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→Pharmacokinetic Considerations
==Pharmacokinetic Considerations==
==Pharmacokinetic Considerations==
Local anaesthetic agents consist of a lipid-soluble (hydrophobic) aromatic ring joined to a basic (hydrophilic) amide group. The two groups may be either:
* '''Ester linked'''
** For example, [[#Procaine|procaine]] and cocaine.
** Local anaesthetics linked in this way are less stable in solution.
** Metabolism by tissue esterases, hepatic esterases and hydrolysis occurs. Products are subsequently excreted by the kidney. However, one product of metabolism is para-amino benzoic acid (PABA), which may cause allergic reactions.
* '''Amide linked'''
** For example, [[#Lidocaine|lidocaine]] and [[#Bupivicaine|bupivicaine]].
** Amide linked local anaesthetics can be stored longer than ester-linked drugs and are heat stable.
** Metabolism is by hepatic amidases, and excretion occurs via the kidney.
Local anaesthetics are weak bases and so at body pH of 7.4, more molecules are ionised than unionised. This makes it more difficult for drugs to cross the plasma membrane. Infected tissue has a lower pH than healthy tissue, causing the ratio of ionised:unionised molecules to increase. Because of this, there is poorly cellular uptake of local anaethetics in infected tisse, as they cannot cross the cell membrane. For more about the effect of pH on drugs, see the [[Pharmacokinetics#Physiological Variables|pharmacokinetics]] page.
Local anaesthetics are weak bases and so at body pH of 7.4, more molecules are ionised than unionised. This makes it more difficult for drugs to cross the plasma membrane. Infected tissue has a lower pH than healthy tissue, causing the ratio of ionised:unionised molecules to increase. Because of this, there is poorly cellular uptake of local anaethetics in infected tisse, as they cannot cross the cell membrane. For more about the effect of pH on drugs, see the [[Pharmacokinetics#Physiological Variables|pharmacokinetics]] page.