Pain: Pharm - Acetaminophen

Question 1

Pain

Pharmacological Management of Pain

Non‐prescription options: (3)

Answer 1

1. Non‐opioids
   ◦ Acetaminophen
   ◦ NSAIDs
2. Counter irritants and topical products
3. Muscle relaxants

Question 2

Pain

Pharmacological Management of Pain

According to World Health Organization Analgesic Ladder, what is the recommendation for treating MILD pain?

Answer 2

Non-opioid:
  Acetaminophen (paracetamol)
  Aspirin,
  NSAID
  \+- adjuvant (drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs)

Question 3

Pain

Pharmacological Management of Pain

According to World Health Organization Analgesic Ladder, what is the recommendation for treating MILD to MODERATE pain?

Answer 3

Opioid:
Codeine, Tramadol, etc.
+- non-opioid
+- adjuvant

Question 4

Pain

Pharmacological Management of Pain

According to World Health Organization Analgesic Ladder, what is the recommendation for treating MODERATE to SEVERE pain?

Answer 4

Opioid:
Morphine, Fentanyl, etc.
+- non-opioid
+- adjuvant

Question 5

Pain - Acetaminophen

What is it used for?

Answer 5

Analgesic, antipyretic

Used for mild – moderate pain (≤ 4‐6/10)

Question 6

Pain - Acetaminophen

What is its MOA?

Answer 6

MOA:
inhibits prostaglandin synthesis in CNS (?COX‐3),
inhibits heat regulation in hypothalamus

Question 7

Pain - Acetaminophen

Can also found in what other medications?

Answer 7

Also found in combination with OTC products & opioids (e.g. codeine, oxycodone)
◦ e.g. Tylenol No. 1 (OTC) or Percocet 352/5mg (Rx)

Question 8

Pain - Acetaminophen

Adult Dosage forms?

Answer 8

◦ PO Immediate release 325mg, 500 mg (available in
tabs, caps, etc.)

◦ PO Extended release 650mg (i.e., Tylenol Arthritis®)

◦ PR 325 & 650mg (Why would we select this dosage
form?)

Question 9

Pain - Acetaminophen

Pediatric Dosage forms?

Answer 9

◦ PO liquid 80mg/ml & 160mg/5ml (Why might we
select one concentration over the other?)

◦ PO chew tabs 160mg

Question 10

Pain - Acetaminophen

Plasma levels peak ____ h post ingestion, t1⁄2 2 hours

Answer 10

1‐2 h

Question 11

Pain - Acetaminophen

Metabolized in the _____ & excreted by

Answer 11

liver

kidney

Question 12

Pain - Acetaminophen

Acetaminophen Dosing

Adult Dosing?

Answer 12

◦ Max 4 g/day; in the elderly, often max at 3.2 g

◦ 325–500 mg Q3H PRN PO or 325–650 mg Q4H PRN
PO or 650–1000 mg Q6H PRN PO

◦ (extended) 1300 mg po q8h

◦ Maximum dose: 4 g/day from all sources

Question 13

Pain - Acetaminophen

Acetaminophen Dosing

Renal dysfunction?

Answer 13

◦ CrCl< 50 ml/min – q6h

◦ CrCl<10ml/min – q8h

Question 14

Pain - Acetaminophen

Acetaminophen Dosing

Hepatic dysfunction – caution?

Answer 14

◦ low dose usually well tolerated(< 2.6 g / day)

Question 15

Pain - Acetaminophen

Acetaminophen Dosing

Children?

Answer 15

◦ 10‐15 mg/kg po q4‐6h (max 5 doses/day)

◦ Fixed dosing (weight preferred to patient age)

Question 16

Pain - Acetaminophen

What cause Acetaminophen Adverse Effects?

Answer 16

acute hepatotoxicity with acute overdose or chronic ingestion of high doses

Question 17

Pain - Acetaminophen

What are some Acetaminophen Adverse Effects findings?

Answer 17

◦ In Canada, more than 4,000 hospitalizations each
year (2014)
◦ Most common drug overdose (1/5 cases due to
unintentional dosing)
◦ Common in adolescents and young adults
◦ 1/5 cases occur even after dosing within
recommended guidelines, but this may be due to risk
factors such as alcoholism or liver disease

Question 18

Pain - Acetaminophen

Toxic levels?

Answer 18

10 g/d or 150 mg/kg/day are known to be toxic

BUT toxicity can occur at doses < 4 g/day

Question 19

Pain - Acetaminophen

Acetaminophen Adverse Effects Early symptoms? (4)

Answer 19

abdominal pain
fatigue
anorexia
fever

Question 20

Pain - Acetaminophen

Acetaminophen Adverse Effects Allergy Alerts?

Answer 20

Allergy Alert – has been associated with
SJS
urticaria
angioedema

Question 21

Pain - Acetaminophen

Acetaminophen Drug – Disease interactions?

Answer 21

◦ increase risk of toxicity with EtOH > 3 drinks/day,

malnutrition, & preexisting hepatic disease

Question 22

Pain - Acetaminophen

Acetaminophen Drug – Drug interactions?

Answer 22

Few clinically significant drug‐drug interactions

◦ Warfarin & acetaminophen ≥2g/day for >3 days

◦ Anticonvulsants PHT, CBZ may increase risk of
hepatotoxicity
- i.e., phenytoin, carbamazepine

Question 23

Pain - Acetaminophen

Acute Acetaminophen Toxicity can be impacted by: (5)

Answer 23

the quantity
duration
co‐ingestion
comorbidities
timing of medical interventions

Question 24

Pain - Acetaminophen

Acute Acetaminophen Toxicity level: __ g/day or
___ mg/kg/day

Answer 24

10 g/day or 150 mg/kg/day

Question 25

Pain - Acetaminophen

How many stages in Acute Acetaminophen Toxicity?

Answer 25

4

Question 26

Pain - Acetaminophen

Stage 1 in Acute Acetaminophen Toxicity:

Answer 26

Stage 1 – 0.5‐24 h post
◦ May be asymptomatic or generalized symptoms
(nausea, vomiting, malaise, pallor, diaphoresis, and
anorexia)

◦ LFT WNL; usually normal PT

Question 27

Pain - Acetaminophen

Stage 2 in Acute Acetaminophen Toxicity:

Answer 27

Stage 2 – 24‐48 h post (hepatic injury)
◦ increase AST/ALT, PT/INR? Bili?

◦ RUQ pain, abd tenderness, oliguria (decreased urine
output)

Question 28

Pain - Acetaminophen

Stage 3 in Acute Acetaminophen Toxicity:

Answer 28

Stage 3 – 72‐96 h post (hepatic failure)
◦ Variable peaks in transaminases

◦ Hepatic necrosis and dysfunction are associated
with jaundice, coagulopathy, hypoglycemia, and
hepatic encephalopathy

Question 29

Pain - Acetaminophen

Stage 4 in Acute Acetaminophen Toxicity:

Answer 29

Stage 4 ‐ > 4 days to weeks (recovery)

Question 30

Pain - Acetaminophen

Why avoid Tylenol #1s if possible?

Answer 30

Schedule 2 product

Acetaminophen 300 mg/codeine 8 mg/caffeine 15 mg

Limited evidence for efficacy vs other simple analgesics
◦ Combination products containing acetaminophen,
caffeine and codeine (8 mg) have not demonstrated
benefit in the management of acute or chronic
nonspecific low back pain.

Risk of dependence and diversion

Avoid if possible!