Lecture 3: Distribution Flashcards
concentration vs time cuves: drug distributes to and is restrivted to these tissues (INITIAL COMPARTMENT)
-constant slope downwards
concentration vs time cuves: drug distributes to tissues at different rates (AFTER FULL DISTRIBUTION)
-curved increase and decrease
what causes the offset of the pharmacologic effect for thiopental?
-driven by redistribution of drug
-hits peak concentration in brain then redistributes concentration to lean tissue
perfusion rate limited
-how quickly drug can be delivered
permeability rate limited
-how quickly drug moves across membrane
which condition shows slower tissue distribution
permeability rate limited
Convection
-rate related to pressure
Diffusion
-rate related to concentration
which method of transport is likely to be important for monoclonal antibodies?
-convection
-increase pressure = increase gaps to push big molecules out
Movement of drug within blood
-drug can be free, bound, inside cells, etc
-only free drugs can get across membranes
Shift tissue binding or plasma protein binding
-change distribution of drugs
most drugs in tissue is bound to:
-nonspecific sites and not receptors
Sites of action
-plasma (epithelial barrier)
-intersitial space (cappilary barrier)
-intracellular (membrane barrier)
Adverse reactions to phenytoin (antiseizure) increases
as serum albumin decreaases
drug trapping
-changing equilibrium between compartments by using differences in ptoyonation states/pH environments
Drug trapping in urine
-increases elimination
phenytoin
-anti seizure
-binds to albumin
-if reduce albumin = adverse reactions
-changes ability of drug to move between compartments
Drug trapping mech
-drive drug out of blood and into urine
-unionized drug can pass to compartment with pH that will ionize it
-ionized drug cannot cross back
acidic urine effect on basic drug
-increase elimination
basic urine effect on acidic drug
-increase elimination by trapping
properties of capillaries to the brain
-tight junctions (little permeation)
-negative head groups (limit acid diffusion)
-high Pgp concentration (high efflux activity)
Brain barriers
- Blood-brain
- Blood-CSF
- Blood-arachnoid barrier
Blood-brain barrier
-tight junctions
blood-CSF barrier
-fenestrated (gaps) cells
-layer of tight junctions beneath
arachnoid barrier
-layers of very tight junctions
Distribution of drugs into brain
-plasma
-CSF
-intersitial
-intracellular
-lysosome
-different pHs of compartments can mean drug trapping
Ability of compounds to enter brain from blood
-lipophilicity
-glucose and L-DOPA (very polar) are exception and get into brain
lipophillic (hydrophobic) drug penetration
-higher
-more likely to cross brain bariers
-ethanol, nictotine
lipophobic (hydrophillic) drug penetration
-LOW
-sodium, penicilin, dopamine
How drugs can get into CNS
-physiochem properties
-use existing transporter
-direct administration into CNS (yeouch how much u supposed to put in there)
-disturb barrier (yikes that lets other stuff in)
Focused ultrasound
-temporarily open tight junctions of BBB
-irradiation vibrates microbubbles = opens junctions
-AuNPs can cross depending on size
Maternal-Fetal drug distribution
-placenta barrier
-most drugs enter fetal circulation
-large polar molecules less likely to cross placenta
-pH differences may demonstrate ion trapping
