Weak Acids/Bases in Drugs: Many drugs are weak acids or weak bases.
Weak Acid: Donates or loses a proton, becoming negatively ionized.
Weak Base: Accepts or gains a proton, becoming positively ionized.
Influence of pH on Drug Properties
Ionization and Membrane Crossing:
Charged molecules (positive or negative) have a reduced ability to cross biological membranes via passive diffusion.
Drug Ionization and Absorption:
The proportion of ionized drug depends on the pH of the compartment compared to the drug's pKa (pH at which 50% is charged).
pH Levels in Various Body Compartments
Stomach: Acidic environment
Acidic drugs are uncharged and may be efficiently absorbed.
Basic drugs become charged and are poorly absorbed.
Small Intestine: Weakly basic environment
Acidic drugs are charged and poorly absorbed.
Basic drugs are uncharged and efficiently absorbed.
Blood: pH ~7
Urine: pH can vary from acidic to basic
Clinical Implications
Law of Mass Action:
As uncharged drugs leave a compartment, the balance of charged/uncharged is maintained by the law of mass action.
Manipulating pH for Drug Clearance:
Drug Overdose Treatment: Altering pH can change drug ionization to influence drug clearance.
Example: Increasing pH in the kidney with sodium lactate can sequester acidic drugs in urine, enhancing excretion and reducing reabsorption.
Summary
Understanding the relationship between drug ionization, pH, and membrane crossing is crucial for optimizing drug absorption, distribution, and elimination in the body. Manipulating the pH of body compartments can be a strategic approach in treating overdoses and enhancing drug clearance.