Chapter 4 Flashcards
Which ionization state is preferred for SOLUTION and ABSORPTION?
ABSORPTION -> Unionized (passive Diffusion through the membrane without a transporter)
SOLUBILITY -> Ionized
SOLUBILITY followed by PERMEABILITY - the drug needs to get dissolved and then absorbed
What is the function of the ionization constant pKa?
It indicates the strength of an acid or base
What is the difference between pH and pKa?
pH is a function of the environment -> can be altered
pKa is a function of structure (steric and electronic factors) -> cant be altered
How can the tendency to donate or accept a proton be increased?
by changing the pH -> for acids to donate a proton, make it more basic
for bases to accept a proton make it more acidic
What does the pKa tell about the ratio between ionized and unionized forms?
-Once pH equals pKa there is 50% of the ionized and 50% of the unionized form
-There is a buffer region where there is a mix of both
-once the buffer region in either direction is passed, you will get 100% of the ionized or unionized form
??? why is the ratio in our calculations??
What is the pH in different parts of the body?
Blood: 7.35 - 7.45
Saliva: 6.8
Stomach (acidic): 1-2 (can vary)
Small intestine: 5.5-6 (gradient starting low and gets higher up to 8)
What is the Henderson-Hasselbach equation?
pH = pKa + log base form/ acid form
The base form refers to the unprotonated form (the base want to accept a proton)
-> so if I am an acid that is the ionized form is CH3CO(-)
-> if I am a base that is the unionized form NH3 (no extra proton)
The acid form refers to the protonated form
-> Acids: Unionized -> CH3COOH
->Bases: Ionized -> NH4(+)
Importance of pH and pKa in drug therapy: Solubility and Absorption (Permeability)
If administered orally it has to be soluble (ionized form) and absorbed (unionized form)
Importance of pH and pKa in drug therapy: Duration of action
-For excretion in urine, it has to be soluble ->pH in urine (4.5 - 8)
it the drug is not soluble in that range, it will stay in the system longer bc the body needs to do something to make it soluble
-Protein-binding in the plasma: Albumin is basic it will bind longer with acidic drugs -> acidic drugs tend to stay longer in the system
Importance of pH and pKa in drug therapy: Duration target binding
Most of the targets are proteins -> some amino acids are basic or acidic -> so if the target is basic and I have an acidic drug it will interact very well
Importance of pH and pKa in drug therapy: Drug interaction
Important for drugs administered together, often IV -> it has to be soluble, any precipitation is dangerous for the patient
-> IV solubilities and compatibility
BASIC solution with ACIDIC drug works
BASIC solution and BASIC drugs wont
