test 1: lecture 9 Flashcards
how do genetics effect pharmacokinetics
ADME
absorption: different types of GI tracts= different pH
distribution: variations in genes and receptors means drugs move through at different rates
metabolism: fast or slow metabolizers from mutations in CYP
excretion: mammals vs birds different urinary tracts
with age absorption will change because of — in acid secretion and — splanchnic blood flow
decreased
decreased
with age things slow down
what happens to distribution with age
increase fat
decreased water= decreased plasma protein levels with age
how does age change metabolism
decreased metabolism in babies and old people = drugs stay in system at higher levels for longer
decreased hepatic enzyme activity, liver weight, hepatic blood flow
how does age effect excretion
decreased renal function with age= drugs stay in system longer
how does age effect 1/2 life of drugs?
overall increased 1/2 life
if lipophilic: drug stays in system longer
exception: if bound to albumin (plasma protein): drug will have shorter half life (less overall water with age)
metabolism slows down and GFR decreases= longer 1/2 life
— is rapid drug induced loss of response
tachyphylaxis
becomes resistant very quickly
what are some things that lead to decrease in response/tolerance
receptors changed, broken, degraded
2nd messangers used up
increased degradation
body tries to maintain set point (physiological adaptation)
what are some diseases or diseased states what alter absorption
gastic stasis
malabsorption
mucosal edema
what are some disease or disease states that effect distribution
- pH changes
- Alterations in plasma protein levels
- Impaired blood-brain
barrier
what are some disease or disease states that effect metabolism
- liver disease
- hypothermia
what are some disease or disease states that effect excretion
- renal failure
- proteins in tubular fluid will bind drugs
explain
drug interaction between 2 drugs leads to toxic effects
can also have beneficial effect (work together)
what is site of action drug interactions
two drugs interact when given
can be external: mix to form new drug
can be internal: change in pH of GI changes how drugs work, receptors can change, drugs can alter the genome
physiologic mechanism of drug interactions
Two drugs act at different sites to alter function may augment or offset each other
(example: effects on both the heart, arterioles, and kidneys will alter blood pressure)
One drug changes the concentration of the other
PK
Pharmacokinetic
One drug changes the effect of another
pharmacodynamics
Any drug that affects — has the potential to alter absorption profiles of any additional drugs taken by the patient
gastrointestinal function
if you slow or speed up GI will effect the absorption of other drugs
4 ways drug interaction can change PK mechanisms of distribution
alter blood flow: clearance or 1st pass effect
alter tissue uptake
alter active transport at site of action
alter plasma protein binding
explain
give a 2nd drug that binds to receptor better, causes 1st drug to be kicked off and floating in plasma, this increases the level of free drug A→can lead to toxic levels
eventually body will find a way to balance new drugs by redistribution or excretion, levels return to normal
— is well known to induce cytochrome P450 enzymes, an important mechanism for metabolism of many drugs.
Phenobarbital
how does phenobarbital effect warfarin
pheno = increases activity of CYP450
this means will decrease effectivness of warfarin, will need to increase warfarin dose
if you stop phenobarbital suddenly, can result in too high warfarin and dose will need to be lowered again
