Acute Pain & OFA pt2

Question 1

Codeine metabolism is variable due to more than ____ polymorphisms resulting in analgesic variability.

Answer 1

50

Question 2

What is the adult dose and max of codeine?

Answer 2

15 - 60 mg q4

360mg max per day

Question 3

What is the pediatric dose and max of codeine?

Answer 3

0.5 - 1 mg/kg/dose

60mg max per day

should be avoided in children?

Question 3

60mg of codeine (maximal dose) is equivalent to how much aspirin?

Answer 3

650mg

Question 4

What drugs does codeine have interactions with? (3)

Answer 4

Opioids, EtOH, and Anticholinergics

Question 5

What drug is described by the following?

Answer 5

Tramadol

Question 6

Where does the + enantiomer of tramadol have affinity and what does it do? (3)

Answer 6

Centrally acting opioid agonist:
- μ → moderate affinity
- K & δ → weak affinity
- Opposes serotonin reuptake

Question 7

What does the - entantiomer of tramadol do? (2)

Answer 7

• Inhibits NE reuptake
• Stimulates α2 receptors

Question 8

What is tramadol metabolized into and what is the relevance of its metabolite?

Answer 8

Tramadol → CYP3A4 & 2D6 → O-desmethyltramadol (2-4 times more potent)

Question 9

What is tramadol’s potency compared to morphine?

Answer 9

1/5 to 1/10

Question 10

What is the oral onset for tramadol?

Answer 10

1-2 hours

Question 11

What is the half life of tramadol?

Answer 11

6.3 hours

Question 12

When is tramadol contraindicated? (2)

Answer 12

• Seizure Disorders
• PONV

Question 13

What are the benefits of tramadol vs other opioids? (3)

Answer 13

• Minimal respiratory depression
• Minimal-none addiction
• Minimal constipation

Question 14

Oral morphine dose is ____ times the IM or IV route.

Answer 14

3

Question 15

What receptors are primary affected by morphine?

Answer 15

μ-1 and μ-2

Question 16

What are the two principle active metabolites of morphine? (also list effects)

Answer 16

• Morphine-6-glucuronide → analgesia
• Morphine-3-glucuronide → neurotoxicity & hyperalgesia

Question 17

How is morphine metabolized?

Answer 17

• Hepatic: conjugation w/ glucuronic acid
• Kidneys

Question 18

What factors contribute to morphine’s minimal CNS absorption?

Answer 18

• ↓ lipid solubility
• ↑ protein binding
• ↑ Ionization at normal bodily pH

Question 19

What is the IV/IM onset and peak of action for morphine?

Answer 19

Onset: 15-30 min
Peak: 45-90 min

Question 20

What differences does morphine exhibit in women vs men?

Answer 20

In women:
↑ analgesic potency
↓ speed of offset

Question 21

What is the protein binding of morphine?
What about the half-time?

Answer 21

35% protein binding
1.7 - 3.3 hours

Question 22

What is released from morphine administration?
What is the result?

Answer 22

Histamine → vasodilation and hypotension

Question 23

Morphine should be avoided in patients with ____ impairment as the metabolite morphine–6-glucuronide can accumulate and lead to _________ ________.

Answer 23

Renal impairment : respiratory depression

Question 24

What drug is a semisynthetic derivative of thebaine and is the most used opioid worldwide?

Answer 24

Oxycodone

Question 25

What are the metabolites of oxycodone?

Answer 25

Oxymorphone (active) Noroxycodone (inactive) *Oxycodone is primarily a prodrug*.

Question 26

What is the site of action of oxycodone?

Answer 26

μ and κ receptors of the CNS

Question 27

What are the two types of PO oxycodone?

Answer 27

IR = Immediate release CR = Controlled release

Question 28

What is the dose of oxycodone?

Answer 28

10 - 15mg (equivalence with 10 mg morphine)

Question 29

What is the onset of action of oxycodone?

Answer 29

< 1 hour

Question 30

Opioids (in general) exhibit an ____ effect with other drugs that are CNS depressants

Answer 30

additive

Question 31

Why is methadone used for opioid addiction maintenance? (3)

Answer 31

- 60-95% oral bioavailability - High potency - Long duration of action

Question 32

What should be known about methadone's half life?

Answer 32

Very long and unpredictable (up to 36 hours) Can accumulate w/ repeated doses

Question 33

What various receptors affinities does methadone have? (4)

Answer 33

- Weak noncompetitive NMDA antagonist - Serotonin reuptake inhibitor - Monoamine reuptake inhibitor - High μ receptor affinity

Question 34

What would occur with concurrent methadone and carbamazepine use?

Answer 34

Carbamazepine is a CYP450 inducer thus methadone will be **metabolized faster.**

Question 35

What agents can inhibit the metabolism of methadone?

Answer 35

CYP450 Inhibitors: - Antiretrovirals - Grapefruit juice

Question 36

How much is methadone clearance affected by hepatic and renal impairment?

Answer 36

Not much

Question 37

What is the dose of methadone?

Answer 37

2.5 - 10 mg PO/IM/SC q4-12 hours

Question 38

Why are standardized simple dosing guidelines unachievable for methadone?

Answer 38

High variable half life (8-80 hours)

Question 39

What is the worst med interaction associated with methadone?

Answer 39

MAOI's

Question 40

What drugs are known to increase the concentration/effects of methadone? (3)

Answer 40

- Cipro - Diazepam - Acute EtOH

Question 41

What drugs are known to decrease concentration/effects of methadone? (5)

Answer 41

- Anti-retrovirals - Phenobarbital - Phenytoin - Rifampin - MAOI's

Question 42

What cardiac complication can occur in rare cases with methadone usage?

Answer 42

Pause dependent dysrhythmia

Question 43

What is the half life of codeine?

Answer 43

3-3.5 hours