pharmokinetics 2

Question 1

Where do most drugs end up after absorption?

Answer 1

Systemic circulation

Question 2

what is drug distribution

Answer 2

process where drug is transferred reversibly from systemic circulation into tissues as conc inc in blood, then tissues when blood conc dec during elimination
distribution of drug into vascular, interstitial and intracellular compartments

Question 3

how does distribution occur

Answer 3

most drugs transfer via passive diffusion
across capillary walls down conc gradient
into interstitial fluid until conc of free drug molecules in interstitium is equal to plasma

Question 4

how do drugs pass from systemic circulation into tissues

Answer 4

diffusion (lipid soluble)
facilitated diffusion 
nutrients and glucose
diffusion via open ion channels (water soluble drugs, small molecules)
active transport

Question 5

what is plasma protein binding

Answer 5

drugs bind non specifically to albumin in plasma = drug protein complex
reversible and saturable
unbound or free fraction distributes
unbound portion responsible for clinical effect

Question 6

what are highly protein bound drugs

Answer 6

Warfarin
Phenytoin
Aspirin 
Thyroxine
Ibuprofen
Heparin
Furosemide

Question 7

what are the body fluid compartments

Answer 7

intracellular fluid volume 40% BW
20% BW extracellular fluid volume
interstitial fluid 80% ECF
plasma volume 20% ECF

Question 8

factors that influence drug distribution

Answer 8

Drug physicochemical properties (Lipid solubility, Water solubility)
Drug particle size
Drug protein binding
environment – blood flow, pH

Question 9

what is apparent volume of distribution

Answer 9

A concept that predicts how extensively a drug is distributed throughout body
Volume where drug distributed with concentration equal to that of plasma.
Vd=Dose (mg)/Concentration (mg/L)

Question 10

what is the volume of distribution

Answer 10

dose (mg)/ plasma concentration (mg/L)

Question 11

what does volume distribution indicate

Answer 11

level above or below that of plasma vol (2.5-3l)
above - large vol of distribution
below - little distribution, mostly remains in plasma

Question 12

what does a large Vd mean

Answer 12

administered in larger doses to achieve target concentration in plasma

Question 13

how can Vd vary

Answer 13

low <10L (warfarin - highly protein bound so stays in plasma)
mid 10-30L (gentamicin - water soluble, interstitial fluid not cells, dose on ideal BW to avoid toxicity)
>100L (Amiodarone - fat soluble drug distributes into tissues)