Lec 8

Question 1

The three major routes of elimination (clearance) are :

Answer 1

• Hepatic metabolism.
• Biliary elimination.
• Urinary elimination.

Question 2

elimination processes decrease the plasma concentration exponentially . (T/F) ?

Answer 2

T

Question 3

estimates the amount of drug cleared from the body per unit of time is called ?

Answer 3

Clearance (CL)

Question 4

Total CL calculated as follows

Answer 4

CL= 0.7*Vd/ t1/2

Question 5

Most drugs are eliminated according to zero-order kinetics . (T/F) ?

Answer 5

F—>( first-order kinetics)

Question 6

aspirin in high doses, are eliminated according to ?

Answer 6

zero-order or nonlinear kinetics

Question 7

Metabolism leads to production of products with ?

Answer 7

increased polarity, which allows the drug to be eliminated

Question 8

the rate of drug metabolism and elimination is directly proportional to the concentration of free drug . This statement describe?

Answer 8

First-order kinetics (linear kinetics)

Question 9

Constant fraction of drug is metabolized per unit of time (that is, with each half-life, the concentration decreases by 50%). (T/F) ?

Answer 9

T

Question 10

With a few drugs the doses are very large such as :

Answer 10

● Aspirin.
● Ethanol.
● Phenytoin.

Question 11

In the zero-order kinetics , the rate of drug metabolism = ?

Answer 11

Vmax

Question 12

The enzyme is saturated by a high free drug concentration, and the rate of metabolism remains constant over time . This statement describe?

Answer 12

Zero-order kinetics (nonlinear kinetics)

Question 13

The rate of elimination is constant and does not depend on the drug concentration in zero-order kinetics . (T/F) ?

Answer 13

T

Question 14

The kidney cannot efficiently eliminate lipophilic drugs that readily cross cell membranes and are reabsorbed in the distal convoluted tubules. (T/F) ?

Answer 14

T

Question 15

Lipid-soluble agents are first metabolized into more polar (hydrophilic) substances in the liver via two general sets of reactions mention them :

Answer 15

phase I and phase II

Question 16

The function of Phase I Reactions is ?

Answer 16

Convert lipophilic drugs into more polar molecules by introducing or unmasking a polar functional group, such as –OH or –NH2.

Question 17

Phase I Reactions Involve?

Answer 17

reduction, oxidation, or hydrolysis.

Question 18

Phase I Reactions can’t increase, decrease, or have no effect on
pharmacologic activity. (T/F) .

Answer 18

F —>(May increase, decrease, or have no effect on pharmacologic activity) .

Question 19

Phase I reaction have two forms, mention them:

Answer 19

1. Involves P450 system
2. Does not involve P450 system

Question 20

The phase I reactions most frequently involved in drug metabolism are catalyzed by ?

Answer 20

the cytochrome P450 system (also called microsomal mixed-function oxidases).

Question 21

The P450 system is important for:

Answer 21

● Metabolism of many endogenous compounds (such as steroids, lipids)
● For the biotransformation of exogenous substances
(xenobiotics).

Question 22

Why there are many different P450 isoforms ?

Answer 22

Because there are many different genes that encode multiple enzymes

Question 23

Four isozymes are responsible for the vast of P450-catalyzed reactions. They are:

Answer 23

• CYP3A4/5.
• CYP2D6.
• CYP2C8/9.
• CYP1A2.

Question 24

CYP2D6, in particular, has been shown to exhibit

Answer 24

genetic polymorphism

Question 25

CYP2D6 mutations result in very low capacities to metabolize substrates. (T/F) ?

Answer 25

True

Question 26

Clopidogrel is a prodrug that can be active metabolite through?

Answer 26

CYP2C19

Question 27

patients who are poor CYP2C19 metabolizers have a higher incidence of ?

Answer 27

Cardiovascular events (for example, stroke or myocardial infarction).

Question 28

Some individuals obtain no benefit from the opioid analgesic codeine, because ?

Answer 28

they lack the CYP2D6 enzyme

Question 29

Similar polymorphisms have been characterized for the CYP2C subfamily of isozymes . (T/F) ?

Answer 29

T

Question 30

chemicals not normally produced or expected to be present in the body, for example, drugs or environmental pollutants is called ?

Answer 30

Xenobiotics

Question 31

Xenobiotics may induce the activity of these enzymes . (T/F) ?

Answer 31

T

Question 32

The functions of these drugs( Phenobarbital, rifampin, and carbamazepine) are ?

Answer 32

1. inc. CYP isozymes synthesis 2. inc. some drugs metabolism 3. reduced effect

Question 33

Consequences of increased drug metabolism include:

Answer 33

1. Decreased Plasma Drug Concentrations. 2. Decreased drug activity if the metabolite is inactive. 3. Increased drug activity if the metabolite is active. 4. Decreased therapeutic drug effect.

Question 34

The most common form of inhibition is through?

Answer 34

competition for the same isozyme which leads to serious adverse events

Question 35

The effect of Omeprazole is .

Answer 35

inhibits three of the CYP isozymes responsible for warfarin metabolism —> accumulation Of warfarin —> increase anticoagulant effect—> bleeding

Question 36

Mention the inhibitors drugs :

Answer 36

1. Omeprazole 2. erythromycin 3. ketoconazole 4. ritonavir

Question 37

Grapefruit juice inhibits?

Answer 37

CYP3A4

Question 38

Grapefruit juice inhibits CYP3A4 which leads to :

Answer 38

higher conc. Of nifedipine, clarithromycin, and simvastatin

Question 39

Give me examples about phase I reactions that not involving the P450 system:

Answer 39

•Amine Oxidation (Oxidation of Catecholamines or Histamine) •Alcohol Dehydrogenation (Ethanol oxidation) •Esterases (metabolism of Aspirin in the liver) •Hydrolysis (Procaine).

Question 40

phase II reactions consists of ?

Answer 40

conjugation reactions

Question 41

We have water-soluble compounds that are often therapeutically inactive , mention them:

Answer 41

((glucuronic acid )), sulfuric acid, acetic acid, or an amino acid .

Question 42

notable exception is morphine-6-glucuronide, which is less potent than morphine . (T/F) ?

Answer 42

F—> (more)

Question 43

Drugs already possessing an ?

Answer 43

–OH, –NH2, or –COOH group

Question 44

These group may enter phase II directly and become conjugated without prior phase I metabolism. (T/F) ?

Answer 44

T

Question 45

The highly polar drug conjugates are then excreted by ?

Answer 45

kidney or in bile