Degree of ionisation
This is really important with regard to local anaesthetics. The essential fact to know is that highly ionized drugs cannnot cross lipid membranes (basically they can't go anywhere) and unionised drugs can cross freely. Morphine is highly ionised, fentanyl is the opposite. Consequently the latter has a faster onset of action. The degree of ionisation depends on the pKa of the drug and the pH of the local environment. The pKa is the the pH at which the drug is 50% ionised. Most drugs are either weak acids or weak bases. Acids are most highly ionised at a high pH (i.e. in an alkaline environment). Bases are most highly ionised in an acidic environment (low pH). For a weak acid, the more acidic the environment, the less ionised the drug, and the more easily it crosses lipid membranes. If you take this acid, at pKa it is 50% ionised, if you add 2 pH points to this (more alkaline), it becomes 90% ionised, if you reduce the pH (more acidic) by two units, it becomes 10% ionised. Weak bases have the opposite effect.
Local anaesthetics are weak bases: the closer the pKa of the local anaesthetic to the local tissue pH, the more unionised the drug is. That is why lignocaine(pKa 7.7) has a faster onset of action than bupivicaine (pKa 8.3). If the local tissues are alkalinised (e.g. by adding bicarbonate to the local anaesthetic), then the tisssue pH is brought closer to the pKa, and the onset of action is hastened.
This is really important with regard to local anaesthetics. The essential fact to know is that highly ionized drugs cannnot cross lipid membranes (basically they can't go anywhere) and unionised drugs can cross freely. Morphine is highly ionised, fentanyl is the opposite. Consequently the latter has a faster onset of action. The degree of ionisation depends on the pKa of the drug and the pH of the local environment. The pKa is the the pH at which the drug is 50% ionised. Most drugs are either weak acids or weak bases. Acids are most highly ionised at a high pH (i.e. in an alkaline environment). Bases are most highly ionised in an acidic environment (low pH). For a weak acid, the more acidic the environment, the less ionised the drug, and the more easily it crosses lipid membranes. If you take this acid, at pKa it is 50% ionised, if you add 2 pH points to this (more alkaline), it becomes 90% ionised, if you reduce the pH (more acidic) by two units, it becomes 10% ionised. Weak bases have the opposite effect.
Local anaesthetics are weak bases: the closer the pKa of the local anaesthetic to the local tissue pH, the more unionised the drug is. That is why lignocaine(pKa 7.7) has a faster onset of action than bupivicaine (pKa 8.3). If the local tissues are alkalinised (e.g. by adding bicarbonate to the local anaesthetic), then the tisssue pH is brought closer to the pKa, and the onset of action is hastened.
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