Local anaesthetics Flashcards
What is a local anaesthetic?
Drug which reversibly blocks neuronal conduction when applied locally.
How is a neuronal action potential generated?
Depolarisation of presynaptic membrane occurs.
Resting sodium channels open and sodium enters cells- membrane potential becomes more positive.
Sodium channels close (inactivation), potassium channels open, potassium leaves cells- membrane potential begins to become more negative, repolarisation.
Sodium channels restored to resting state but potassium channels still open, therefore cell refractory.
Sodium and potassium channels restored to resting state therefore cell will respond normally to further depolarising stimulus.
What are the three structural features all local anaesthetics have in common?
Aromatic region (benzene ring).
Ester or amide bond.
Basic amine side-chain (nitrogen group).
Give an example of an ester local anaesthetic.
Cocaine.
Give an example of an amide local anaesthetic.
Lidocaine.
What is the only local anaesthetic that does not have a basic amine side-chain, but instead an alkyl group?
Benzocaine.
How do local anaesthetics interact with sodium channels?
Local anaesthetic (weak base) is injected close to the sensory neuron. There is an equilibrium between charged and unionised forms of the LA. Only unionised form (free base) is lipid-soluble and can pass through the connective tissue sheath to gain access to the sensory axons inside the neuron. Equilibrium is reestablished between ionised and unionised forms of LA. Unionised form can pass through the outer membrane of the axon and gain access to the inside of the sensory axon. LAs work from inside the axons- can't work from outside. Equilibrium reestablished. Charged form has local anaesthetic property and blocks voltage sensitive sodium channels. Cationic form (BH+) reformed inside neuron and binds to inside of VSSCs and stereochemically hinders influx of sodium channels. Ion channel blocker. To bind to inside of channel, channel has to be open. HYDROPHILIC PATHWAY.
What are the effects of local anaesthetics?
Prevent generation and conduction of action potentials- block VSSCs.
Do not influence resting membrane potential.
May also influence channel gating.
Selectively block small diameter fibres and non-myelinated fibres.
Local anaesthetics are weak bases (pKa 8-9).
Infected tissue is more difficult to anaesthetise than normal tissue- tends to be more acidic, so more LA in ionised state.
What are the different routes/methods of administration of local anaesthetics?
Surface anaesthesia Infiltration anaesthesia Intravenous regional anaesthesia Nerve block anaesthesia Spinal anaesthesia Epidural anaesthesia
What is surface anaesthesia?
Applied to mucosal surface (mouth, bronchial tree, eyes, etc).
Spray (or powder).
High concentrations needed → systemic toxicity.
What is infiltration anaesthesia?
Directly into tissues → sensory nerve terminals.
Minor surgery- suturing, abscesses, etc.
Subcutaneous injection.
Adrenaline co-injection (not extremities)- local vasoconstriction to increase duration of action and reduce risk of toxicity, staunches bleeding.
What is intravenous regional anaesthesia?
i.v. distal to pressure cuff.
Limb surgery- e.g. setting fractured bone, removing plates or screws, etc.
Systemic toxicity of premature cuff release.
What is nerve block anaesthesia?
Close to nerve trunks, e.g. dental nerves.
Widely used, low doses, slow onset.
Vasoconstrictor co-injection retains LA at site of injection.
What is spinal anaesthesia?
Injected into subarachnoid space (intrathecal)- acts on spinal roots, mixes with CSF. Usually injected L3-L4, below the area where the spinal cord terminates to avoid spinal cord damage. Abdominal, pelvic, lower limb surgery, e.g. hip replacement surgery. Decreased blood pressure, prolonged headache- mixes with CSF so gains access to brain. Add glucose (increased specific gravity).
What is epidural anaesthesia?
Fatty tissue of epidural space- action on spinal roots.
Abdominal, pelvic, and lower limb surgery, painless childbirth.
Slower onset- higher doses.
More restricted action- less effect on blood pressure.
