Basic of Pharmacokinetics Flashcards Preview

Pharmacotherapeutics I > Basic of Pharmacokinetics > Flashcards

Flashcards in Basic of Pharmacokinetics Deck (40):
1

Pharmacokinetics

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

2

Absorption

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

3

Distribution

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

4

Metabolism

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

5

Elimination

Removal of the drug from the body

6

SIte of action

where a drug acts in the tissues

7

Transfer of drugs across membranes

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.

8

1st pass metabolism

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

9

Bioavailability

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

10

Drug Distribution

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

11

Volume of distribution

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

12

Protein Binding

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

13

Free drugs

Can act on target site and elicit biological response

14

Blood/brain barrier

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.

15

Primary elimination

Through a renal mechanism

16

Metabolism (biotransformation)

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

17

Prodrugs

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

18

Reactions of drug metabolism- Phase I

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.

19

Reactions of drug metabolism- Phase II

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

20

Oxidation/reduction reactions

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.

21

Conjugation

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

22

Primary mechanism of P450 induction

to induce the expression of the enzyme through increased transcription.

23

Competitive inhibition

Ketaconazole has a nitrogen moiety that binds to active site

24

Irreversible inhibition

Secobaritol alkylates and permanently inactivates P450

25

Drug-drug interactions

Drugs can substrate for P450 rxn

26

Drugs inhibit _450 activity

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

27

Drugs that induce P450 activity

Barbituates, phenytoin, steroids, isoniazid, rifampin, ETOH

28

Routes of Elimination

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

29

Half-life

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

30

1st order kinetics

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

31

Zero-order kinetics

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

32

Steady state drug levels

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.

33

Distribution in the Elderly

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

34

Metabolism in the Elderly

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

35

Effects of aging on kindeys

Lower GFR

36

Key concept in elimination

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

37

Distribution in the Elderly

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

38

Metabolism in the Elderly

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

39

Effects of aging on kindeys

Lower GFR

40

Key concept in elimination

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