Opioids - Dosages and Pharmacokinetics

Question 1

What is the dose of Morphine?
Onset?
Peak?
Duration?
First-pass pulmonary clearance?

Answer 1

1-10 mg IV
Onset: 10-20 minutes
Peak IV: 15-30 minutes
Peak IM: 45-90 minutes
Duration: 4-5 hours
No first pass pulmonary clearance

Question 2

What is this graph teaching us?

Answer 2

Plasma concentration of morphine increases progressively with advancing age

Question 3

What do we learn about morphine-6-glucuronide and morphine from this graph?

Answer 3

The effects of morphine and morphine-6-glucuronide on ventilation and PetCO2 are strikingly similar

Question 4

What is the other name for meperidine (demerol)?

Answer 4

Pethidine

Question 5

What is the dose for meperidine?
What is the duration?
Where is it primarily metabolized? What is the metabolite of meperidine?
Elimination 1/2 time? Elimination 1/2 time with renal failure?
Toxic effects?

Answer 5

12.5 mg post-op shivering
Duration: 2-4 hours
Hepatic metabolism (90%) Normeperidine
E1/2 time: 3-5 hours. 35 hours with renal failure
Toxicity: myoclonus, seizures

Question 6

S/E’s of Meperidine?

Answer 6

tachycardia, mydriasis, (-) inotropy, serotonin syndrome

Question 7

What other drugs can be administered for post-op shivering?

Answer 7

Clonidine, physostigmine, butorphenol

Question 8

What is the other name for fentanyl?

Answer 8

Sublimaze

Question 9

What does this graph show us about relative context-sensitive half times?

Answer 9

Fentanyl has a much higher context-sensitive half-time than other derivatives d/t increased lipid solubility –> saturation of “inactive tissue” (fat, skeletal muscle) occurs, then offsets from inactive tissue to replace those that are metabolized

Remifentanil has a very LOW context-sensitive half-time d/t rapid metabolism via tissue/plasma esterases

Question 10

What is the analgesic dose of fentanyl?
Induction dose?
Dose as an adjunct with inhaled anesthetics?
Maintenance dosing for surgical anesthesia?
Intrathecal?
Transmucosal?
Transdermal?

Answer 10

Analgesic: 1-2 mcg/kg IV
Induction: 1.5-3 mcg/kg IV
Adjunct with volatiles: 2-20 mcg/kg
Surgical Anesthesia: 50-150 mcg/kg IV
Intrathecal: 25 mcg
Transmucosal: 5-20 mcg/kg
Transdermal: 75-100 mcg

Question 11

Fentanyl S/E’s

Answer 11

-seizure like activity
-SSEP and EEG (>30mcg/kg IV)
-Modest increase in ICP 6-9 mmHg

Question 12

Fentanyl:
E1/2 time:
Context-sensitive 1/2 time

Answer 12

E1/2 time: 3.1-6.6h
Context sensitive 1/2 time: 260 minutes

Question 13

Fentanyl:
Pulmonary first-pass?
Metabolism/metabolite
Excretion
Vd
Onset
Duration

Answer 13

75% pulmonary first-pass
CYP3A –> norfentanyl
Excretion: kidneys
Vd: LARGE (<5 mins, 80% is gone)
Onset: 30-60 seconds
Duration: 60-90 min

Question 14

Sufentanil
Pulmonary-first pass?
Protein binding?
Metabolism?
Excretion?
E1/2 time:

Answer 14

60% pulmonary first-pass
92.5% protein binding
Hepatic: CYP3A
Excretion: renal and fecal
E1/2 time: 2.2-4.6 h

Question 15

Sufentanil dosing:
Analgesia:
Induction:
Intraop:
Infusion:

Answer 15

Analgesia: 0.1-0.4 mcg/kg IV
Induction: 18.9 mcg/kg IV
Intraop: 0.3 to 1 mcg/kg IV
Infusion: 0.5 to 1 mcg/kg/hr

Question 16

Sufentanil:
E1/2 time:
Context-sensitive 1/2 time:

Answer 16

E1/2 time: 2.2-4.6 h
Context-sensitive 1/2 time: 30 minutes

Question 17

Alfentanil dosing:
laryngoscopy
Induction
Maintenance

Answer 17

Laryngoscopy: 15-30 mcg/kg
Induction: 150-300 mcg/kg
Maintenance: 25-150 mcg/kg/hr

Question 18

Alfentanil
E1/2 time
Context sensitive 1/2 time

Answer 18

E1/2 time: 1.4-1.5 hours
Context sensitive 1/2 time: 60 minutes

Question 19

Remifentanil
Peak effect
Clearance
Plasma steady-state
Excretion

Answer 19

peak effect: 30-60 seconds
clearance: 3L/min
plasma steady state: 10 minutes
Excretion: kidneys

Question 20

Remifentanil
Induction
Maintenance

Answer 20

Induction: 0.5-1 mcg/kg IV
Maintenance: 0.005 to 2 mcg/kg/min IV

Question 21

Remifentanil:
E1/2 time:
Context sensitive 1/2 time

Answer 21

E1/2 time: 0.17-0.33 h
Context sensitive 1/2 time: 4 min