principles of drug action Flashcards
what is the objective of drug therapy
provide max benefit with min harm
t/f: drug response determined by interaction within the body
true
what charge should most drugs have to be to go into a cell
neutral charge
ways that drugs can cross cell membrane (3)
- between spaces or channels
- transport system (p-glycoprotein)
- penetrate membrane directly (most drugs)
job of p-glycoprotein
protein that helps transport drug out of cell for elimination
p-glycoprotein and the liver?
transport drugs into bile for excretion
p-glycoprotein and the kidneys?
transports drugs into urine for elimination
p-glycoprotein and the placenta?
transports drugs back into maternal blood
p-glycoprotein and the brain?
transports drugs circulating blood to limit access to the brain
pharmacokinetics
study of drug movement throughout the body
absorption
movement of a drug from its site of administration into the blood
bioavailability
fraction of a drug that is absorbed into the circulation after administration
- can be different b/w generic + trade
explain how to determine bioavailability between IV and PO dose
at home –> PO levothyroxine 100mg
bioavailability IV = 1 and PO = 0.5
how much should the pt take IV at hosp?
pt had PO levothyroxine (Cynthroid) 100mg
–> routes always compared to IV
if IV ba = 1 and 100mg and PO = 0.5
then IV dose should be 50 mg
what are 6 factors that can affect absorption?
- solubility
- surface area
- ionization
- blood flow
- GI motility
- drug-drug/drug-food interactions
distribution
how drug molecule in bloodstream finds target receptor and into cells
what are 3 factors that can affect distribution?
- blood flow to tissues
- ability to leave blood
- ability to enter cells
what is tissue binding
some drugs = high affinity for specific tissues in body –> bind to tissue inappropriately –> attaches, no distribution
placental distribution vs BBB
opposite; drugs can easily pass through in the placenta, putting fetus at risk for whatever substances the mother is taking
protein binding
when drug is bound to protein = CAN’T pass through capillary walls (drug can’t do its job until unbound to protein)
- ex football player and cheerleader
high protein bound drug
- do you need higher or lower dose and why?
high affinity to protein, need HIGHER dose so that some drug molecules will able to distribute
low protein bound drug
low affinity to protein, do not necessarily need a higher dose since lower chance for the molecule to attach to protein
biotransformation/metabolism
- what chemical change occurs
how the body takes the drug molecule and transforms it into a different substance
lipophilic –> hydrophilic for excretions
does biotransformation always result in a smaller molecule?
naur
where are most drugs metabolized
liver
prodrug
- is first pass effect okay for prodrugs?
drug INACTIVE BEFORE metabolism by liver, then ACTIVATED
- first pass effect okay for prodrugs since the liver is needed to activate it
first pass effect
drug absorbed through GI tract –> splenic vein –> liver metabolize –> systemic circulation –> decreased amount of drug is available for the intended site
- only okay for prodrugs
t/f: drugs with high pass rates are given PO or G tube
FALSE
- given topical or IV to bypass liver metabolism
what are 7 factors affecting metabolism?
- age
- pregnancy
- drug metabolizing enzymes (P450)
- competition between drugs
- nutritional status
- disease
- genetics
excretion
how body gets rid of drug molecule
what are 6 ways the body excretes drugs
- urine
- bile
- expired air
- breast milk
- sweat
- saliva
what are 4 factors that affect excretion?
- renal function
- pH dependent ionization
- competition for active tubular transport
- age
bile circulation (vicious cycle)
- what does this mean for the drug?
drug molecule gets absorbed in portal circulation and excreted into bile –> collecting in gall bladder –> returns to intestine through common bile duct and cycle continues
- drug has increased half life and prolonged duration of action
p-450 system
- what is the most common isozyme
enzymes (CYPs) in liver that helps METABOLISM, each enzyme as specific drug or food to metabolize
- most common = CYP3a4
what does the p-450 system determine
determines the SPEED at which drug is metabolized where we can start to see drug interaction
- some drugs induce or inhibit P450
drug substrates
drugs metabolized by CYP enzyme
drug enzyme inhibitors
drug inhibits action of CYP isoenzymes = contribute to toxic levels (bc no metabolizing drug)
enzyme inducers
accelerate metabolism action of specific enzyme = drug level decrease fast
_____ population’s P450 system has not been developed
infant
_____ population’s P450 system has decreased and reduced action
elderly
dangers of eating grapefruit while taking drugs
grapefruit can inhibit CYP3a4 = inhibit metabolism of drugs = risk of toxicity
what are 4 variables that influence dose of drug
- maintenance and loading dose
- blood concentration
- potency
- efficacy
maintenance vs loading dose
maintenance: daily dose
loading dose: larger than usual dose to reach therapeutic effect faster
why does blood concentration determine drug dose
helps determine if dose is in therapeutic range, toxic, or subtherapeutic
potency
amount of drug that must be given to produce particular response (DOSE NEEDED TO PROD EFFECTS)
efficacy
how well a drug produces its desired effect
adverse response vs side effect
adverse response: unexpected or unintended response
side effect: unavoidable secondary drug effect produced at therapeutic doses, usually predictable
cumulative effects
- example
rate of admin exceeds rate of biotransformation and elimination
ex. chemotherapy can accumulate in body
idiosyncratic response
- ex?
what happened to patient is OPPOSITE than what is expected to happen
- benadryl supposed to make you drowsy –> makes some ppl wide awake
anaphylactic reaction
more severe allergic reaction that impairs breathing and circulation
iatrogenic response
due to physician or treatment –> given too much drug –> toxicity
pharmacodynamics
what the DRUG is doing to the BODY, how the drug effects the body
how do drugs create an effect
attach to a receptor
agonist
stimulates a cell (turn ON)
antagonist
blocks a cell (turn OFF), prevents another chemical from attaching and causing an effect
competitive antagonist
- ex?
can be overcome if increasing the dose of the agonist; can fall off and another chemical can attach and turn back ON
- ex. naloxone and opioids
non competitive antagonist
- ex?
irreversibly binds until cell dies
- ex. aspirin prevents platelets from being sticky
chemical antagonist
- ex?
receptorless drug; doesn’t sit on receptor but instead attaches to target cell to change its shape to prevent it from attaching to a receptor
- ex. protamine sulfate: sits on heparin and reverses its action
selectivity/selective toxicity (and what does this have to do with receptors?
ability of a drug to injure a target cell/organism without injuring other cells
(more receptors drug can sit on = more side effects = less selectivity)
t/f: when a drug has narrow therapeutic range, there is a higher risk for toxicity OR for drug to not work
true
half life
- what does this determine
how long before half of a drug is removed from the body = DETERMINES DOSING INTERVAL
what determines the dosing interval for a drug
half life
what route to admin short half life meds?
continuous or IV (EPI)
steady state/plateau
point where amount of drug being admin and amount of drug being eliminated balance off and are equal in which increasing dose has no effect
what is measured once steady state is achieved
full pharmacotherapeutic response of drug dose
it takes ____ half lives to reach steady state and ____ half lives after quitting cold turnkey to be fully eliminated
4-5
drug interactions
change in magnitude or duration of a response to one drug in presence of another a drug (increase or decreased response)
additive effects
- ex?
drug a (1) + drug b (1) = 2; drugs that if put together, give better effect
- tylenol + codeine
synergist effects
- ex?
drug a (1) + drug b (1) = 3; drugs that if put together, give more enhanced effect
- analopril (ace inhibitor) + HCTZ (diuretic) - lower BP
potentiation
drug a (1/2) + drug b (1) = 2; give one drug to help another drug work
antagonism
- ex?
drug a (1) + drug b(1) = 0; admin drugs together will cancel any effect, one drug blocks another
- ex: Narcan blocks morphine
