Qualitative Pharmacokinetics

Question 1

Weak acids and weak bases

Answer 1

Acids can be trapped in basic compartments, bases trapped in acidic. Relates to excretion in urine, breast milk, gut, ect.

Question 2

Bioavailability

Answer 2

The percenta of oral dose that reaches systemic circulation. Decreased bioavailability is compensated for by increasing the oral dose

Question 3

First pass metabolism

Answer 3

Portal circulation brings drugs from intestine first to liver, where it can be altered before it reaches therapeutic targets

Question 4

Volume of distribution - how to calculate

Answer 4

Administer known drug concentration IV, take blood samples at timed intervals, plot concentration on a log graph, extrapolate straight line to time 0.

Question 5

Vd equation

Answer 5

= (amount administered)/(concentration at t=0)

Question 6

Lipid solubility and Vd

Answer 6

High lipid solubility = low plasma concetration = large Vd

Question 7

Binding to plasma protein and Vd

Answer 7

High binding affinity to plasma proteins = trapping of the drug in blood = small Vd

Question 8

Significance of Vd

Answer 8

Apparent volume of plasma that would have yielded the extrapolated concentration. Relates the amount of drug in the body to the concentration in the blood/plasma

Question 9

Vd = 5-10L

Answer 9

highly charged species or bound to plasma protein

Question 10

Vd = 20-40L

Answer 10

Moderately lipid soluble

Question 11

Vd = 40L

Answer 11

Lipid soluble enough to distribute to total body water

Question 12

Vd > 40L

Answer 12

Highly lipid soluble, sequestered in fat, nervous tissue and muscle

Question 13

Hepatic metabolism

Answer 13

Highly lipid soluble drugs will accumulate in hepatocytes and be acted on by CYP450 system. CNS drugs that can cross BBB will be hepatically eliminated

Question 14

Urinary excretion

Answer 14

Hydrophilic xenobiotics eliminated renally, highly polar molecules remain in filtrate unless specifically reabsorbed by carriers and transporters

Question 15

Probenecid

Answer 15

Gout medication. Kidney can normal transport some drugs against the concentration gradient into the urine. Probenecid inhibit tubular secretion of penicillins increasing and prolonging plasma concentrations

Question 16

Passive Renal Tubular Re-absorption

Answer 16

Non-ionized, lipid soluble drugs are take back up into plasma. Higher urine pH favors weak acid excretion to urine

Question 17

Biliary Excretion

Answer 17

Not well understood, can be reabsorbed in intestine leading to enterohepatic cycling. Cholestyramine used to interrupt cycling. Ezetimibe harnesses enterohepatic cycling to decrease LDL blood levels by competing with the reabsorption of cholesterol