Pharmacokinetics Flashcards
pharmacokinetics
what the body does to the drug
pharmacokinetic properties
ADME
how to get the drug into the body, where/how a drug is administered
absorption
factors affecting drug absorption
- pH
- blood flow
- surface area
- contact time
- presence of transporter proteins
partially ionizes/charges in water
weak acid
partially takes a H+ from water
weak base
uncharged drug passes through membranes more readily
true
increased blood flow =
increased absorption
increased surface area =
increased absorption
increased contact time =
increased absorption
increased transporter proteins =
decreased absorption
drug formulations
how a company manufactures drugs, dependent on barriers, setting, stability, first pass effect
Routes of administration
rate and efficiency of absorption differs based on ROA
enteral
by mouth, safest/most common
parenteral
directly into systemic circulation
other
neither oral or parental
enteral
oral, sublingual, buccal,
other
inhalation/nasal, intrathecal/intraventricular, topical, transdermal, rectal
parenteral
IM, IV, SubQ
enteric coated
chemical envelope that protects drug from stomach acid/if irritable. allows drug to reach intestines
extended release
coating that control drug release
factors affecting oral absorption
physiologic variability, areas with different pH, gastric emptying, first pass metabolism, bioavailability
gastric emptyign rate
rate which stomach empties into small intestines
first pass metabolism
blood supply draining GI passes through liver before reaching systemic circulation, results in less unchanged drug entering systemic circulation
prodrug
administering an inactive form of the drug to be activated by naturally occurring enzymes in the body (metabolism)
advantage of prodrug
protection, solubility, lipophilicity, site selective, avoid first pass metabolism effect
bioavailability
rate/extend at which administered drug reaches systemic circulation
PO bioavailability
solution > suspension > capsule > tablet > coated tablet > extended release
low bioavailability =
poor absorption in GI
IV results in
100% bioavailability
can drugs have equivalent bioavailability
yes
sublingual
placed under tongue, unionized, highly lipid soluble, potent agent, rapid absorption
rectal administration
suppository/enema, for pts unable to tolerate meds, absorption highly variable, systemic/local effect, defication terminates drug exposure
inhalation
oral/nasal, administered as gas/aerosol, fast action, may irritate lung tissue (albuterol)
topical administration
application direct to membrane or skin, local or systemic effect, many dosage forms (nalaxone, eye drops, creams)
transdermal administration
patch containing drug applied to skin, continuous/long acting, lipophilic, pt skin characteristics affect rate
intramuscular
directly to muscle, rapid absorption of aqueous solution, pain @ site, volume restriction
subcutaneous
loose tissue injection, slow and constant absorption, volume restrictions
IV
most common parenteral route, 100% bioavail, greater risk of adverse effects
4 mechanisms of passage of drugs across membranes
- passive diffusion
- facilitated diffusion
- active transport
- endo/exocytosis
drug distribution
drug leaves blood stream and enters into interstitum and tissues
drug distribution is dependent on
blood flow, capillary permeability, drug binding to proteins/tissues, lipohilicity, volume of distribution
blood flow
rate of drug diffusion into tissue is primary function of blood flow
brain/heart/liver/kidney
highly vascular
central compartments
rapid distribution 1st, diffuse 1st
peripheral compartments
slower distribution, 2nd to diffuse
capillary permeability
determined by structure (leaky v tight) and chemical nature (ionized/polar vs lipid soluble)
continuous capillary (tight)
skin, muscle, lung, CNS
fenestrated capillary (semi)
exocrine glands, renal glomeruli, intestinal mucosa
sinusoid capillary
liver, spleen, bone marrow
blood brain barrier
contains tight junctions, must pass as lipid soluble and active transport. Ionized/polar cannot pass thru BBB
ion trapping
occurs when pH of 2 water compartments differ, weak acids/bases concentrate in the compartments which they are most highly ionized. once ionized they cannot cross membranes
plasma protein binding
reversible, determines extent of drugs distribution/elimination rate, only free drug can leave circulation
when drug levels are too high, plasma protein binding sites are
saturated
binding does not prevent drug from reaching site of action but lessens rate at which it occurs. T/F?
true
lipophilicity
lipophilic drugs readily move across biologic membranes, hydrophilic drugs do not readily penetrate cell membranes
volume of distrubution
measure of the apparent space in the body available to contain a drug
volume of distribution is useful for caclulating the loading dose of a drug
true
volume of distribution
relates amount of drug in the body to concentration of drug in blood / plasma
plasma vol, ECF vol, total body water vol
3L, 15L, 40L
Vd
Total amount (dose) of drug / blood or plasma concentration
low molecular weight, low protein binding, high tissue binding, high membrane permeability, lipophilic, un-ionized
high Vd
high molecular weight, high protein binding, low tissue binding, low membrane permeability, lipophobic, ionized
low Vd
excretion 3 major routes
hepatic metabolism, biliary excretion, urinary excretion
sites of drug metabolism
kidneys/liver/GI tract
kidney drug metabolism
eliminates small molecules, polar, fully ionized at physiologic pH
liver drug metabolism
primary organ, biotransformation of drug molecules
other sites of drug metabolism
GI (most important extrahepatic site)
metabolism phase 1
makes the drug more polar by introducing polar functional groups, catalyzed by cytochrome P450
metabolism phase 2
phase 1 products that were not able to be eliminiated rapidly undergo conjugation
cytochrome P450
oxidations catalyzed by iron containing proteins located in liver and GI, has relative specificity
factors affecting CYP450 isoenzymes
age, disease states, genetics, environmental factors, exposure to drugs/chemicals
CYP 450 induction
↑metabolism = ↓ drug concentration
lose therapeutic effect
can increase toxicity
St Johns wort
CYP450 inhibition
↓ metabolism = ↑ drug concentration
Ex. -azole antifungals
poor metabolizers
lack a gene to produce the CYP450 isoenzyme
drug excretion (3 processes)
glomerular filtration, tubular secretion, tubular reabsorption
drug must be polar/nonpolar and fully ionized/unionized to be excreted in urine
POLAR, FULLY IONIZED
glomerular filtration
produce protein free ultra filtrate that will become urine. protein bound drug and large molecule not filtered
tubular secretion
energy consuming secretion from capillaries to renal tubule. potential target of drug action
tubular reabsorption
drug concentration inceases as moves through tubule, reabsorb unionized drugs into blood stream
urinary pH
impacts rate of excretion, pH may be adjusted, ionized excreted in urine
weak base excreted at low pH
true
weak acids excreted at high pH
true
clearance
estimates amount of drug cleared per unit time, total clearance estimates all mechaisms of drug elimination
excretion
fecal route, tylenol vs ibuprofen, etc
