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Ionization

Table of Contents

Introduction

  • Mammalian cell membranes are charge neutral
    • Uncharged molecules can pass through the membrane 
    • Charged or ionized molecules cannot
      • Must go through channels 
  • Most drugs are weak acids or weak bases 
  • Their dissociation tendencies are based on pKa and the Hendersen-Hasselbach equation:

Weak Base

  BH+ = B + H+ 

  • pKa = pH + log [BH+]/[B] 
  • In an ACIDIC environment, this equation will shift left to the ionized form 
    • Example:  
      • In an acidic environment, the drug will be associated and in its ionized form thus trapping it outside of the cell in the compartment with a low pH 
  • In an ALKALINE environment, this equation will shift right to the uncharged form 
    • Example: 
      • In an alkaline environment, the drug will be dissociated and in its uncharged form allowing it to cross the lipid membrane  

Weak Acid

AH = A- + H+ 

  • pKa = pH + log [AH]/[A] 
  • In an ACIDIC environment, this equation will shift left to the uncharged form 
    • Example:  
      • In an acidic environment, the drug will be associated and in its uncharged form allowing it to cross the lipid membrane  
  • In an ALKALINE environment, this equation will shift right to the ionized form 
    • Example: 
      • In an alkaline environment, the drug will be dissociated and in its ionized form thus trapping it outside of the cell in the compartment with a high pH 

Important Consequences

  • A weak acid is more likely to be absorbed from the stomach 
  • Urinary acidification will accelerate the excretion of weak bases and retard that of weak acids 
  • Increasing the plasma pH will cause weakly acidic drugs to be extracted from the CNS to the plasma