Pharmacokinetics and Metabolism and Excretion

Question 1

What are the 3 places where permanently charged drugs cant cross the endothelium?

Answer 1

GI, Blood Brain Barrier (placenta), Renal tubules

Question 2

Give examples of Favored Absorption and Ion Trapping?

Answer 2

Weak acid drug is absorbed from the stomach to the Plasma. In the plasma, the acid is deprotonated and thus stays in the plasma.

A weak base will not be absorbed in the stomach because it is charged. This is ion trapping

Question 3

When would a Protein Binding Displacement drug have clinical consequence?

Answer 3

1. Displaced drug has narrow therapeutic index
2. Displacing drug is started in high does
3. Vd of the displaced drug is small
4. Response to drug occurs more rapidly that redistribution.

Question 4

What is Vd and how is it calculated?

Answer 4

It is the Volume of Distribution and is calculated by the amount of drug in body (Ab)/ [drug in plasma]

Another way to think of it is Dose= Cp * Vd

Question 5

What are the expected compartments for drugs of varying Vd?

Answer 5

3-5 L=Blood/Plasma
Highly bound to plasma proteins
12-15L= ECF highly water soluble
42= Total Body Water, drugs freely enter cells
+50L= Other compartments, highly lipid soluble

• its assumed that Vd, if given in L, is for a 70kg patient.

Question 6

How is Loading Dose calculated?

Answer 6

Cp (desired) x Vd

Question 7

Does metabolism generally make drugs more or less lipid soluble?

Answer 7

Less lipid soluble.

Question 8

What is responsible for most Phase I metabolisms? What type of reaction occurs? Are they subject to induction/inhibition reactions?

Answer 8

P450

Oxidations* (most common)
Reductions
Hydrolysis

Yes

Question 9

What is responsible for most Phase II metabolisms? What type of reaction occurs? Are they subject to induction/inhibition reactions?

Answer 9

Transferases

Conjugation

Not really

Question 10

Is there postnatal development in Phase 1 oxidations?

Answer 10

Yes

Question 11

Which type of metabolism doesn’t get “saturated” why?

Answer 11

Phase I- we probably wont run out of O2 and NADPH

Question 12

Which drugs are activated by Phase I metabolism?

Answer 12

Codine-> Morphine
Hydrocodone->delodid (hydromorphone)

Valacyclovir->acyclovir

Acetametophen->N- something toxic

Question 13

What role does glutathione conjugation play?

Answer 13

It detoxifies the toxic metabolite of Acetaminophen.

Question 14

What does CYP2E1 do?

Answer 14

Turns Acetaminophen into the toxic metabolite

Question 15

CYP3A4

Answer 15

Metabolizes most drugs

Question 16

CYP2D6

Answer 16

Major metabolizer of Opioids and antipsychotic and antidepressants (Genetic polymorphisms are present)

Question 17

CYP2C9

Answer 17

Metabolizes Warfarin

Question 18

What happens with UM (Ultra rapid metabolizers) in CYP2D6 patients?

Answer 18

Non-responsive to Antidepressants (Dad)

Codine intoxication due to rapid conversion into morphine

Question 19

What happens with PM (Poor metabolizers) in CYP2D6 patients?

Answer 19

Increased antipsychotic drug toxicity

Also decreased pain relief from codeine due to failure to metabolize to morphine. (dead baby from moms breast milk)

Question 20

Give an example why esterases are important?

Answer 20

We use them to make prodrugs like Valacyclovir. It makes them absorb better.

Question 21

Acetametophin will be metabolized by __________ in infants and ____________ in adults?

Answer 21

Sulphone transferase in infant

Glucuronyl transferase in adults (after age 3)

Question 22

Which class of drug metabolism is most likely to decline with increased age?

Answer 22

Phase I

Question 23

What do P-glycoprotein transporters do?

Answer 23

move drugs OUT of cells.

Question 24

Make card of inducers/inhibitors (see first aid for mnemonics)

Answer 24

.