2 - Drug movement in the body/ Drug Disposition Flashcards
define distribution?
the process by which a drug leaves the circulation and enters the tissues perfused by the blood. Once within a tissue further, blood-independent, distribution may occur (or carrier- mediated transport)
define metabolism?
the process by which tissue enzymes (principally in the liver - hepatic metabolism) catalyse the chemical conversion of a drug to a more polar form that is more readily excreted from the body
____ drugs are more readily excreted by the body?
polar
where is the principle site for excretion?
the kidneys
where is the interstitial fluid?
fluid between cells
___ absorbs very little apart from ethanol
stomach
partition coefficient
the ratio of the concentrations of a solute in two _____ or slightly _____ liquids, or in two ____, when it is in ______ across the interface between them
partition coefficient
the ratio of the concentrations of a solute in two immiscible or slightly miscible liquids, or in two solids, when it is in equilibrium across the interface between them
drugs must ___ in order to release the active drug molecule
dissolve
absorption of a drug occurs by ___ ____ across membranes - although some agents are ____ .
simple diffusion, transported
for a given drug concentration gradient across a membrane, the rate of diffusion increases with the ___ ____ of the drug
lipid solubility
what is delta CM
the difference in concentration of a drug in the outer part of the membrane to the innermost part of the membrane
why is it important for drugs to be lipid soluble
so that a concentration gradient is set up between the outside and inside of the cell
only ____ forms of drugs readily diffuse across the lipid bilayer
unionised
acids become more ionised as the pH ______
increases
Bases become more ionised as the pH ______
decreases
acids ____ protons
donate
bases ___ protons
accept
the degreee of ionisation depends on the ____ of the drug and the ____ ____
pKa, local pH
what is pKa
the pH at which 50% of the drug is ionised and 50% unionised
acid = pKa - pH = log (\_\_\_/\_\_\_ ) base = pKa - pH = log (\_\_\_/\_\_\_ )
acid= pKa - pH = log (HA/A-) or pH- pKa = log (A-/HA) base= pKa - pH = log (BH+/B)
absorption of __ ___ is facilitated by the pH of the stomach
weak acids
weak acids and bases are ___ absorbed and strong acids and bases are ___ absorbed
well, poorly
the rate of absorption of a drug is modified by ___ rich foods as the drug becomes ____ if bound to this
calcium, charged
what is oral availability?
the fraction of the drug that reaches the systemic circulation after oral ingestion
what is systemic availability?
the fraction of the drug that reaches the systemic circulation after absorption
what is first pass or presystemic metabolism
when drugs administered orally, once absorbed are inactivated by enzymes in the gut wall and liver before reaching the systemic circulation and body tissues in general.
which administration routes avoid first pass metabolism?
sublingual/buccal
transdermal/subcutaneous
IV
Intramuscular
partly rectal and partly not
ionised and unionised drugs that are NOT BOUND TO PROTEIN can move freely by _____ between ___ ___ and ___ ___
diffusion, between plasma water and interstitial water
____ drugs cannot move between compartments
bound
only unionised drugs can move readily by ___ between interstitial water and ___ , ____ ___ and ______ ____
diffusion, between fat, intracellular water and transcellular water
