation
Pulse Hemorrhage

Skin color Skin temperature Skin Condition

Redness

History
When, what, how much ? Why? Circumstances Drug history Psychiatric history Assess mental status and capacity

Specific Medical Questions

Poisoning & Overdose History
Substance When exposed/ingested Amount Time Period Estimated weight

Obtains SAMPLE History

S = Signs and symptoms A = Allergies M = Medication P = Pertinent medical history L = Last oral intake E = Events

Initial Symptoms of Poisoning

Pain Fluid imbalance Water and electrolyte imbalance Acidosis Body temperature disregulation Malnutrition

Signs and Symptoms of Poisoning

Central Nervous System Involvement
Convulsion Coma Hyperactivity, Delirium, and Mania

Hypoglycemia Hypoxia and depressed respiration

Maintenance of Adequate Airway Oxygen Administration Pulmonary Edema

Sign&Symptoms of Poisoning
Circulatory System Involvement
Circulatory failure or shock Congestive heart failure Cardiac arrest

Genitourinary Tract Involvement

Acute renal failure Urine retention

S&S of Poisoning
Gastrointestinal Tract Involvement
Vomiting Diarrhea Abdominal distention

Blood and Hematopoietic System Involvement

Methemoglobinemia Agranulocytosis and other blood dyscrasias Hemolytic reactions

General Comments
Try and get as much history as possible including witnesses People truly wanting to commit suicide often lie Remember the ABCs: Airway Clear mouth & throat, gag reflex Breathing O2 saturation, ABGs (Arterial BloodGas Circulation Venous access, IV fluids if shocked

Examination

Investigations
Always check blood glucose.
Send blood & urine for toxicology screening. ALWAYS measure paracetamol & salicylate levels Failure to diagnose & treat is negligent. U&Es, LFTs, glucose, clotting, bicarbonate ECG, CXR (Chest X Ray) Specific blood levels

Management
Supportive
Correct hypoxia, hypotension, dehydration, hypohyperthermia, and acidosis Control seizures

Monitor
TPR, BP, ECG, Oxygenation,

General
Absorption Elimination Specific antidotes

 Absorption
Gastric lavage
Only if within 1 hour & life-threatening amount Never for corrosives

Activated charcoal
50 g single or repeated dose ( elimination) Doesnt bind heavy metals, ethanol, acids

 Elimination
Multiple dose activated charcoal
Quinine, phenobarbitone

Diuresis Urinary alkalinization

salicylates

Dialysis

Drug Toxicology
Paracetamol Salicylates CNS depressants CNS stimulants Antidepressants Digitalis Organophosphates

Paracetamol Overdose
Acetaminophen Most common analgesic drug taken in overdose Often found in combination with antihistamines, codeine Few symptoms or early signs As little as 12g can be fatal Hepatic and renal toxin
Centrolobular necrosis, jaundice

More toxic if liver enzymes induced or reduced ability to conjugate toxin

Pharmacokinetics
Tablets dissolve rapidly Peak level 3-4 hours after ingestion
May be delayed in the presence of other drugs (eg, antihistamines, anticholinergics, opiates)

Volume of Distribution approx. 1L/kg Elimination half-life normally 1-3 hours

Increased to 4-6 hours or more after overdose

Acetaminophen Metabolism
~ 45% P450 ~ 50%

Glucuronidation (non toxic)

~ 5%

Sulfation (non toxic)

NAPQI
Glutathione + NAPQI = nontoxic product

N-acetylcysteine (NAC)

Liver cell damage

N-acetylcysteine
Supplies glutathione Dosage for NAC infusion - ADULT
(1) 150mg/kg IV infusion in 200ml 5% dextrose over 15 minutes, then (2) 50mg/kg IV infusion in 500ml 5% dextrose over 4 hours, then (3) 100mg/kg IV infusion in 1000ml 5% dextrose over 16 hours

Side-effects
Flushing, hypotension, wheezing, anaphylactoid reaction

Alternative is methionine PO (<12 hours)

Management
General measures including
U&Es, LFTs, glucose, clotting, bicarbonate, paracetamol and salicylate levels Activated charcoal

<8 hours
Start N-aceylcysteine if above treatment line Patients are usually declared fit for discharge from medical care on completion of its administration. However, check creatinine and ALT before discharge. Patients should be advised to return to hospital if vomiting or abdominal pain develop or recur.

Management
>8 hours
Urgent action required because the efficacy of NAC declines progressively from 8 hours after the overdose Therefore, if > 150mg/kg or > 12g (whichever is the smaller) has been ingested, start NAC immediately, without waiting for the result of the plasma paracetamol concentration >24 hours Still benefit from starting NAC

Aspirin
Aspirin is a widely prescribed antiplatelet therapy for cardiovascular and cerebrovascular disease When combined with the fact that aspirin is readily available, aspirin toxicity remains an important clinical problem

Biochemical pathway inhibited by aspirin

Pharmacokinetics
Rapidly absorbed in the stomach
Reach peak levels in 15-60 minutes

90% bound to albumin in the blood at a dose of 10 mg/dL 90% metabolized in the liver, 10% unchanged T1/2 = 15-20 minutes Metabolites and unchanged drug are filtered and secreted by the kidneys

Toxicokinetics
Peak blood concentrations may be delayed 24 hours

76% bound to albumin at a dose of 40 mg/dL

increased free drug in the blood

Hepatic enzymes become saturated and elimination follows zero-order kinetics

Functional half-life can be over 20 hours

Diagnosis
Serum salicylate concentrations and concomitant arterial blood pH values can definitively confirm or exclude toxic salicylate levels

Management
General measures Blood
Salicylate level >2 hours, and after 2hrs >700mg/L potentially lethal >500mg/L moderate-severe poisoning U&Es, glucose, ABG, bicarbonate

Activated charcoal Rehydrate, monitor glucose, correct acidosis and K+ If levels >500mg/L alkalinize urine (HCO3-) Levels > 700 mg/L before rehydration, renal failure or pulmonary oedema consider haemodialysis