Exam 1: Pharmacokinetics

Question 1

ADME

Answer 1

Absorption, Distribution, Metabolism, Excretion

Question 2

Permeation

Answer 2

• part of absorption
• different ways the drug can cross barriers
• 4 ways

Question 3

aqueous diffusion (permeation)

Answer 3

• water soluble
• larger aqueous compartments (cytosol, blood, ISF)
• aquaporins (water channels)
• diffusion by concentration gradient
• molecules can be quite large
• highly charged or bound to large carrier proteins CANNOT cross

Question 4

lipid diffusion

Answer 4

• lipid soluble (steroid drugs)
• limiting factor for drug permeation
• ## ability to move between lipid and aqueous phrases is most important for a good drug (cholesterol)

Question 5

special carriers

Answer 5

• some drugs have carrier that they bind to and then those carriers bring them into the cell and deposit them inside (think GI system)
• molecules bind to drug and move across the barriers
• active transport and facilitated diffusion

Question 6

endocytosis

Answer 6

membrane engulfment or cell’s surface membrane surrounds drug and pulls it inside (receptor mediated endocytosis, think RTKs)

Question 7

exocytosis

Answer 7

merging vesicle with membrane (drug being released)

Question 8

rational dosing

Answer 8

• goal: to achieve desired beneficial effect with minimal adverse effects
• takes into account for all the pharmacokinetic variables

Question 9

standard drug dosing

Answer 9

• based on healthy volunteers
• dose adjustments sometimes necessary due to volume of distribution (space available in the body to contain a drug) and clearance (ability of body to eliminate drug)

Question 10

volume of distribution

Answer 10

• space available in the body to contain a drug
• relates the amount of drug in the body to the concentration in the blood
• in practice: multiply Vd by target concentration
• Vd = (dose)/(initial drug concentration)
• 3 sub-definitions
• 1) concentration in blood (whole blood = 0.08 L/kg; Cb)
• 2) concentration in plasma (plasma = 0.04 L/kg; Cp)
• 3) concentration in water (unbound drug; Cu)

Question 11

clearance

Answer 11

predicts rate of elimination in relation to drug concentration; usually expressed in mg/L [CL = (rate of elimination)/(concentration)]

Question 12

first order elimination

Answer 12

• applies to most drugs
• CLEARANCE IS CONSTANT, rate of elimination caries (is dependent) with concentration

Question 13

rate of elimination

Answer 13

rate of elimination = CL x C (time)

Question 14

zero order elimination

Answer 14

• rate of elimination = CL x C
• RATE OF ELIMINATION IS CONSTANT, clearance varies with concentration
• examples: ethanol, phenytoin, salicylates, cisplatin, fluoxetine, omeprazole
• occurs when the body’s ability to eliminate a drug has reached its MAX CAPABILITY (all transporters are being used)
• as the dose and drug concentration increase, the amount of drug eliminated per hour does not increase and the fraction of drug removed declines