Basic of Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

How drugs get absorbed, to its receptors, and how long it stays there

Question 2

Absorption

Answer 2

The process by which a drug leaves its site of administration and reaches the blood stream

Question 3

Distribution

Answer 3

Drug leaves the blood stream and enters the interstitial and/ or cellular fluid

Question 4

Metabolism

Answer 4

The alteration of the chemical structure of a drug by an enzyme

Question 5

Elimination

Answer 5

Removal of the drug from the body

Question 6

SIte of action

Answer 6

where a drug acts in the tissues

Question 7

Transfer of drugs across membranes

Answer 7

Passive process-diffusion along a concentration gradient by virtue of its solubility in the lipid bilayer.
Carrier-mediated membrane transport- active transport which is energy dependent, against a electrochemical gradient.
Facilitated diffusion requires no energy, down a gradient, and is carrier mediated.

Question 8

1st pass metabolism

Answer 8

Due to portal circulation due to the blood going straight from the portal to the liver. This inactivates some drugs.

Question 9

Bioavailability

Answer 9

Fraction of administered drug that reaches systemic circulation following administration by any route.

Question 10

Drug Distribution

Answer 10

Based on blood flow, capillary permeability, and drug structure.

Question 11

Volume of distribution

Answer 11

drugs with large volumes of distribution may require higher initial doses to establish a therapeutic plasma concentration

Question 12

Protein Binding

Answer 12

drug binds to protein such as albumin (acidic drugs) or alpha1-acid glycoprotein (basic drugs) and are pharmacologically inactive when bound.

Question 13

Free drugs

Answer 13

Can act on target site and elicit biological response

Question 14

Blood/brain barrier

Answer 14

Decreased permeability to water-soluable or ionized molecules. Lipid-soluble substances diffused easily. Water-soluble drugs may be used purposely when it is desirable to exclude effects on the brain. The intrathecal route of administration avoids the blood brain barrier.

Question 15

Primary elimination

Answer 15

Through a renal mechanism

Question 16

Metabolism (biotransformation)

Answer 16

refers to the disappearance of a drug when it is changed chemically into another compound.

Question 17

Prodrugs

Answer 17

Inactive or less active to promote absorption. Activated by metabolism.

Question 18

Reactions of drug metabolism- Phase I

Answer 18

Cytochrome P450 System. P450 isozymes located in most cells but mainly liver and intestinal tract. Oxidation, reduction, oxygentation, dealkylation, and hydrolysis. Primarily CYP1, CYP2, CYP3 families.

Question 19

Reactions of drug metabolism- Phase II

Answer 19

Conjugation with 2nd endogenous substrate. Glucuronidation, sulfation, glutathione conjugation, acetylation, methylation, and glycine conjugation.

Question 20

Oxidation/reduction reactions

Answer 20

Primarily P-450 dependent oxidation (95%). Non-P450 pathways ie alcohol dehydrogenase. Monoamine oxidase (MAO) oxidation of amino containing compounds such as catecholamines and tyramine.

Question 21

Conjugation

Answer 21

Virtually all conjugated products are pharmacologically inactive. Neonates have not fully developed this ability.

Question 22

Primary mechanism of P450 induction

Answer 22

to induce the expression of the enzyme through increased transcription.

Question 23

Competitive inhibition

Answer 23

Ketaconazole has a nitrogen moiety that binds to active site

Question 24

Irreversible inhibition

Answer 24

Secobaritol alkylates and permanently inactivates P450

Question 25

Drug-drug interactions

Answer 25

Drugs can substrate for P450 rxn

Question 26

Drugs inhibit _450 activity

Answer 26

Cimetidine, ciprofloxacin, erythromycin, ketoconazole, OCPs, quinidine, ETOH

Question 27

Drugs that induce P450 activity

Answer 27

Barbituates, phenytoin, steroids, isoniazid, rifampin, ETOH

Question 28

Routes of Elimination

Answer 28

Biliary secretion and enterohepatic cycling, exhalation, sweat, and secretion into breast milk

Question 29

Half-life

Answer 29

the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%

Question 30

1st order kinetics

Answer 30

Drugs catalyzed by enzymes and follows Michaelis-Menten kinetics. The rate of metabolism is directly proportional to the concentration of free drug.

Question 31

Zero-order kinetics

Answer 31

Non-linear kinetics where a constant amount of drug is metabolized per unit time.

Question 32

Steady state drug levels

Answer 32

when input=output. Influence of the rate of drug infusion on the steady state are plasma concentration of drug and infusion rate, clearance of drug and volume of distribution. Time required to see steady state drug concentration is 4-5 half lives.

Question 33

Distribution in the Elderly

Answer 33

Serum albumin levels are not altered in the majority of the elderly in the absence of chronic disease or severe malnutrition.

Question 34

Metabolism in the Elderly

Answer 34

Phase II is preferred route of administration due to decreased metabolism in the elderly

Question 35

Effects of aging on kindeys

Answer 35

Lower GFR

Question 36

Key concept in elimination

Answer 36

BUN and serum creatinine may not accurately reflect true renal function in the elderly.

Question 37

Distribution in the Elderly

Answer 37

Serum albumin levels are not altered in the majority of the elderly in the absence of chronic disease or severe malnutrition.

Question 38

Metabolism in the Elderly

Answer 38

Phase II is preferred route of administration due to decreased metabolism in the elderly

Question 39

Effects of aging on kindeys

Answer 39

Lower GFR

Question 40

Key concept in elimination

Answer 40

BUN and serum creatinine may not accurately reflect true renal function in the elderly.