to receive drug, from minutes to hours.
Diffusion into InterstitialCompartments
rapid diffusion occurs in most areas because of permeable capillaries. E.g..Liver capillaries have much of basement membrane exposed by slit junctionswhich enables rapid diffusion including large plasma proteins.
Blood brain Barrier
no slit junctions in brain so drugs must either pass directly through (lipidsoluble) or via active transport.
Drug metabolism. The most important consequence of metabolism ispromotion of renal excretion.
Most important factor inbiotransformation
Induction, first pass effect, extremes of age, nutritional status, competitionamong drugs.
Some drugs, acting on the liver, can increase the rate of their own or another drug's metabolism. E.G.. Phenobarbital the classic enzyme inducer
rapid inactivation of oral drugs due to liver metabolism.
Metabolism relating tolipophilic drugs
Lipophilic properties that promote a drug's passage through biologicmembranes and subsequent access to their sites of action also hinderselimination of the drug.
Usual biotransformation of drugs
usually biotransformed into more polar, inactive metabolites that are easilyexcreted by body.
Metabolites with increased biologic activity or even toxic properties may becreated through metabolism E.G.: Tylenol has a hepatotoxic metabolite.
chemical-driven liver damage. It is a possible side-effect of certainmedications
Renal, billiary, fecal, breast milk, lungs, saliva, sweat
glomerular filtration, proximal tubule secretion, distal tubular secretion, renalexcretion
Plasma Drug Levels
there is a direct relationship between therapeutic and toxic responses and theamount of drug present in plasma
Minimum effective concentration
the plasma drug level below which therapeutic effects will not occur
the plasma drug level at which toxic effects occur
the range of plama drug levels falling between the MEC and the toxicconcentration. Drugs with narrow range of therapeutic window are more apt tocause toxicity. Digoxin is the classic example