Pharmacokinetics 1 Flashcards
BioPhase Def
Liquid at site of action
Why would drug not be readily available
Bound to protein (eg prodrugs) or pooled in a tissue compartment (transportation complications)
1st pass metabolism Outline
Breaking down of a substance in the liver (detoxification). IV and buccal admin bypass process
Absorption Outline
Mechanisms by which drugs cross cell membranes. Has to have been administered as/ converted to a solution. Types: aquaporins diffusion, lipid diffusion, carrier mediated transport (facilitated diffusion and active transport) and pinocytosis
What form can substances pass lipid membranes
non-ionised, lipophilic substances
Cell membrane composition
Integral proteins, glycoprotein (oligosaccharides), glycolipids (oligosaccharides), peripheral proteins and phospholipid bilayer
Fick’s Law Outline
Flux (conc moving across a square area) is proportional to - diffusivity and the conc gradient
Substances efficient at passive diffusion
Lipids, hydrocarbons, anesthetic and alcohol
Substances inefficient at passive diffusion
Ionised molecules, proteins and carbohydrates
Facilitated Diffusion Outline
Substance specific (due to protein channel shape). No energy required (no conc gradient) . Saturated
Active Transport Outline
Structurally specific. Energy required to induce confirmational change in transport proteins to move against conc gradient. Saturable
Main regions of carrier mediated transport
Renal tubules, biliary tracts, blood-brain barrier and GIT
Pinocytosis Outline
Endocytosis via membrane infused vesicles
Absorption Factors
Pharmaceutical properties (eg liberation speed), pH (ionisation/non-ionisation), Log P, GIT properties and p-glycoproteins (efflux substances absorbed into circulation back out, defence)
Acidic drugs in acidic enviorments outline
In acidic enviorments (low pH) acidic drugs tend to be non-ionised (tend to be steps below pKa, don’t donate their proton). These conditions lead to the absorption of acidic drugs in these regions (non-ionised drugs can pass through lipid memebranes).
Relationship between pH and absorption for acidic drugs
higher absorption = lower pH (non-ionised, steps below pKa)
Relationship between pH and absorption for alkaline drugs
high absorption = high pH (non-ionised, steps above pKa)
Factors of GIT effecting absorption
surface area, GI secretions and motility
How does intaking food effect drug absorption
food stimulates gastric secretions, food can form chelates with drugs (rendering them insoluble), lipids solubilise lipid based drugs and delays gastric emptying (slows absorption)
P-glycoproteins
Push substances absorbed into circulation back out into stomach contents. Active process that goes against conc gradient. Located: intestine (prevent absorption), kidney (urine excretions), liver (bile excretions) and brain (blood brain barrier)
Blood Brain Barrier Outline
Continuous overlapping cells that prevents most molecule entry to brain. Molecules must be neutral in charge, not bound to proteins, lipophilic and small
Bioavailability Def
Fraction of chemically unaltered drug that reaches systemic circulation, Has no units (eg IV is always 100% (bypassing metabolism))
Factors that cause failure in bioavailability
Disintegration/dissolution failure, chemical/enzymatic/pathogenic attack, absorption failure (may include glycoprotein efflux) and 1st pass metabolism (liver and stomach wall)
