The mechanism of action & The structural classification of Local Anesthetics
Local anesthetic drugs are used widely for the provision of anesthesia and analgesia both intra- and post-operatively.
We can inject an anesthetic locally; directly on a nerve; place it into the epidural or subarachnoid space, catching several nerves at once; or paintor spray it on mucous membrane as atopical anesthetic.
The mechanism of action of local anesthetics:
Local anesthetics disrupt ion channel function within the neurone cell membrane preventing the transmission of the neuronal action potential.
This is thought to occur via specific binding of the local anesthetic molecules (in their ionized form) to sodium channels, holding them in an inactive state so that no further depolarization can occur.
A second mechanism is also thought to operate, involving the disruption of ion channel function by the incorporation of local anesthetic molecules into the cell membrane (the membrane expansion theory). This is thought to be mediated mainly by the unionized form acting from outside the neuron.
The structural classification of local anesthetics:
Local anesthetics come in two chemical classes: esters and amides.
1-Esters (Chloroprocain, Procaine, Tetracaine)
2-Amides (Bupivacain, Etidocaine, Lidocaine, lignocaine, Mepivacaine, Ropivacaine)
Local anesthetics generally have a lipid-soluble hydrophobic aromatic group and a charged, hydrophilic amide group. The bond between these two groups determines the class of the drug, and may be amide or ester.
Structure-activity relationships:
-Potency is related to lipid solubility
-The duration of action is related to protein binding at the site of action and factors which affect removal of drug from the site, e.g. blood supply.
-The speed of onset/latency depends on the local availability of unionized free base. This can be improved by increasing the concentration of local anesthetic or increasing the pH of the local anesthetic/tissues. It is also dependent on the pKa of drug and the pH of the solution (a high pKa is associated with slow onset in normal pH settings, e.g. bupivacaine).
Local anesthetic drugs are used widely for the provision of anesthesia and analgesia both intra- and post-operatively.
We can inject an anesthetic locally; directly on a nerve; place it into the epidural or subarachnoid space, catching several nerves at once; or paintor spray it on mucous membrane as atopical anesthetic.
The mechanism of action of local anesthetics:
Local anesthetics disrupt ion channel function within the neurone cell membrane preventing the transmission of the neuronal action potential.
This is thought to occur via specific binding of the local anesthetic molecules (in their ionized form) to sodium channels, holding them in an inactive state so that no further depolarization can occur.
A second mechanism is also thought to operate, involving the disruption of ion channel function by the incorporation of local anesthetic molecules into the cell membrane (the membrane expansion theory). This is thought to be mediated mainly by the unionized form acting from outside the neuron.
The structural classification of local anesthetics:
Local anesthetics come in two chemical classes: esters and amides.
1-Esters (Chloroprocain, Procaine, Tetracaine)
2-Amides (Bupivacain, Etidocaine, Lidocaine, lignocaine, Mepivacaine, Ropivacaine)
Local anesthetics generally have a lipid-soluble hydrophobic aromatic group and a charged, hydrophilic amide group. The bond between these two groups determines the class of the drug, and may be amide or ester.
Structure-activity relationships:
-Potency is related to lipid solubility
-The duration of action is related to protein binding at the site of action and factors which affect removal of drug from the site, e.g. blood supply.
-The speed of onset/latency depends on the local availability of unionized free base. This can be improved by increasing the concentration of local anesthetic or increasing the pH of the local anesthetic/tissues. It is also dependent on the pKa of drug and the pH of the solution (a high pKa is associated with slow onset in normal pH settings, e.g. bupivacaine).
