Clinical Toxicology Exam 2 Part 2: APAP, salicylates, NSAIDS

APAP

Dr. Yue

Describe the ADME (absorption, distribution, metabolism, and excretion) of acetaminophen

1. Absorption → ____ _____ _____

2. Distribution → High volume of distribution _____

3. Elimination → _____ of elimination through ______

4. Normal half life ____, overdose halflife _____

1. Well orally absorbed

2. 0.75-1L/kg

3. 95% ; metabolism

4. 2-3 hours ; 4-8 hours

Explain the mechanisms of acute acetaminophen toxicity due to overdose

In acetaminophen overdose, _____, _____ and _____ is _____ . The toxic metabolite _____ will react with cellular proteins, cause hepatotoxicity.

1. PAPS →

2. UDPGA →

3. GSH →

Biosynthesis of GSH is often limited by _____ availability. So the specific antidote for acetaminophen overdose is ____

UDPGA, PAPS and glutathione (GSH) ; depleted ; NAPQI

1. Sulfation

2. Glucuronidation

3. GSH conjugation

cysteine ; NAC

Recognize conditions that may increase risk of acetaminophen toxicity

1. CYP2E1

2. CYP3A4

3. _____

1. CYP2E1 → Turns APAP into NAPQI. Inducable by isoniazid

2. CYP3A4 → inducible by rifampicin

3. Malnutrition

Outline the management of acetaminophen overdoses

Refer to emergency department if:

1. >6 y/o & _____

2. <6 y/o & _____

3. _____

4. _____

5. _____.

1. >10g or 200mg/kg

2. >200mg/kg

3. Attempted suicides

4. Unknown dose

5. Someone else poisoned them

Gastric decontamination of APAP by AC is best given NMT _____ after ; if they need NAC and could still benefit from charcoal give it ____.

1-2 hours ; IV

Interpret acetaminophen concentration after acute exposure using Rumack-Matthew Nomogram.

Hepatotoxic levels ____ when measured ____ after the acetaminophen dose.

> 150 μg/ml ; 4 hours

NAC is best started within ____ hours of overdose. Has beneficial effects even after APAP had been metabolized and hepatic ___ has developed.

8 hours ; necrosis

NAC oral dosing: (Given over 72 hours)

1. Loading dose: ____

2. Maintainence dose: ____

3. Dilution:

1. 140mg NAC/kg

2. 70mg NAC/kg every 4 hours for 72 hours (17 MT doses)

3. NAC 20% → x3 dilution.. NAC 10% → 2x dilution

NAC IV dosing: (Given over 21 hours)'

1. Adults → ____, ____, _____

2. Children >20kg → _____

3. Children <20 → _____

1. 200ml, 500ml, 1000ml

2. Half it

3. 3ml/kg, 7ml/kg, 14ml/kg

NAC in chronic overdose:

1. WHO should be treated with NAC?

2. NAC is useful, but not widely recommended guidelines. Based primarily on ____, ___and ___ levels, and other patient symptoms.

3. If duration of ingestion exceeds ____ but AST/ALT are near normal, and patient is not ill, no treatment may be needed

4. Shortened periods of NAC may be used if ____ ____ levels and _____concentrations remain low

1. Patients who develop highly elevated AST after chronic acetaminophen overdose should be treated.

2. clinical judgement, ALT/AST

3. 48h

4. Serum Aminase ; APAP

NAC oral Loading dose = 140 mg/kg

Woman weighs 121 pounds (55 kg)

1. How much volume (ml) of 20% (200 mg/ml) NAT is needed?

2. How much volume of juice is needed?

1. 38.5mL

2. 3 x 38.5mL → 115.5mL