Pharmacokinetics Flashcards
what are the 4 primary actions of the body on the drug?
- absorption
- distribution
- metabolism
- excretion
define absorption
process of unchanged drug moving from site of administration to site of measurement within the body
usually the peripheral venous circulation
what are the 5 primary processes that can influence the absorption of a drug?
- dose
- dosage form
- route of administration
- drug’s physicochemical properties
- A&P @ site of absorption
describe some characteristics of membrane permeable drugs
- non-polar
- lipid soluble
- low MW
explain the mode of transportation of drugs that are not
- non-polar
- lipid soluble
- low MW
must make use of receptor mediated transport systems or channels across the membrane
generally only what types of molecules cross the membrane?
uncharged
define what the pKa is
- pH @ which the drug is 50% dissociated and 50% associated
in its associated form a weak acid is
non-ionized
as a weak acid dissociates the acid and hydrogen are
ionized
in the associated form a weak base is
ionized
as a base drug dissociates the base is
non-ionized
what form of the drugs can more readily pass through the phospholipid membrane?
the non-ionized (uncharged) form
a decrease in pH means there are ________ ________ for binding
increased acidity
more H+ ions
protonated form of the drug predominates
an increase in acidity means there is more weak ________ mobilized across the membrane an less weak ________
- acid
- base
if the pH is greater than the pKa which form of the drug predominates?
- dissociated or non-protonated form
describe ion trapping for a weak acid drug
- pH rises above the pKa (more basic), more of the drug dissociates trapping the drug in
describe ion trapping for a weak base drug
- pH drops below the pKa (more acidic) more of the drug is in its associated form
The pH of the stomach is approximately 2 which is going to be less than the pKa of most drugs. This would mean that weak acids and weak bases (drugs) are in the protonated or associated form. Which of these two types of drugs will more readily be absorbed from the stomach and which is more likely “trapped” in the stomach?
absorbed: weak acid
trapped: weak base
what is the primary location of absorption of orally administered drugs?
the small intestine
larger surface area increases amount of drug absorbed
define bioavailability
fraction of administered drug that reaches the site of measurement in the body
measured in the peripheral venous blood
describe the 1st pass effect
following absorption from the small intestine high drug concentration in the blood passes through the liver where its metabolized. from the liver the blood concentration of the drug (bioavaliability) is decreased
bioavaliability following IV administration is 100%, why?
b/c it is administered straight into the blood
other routes (not IV) will haver lower bioavaliability why?
b/c the drug will be absorbed by the small intestine and the liver
define distribution
delivery and uptake of drugs into tissues in order to reach site of action and exert their biological effect
what are the system related factors that influence distribution?
- blood flow
- capillary surface
- capillary permeability
- cellular uptake systems
- plasma protein binding
- organ size/fluid vol.
what are the drug related factors that influence distribution?
- lipid solubility
- charge
- polarity
- MW/ size
higher blood flow = higher
capillary surface
which tissues will receive larger drug concentrations?
well-perfused tissues
poorly-perfused tissues will recieve the drug at a
slower rate
if drug permeability is sufficiently high what becomes rate-limiting?
blood flow
known as perfussion/ flow-limited drugs
describe permeability-limited drugs
those whose uptake is slow enough that transport across capillaries/ cell mem. is rate limiting
permeability-limited drugs generally have what characteristics?
- polar
- charged
- low lipid solubility
describe plasma protein binding
only free unbound fraction of a drug is capable of binding to receptors to produce the desired effect
give an example of a tissue that is leakier to drugs
the small intestine
small ions/ polar solutes pass through paracellular pores
give examples of tissues that are more tight to drugs
- skin
- stomach
- large intestine
- bv of brain and testes
the primary route of drug entry into the CNS is
passive diffusion across membranes
most of the drugs that cross the BBB are…
BBB: blood brain barrier
highly lipid soluble
what is a disadvantage to the highly lipid soluble drugs that have to cross the BBB
puts a limitation to the avaliable compounds for brain disorder treatments
what is a benefit to the highly lipid soluble drugs that have to cross the BBB
restricts entry of toxic substances
drugs that can cross the BBB can be compromised in which patiens?
- infants
- elderly
- brain injuries
- certain diseases
most drugs are metabolized in the liver by
microsomal enzymes
microsomal enzymes in the liver form ___________ which increases the _________ _________ for excretion.
- metabolites
- water solubility
drugs can be __________ or __________
inactive or active
what is the term for the inactive form of a drug?
prodrug
most prodrugs are inactive until they are
passed through the liver
what are the phases in drug metabolism?
- phase 1: functionalization
- phase 2: conjugation
phase 1 reactions include what type of enzymes? where are they localized?
- oxidative
- SER
phase 1 is aka
bioactivation/ inactivation
phase 1 reactions make drugs slightly more ________. How?
soluble
- by the addition of polar functional groups
known as functionalization
what are the functional groups that are added during phase 1 that make the drugs slightly more soluble?
-OH
-COOH
-NH2
-SH
-O
phase 2 reactions in drug metabolism include what type of enzymes? these can be integral to the…
- cytosolic
- SER
define conjugation
the attachment of highly polar groups to increase polarity making the drug more soluble for elimination
what are the highly polar groups that are used to make drugs more soluble?
- glucuronide
- glutathione
what is the primary group of enzyme families that mediate drug metabolism?
cytochrome P450 superfamily
what are some mechanisms in the regulation of drug metabolism? (specifically enzyme systems)
up or downregulating enzyme systems such as cytochrome P450
phase 2 reactions are aka
bioinactivatioin or conjugation
describe the induction of CYP-450 enzyme metabolism
induction=activation
factors that increase hepatic metabolizing enzymes increase enzyme metabolism and decrease the active drug concentration in the body therefore decreasing the desired effect
describe the inhibition of CYP-450 enzyme metabolism
competition between compoundds causes enzyme saturation which
- slows the patent drug metabolism
- raises [plasma]
increasing the effect or toxicity of the drug
give an example of ‘inhibition of CYP-450 enzyme metabolism’
grapefruit juice competes for cytochrome enzymes leading to an increase [drug]
define 1st order kinetics
a constant percentage of drug is metabolized over a period of time
1st order kinetics is proportional to it concentration therefore it is
concentration dependent
define 0 order kinetics
a constant amount of drug is metabolized over a given period of time
zero order kinetics is independent to the drug’s concentration therefore it is
concentration independent
what is a drug half-life?
the time for a drug to lose half of its pharmacological activity
elimination is the
irrevesible loss of drug from a body
what are 2 methods of elimination?
- metabolism
- excretion
elimination of a drug through metabolism occurs in which body parts?
liver, GI tract, kidney, lung
elimination of a drug through metabolism is aka
chemical conversion
elimination of a drug through excretion occurs in which body parts?
kidney, liver, lung, skin
elimination of a drug through excretion is aka
diffusion, flow, evaporation
renal elimination =
glomerular filtration + tubular secretion - tubular reabsorption
___________________________
[D] in plasma
KD= ____/____ = _____/_____
k2/k1
[L][R]/[LR]
