Toxicology Lect 2

7/29/2019 Toxicology Lect 2

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Naeem Riaz

Pharmacology and Therapeutics-IVSemester VI

Poisoning and Overdose



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, hypo-

hyperthermia, 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)

– Doesn’t 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



Acetaminophen

Metabolism

Glucuronidation

(non toxic)

Sulfation

(non toxic)

NAPQI

P450

~ 5%

Glutathione +

NAPQI

= nontoxic product

Liver cell damage

N-acetylcysteine (NAC

~ 45% ~ 50%



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 4hours, then

– (3) 100mg/kg IV infusion in 1000ml 5% dextrose over 16hours

• 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 frommedical care on completion of its administration.

However, check creatinine and ALT beforedischarge. Patients should be advised to return tohospital 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 isthe smaller) has been ingested, start NACimmediately, without waiting for the result of theplasma paracetamol concentration

• >24 hours

– Still benefit from starting NAC



Aspirin

• Aspirin is a widely prescribedantiplatelet therapy for cardiovascular andcerebrovascular disease

• When combined with the factthat aspirin is readilyavailable, aspirin toxicityremains an important clinicalproblem



Biochemical

pathway

inhibited byaspirin





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 2-4 hours

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

– increased free drug in the blood

• Hepatic enzymes become saturated andelimination follows zero-order kinetics

– Functional half-life can be over 20 hours



Diagnosis

• Serum salicylate concentrations andconcomitant 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

Documents

Toxicology Lect 2