Local Anaesthetics

Frage	Antworten
What are local anaesthetics?	Substances which produce a local loss of pain sensation without affecting consciousness
What was the first LA discovered? What has been developed since, that is used instead of the original substance?	Cocaine was first LA to be discovered, then a synthetic substitue 'procaine', now developed to lignocaine
How do LAs produce a loss of pain sensation?	Block Na+ channels so afferents cannot fire APs on response to painful stimuli.
Chemically, what are LAs?	Weak bases (pKa 7 - 9)
What is the key difference between procaine and lignocaine? Why is this significant?	Procaine has an ester bond, whereas lignocaine has an amide bond. The ester bond in procaine is susceptible to hydrolysis, thus lignocaine will have a longer half-life and its effects will last for longer.
How do Na+ channels play a part in transmission of APs?	In order for an AP to be generated, voltage-gated Na+ channels must open to allow an influx of Na+ ions, causing a rapid depolarisation of the membrane.
How does this stop the perception of pain?	If the Na+ channels are blocked, then APs cannot be generated or conducted. This means that the response to the painful stimulus cannot be transmitted to the CNS, where it is usually perceived as pain.
Why are local anaesthetics only given locally and not taken systemically?	If they were to enter the circulation, LAs would block any Na+ channel, so would have profoundly negative effects on other tissues such as the heart.
Where do the LAs have to be to be effective?	Inside the cell
How can LAs enter the cell? What prevents them from diffusing out again?	In alkaline solutions, the LA will act as a proton donor and exist in its unionised form so it can diffuse into the cell. Once inside the cell, the pH is 7.2 and thus favours the LA existing in its ionised form, causing it to become 'trapped' in the cell.
Which form of LA is most effective at blocking Na+ channels?	Ionised
In what 3 states can Na+ channels exist?	1. Closed state (at RMP) 2. Open state (on depolarisation) 3. Inactive state (on hyperpolarisation)
What is the idea of use-dependence?	Some LAs only work when they are in the inactivated state, so in areas where there are lots of APs firing (such as in damaged tissue), there are lots of Na+ channels in their inactivated state and thus the LA can have a large effect there. In areas of normal tissue where there are not lots of APs firing, there are not many inactive Na+ for LAs to work on, and thus they would not have an effect here. This enables the LA to only be effective on the damaged tissue itself.
Why are pain fibres blocked before other sensory and motor fibres?	The pain fibres (A-delta and C) are the smallest and least myelinated fibres, which LAs will act on first.
What are the side effects if LAs enter the CNS?	initially they can cause stimulation resulting in tremors and convulsions, but then would lead to CNS depression, resulting in respiratory problems
What happens if LAs enter the circulation?	They would have effects on the Na+ channels in the heart, causing less Ca++ influx and therefore a lower force of contraction. The sympathetic fibres giving vascular tone would also be inhibited so vessels would dilate, both causing a decrease in blood pressure, which can result in end organ damage.
What are 4 ways of administering local anaesthetics?	1. On the surface, as creams or sprays onto mucosal surfaces 2. Nerve block, where LA is injected close to a sensory nerve 3. Spinal anaesthesia into the subarachnoid space 4. Epidural
What is sometimes also administered with LAs?	Adrenaline
What effect does this have?	Adrenaline produces local vasoconstriction by acting on the alpha-1 receptors in VSMCs. This helps keep the LA in the local area and therefore prolongs the action.
What can be a side-effect of this?	1. If vasoconstricting an end-artery, could result in local hypoxia and loss of digits. 2. If adrenaline is absorbed into the systemic circulation, can cause arrhythmias.

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