Metabolism + Excretion - FORNO

Question 1

________ is everything the drug does to the body

Answer 1

Pharmacodynamics

Question 2

__________ is everything the body does to the drug after administration

Answer 2

Pharmacokinetics

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 3

What are the main effects of drug biotransformation?

Answer 3

1. Change in physicochemical properties of the drug
2. Change in pharmacologic activity

Question 4

What is the most common site of biotransformation?

Answer 4

liver

Question 5

What are examples of biotransformation?

Answer 5

1. Active drug to inactive metabolite
2. Active drug to active metabolite
3. Inactive drug to active metabolite
4. Non toxic drug to toxic metabolite

Question 6

What is bioinactivation?

Answer 6

Conversion of a parent drug to an inactive metabolite

Question 7

_________ is an enzyme that plays a key role in metabolism of drugs

Answer 7

Cytochrome P450

Question 8

What does it mean that enzymatic reactions are saturable?

Answer 8

Increasing the concentration of a drug does NOT affect reaction rate

Question 9

What occurs if drug A inhibits the enzyme for drug B?

Answer 9

Drug B will not be metabolized + remains in the body longer

• cant be eliminated as quickly

Question 10

What occurs if Drug A induces the enzyme for Drug B?

Answer 10

This induces Drug B to be metabolized and excreted faster

Question 11

What is the outcome of phase 1 biotransformation?

Answer 11

Metabolites can be more or less water soluble + may be inactive, less active, or more active than parent compound

Question 12

What drugs must go to Phase II biotransformation prior to excretion?

Answer 12

Lipophilic drugs

Question 13

Conjugation is deficient in?

Answer 13

Cats and neonates

** deficient in cats bc they lack glucuronyl transferases

Question 14

What is the goal of a drug that has gone through phase II biotransformation?

Answer 14

Drug is usually inactive, water soluble, and non toxic

Question 15

What enzymes are dogs deficient in?

Answer 15

Acetylating enzymes

Question 16

What enzymes are cats deficient in?

Answer 16

1. Glucuronyl transferases
2. Salivary amylase

** also deficient in hydroxylation and dealkylation

Question 17

Which route of drug administration has a first-pass effect?

Answer 17

Oral meds- given PO

Question 18

________ enzymes are inducible by drugs

Answer 18

microsomal

Question 19

Renal excretion is dependent on what factors?

Answer 19

1. GFR
2. Active tubular secretion
3. Passive tubular reabsorption

Sum of all 3 = total renal excretion

Question 20

How is total renal excretion measured?

Answer 20

By adding

1. GFR
2. Active tubular secretion
3. Passive tubular reabsorption

Question 21

What factors affect glomerular filtration?

Answer 21

1. Blood flow / BP
2. Molecular size (small moves fastest)
3. Molecular charge ( + charged molecules can pass and be excreted )
4. Plasma protein binding (only unbound drugs are freely filtered)

Question 22

How does degree of ionization affect passive tubular reabsorption?

Answer 22

The more ionized the drug, the less reabsorption occurs = MORE drug is excreted

Question 23

What type of drugs are excreted quicker by the kidney if pH of urine is low/acidic?

Answer 23

Weak basic drugs

Question 24

What type of drugs are excreted quicker by the kidney if pH of urine is high/alkaline?

Answer 24

Weak acidic drugs

Question 25

What factors affect passive tubular reabsorption?

Answer 25

1. Physicochemical properties of the drug - water soluble, ionized, polar drugs cant be reabsorbed and are excreted 2. Degree of ionization - more ionized = less reabsorption 3. pH of urine 4. Fluid therapy / diuretics - decreases renal absorption

Question 26

What is the 2nd most important organ for excretion of drugs?

Answer 26

Liver ** drug excreted in bile

Question 27

What is enterohepatic circulation?

Answer 27

conjugates of lipophilic compounds are excreted into bile, travel to SI where they are converted back into lipid soluble free drugs to be reabsorbed ** prolongs half life of drug

Question 28

What is first order kinetics?

Answer 28

rate of removal of a drug from plasma is proportional to the concentration present at a given time constant % of a drug is eliminated per unit time

Question 29

What is half life?

Answer 29

time required for the body to eliminate 1/2 of the drug

Question 30

After how many half lives is a drug almost completely eliminated from plasma?

Answer 30

5-6

Question 31

What is total body clearance?

Answer 31

Rate of drug elimination from the body, from all routes, relative to the conc. of drug in plasma

Question 32

Increased Vd results in ________ half life, and ________ clearance

Answer 32

Increased, decreased -stays in body longer

Question 33

Increased half life results in _________ clearance

Answer 33

Decreased

Question 34

Decreased Vd results in ________ half life

Answer 34

Decreased -eliminated from body faster

Question 35

What if the extraction ratio is 0?

Answer 35

No drug is taken out/ eliminated = decreased clearance of drug

Question 36

What if the extraction ratio is 1?

Answer 36

All the drug has been taken out / eliminated = increased clearance of drug