LECTURE 2 Flashcards
Identify the drug properties that are affected by the change in pH
Solubility of the drug
Extent of absorption (bioavailability)
Drug binding to its receptor
Identify ionizable groups in drug structures
Arylcarboxylic acid
Arylamine
Atomic amines
Alkylcarboxylic acid
Alkyl amines
Alkyl amines (cyclic)
Phenol
Guanidine
Predict the ionized form of drugs from their structures
Bases are ionized when H is added, becomes BH+
– In low pH → weak conjugate acid (protonated)
Acids are ionized when H is removed, becomes A-
– In high pH → weak conjugate base (deprotonated)
When pH < pKa, what is the degree of drug ionization?
molecule will primarily be in its protonated (acidic) form due to an acidic environment
When pH > pKa, what is the degree of drug ionization?
molecule will primarily be in its deprotonated (basic) form due to an acidic environment
When pH = pKa, what is the degree of drug ionization?
The drug is 50% ionized and 50% unionized
What is the range of pH where a drug would be more soluble in water?
The pH where is the drug is mostly ionized, polar molecules dissolve better in water, and ionic groups make molecules more polar
How do you predict the efficiency of passive diffusion of a drug with a known pKa at a given pH?
The pH where is the drug is mostly UNionized
– In general, more lipophilic (less ionized) drugs are absorbed more efficiently
– Therefore, higher lipophilicity = more efficient passive diffusion
How do you predict where a drug will be absorbed in the digestive system based on the drug’s pKa value?
DRUGS ARE ABSORBED BEST @ pH WHERE THEY ARE MOSTLY NEUTRAL
– Where pH and pKa are mostly equal
Where are most drugs absorbed?
In the jejunum (middle intestine) where the pH is generally between 5 and 7
Where are acidic drugs usually absorbed?
In the stomach where the pH is generally between 1 and 3
