Pharmacokinetics Ch 11

Question 1

Pharmacodynamics

Answer 1

Study of how drugs interact with their targets.

Question 2

Pharmocokinetics (acronym?)

Answer 2

Study of drug reaches its target and how it is affected along the way.
Absorption
Distribution
Metabolism
Excretion

Question 3

Oral drug absorption (3)

Answer 3

Need to survive acidic conditions of stomach and digestive enzymes.
Need to absorbed by intestinal lining and pass through pores into blood stream (polar enough to dissolve in blood but hydrophobic enough to pass through cell membrane).
Processed by liver.

Question 4

Lipinkski’s Rule of 5

Answer 4

MW<+5

Question 5

Henderson Hasselbalch equation

Answer 5

pH=pKa+log[A-]/[HA]

Question 6

logP

Answer 6

logP= log([solute]oct/[solute]water)

Question 7

logD

Answer 7

logD=log(([A-]oct/[HA]oct)/([A-]wat/[HA]wat))

Question 8

Oral Absorption of Polar drugs (3)

Answer 8

Small enough to pass between cells.
Recognized by carrier proteins.
Carried across by pinocytosis.

Question 9

Drug distribution

Speed? What can slow it down?

Answer 9

Distribution is rapid once drug is in blood stream.

Binding to plasma proteins slows because capillary cells have pores that do not let proteins cross.

Question 10

Blood brain barrier

Answer 10

Capillaries do not contain pores and are coated with fatty layer so polar drugs cannot cross.

Question 11

Phase I Drug Metabolism (3)

Answer 11

Oxidation by Cytochorome P450 enzymes.
Oxidation by Flavin Monooxygenases.
Transformation by other enzymes.

Question 12

Cyochrome P450 Enzymes

Answer 12

33 Heme containing monooygenases in 4 families. Use NADPH and O2.

Question 13

Phase II Drug Metabolism (3)

Answer 13

Conjugation reactions
Methylation
Acetylation

Question 14

Glucuronidation

Answer 14

Glucuronyltransferase adds glucuronate from UDFP glucuronate to phenol, alcohol, or carboxylic acids.

Question 15

Sulfoconjugations

Answer 15

Sulfotransferases add to phenols, alcohols, and amines.

Question 16

Amino acid conjugation

Answer 16

Adds amino acid to carboxylic acid via CoA intermediate (preceded by AMP intermediate).

Question 17

Glutathione

Answer 17

Gly-Cys-Glu added through Michael addition with thiol as nucleophile.

Question 18

First Pass Effect

Answer 18

Oral drugs pass directly into liver, so high percentage of drug is metabolized before it reaches target.

Question 19

Indinavir

Answer 19

HIV protease inhibitor

Question 20

Drug excretion (4)

Answer 20

Kidneys, Sweat, Exhalation, Bile.

Question 21

Kidney function

Answer 21

Filter blood so that drugs and metabolites enter nephrons, where nonpolar substances get reabsorbed and polar substances are retained.

Question 22

7 methods of drug administration

Answer 22

Oral, mucous membrane, topical, inhalation, injection, rectal, implant.

Question 23

Example of drug absorbed through mucous membrane

Answer 23

nitroglycerine

Question 24

5 types of injections

Answer 24

Intravernous, intramuscular, subcutaneous, intraperitoneal, intrathecal.

Question 25

Half life (3 ex)

Answer 25

Time required for drug concentration in blood stream to be reduced by 1/2.
Fentanyl (pain reliever)-45 min
Diazepam (valium)- days
Azithromycin-days

Question 26

Therapeutic window

Answer 26

Between therapeutic level and toxic level.

Question 27

4 methods of drug delivery

Answer 27

Polymer drug conjugates, antibodies, liposomes, microspheres.