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

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 oral dosing: (Given over 72 hours)

1. Dilution:

NAC IV dosing: (Given over 21 hours)

1. NAC should be 5% of the final solution. (Add 3 times volumes to dilute 20 conc)

Severe hyponatremia and seizures have occurred in pediatric patients given the standard adult IV guidelines, due to the excess in _____. Volume of D5W used to dilute the NAC in pediatric is ____than that in adult

free water ; less

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

Toxicology of ASA and NSAIDS

Dr. Eleden

Recognize the products in which aspirin or a derivative of aspirin is commonly found (5)

1. Peppermint flavored → Icy-hot/Bengay

2. Chalk flavored → pepto-bismol

3. APAP flavored → Excedrin

4. Wintergreen flavored → salicylate in the oil

5. Alka-selzter

Be able to calculate the aspirin equivalent dose per patient body weight when given a patient case

1. Methyl salicylate:

2. Bismuth subsalicylate:

3. Homosalate:

4. Octisalate:

1. mg x 1.4

2. mg x 0.5

3. mg x 0.7154

4. mg x 0.7303

When to refer for salicylate poisoning?

1. ______

2. <6 y/o and ______ of wintergreen oil

3. >6y/o and ingestion ______

4. ______ ______ exposure + signs of toxicity

1. Ingestion 150 mg/kg or 6.5g

2. more than a lick

3. >4mL

4. Significant topical

One milliliter (1 mL) of 98% methyl salicylate is approximately equivalent to ____ of ASA

1.4 grams

Mechanism of Toxicity of salicylate

1. impairs cellular energy production

   • ______

   • ______

2. Lactate and other organic acids accumulate and produce an ____ _____

3. Direct effect to stimulate the respiratory center in the brain leading to ____ & ____ _____

1. impairs cellular energy production

   • interference with the Krebs cycle

   • Uncoupling of oxidative phosphorylation

2. elevated anion gap metabolic acidosis

3. hyperventilation and respiratory alkalosis.

Recognize signs and symptoms of aspirin in the overdosed patient.

1. _______

2. ______ & ______

3. ______/acid base disturbance

4. ______

5. ______

6. ______

7. N/V

8. Fever, sweating, dehydration

1. Tinnitus

2. Tachypnea & hypernea

3. Hypokalemmia

4. Neurglycopenia

5. AMS

6. ARDs

List and discuss the major management concerns of a patient who has aspirin systemic toxicity

1. If intubation considered →

2. ____ can be used

3. Get Salicylate Level ____ ____

4. peat every ____ until ___declining levels

1. set a higher tidal volume on the vent and hyperventilate
   patient

2. AC

3. upon presentation (NOTE: very different from APAP exposure!)

4. 2-4 hours; two

Discuss the recommended treatments in aspirin systemic toxicity.

1. 54321

2. Urinary alkalinization

3. Hemodialysis (indicated when?) (5 things)

1. 54321

   1. D5W, 40mEq K, 3 AMPS bicarb, 2x/per maintainence fluid, all in 1 bag

2. Urinary alkalinization

   1. Don’t forget to supplement potassium

3. Hemodialysis

   1. AMS

   2. ARDs

   3. AKI

   4. Can’t administer bicarb

   5. Significant elevations

Describe the general concerns and management for other NSAIDs (ibuprofen)

1. Mostly supportive

2. Most asx patients with intentional overdose and those with normal vs require observation for ____ and a___ ____ concentration before being medically cleared.

3. Patients who ingest greater than ____ are at high risk for toxicity and require medical evaluation.

4. GI decontamination with ____ for asymptomatic patients
   with the potential for a large ingestion

5. Electrolyte imbalances and hypotension handled with _____ and ____

1. 4-6h ; serum APAP

2. 400mg/kg

3. AC

4. bicarb ; fluids/vasopressors