The Uses and Actions of Local Anaesthetics Flashcards
Define local anaesthetic.
A drug that reversibly blocks nerve conduction when applied to a restricted area of the body to enable a procedure to be carried out without loss of consciousness.
What is the difference between local and general anaesthetics?
General anaesthetics are used to render a patient unconscious (eg with surgery), whereas local anaesthetics are not.
Describe the general chemical structure of local anaesthetics.
1 - An aromatic ring.
2 - An amine group.
3 - A linkage group between them.
What are the possible chemical forms of the linkage group in local anaesthetics?
Amide or ester.
At which point on the chemical structure are local anaesthetics metabolised?
Why is metabolism of local anaesthetics important?
- At the linkage group.
- Metabolism is important as the effect of local anaesthetic must be reversible.
Why do most modern local anesthetics have amide linkages?
- Ester linkages are metabolised faster then amide linkages.
- The metabolites of ester linkages are more toxic than that of amide linkages.
Give an example of a local anaesthetic that has an ester linkage.
Procaine.
List 3 examples of local anesthetics that have amide linkages.
State their relative durations of effect.
1 - Lidocaine (medium duration).
2 - Prilocaine (medium duration).
3 - Bupivacaine (long duration).
What important property does the aromatic ring of a local anaesthetic possess?
Lipid solubility.
What important property does the amine group of a local anaesthetic possess?
- The ability to become positively charged (gain a H+).
- Its ionisation state is determined by pH
Describe the equilibrium that exists between ionised and unionised local anaesthetics.
How does increasing alkalinity and acidity affect this equilibrium?
Anaesthetic + H2O -> Anaesthetic+ + OH-
- Increasing alkalinity shifts the equilibrium to the side with unionised anaesthetic.
- Increasing acidity shifts the equilibrium to the side with ionised anaesthetic.
At physiological pH (~7.4), which form of anaesthetic (ionised or unionised) is greater?
Ionised.
Describe the process by which local anaesthetic block nerve conduction at nociceptors.
1 - Unionised and ionised local anaesthetic exists outside the membrane of an axon of a nociceptor.
2 - The unionised local anaesthetic diffuses across the membrane to the inside of the axon.
3 - Some of the unionised local anaesthetic inside the axon dissociates to ionised local anesthetic (the pH inside is the same as the outside so the equilibrium is the same).
4 -The ionised local anaesthetic blocks Na+ channels, preventing nerve conduction.
What is use-dependent block?
- Local anaesthetics are said to be use-dependent as the degree of blockage of open channels is proportional to the rate of nerve stimulation (as there will be more open channels).
- Increase pain = increase block.
Give an example of a biological factor that can affect the effectiveness of local anaesthetic.
What might bring about a change in this factor to decrease effectiveness of local anaesthetic?
- Tissue pH.
- Inflammation / infection will increase pH.
What does the sensitivity of neurones to local anaesthetics depend on?
- Thickness.
- Myelination.
Which fibres convey information from nociceptors to the CNS?
1 - A-delta fibres.
2 - C fibres.
Why are motor neurones less sensitive to local anaesthetics than A-delta or C fibres?
Because motor neurones are thicker and more heavily myelinated.
What is the general principle for the routes of administration of local anaesthetics?
The more proximal the site of administration to the CNS, the greater the area anaesthetised.
List and describe the 5 possible routes of anaesthesia.
1 - Topical.
2 - Infiltration (inject into tissue being anaesthetised).
3 - Nerve block (inject more proximal to CNS).
4 - Epidural (inject into epidural space).
5 - Spinal (inject into subarachnoid space).
TINES!
List 6 side effects of local anaesthetics.
1 - Allergic reactions.
2 - Tremors.
3 - Convulsions.
4 - Respiratory failure.
5 - Decreased contractility of cardiac muscle.
6 - Vasodilation (so decreased blood pressure).
What causes the side effects of local anaesthetics?
The local anaesthetic will affect other excitable tissues (e.g. CNS, cardiovascular system) that operate using voltage gated Na+ channels.
Which local anaesthetic is the most cardiotoxic?
Bupivacaine.
What other drugs are often administered with local anaesthetics?
Vasoconstrictors (e.g. adrenaline / felypressin).
List 4 properties of good local anaesthetics.
1 - Reversible.
2 - Block nerve conduction in nociceptive neurones.
3 - Effective for time of procedure.
4 - Low toxicity.
