pharm: pharmacokinetics 3

Question 1

What is the most common mechanism of drug metabolism?

Answer 1

Mechanism of termination of drug action

Question 2

What results from drug metabolism as a mechanism of termination of drug action?

Answer 2

More polar, more water soluble drugs

Question 3

How is renal absorption impacted by drug metabolism as a mechanism of termination of drug action?

Answer 3

Less renal absorption

Question 4

How is drug excretion impacted by drug metabolism as a mechanism of termination of drug action?

Answer 4

Increases drug excretion

Question 5

What are prodrugs as administered?

Answer 5

Inactive

Question 6

What do prodrugs become after being metabolized in the body?

Answer 6

Active

Question 7

What must drugs do to become active?

Answer 7

Drugs must be metabolized in the body to become active

Question 8

Can drug elimination occur without metabolism?

Answer 8

Yes

Question 9

Is lithium metabolized?

Answer 9

No, it is not modified by the body

Question 10

What type of drugs cannot be efficiently excreted by the kidney?

Answer 10

Small, nonpolar, hydrophobic drugs that readily cross cell membranes-> they are reabsorbed in the distal convoluted tubules

Question 11

What are the two general sets of reactions in the liver that metabolize drugs?

Answer 11

Phase I and Phase II

Question 12

What happens to the drug following phase 1?

Answer 12

Activated, unchanged or most often inactivated

Question 13

What does Phase 1 of metabolism convert?

Answer 13

Nonpolar, Lipophilic molecules into more polar and water soluble molecules

Question 14

What enzymes accompany Phase 1 of metabolism?

Answer 14

CYP/Cytochrome P450 enzymes

Question 15

What three reactions occur from Phase I to Phase II?

Answer 15

Oxidation, Reduction, Hydrolysis

Question 16

Where are CYP enzymes primarily located?

Answer 16

Liver and GI

Question 17

Can CYP enzymes exhibit genetic variability?

Answer 17

Yes

Question 18

How many CYPs metabolize drugs in humans?

Answer 18

12

Question 19

Can drugs be metabolized by multiple CYPs?

Answer 19

Yes

Question 20

What does Phase II of metabolism involve?

Answer 20

Conjugation reactions

Question 21

What type of enzyme is involved in conjugation reactions of Phase II?

Answer 21

Transferase

Question 22

What happens to the drug-conjugate size and lipophilicity during Phase II?

Answer 22

Size is increased and lipophilicity is decreased (becomes more polar)

Question 23

What happens if a transferase/system is lacking?

Answer 23

The drug does not get eliminated and can increase to toxic level

Question 24

Is the Phase II system present in neonates?

Answer 24

No, liver enzymes not fully developed, makes them susceptible to drugs metabolized in this manner

Question 25

Where are most drugs metabolized?

Answer 25

Liver

Question 26

Where do Phase I reactions occur?

Answer 26

Smooth endoplasmic reticulum

Question 27

Where do Phase II reactions occur?

Answer 27

Cytoplasm and mitochondria/cell membrane

Question 28

What is the second site of metabolism after the liver?

Answer 28

Kidneys

Question 29

What is the most common Phase I reaction?

Answer 29

Oxidation by P450 pathway

Question 30

What do CYP inducers increase?

Answer 30

The expression of P450 enzymes

Question 31

What do CYP inducers do to the plasma level of substrate drugs?

Answer 31

Reduce

Question 32

What are some examples of CYP inducers?

Answer 32

Benzopyrenes in cigarette smoke, Chronic ethanol, Barbiturates (phenobarbital), Carbamazepine, Rifampin, Phenytoin

Question 33

What type of drug is rifampin?

Answer 33

Antibiotic

Question 34

What do barbiturates (phenobarbital), carbamazepine, and phenytoin treat?

Answer 34

Seizures

Question 35

What happens to oral contraceptives when rifampin is prescribed?

Answer 35

The active drug (oral contraceptive) becomes inactive

Question 36

What happens to a prodrug (platelet inhibitor) when rifampin is prescribed?

Answer 36

Increased amount of active drug which increases the likelihood of bleeding

Question 37

What do CYP inhibitors do to the expression of P450 enzymes?

Answer 37

Decrease

Question 38

What do CYP inhibitors do to the plasma level and toxicity risk of substrate drugs?

Answer 38

Increase plasma level and increase toxicity risk

Question 39

What are some examples of CYP inhibitors?

Answer 39

Cimetidine, omeprazole, Ketoconazole, Erythromycin, Grapefruit juice

Question 40

What happens to warfarin when cimetidine is prescribed?

Answer 40

Cimetidine causes more active warfarin

Question 41

What happens to a prodrug (clopidogrel) when omeprazole is prescribed?

Answer 41

Inactive prodrug is increased, leading to more likelihood for a clot and stroke

Question 42

What is the risk associated with increased simvastatin levels?

Answer 42

Myopathy and muscle aches

Question 43

What recent change is likely responsible for increased risk of simvastatin-related muscle toxicity?

Answer 43

The patient began a grapefruit-based diet