pK Flashcards
what affects the rate and extent of absorption?
1.anatomical site
2.disease state
3.drug properties
4.formulation
how are drugs absorbed ?
transcellular - thru the cell using carriers
paracellular - AQ environment between cells
what does the rate of passive diffusion depend on?
-drug lipophilicity
-surface area available
-increase drug concentration
-thickness of epithelial layer
-potential mucus layer
-absorption area
what does the rate of carrier mediated depend on?
why are efflux transporters not good for absorption?
bring the drug back into the lumen, instead of being absorbed
what order of kinetics is used if the carrier transporter is saturated?
zero order
how are drugs effluxed in the gut?
active transport
needs ATP to go against the drug conc. gradient
what drugs influence the effect of efflux receptors?
Substrates- can be taken out of the cell
Inhibitors- inhibit efflux transport, affcting bioavailability
Inducer- increase number of efflux transporters, increasing activity
how are nanomedicines removed?
phagocytosis
what happens in endocytosis?
The binding of a substrate to a receptor on cell wall, triggers formation of vesicles (endosome)
how are drugs absorbed into the cell?
phagocytosis
pinocytosis
endocytosis
What is Pinocytosis
A process by which the cell takes in the fluids along with dissolved small molecules
characteristics of subcutaneous injection
characteristics of intradermal injection
characteristics of intramuscular injection
what are the drug properties that affect absorption?
what is biopharmaceutical drug disposition system classification (BDDSC)?
class I - high solubility, high metabolism
class II - low solubility, high metabolism
class III - high solubility, poor metabolism
class IV - low solubility, poor metabolism
what are the formulation considerations of non-enteral routes? (Oro-mucosal, rectal, intranasal, pulmonary, transdermal)
what are some non-enteral routes?
Oro-mucosal, rectal, intranasal, pulmonary, transdermal
what does zero order absorption mean?
constant rate of absorption
independent of the dose
- carrier-mediated transport
- must have a high drug concentration
- modified release formulation
- must be a constant release rate
what does first order absorption mean?
dependent on concentration
applies to MOST drugs
- rate is initially high
- rate decreases over time
when may absorption be delayed?
using oral dosage forms
what factors can affect absorption?
- physiological factions
e.g. delayed gastric emptying for oral dosage forms - formulation factors
- site specific delivery (e.g. colon)
- dosage form
- modified release
how does bioavailability affect absorption?
Bioavailability is the fraction of the administered drug that reaches the systemic circulation in the unchanged form
what are some examples at each stage of first pass effect/pre-systemic circulation?
what type of receptor do we ideally want on the apical or basal lateral side?
influx - apical side
efflux - basal lateral
what are ATP-binding cassette (ABC’s)?
generally efflux transporters
which requires energy due to going against the concentration gradient
what are ATP-binding cassette examples?
P-glycoprotein (ABC1, Pgp)
multi-drug resistant associated protein (MRP, ABCC)
Breast cancer resistant protein (BCRP, ABCG2)
what are solute carrier transporter (SLC)?
generally influx transporters
what are solute carrier transporter examples
what are the efflux/influx transporters name in the GIT?
efflux - ATP-binding cassette (ABC)
influx - solute carrier transporter (SLC)
which transporter (influx/efflux) in the GIT requires energy? and why?
efflux - ATP-binding cassette (ABC)
as they go against the concentration gradient
when are proton dependent oligopeptide transporters used?
for the use of prodrug
where are p-glycoprotein (ABC1, Pgp) expressed?
gut wall, BBB, kidney, liver, lung, colon
Pgp also found in the small intestine on the APICAL side of enterocytes
what are some examples of Pgp inhibitors?
what are some examples of Pgp inducers?
what are some examples of Pgp substrates?
what some enzymes that metabolise drugs in the small intestine?
CYP3A4
CYP2C9
UDP-glucuronosyltransferase
sulfotransferases
which enzymes in the small intestine detoxicify the drug and how?
UDP-glucuronosyltransferase and sulfotransferases
by decreasing the lipophilicity and increasing the hydrophilicity
where is mainly CYP3A4 located?
gut, small percentage in the liver
what enzyme is responsible for most drug metabolism?
CYP3A4
what are characteristics of CYP3A4?
what are some examples of CYP2C9 drug metabolisers?
warfarin
phenytoin
losartan
diclofenac
how does UDP-glucuronosyltransferase drug metabolise?
conjugation of lipophilic drugs with glucuronic acid
how does sulfotransferases drug metabolise?
sulfation of hydrophobic drug molecules
what are the factors that affect rate of distribution?
tissue perfusion
membrane permeability
drug properties (plasma binding/tissue binding)
anatomical factors
tissue composition
physiological factors/barriers
what are some examples of well/poor perfused tissue?
well perfused tissue -liver, kidney, lung
poorly perfused tissue -fatty tissue
what are the extent of distribution?
MW
lipophilicity
ionisation - pH/pKa
protein binding
intracellular binding
patient factors
what factors means there’s an increase volume of distribution?
small MW
lipophilic
poorly perfused
unionised at a pH