Fundamentals Flashcards
What is enternal route of drug administeration
Across a membrane (oral, topical etc)
What is the perenteral route of druug administeration
Administeration bypasses membrane
IV, Intrathecal into spinal cord etc
What is the main site of drug bio transformation
liver
What are the 2 reasons a liver changes parent drug to metabolites
- generally (but not always) liver turns parent drug into something that is toxicologically inactive
- Increase water solubility for allowing easy excretion via kidneys
What is free drug vs bound drug
free- disolved in the blood
Bound- distribibuted via plasma proteins (attached to albuminin)
creating free:bound
free vs bound drug biotransformations + excretion
free drug is type that undergoes biotransformation in liver by entering hepatocytes (bound to large to enter)
-Kidney glomerus allows movement/filtration of drugs up to 1000da and bound drg is too large for this
What is the drug receptor complexes
is at site of action formed with free drug (initiates pharmacological action)
Most drugs are what weight
40-450 daltons
To be pharmalogically active a drug must have these 2 characteristics
Some solubility within aqueos fluids of body in order to reach site of action + some lipid solubility to cross membrane barriers
what is ionization
When a substance releases or accepts ions
What will acid and basic drugs do with there protons in low ph env
Acidic drugs will keep proton (unionized)
Basic drugs will accept proton (becoming pos- ionized)
How does ionization affect solubility
A substance that is ionized will prefer to disolve in highly polar area (water)
A substance that is unionized will prefer to disolve in more lipid areas
What does pKa represent
ratio calculated to understand what fraction of the drug is ionized (water solube) vs unionized (lipid soluble)
What will acid drugs tend to do in high ph environments
donate proton and become ionized (more soluble in water)
What happens when acid drugs enter the stomach
Will encounter low ph and stay unionized and easily be able to move thru lipid mucosa
-when ionized form encounters high ph of plasma it donates H and becomes ionized at high amount (do calculation)
Acid and base formula for ionization
Acids- pKa-pH=log (unionized/ionized)
Bases- Pka-ph=log(ionized/unionized)
when basic drug eneters stomach what happens
Will enter as unionized form and accept protons becoming ionized form and only small amount of unionized form will cross
When unionized form reaches high ph of plasma it will convert to ionized at lower level
When Pka=ph what does it mean for ionized and unionized forms of druge
50/50 distribution
If ph
Pronated forms predominat
low ph environment favours movement of acid drugs across biological membranes
if ph>pka
depronated forms predominant
High ph environment favours basic movement
What are anatomical vs functional barriers
Anatomical- formed by cells that are linked together in ways that block passage of drugs they intercellular spaces
Functional-Formed by drug transport systems that carry drug molecules out agains a drug conc
Capillaries w/ maculae- what can pass thru
has transient intercellular spaces present allowing movement of free drug molecules (bound is too big)
What can move thru fenestrated capillaries and where are they present
Present usually in excratory and secretory organs (urine system)
-Only allows free drugs to move thru it
Capilaries with occluding zones are in all areas of the brain except (5)
choroid plexus median eminence area postrema pineal gland pituitary gland
What is the cut off phenomenon of solubility
absorbtion rate of a substance in ralation to its partition coefficient (lipid:aques)
-as partition coefficient increases solubility will increase to a certain point then drop off quick (results in need for some h2o solubility
What are the 3 major aspects that influence absorbtion
Molecular size
solubilutu
degree of ionization
