Pharmacokinetics

Question 1

Metabolism of etomidate

Answer 1

Hydrolysis in liver

Question 2

Metabolism of ketamine

Answer 2

CYP450 demethylation to active metabolite norketamine

Question 3

Metabolism of propofol

Answer 3

Large first pass uptake in lungs
CYP450 glucordination
Active metabolite 4-hydroxypropofol

Question 4

Does diazepam cross the placenta?

Answer 4

Yes

Question 5

Describe the metabolism of diazepam

Answer 5

Oxidative methylation to active metabolite desmethyl diazepam which is long lasting, and half as potent

Question 6

You have an elderly person that has taken a dose of diazepam, what do you expect?

Answer 6

Prolonged elimination (linear relationship with age - the older you are, the longer it takes to eliminate)

Question 7

Describe the metabolism and clearance of lorazepam

Answer 7

Conjugation with glucuronic acid

Slow liver clearance which increases DOA to 6-10 hours

Question 8

Why is midazolam painless on injection

Answer 8

Because it is water soluble with an imidazole ring

Question 9

Describe the metabolism of midazolam

Answer 9

Rapid with 2 active metabolites
1-hydroxymidazolam (1/2 potency)
This is then conjugated with glucuronic acid to be excreted
Accumulation of this metabolite is not usually a problem because metab is so rapid, but it does become a problem when pt on gtts in ICU
4-hydroxymidazolam is also active but is minimal

The rapid metabolism can be slowed buy inhibition of CYP450 enzymes

Question 10

Describe the metabolism of thiopental

Answer 10

Oxiadation in liver to active metabolite pentobarbital

Question 11

Is methohexital metabolized via oxidation or hydrolysis?

Answer 11

Oxidation

Question 12

Describe the distribution of morphine

Answer 12

It is poorly lipid soluble so only a small lounge reaches the CNS, and it does not cross the placenta, and it is protein bound

Question 13

Describe the metabolism of morphine

Answer 13

It does NOT undergo first pass in the lungs, it is rapidly metabolized in the liver via conjugation to active metab morphine - 6 - glucuronide (65x potency), and this will accumulate rapidly with impaired renal function

Question 14

Metabolism of meperidine

Answer 14

First pass in liver when given PO makes it useless
90% demethylation to normeperidine which is half as a active but long lasting and accumulation can lead to delirium (with renal dysfunction)
10% hydrolysis to meperinic acid

Question 15

Metabolism of fentanyl

Answer 15

N-dealkylation and hydroxylation

Question 16

Rank the potency of the phenylpiperidines from most to least

Answer 16

1. Sufentanil
   2/3. Fentanyl remifentanil
2. Alfentanil
3. Meperidine

Question 17

Metabolism of sufentanil

Answer 17

First pass uptake in lungs
O-demethylation = desmethyl sufentanil
N - dealkylation
Normal renal function important for elimination

Question 18

Metabolism of acetaminophen

Answer 18

Metabolized in liver into active metabolite
N-acetyl-p-benzoquinoneimine which can lead to liver failure d/t decreased glutathione

Overdose can be treated with charcoal , glutathione, and acetylcysteine

Question 19

What is the mechanism of action of scopolamine?

Answer 19

Scop is a muscarinic antagonist/anticholinergic that inhibits ach at PSNS sites in smooth muscle, CNS, and secretory glands - blocks communication to vomit center in brain

Question 20

Describe the PK similarities and differences between pancuronium and vecuronium

Answer 20

Pancuronium and vecuronium are both metabolized by deacetylation in the liver causing a 3-OH metabolite that is 80% as potent, however vec is more molecularly unstable so it has a shorter duration of action as well as a decreased potency and lipid solubility than pancuronium