3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.1. Pharmacology principles
                      3.1.3.1.1. Pharmacokinetics
                          3.1.3.1.1.3. Distribution of drugs
 3.1.3.1.1.3.2. Ionisation 

Ionisation

[SH4:p11]

Also see [Acid-base ionisation]

Ionisation and pH

Most drugs are either weak acids or base
--> Exist in 2 forms in solution

  • Ionised
    * Poor lipid sobility
  • Non-ionised
    * Lipid soluble

NB:

  • When pH = pK
    --> Ionised fraction = non-ionised fraction

Acidic drugs

  • More ionised at alkaline pH (high pH)
  • e.g. barbituates

Basic drugs

  • More ionised at acidic pH (low pH)
  • e.g. opioids, local anaesthetics

Ion trapping

  • Non-ionised fraction
    --> High lipid solubility
    --> Equilibrate across cell membrane
  • When pH differs across cell membranes
    --> Total drug level across the membrane will differ

For example,

  • Non-ionised weak basic drug diffuses into stomach
    --> Low pH causes the drug to become ionised
  • Ionised fraction becomes "trapped"
  • Concentration of non-ionised drug drops
    --> Concentration gradient is maintained

Thus,

  • Weak base accumulates in stomach

Similarly,

  • Local anaesthetics (weak base) accumulates in foetus (lower pH)