Lecture 10: Pharmacology of Pain 3: Local anaesthetics Flashcards
What are local anaesthetics?
- Produce a transient and reversible loss of sensation (analgesia) in a region of the body without loss of consiousness
- Usually completely reversible
What are some examples of local anaesthetics?
- Benzocaine, Cocaine, lidocaine, bupivacaine (delayed onset but longer duration)
What are the classes (depending on structure) of local anaesthetics?
- Esters (of benzoic acid): Cocaine, butacaine, tetracaine
- Amides: Bupivacaine, Lidocaine
What is the general structure of local anaesthetics?
- Aromatic Ring: lipophilic portion (can travel through membrane)
- Intermediate linkage: Ester or amide bond. Can separate into both classes
- Terminal amine: hydrophilic portion (different between different anaesthetics)
How do local anaesthetics work?
- Binding to Sodium Channels: Target voltage-gated sodium channels on the nerve cell membrane.
- Preventing Action Potentials: By binding to the sodium channels. They inhibit influx of Na+. This prevents depolarization and action potentials. Without action potentials, the nerve cannot transmit signals.
- Localized Effect
- Reversibility: Once anesthetic is metabolized or washed away, normal nerve function resumes.
What are the 3 states of a voltage gated channel?
- Resting State: The ion channel is closed. Prepared to open in response to a specific stimulus, such as a change in voltage or binding of a ligand. (start)
- Activated Open State: When activated (for example, by depolarization). Ions flow through the channel, allowing for rapid changes in the membrane potential and the propagation of impulses.
- Inactivated State: After a period in the open state, they enter an inactivated state. In this state, the channel is temporarily unable to open, even if the conditions for opening are met (e.g., the membrane potential is still depolarized). This state is crucial for ensuring the unidirectional flow of action potentials and allows for recovery of the membrane potential.
Which nerve fibres are the most responsive to local anaesthetics?
- C dorsal root and sympathetic fibres
What is a main effect of local anaesthetics?
- Vasodilation
- Ester anaesthetics are potent vasodilating drugs (go through BBB and blood stream quickly)
Does cocaine have a vasoconstricting or vasodilating effect?
- Vasoconstriction. It stimulates the sympathetic nervous system. Cocaine blocks the reuptake of noradrenaline at nerve terminals, which leads to increased levels in the synaptic cleft. This stimulates alpha-adrenergic receptors on blood vessels, resulting in vasoconstriction.
- Cocaine can lead to increased BP and reduced blood flow to certain areas
What property of an anaesthetic makes it more potent?
- Higher lipid solubility = more potent
- Can use a lower concentration and reduce toxicity
How is the duration of action determined in anaesthetics?
- Protein binding
- How long it occupies channels
How long does it take for anaesthetics to be effective and which classification is more stable?
- Effective within 5 mins
- Duration of action - 1-1.5 hrs
- Amides more stable, longer half life
- Activity is pH dependent
How are ester and amide anaesthetics cleared?
- Esters: hydrolysis via plasma cholinesterase
- Amides: metabolism via hepatic enzymes
Which organ is the main excretory organ for local anaesthetics ?
- Kidneys
- Esters appear in small conc in urine - cause they are almost completely hydrolyzed in plasma
- Patients on dialysis are unlikely able to excrete unchanged portion thus increasing toxicity
What are the main systemic effects of local anaesthetics?
- CNS depression
- High levels of: tonic clonic convulsions
- Procaine, lidocaine, cocaine - anticonvulsant properties
