Handout objectives Metabolism Caldwell

Question 1

List three organs, other than the liver, that also contribute to systemic drug metabolism.

Answer 1

Kidney lungs GI Skin

Question 2

Give the two general categories of drug metabolism reactions.

Answer 2

phase I : redox, deaminate, hydrolysis

phase II: conjugation

Question 3

Describe the main function of conjugation/hydrolysis metabolic reactions.

Answer 3

hydrolysis attempts to polarize the drug while conjugation adds bulky polar groups, all of which neutralizes the drug action and increases it’s solubility

Question 4

Give the abbreviations for the three cytochrome 450s isoforms that metabolize the most drugs.

Answer 4

3A4 > 2C9 > 1A2

Question 5

Describe metabolic enzyme inducers and inhibitors and analyze how they influence drug interactions.

Answer 5

Inducers: increase or activates the enzyme which in turn will decrease the effect/duration of the drug/molecule it metabolizes so it will need to be given at a higher doseinhibitors: decreases the activity of the enzyme –> will require a lower dose/longer dose schedule of the drug it effects otherwise may reach toxic amts

Question 6

Describe three factors that increase drug excretion rates.

Answer 6

RBF GFR Plasma protein binding

Question 7

Describe the pH of renal proximal tubular fluid and how this affects drugs of a certain pH.

Answer 7

Renal lumen is acidic –> traps weak basesweak acids can be trapped is renal lumen is alkalinized (sodium bicarb admin)

Question 8

Describe the difference between first- and zero-order kinetics and explain what excretory function needs to change to go from first- to zero-order.

Answer 8

first order excretion-> amt excreted is by % of drug for each half life, most drugs are first order

zero order excretion-> amt excreted is set amount per half life –> clearance mechanisms are saturated

1’ -> 0’ = too high of a concentration than clearance can handle
0’ -> 1’ = concentrations reach below clearance maximum rate

Question 9

Apply the equation appropriate in the special case where the body can be modeled as a single compartment with a volume that is equivalent to the volume of distribution to a clinical scenario

Answer 9

half life = .7*Vd/CL –> used for drug elimination, Vd does not actually represent real total body volume