Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

• Absorption
• Distribution
• Metabolism
• Excretion

Question 2

Pharmacodynamics

Answer 2

• Drug-receptor interaction
• Patient’s functional state
• Placebo effects

Question 3

Factors affecting drug absorption

Answer 3

• rate of dissolution
• surface area
• blood flow
• lipid solubility
• pH partitioning

Question 4

3 ways for drugs to cross the cell membrane

Answer 4

• facilitated diffusion through channels and pores (rare)
• active transport system (requires energy, saturable)
• direct penetration of the membrane = simple diffusion

Question 5

Polar drugs have either:

Answer 5

• a fixed charge
• no net charge but charge separation
  (are more readily dissolved in polar solvents. Do not dissolve in and cannot readily cross cell membranes)

Question 6

Nonpolar drugs

Answer 6

• readily dissolve in nonpolar solvents

- readily cross cell membranes

Question 7

pKa

Answer 7

pH where exactly one half of weak acid is ionized

Question 8

Weak acids and bases can only cross membranes in their _______ form

Answer 8

unionized

Question 9

Ka

Answer 9

rate constant for absorption

Question 10

S

Answer 10

salt factor

- drugs often administered as their salt, but only parent compound is measured

Question 11

F

Answer 11

bioavailability, fraction of drug that reaches the bloodstream

Question 12

Amount absorbed equation

Answer 12

S x F x Dose

Question 13

F equation

Answer 13

AUC(oral) / AUC(iv)

Question 14

Factors affecting drug distribution

Answer 14

• ability of drugs to enter the cells
• blood flow to tissues
• ability of drugs to exit the vascular system

Question 15

Protein binding of drugs

Answer 15

• get partial retention of drugs in vasculature
• there’s a finite number of protein binding sites in the plasma. because of this, addition of new drug can displace bound protein
• of concern if drug has small therapeutic window

Question 16

Blood-Brain Barrier

Answer 16

barrier to ionized or polar drugs unless they have a transporter

Question 17

Concentration in Plasma (Cp) Equation

Answer 17

S x F x Dose / Vd

Vd = volume of distribution

Question 18

Vd Equation

Answer 18

Amount of Drug in body / Plasma concentration

Question 19

Sites of Peripheral Drug Concentration

Answer 19

• fat (lipid soluble)
• tissue
• bone (calcium rich regions)
• transcellular reservoirs (GI tract for drugs slowly absorbed or undergoing enterohepatic circulation)

Question 20

Primary site of biotransformation

Answer 20

• liver

Question 21

Drug metabolism

Answer 21

• may activate a pro-drug, but primarily inactivates drugs
• metabolites may be more or less active and have a longer or shorter half-life
• crucial for the renal elimination of lipophilic drugs, which must be made more polar so they can be trapped in the renal tubular fluid

Question 22

Secondary Sites/Organs of Drug Metabolism

Answer 22

• kidney proximal tubules
• lungs (type II cells)
• intestines
• testes (Sertoli cells)
• skin epithelial cells
• brain
• plasma

Question 23

Biotransformation

Answer 23

• types of drug metabolism

Question 24

Phase I metabolism

Answer 24

Oxidation, reduction, hydrolysis

Question 25

Phase II metabolism

Answer 25

conjugation

Question 26

Phase I biotransformation

Answer 26

• products are usually more polar metabolites (from unmaking or introducing a functional group)
• oxidative processes often involve enzymes located in the SER

Question 27

CYP P-450 inducers

Answer 27

• increase level of the enzyme and speeds up metabolism
• phenobarbitol
• carbamazepine

Question 28

CYP P-450 inhibitors

Answer 28

• inhibit enzyme and slows metabolism
• can lead to toxic level
• erythromycin
• ketoconzaole

Question 29

Grapefruit juice

Answer 29

• inhibitor of CYP3A4 enzyme

- inhibition in the intestinal epithelial cells increases the bioavailability of other drugs metabolized by the enzyme

Question 30

Phase II Biotransformation

Answer 30

• synthesis reactions

Question 31

Phase II - conjugation

Answer 31

• usually makes drugs more water soluble and more excretable since the molecule added is highly polar
• glucoronidation
• sulfanation

Question 32

Glucaronidation

Answer 32

• major route of metabolism for drugs and endogenous compounds (steroids, bilurubin)
• occurs in ER
• inducible

Question 33

Sulfanation

Answer 33

• another major route of drug metabolism

- occurs in cytoplasm

Question 34

Phase II - acetylation and methylation

Answer 34

• typically makes drugs less water soluble

- addition of these groups by transferases tends to reduce drug activity; inactivates drug

Question 35

First-Pass Metabolism

Answer 35

• can greatly decrease the bioavailability of orally administered drugs

Question 36

Drug Elimination

Answer 36

• renal route of drug excretion (major)

- nonrenal routes of drug excretion (bile, sweat, breath, breast milk)

Question 37

Steps in Renal Drug Excretion

Answer 37

• glomerular filtration: small drugs
• passive tubular reabsorption: lipid soluble drugs, unionized weak acids and bases
• active tubular secretion: protein-bound drugs

Question 38

Factors that modify renal drug excretion

Answer 38

• pH dependent ionization
• competition for active tubular transport
• age: GFR falls as we age

Question 39

Excretion Rate

Answer 39

• mass eliminated per unit time

- increases as plasma concentration increases in first order kinetics

Question 40

Clearance

Answer 40

• the plasma volume from which all of the solute is removed per unit time
• with first order kinetics, remains constance as plasma concentrations change

Question 41

Total Clearance

Answer 41

renal clearance + hepatic clearance + other clearance