LG 7.4 - Pharm - PK part 2

Question 1

What is steady state?

Answer 1

when drug serum levels are no longer changing. Takes ~ 4 T1/2 - worth of time

Question 2

1. What factor determines steady state? 2. How long does it take to get to steady state?

Answer 2

1. T1/2. 2. after 4 T1/2s, serum levels are 94% of steady state. giving a loading dose (LD) can decrease time to steady state

Question 3

what’s a prodrug?

Answer 3

it’s an inactive parent drug which requires bio-activation to form an active metabolite

Question 4

List the 4 possible outcomes of drug metabolism performed by the liver.

Answer 4

1. Termination of drug action (bio-inactivation) 2. formation of active metabolite(s) from active parent drug 3. bioactivation of an active metabolite from an inactive parent drug 4. toxification: toxic metabolite formed from parent drug

Question 5

Describe Phase I metabolism.

Answer 5

involves the CYP liver enzyme system (eg, CYP 3A4, CYP 3A5) - changes highly lipophilic compound to a slightly water soluble compound

Question 6

Describe Phase II metabolism.

Answer 6

conjugation step. conjugation of a drug with glucuronic acid is the most common reaction - changes slightly water soluble compound to a very water soluble, inactive compound

Question 7

1. What’s a CYP enzyme inducer? 2. what can result from this potential drug-drug interaction?

Answer 7

1. this induces - or speeds up - the metabolism of certain drugs. 2. if this inducer if taken at the same time as certain meds, the inducer will DECREASE the effectiveness/duration of action of the other drug (affected drug may be ineffective)

Question 8

1. What’s a CYP enzyme inhibitor? 2. what can result from this potential drug-drug interaction?

Answer 8

1. This inhibits - or slows down - the metabolism of certain drugs. 2. If this inhibitor is taken at the same time as certain meds, the inhibitor will INCREASE the effect/duration of the other med (affected drug may reach toxic levels)

Question 9

Explain what’s going on in step 1 of enterohepatic Drug recycling:

Answer 9

conjugated version of drug is transferred to the gallbladder

Question 10

Eplain what’s happending in step 2 of enterohepatic drug recycling.

Answer 10

drug is transferred from the gallbladder to the intestine for excretion.

Question 11

Eplain what’s happending in step 3 of enterohepatic drug recycling.

Answer 11

While in the intestines, bacteria hydrolize bonds in the drug. This changes the next step from excretion to shuttling the drug toward recirculation in the body.

Question 12

Eplain what’s happending in step 4 of enterohepatic drug recycling.

Answer 12

the drug leaves the intestine and enters portal circulation.

Question 13

Eplain what’s happending in step 5 of enterohepatic drug recycling.

Answer 13

the drug goes from portal circulation into venous cirulation then back into systemic circulation to create drug effect once again.

Question 14

Eplain what’s happending in step 6 of enterohepatic drug recycling.

Answer 14

the drug goes from circulation to be metabolized (with conjugation) in the liver (again). Each time these 6 steps are repeated, some drug is lost to feces. The 6 steps are repeated until no drug remains.

Question 15

How is drug eliminated from kindey?

Answer 15

Parent drug and metabolites undergo filtration at glomerulus, then leave via renal tubular secretion

Question 16

How are drugs collected in the kidey for recirculation in the body?

Answer 16

Renal tubular reabsorption

Question 17

what’s “ion trapping” (aka, pH effect)?

Answer 17

therapeutically changing urine pH to alter drug ionization and lipid solubility

Example: Increase urine pH to increase secretion of aspirin in an overdose situation