Class #5-6 - Pharmacokinetics

Question 1

Magnitude of effect=

Answer 1

dynamicskineticsind. biological properties

Question 2

Fist-pass metabolism=

Answer 2

Goes through liver from GIT before going rest of body

Question 3

Can kidney excrete drugs?

Answer 3

YEs on average 1/3, 2/3 inactivated by liver. ON the 2/3 inactivated 1/3 of metabolite excreted by liver and other 1/3 by kidneys

Question 4

Total body clearance (Cl)=

Answer 4

renal cl + liver cl + other organs Cl

Question 5

C0=1? What is this concepts?

Answer 5

Hypothetical distribution of drug if done instantly

Question 6

How many T1/2 before drug inactive?

Answer 6

4 half-life (93.8% drug eliminated)

Question 7

First order kinetics?

Answer 7

Half-life independant of dose, drug metabolize at constant fraction of time.

Question 8

Zero order kinetics?

Answer 8

A constant AMOUNT is metabolized per unit of time. Sometime drug can switch (Eg. ASA normally 3hours, but overdose = 15hours)

Question 9

To achieve steady state of drug [] in therapeutic window?

Answer 9

> 4 half-life

Question 10

Outliers?

Answer 10

Slow vs fast metabolizers

Question 11

Loading dose?

Answer 11

increase dose to therapeutic range quickly, calculated with AVD. Only in ER because cannot predict if outliers?

Question 12

GPCRs activation? common second messenger?

Answer 12

exchange of GDP to GTP and dissociation of alpha subunits. cAMP formed by reaction of adenylyl cyclase, calcium another 2nd messenger (usually in mitochondria and ER)

Question 13

Tyrosine Kinase Receptors signaling?

Answer 13

Binding ->dimerization of receptor -> activate tyrosine kinase and receptor subject to phosphorylation -> activate relay p+

Question 14

Drug affinity, low Kd =

Answer 14

High affinity

Question 15

Potency vs efficacy?

Answer 15

1. Amount needed to produce effect (high potency = low dose for same effect, eg codeine and morphine) 2. Maximal effect produced by the drug

Question 16

Full vs Partial agonist

Answer 16

max response, cannot achieve max response (lower efficacy). However if lots of spare receptors, partial agonist can become full agonist at high dose.

Question 17

receptor desensitization?

Answer 17

Homologous: reduce response after prolonged agonist exposure, b/c receptor is uncoupled from its signalling cascade.
Heterologous: Act on other receptors in same cell. Also desensitization of stimulated receptor and other receptors

Question 18

Eg of receptor desensitization?

Answer 18

G protein receptor kinases phosphorylate the receptor after activation. This phosphorylation triggers “Arrestin” to desensitize the receptor for some time.
Down regulation occurs when the receptor is internalized and broken down instead of recycled.

Question 19

total body water, fat% in ages difference. + liver and renal functions in ages?

Answer 19

infant = lots of water, little fat, low liver and renal. Elderly: little water, lots of fat, little liver/renal functions.

Question 20

Change in AVD during pregnancy is?

Answer 20

Specific to gestTION TIME. Eg caffeine: normal half-life 3-5hours, pregnant 12-15hours.

Question 21

Why change in caffeine half-life?

Answer 21

CYP1A2 expression decreased

Question 22

PLacenta and distribution of drug?

Answer 22

lipid = easy, H2O soluble depend on charge. If rapidly diffusion drug = easily get into fetus. Slow diffusing drug = take time but at some point can be higher than in mother

Question 23

Type of effect of drug on fetus?

Answer 23

No effect. transient. Irreversible structural malformation. Delayed effect on behaviour/reproductive functions

Question 24

Major organ dev. occurs?

Answer 24

Early in preg.

Question 25

Thalidomide?

Answer 25

during days 27-30 = arm defect. 30-33 = leg deffects

Question 26

FASD=

Answer 26

Fetal alcohol spectrum disorder

Question 27

Drug in breast milk?

Answer 27

there but smaller concentration. Except for POPS (persistent organic polluants) only way to get rid of them through breast milk.

Question 28

Absorption in neonatal?

Answer 28

Skin more permeable, GI high pH, slower emptying, absence GI flora

Question 29

Rapid increase in… enz. from first few months to 1 year?

Answer 29

Glucoronyl transferase, responsible for bilirubin metabolization

Question 30

Why give caffeine to newborn?

Answer 30

Half-life 2.7-5,4 days. Because broken down into theobromine (Dx for resp. disorders) and easy to control dose.

Question 31

Gray baby syndrome?

Answer 31

Chloramphenicol (antibacterial) w/o glucoronyl transferase cannot eliminate, causing toxicity

Question 32

Absorption affected by age in geriatric?

Answer 32

Not in geriatric vs adult

Question 33

Distribution geriatric?

Answer 33

Fat-soluble = increase AVD, can also accumulate. H2O soluble = decrease AVD

Question 34

Metabolism geriatric?

Answer 34

decrease phase 1 = increase half-life, also decrease first pass = increase bioavailability. Phase 2 not impacted

Question 35

Therapeutic window then… with age?

Answer 35

Narrower.