Class #5-6 - Pharmacokinetics Flashcards
Magnitude of effect=
dynamicskineticsind. biological properties
Fist-pass metabolism=
Goes through liver from GIT before going rest of body
Can kidney excrete drugs?
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
Total body clearance (Cl)=
renal cl + liver cl + other organs Cl
C0=1? What is this concepts?
Hypothetical distribution of drug if done instantly
How many T1/2 before drug inactive?
4 half-life (93.8% drug eliminated)
First order kinetics?
Half-life independant of dose, drug metabolize at constant fraction of time.
Zero order kinetics?
A constant AMOUNT is metabolized per unit of time. Sometime drug can switch (Eg. ASA normally 3hours, but overdose = 15hours)
To achieve steady state of drug [] in therapeutic window?
> 4 half-life
Outliers?
Slow vs fast metabolizers
Loading dose?
increase dose to therapeutic range quickly, calculated with AVD. Only in ER because cannot predict if outliers?
GPCRs activation? common second messenger?
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)
Tyrosine Kinase Receptors signaling?
Binding ->dimerization of receptor -> activate tyrosine kinase and receptor subject to phosphorylation -> activate relay p+
Drug affinity, low Kd =
High affinity
Potency vs efficacy?
- Amount needed to produce effect (high potency = low dose for same effect, eg codeine and morphine) 2. Maximal effect produced by the drug
Full vs Partial agonist
max response, cannot achieve max response (lower efficacy). However if lots of spare receptors, partial agonist can become full agonist at high dose.
receptor desensitization?
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
Eg of receptor desensitization?
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.
total body water, fat% in ages difference. + liver and renal functions in ages?
infant = lots of water, little fat, low liver and renal. Elderly: little water, lots of fat, little liver/renal functions.
Change in AVD during pregnancy is?
Specific to gestTION TIME. Eg caffeine: normal half-life 3-5hours, pregnant 12-15hours.
Why change in caffeine half-life?
CYP1A2 expression decreased
PLacenta and distribution of drug?
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
Type of effect of drug on fetus?
No effect. transient. Irreversible structural malformation. Delayed effect on behaviour/reproductive functions
Major organ dev. occurs?
Early in preg.
Thalidomide?
during days 27-30 = arm defect. 30-33 = leg deffects
FASD=
Fetal alcohol spectrum disorder
Drug in breast milk?
there but smaller concentration. Except for POPS (persistent organic polluants) only way to get rid of them through breast milk.
Absorption in neonatal?
Skin more permeable, GI high pH, slower emptying, absence GI flora
Rapid increase in… enz. from first few months to 1 year?
Glucoronyl transferase, responsible for bilirubin metabolization
Why give caffeine to newborn?
Half-life 2.7-5,4 days. Because broken down into theobromine (Dx for resp. disorders) and easy to control dose.
Gray baby syndrome?
Chloramphenicol (antibacterial) w/o glucoronyl transferase cannot eliminate, causing toxicity
Absorption affected by age in geriatric?
Not in geriatric vs adult
Distribution geriatric?
Fat-soluble = increase AVD, can also accumulate. H2O soluble = decrease AVD
Metabolism geriatric?
decrease phase 1 = increase half-life, also decrease first pass = increase bioavailability. Phase 2 not impacted
Therapeutic window then… with age?
Narrower.
