ADME 4 Flashcards
how long does it take for a drug to distribute throughout the body?
1 minute
is drug distribution evenly distributed?
no, Blood supply is richer to some areas of the body than others
what are the reversible-interactions with blood constituents?
plasma proteins –
erthyrocytes–
tissue membranes
what blood flow is highly perfused?
lung/kidney/liver/brain
what blood flow is poorly prefused?
fat/ muscle/ bone
a cell is no more than how far away from a capillary?
20-30 mm
what cannot pass through capillaries?
plasma proteins
what are the 3 types of capillaries?
contiuous, fenstrated,siduous
what are the 3 main features of capillaries?
Endothelial cells provide an uninterrupted lining allowing only smaller molecules (H2O, ions, urea, etc) to diffuse throughtight junctions Pores (60-80nm diameter) spanned by a diaphragm of radially oriented fibrils allowing small molecules and limited amounts of protein to diffuse Larger openings (30-40 μmdiameter)•allow red and white blood cells (7.5μm -25μm diameter) and various serum proteins to pass
what is the purpose of the blood brain barrier?
maintains homeostasis of the brain
what does the BBB protect against?
non-CNS active hormones and transmitters
how does the BBB protect the brain?
it has tightly-fitted cells that do not contain pores
capillaries are coated in a fatty barrier
how does drugs entering the CNS penetrate the BBB?
penetrate through tightly-fitted cells that do not contain pores and capillaries that are coated in a fatty barrier
is diffusion of small hydrophobic molecules possible through the BBB?
yes
do polar molecules leave the CNS - enter/leave early
yes
what is the volume of distribution?
A measure of the tendency of a drug to move out of the blood plasma to another site (e.g. tissues, organs)
what does the presence of an absorbent do?
The presence of adsorbent reduces drug concentration
what are the 3 main categories of bodily water?
Extracellular Fluid Intracellular fluid (~30-40% ) Transcellular fluid (2.5%)
what are the two forms that drugs exist in?
bound and unbound
how will drugs that are acid or bases exist in equilibrium?
will exist in equilibrium with the ir ionised forms(pH and pKa dependant)
which form of the drug can move between compartments?
free drug
what do drugs bound to the plasma department
Binds so strongly to plasma albumin that its Vdis used to measure plasma volume (~0.05 L kg-1body weight)
what is the VD for most polar molecules and for drugs distributed in an extracellular compartment
0.2 L kg-1
do polar compounds enter cells easily?
no due to low lipid solubility
what is the vd of relatively lipid soluble drugs/distribution throughout bodily water?
0.55 L kg-1
what is the Vd of the distribution intracellularly?
Many drugs with Vd> ~ 0.55 L kg-1
what is the effect of binding the drug outside the plasma or partitioning?
into fat increases Vd beyond total body water.
what does a small medium and large Vd indicate
small: Small Vd Mainly in plasma, little in tissues
medium: Medium Vd Similar concs. in plasma and tissues
large: large Vd Mainly in tissues, little in plasma
what happens when protein binding occurs?
resulting drug-macromolecule complex does not cross membranes
reversible/ non-specific/ comp for sites
what happens with drug interactions in drug distribution?
highly bound drug is partially displaced by another drug or chemical–
large increase in free drug concentration may lead to increase in therapeutic or toxic effect until steady-state re-established
what is the most important plasma protein and why?
albunium, binds both anionic (acidic) and cationic (basic) drugs
the amount of drug bound to the protein depends on 3 factors:
concentration of free drug
–affinity of drug for binding site
–concentration of protein
what is the effect of protein binding on drug action?
Increases the amount of drug that has to be absorbed before a therapeutic level of unbound drug is reached
–May cause elimination of a drug to be delayed
what is Warfarin?
Acidic, low VD(7 L)
–warfarin is strongly bound to plasma proteins (albumin), ~90%
–patient stabilised on ~10% of dose
what competes with warfarin? and how?
Warfarin and aspirin compete for same albumin proteins–through co-administration of aspirin, warfarin may be displaced from plasma proteins
•Increases effective dose
•Decrease in clotting time
what does Phenylbutazone displace and how?
displaces warfarin
–selectively inhibits metabolism of the active S-isomer
–prolongs prothrombintime and may result in increased bleeding
what does Quinidine, verapamil and amiodarone displace?
displace digoxin
–reduce renal excretion
–may lead to dysrhythmias through digoxin toxicity
what is drug-plasma binding?
Surface of drug plasma protein binds with drug molecules
what are the binding forces present in the drug-plasma binding?
ionic interaction–hydrogen bonding–hydrophobic interactions–dipole-dipole interactions–p-pinteraction–p-cationinteraction
