Pharm Principles (325E1) Flashcards
3 phases of drug action
every drug every time
1: pharmaceutic (only for oral)
2: pharmacokinetic (iv drugs enter here)
3: pharmacodynamic
Phases of drug action: pharmaceutic (1)
drug dissolves to be used and absorbed in blood and body (dissolution) all oral drugs and only occurs w/ oral drugs
Phases of drug action: pharmacokinetic (2)
drug moving through the body and what the body does to the body (4 processes: absorption, distribution, metabolism, excretion)
Phases of drug action: pharmacodynamic
what the drug does to the body (MOA, intended effect, therapeutic action)
pharmacokinetic (2): absorption
the drug goes into the small intestines and then into the blood
pharmacokinetic (2): distribution
drug has already been absorbed into the blood and now it leaves the blood stream and goes to the site of action and exerts it effort
pharmacokinetic (2): metabolism / biotransformation
after the drug has been excreted, it is broken down by liver to go from lipid soluble to water soluble so it can be removed from the body method by which drugs are inactivated
pharmacokinetic (2): excretion
kidneys excrete water soluble form of drug (some drugs can be excretede from liver)
drugs must have what type of solubility to pass through the cellular membrane
lipid soluble (water soluble need a transport mechanism to cross)
if we give an drug PO/orally, what does it have to go through
first pass effect
what drugs are 100% bioavailable
IV drugs (PO drugs have a varying of
PO meds bio availability
the amount of drug left after the first pass effect (ex: if first pass is 20%, then the drugs bio avail is 80%)
when would you expect to see a high first pass %
if a drug is taken in a high amount (dose) or is taken often
high first pass % would give what type of bio availability %
low
the first pass effect alters
the amount of a drug that is absorbed
first pass effect
PO meds that are absorbed in the SI have to go through the liver to be turned into its active form before they can enter circulation and this determines their bio availability
routes of absorption (ROA)
enteral
parenteral
topical
enteric coated (EC) meds
intended to break down in the small intestine and not the stomach (still goes through first pass)
ROA: enteral
by way of the GI tract (oral/gastric mucosa, SI, rectum aka po meds & rectal)
PO meds break down starts in the “” and are absorbed in the “” and it does or does not go through first pass?
stomach ; small intestine ; does
what routes of enteral meds do not go through first pass and why
SL, buccal and rectal bc all sites contain highly vascularized tissue
why can you not make a PO drug rectal
no first pass effect due to the bio availability so it by passes the liver
ROA: parenteral
SQ, IM, IV, intrathecal (into spinal canal), epidural (space around the spinal cord)
do parenteral drugs go through first pass effect
no
what route of parental drug is fastest
IV bc there are no barriers to absorption (they are often irreversible)
ROA: topical (transdermal)
application of meds to body surfaces, has a slower onset & more prolonged interaction
do topical drugs go through first pass effect
“not concerned with first pass effect because it will act very localized”
where does the best drug distribution occur
in areas that are highly vascularized w/ good blood flow (decreased blood flow = decreased distribution)
condition that decrease blood flow
peripheral vascular disease, abscesses, tumors
blood brain barrior
cells in the capillary wall in the brain with very tight junctions that prevent drug passages (prevents drugs from going to the brain as a preventive mechanism)
what drugs can’t pass the blood brain barrier
only drugs that have transport systems or are “extremely” lipid soluble
what drugs can pass the blood brain barrier
alcohol, glucose (the brains source of energy)
what is a main consideration when giving drugs to infants
the blood brain barrier is not fully developed so more drugs can pass through
protein binding effect
temporary storage of drug molecule that allows drug to be available for a longer period of time, drugs bind to albumin but can rapidly be unbound
what type of drug, bounded or unbounded, is considered active and free exert effects
unbound (free)
what is the goal of protein binding
maintain a steady free drug concentration “steady state”
what affects protein binding
the amount of protein in the blood
what is the primary plasma protein
albumin (it circulates constantly)
hypo albuminemia
malnutrition or liver disease more free drug is available for distribution to tissue site leading to possibility of overdose and drug toxicity
example of protein binding: warfarin/coumadin
this is a blood thinner that is 97-99% protein bound so if a pt has low albumin a person is at greater risk for bleeding due to higher effect of drug exerted
besides low albumin, what else is a risk factor for toxicity of protein bound drugs
if a person is taking multiple protein bound drugs at the same time bc all the drugs are fighting for the albumin in the body
a drug goes through metabolism (biotransformed) and is inactivated, what is it now called
metabolite
what is the major site for drug metabolism
the liver by cytochrome P-450 enzymes
what organ(s) failure can lead to drug toxicity
the liver bc they don’t get metabolised, the kidneys bc the drug doesn’t get excreted
how many drugs use the CYP450 system
about 1/2 of all drugs ; since so many use it, it creates drug - drug interactions
clinical significance of CYP450 inhibitor
can be a substrate, inducer or inhibitor
if a drug uses CYP450 system as a substrates
the drug uses the system for metabolism (it initiates the drug)
if a drug uses CYP450 system as an inducer
the system increases the breakdown and elimination of the drug to lower the drugs therapeutic effect
if a drug uses CYP450 system as an inhibitor
the system decreases the breakdown and elimination of the drug to increase the amount of drug in the body and increase the therapeutic effect risk for toxicity
example of CYP450 inhibitor
grapefruit -> drinking or eating grapefruit with a CYP450 drug increases the amount of the drug in the body leading to toxicity
teaching point for grapefruit consumption and medications
don’t take medications w/ grapefruit juice and avoid eating grapefruit or drinking it for 2-4 hours after taking me
what is the major site of excretion
the kidney through gglomerular filtration, tubular secretion, and tubular reabsorption all need to be working for the drug to be excreted
reabsorption from the kidneys
some drugs are reabsorbed through the kidney tubules, if low amounts of a drug is reabsorbed, need high dose to maintain levels
what are the renal labs
BUN, creatinine, GFR (main one)
what does half life determine
dosing of a drug and how often it should be given
what process from phase 2 does half life effect
elimination (it takes 5 half lives for 97% of a drug to be eliminated)
serum half life (T 1/2)
the time required for the serum concentration of a drug to decrease by 50%
example for T 1/2: if half life is 1 week, how long will it take for the drug to be gone from the body
5 weeks
how many half livees for a “steady state” to occur
4-5
goal of steady state
when intake of a drug is equal to the amount of drug metabolized and excreted (the state when the BP meds will have BP always under control)
around the clock dosing (ATC)
goal is to maintain 50% concentration in the body (how we treat pain and dose antibiotics)
drug onset
time it takes for drug to elicit therapeutic response (latent period)
drug peak
time it takes for drug to reach its maximum therapeutic effect (when 10mg of morphine feels like 10mg of morphine)
drug duration
time drug concentration is sufficient to elicit a therapeutic response (consistent 5mg)
how do drug create a response in phase 3
increase, decrease, replace, inhibit, destroy, protect, or irritate
what are non desired effects of a drug
side effects (ex: metaproterenol is a broncho dilator so it dilates the bronchial passage but it also increases HR & palpitations beyond normal range)
receptors
proteins located on cell surface that are chemicals (hormones or neurotransmitters) in the body that interact with drugs to produce effects (creates drug receptor complex)
what does the drug receptor complex initiate
a physiochemical reaction by means of agonist (stimulates) or antagonist (inhibits)
agonist
a drug that has the ability to initiate a desired therapeutic effect by binding to a receptor
antagonsit
a drug that produces it action not be stimulating receptors but by preventing or blocking or inhibiting other natural substances (ligands) from binding and causing a response
do all drugs responses involve receptors
no, some drugs act through simple physical or chemical interactions with small molecules (ex: antacids work by neutralizing gastric acidity through direct chemical interaction)
therapeutic index
the measure of relative safety of a drug
narrow therapeutic index (NTI)
a ratio of lowest concentration at which clinical toxicity commonly occurs (if safe range is 10, toxic at 10.1)
black box warning
required by FDA for drugs that are especially dangerous (the strongest safety warning a drug can carry and still remain on the market)
examples of NTI drugs
theophyllin, digoxin, phenobarital, lithium, coumadin
where must the black box warning appear prominently
on the package insert, product label and any magazine or advertising
med errors are a major cause of what
morbidity and mortality
high alert medications
most likely to cause serious harm and death
examples of high alert meds
insulin, heparin, opioids, IV KCL, neuromuscular blocking agents, chemo drugs
what are the types of drug interactions
drug - drug (most concerning w/ NTI)
drug - food
drug - herb
drug - disease
how to minimize drug interactions
lower # of drugs a person is on, reconcile meds, monitor
drug interactions that increase therapeutic effect: additive effects
2 drugs taken w/ similar MOA (they become stronger together)
drug interactions that increase therapeutic effect: synergism/potentiation
2 drugs w/ different MOA but result in a combined drug effect greater than that of either drug alone (still will become stronger together)
drug interactions that increase therapeutic effect: activation
activation of drug - metabolizing enzymes in the liver which decreases metabolism rate of the drug
drug interactions that increase therapeutic effect: displacement
displacement of one drug from plasma protein binding sties by a second drug which increases effect of displaced drug
drug interactions that decrease therapeutic effect: antidote
drug given to a antagonize (stop) the toxic effects of another drug
drug interactions that decrease therapeutic effect: decrease intestinal absorption
applied for PO meds bc some people cannot break down for effect
drug interactions that decrease therapeutic effect: activation
activation of drug metabolizing enzymes in the liver -> enzymes inducers (get the drug out quicker)
pharmacokinetic consequences in older adults
-decreased production of CYP 450 enzymes
-increase risk for drug interactions
changes in older adults
-hepatic: drugs metabolize slower
-cardiac/circ: impaired, slows distri.
-GI: decreases absorption of PO meds
-Renal: drugs excreted less completely
