Local Anaesthetics Flashcards
Briefly describe what a local anaesthetic does
Produces a loss of pain sensation without affecting consciousness
What sort of chemical is a LA?
- Weak bases (pKa 7-9)
- More ionised at a pH of 7.2, more unionised at a higher pH
Why do drugs with ester bonds such as Procaine have a shorter half-life?
Ester bonds can be hydrolysed by esterases
How do we use ion trapping with LAs?
- We get the drug through the myelin sheath and the axonal membrane by making it non-ionised (in alkaline solution).
- Ionised LAs are more effective at blocking Na channels, so inside the cell has a pH closer to the pKa of LAs, allowing it to ionise and block Na channels.
How are APs generated and conducted?
- We have a RMP of -75mV, created by a 3Na+/2K+ pump.
- This wants to bring in Na+ ions
- A stimulus causes the membrane to depolarise enough to reach a threshold (-50mV) where sodium channels open, allowing a rapid influx of sodium ions.
- Potassium channels then open allowing a rapid efflux of potassium, hyperpolarising the membrane.
What is the mechanism of action of LA?
- Block sodium channels, meaning that the generation and conduction of APs is blocked.
- No APs, no information sent to CNS, no pain perception
Why are LAs given locally?
LA will block any voltage-dependent sodium channel irrespective of the tissue. Giving them locally reduces systemic effects
How do LAs block Sodium channels
Na channels have a sequence: closed -> (depolarise) open -> inactive -> (hyperpolarise) closed
- In inactive state, the channel is in refractory, have to hyperpolarise it
- Some LAs block closed state if they are unionised
- If they are ionised, they will block the open state, or more likely the inactivated state.
What is the difference between procaine and lignocaine?
Lignocaine has an amide bond (less susceptible to hydrolysis), whereas procaine has an ester bond
How can we block high activity cells, but leave low ones?
- If a cell has a high activity, it will have more Sodium channels in an inactive state
- We can use “use-dependent” drugs that only block Na channels in the inactivated state.
- Gives less side-effects as low activity neurones are not effected
Why do we use use-dependent drugs for epilepsy?
We just want to stop the high activity cells stop stop the convulsions.
Why are pain fibres blocked before other sensory or motor nerves?
- LAs block unmyelinated, small diameter axons before larger ones as they are easier to get into.
- A-delta fibres are myelinated but have a small diameter
- C-fibres don’t have myelin sheaths
What unwanted effects can LAs have in the CNS?
- If LAs enter the brain, they will initially cause stimulation (tremor, agitation, convulsions)
- After this they will cause depression of centres in the brain such as respiratory - respiratory problems
What unwanted effects can LAs have in the CVS?
- blocking Na channels in the heart will lead to decreased calcium influx and so decreased force of contraction
- it will inhibit sympathetic nerve activity innervating blood vessels, leading to vasodilation and decrease vascular tone
- both of these will reduce blood pressure and could cause hypoperfusion of organs
What are the different routes of administration of LAs?
- Surface anaesthesia-applied to mucosal surfaces (doesnt cross skin well)
- Nerve block - injected close to a sensory nerve
- Spinal - inject LA into CSF as bottom of spine
- Epidural - LA injected into epidural space outside meninges - diffuses to and blocks nerve roots
