Physical Properties Lecture Flashcards
What must an oral drug be able to do?
dissolve survive a rang of pH Survive GI bacteria Cross membranes Survive liver metabolism Avoid active transport to bile Avoid excretion by kidneys Partition into target organ Avoid partition into undesirable places
Dissolution of drug in GI fluids
Solubility in buffer, acid or base
Absorption from small intestine
logP, logD, polar surface area, H bond, MWt
Blood protein binding
Plasma protein binding, logP and log D
Distribution of compound in tissues
logP, acid or base
Define ionization
Protonation or deprotonation resulting in charged molecules
The acidity or basicity plays a major role in controlling?
Absorption and transport to the site of action
Binding of a compound at the active site
Elimination of compound
What are the effects of pH on drug absorption?
Absorb passively when they are unionized
A basic compound in the stomach will?
be more ionized thereby reducing the rate of passive absorption
Acidic compounds administered orally?
Generally have better bioavailability
Define %F
Bioavailability
A value that defines how quickly and how much of a particular drug reaches the blood supply after ADME process
What is a good strategy for increasing %F?
If it is due to poor absorption from the GI tract than synthesis of prodrugs (bioreversible derivatives of drug molecules)
Define absorption
If we have an ionized compound, won’t pass readily through GI tract to blood stream but a neutral compound will
Define binding in ionization
Ionized charge on a compound = stronger H bond than delta + or - charges
Can also form an ionic bond which is strongest bond between drug and target
Define plasma protein binding in ionization
May proteins have a similar structure to plasma proteins which bind to albumin
So drugs might bind to albumin, which isn’t a problem if it wants to say in the blood but is if it needs to get to the target else where
