Ionisation

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)