Flashcards in 12 - Local Anaesthetics Deck (37):
Local anaesthetics work by...
Block Na channels on cell memos so they can't depolarise
Block influx of Na across neuronal membranes
You wish to achieve rapid onset of local anaesthesia for insertion of a large catheter - what LA would you choose to infiltrate the skin?
What is the most important factor determining speed of onset for a local anaesthetic drug injected into health subcutaneous tissue?
The drugs pKa
Summary of nerve conduction physiology?
- terminal boutons link with dendrites of another cell
- APs are conducted by volt gated Na channels
Summary of volt gated Na+ channels
- pore in memba allowing Na movement
- activation and de-activation gate (in resting state act is closed and deact is open)
- the activation gate opens when a threshold depolarisation is reached causing a substantial depolarisation
- after a ms the deactivation gate closes and Na+ can't enter
- K+ leaves and repolarises the cell
Mechanism of action of LAs?
- prevention of voltage dependent increase in Na+
- the non-ionised form of the LA can easily cross the cell memb and enter the cell
- it then becomes re-ionized again and blocks the ion channel from the INSIDE
What is the effect of LAs on an AP?
Depolarisation is prevented and the threshold and resting potential are unchanged
What is the structure of an LA?
- has a hydrophobic (aromatic) and a hydrophilic end (amine) with an amide or ester link
What does whether the LA has an amide or ester link determine?
Determines the site of metabolism and potential to produce allergic reactions.
Esters are more unstable, more rapidly metabolised, shorter acting, more allergenic (aren't used as commonly)
4 examples of ester LAs
- cocaine (numb mucous membranes in the nose - also vasoconstrictor)
(benzocaine and tetracaine are topicals)
4 examples of amide LAs?
What determines potency in an LA?
Lengthening alkyl chain increases lipid solubility - the more lipid soluble the LA is the more potent it is (not really a big deal as can just increase dose)
Relative potencies of lignocaine, procaine, bupivicaine and prilocaine?
Procaine - 1
Prilocaine - 1.8
Lignocaine - 2
Bupivicaine - 8
All LAs are ...
Exists as both an ionised form and free base
What determines the speed of onset of action for an LA?
Only free base can cross membranes and enter cells - the most free base is present the faster the onset of action.
The amount of free base present at physiological pH depends on the pKa of the drug.
Therefore the drugs pKa determines the speed of onset of action
Relative speeds of action of onset?
Slow to fast
Procaine (highest pKa/lowest % free base)
Which LAs have the fastest onset of action?
Those with a pKa closest to physiological pH (lignocaine is 7.9)
Lower pKa > more free base > faster onset of action
Why is there a poor quality of block when LA is injected into hypoxic and infected tissue?
Hypoxic, infected tissue becomes acidic and so changes the pH.
What determines duration of action in LAs?
Duration of action is proportional to degree of protein binding.
The higher the affinity to protein binding the longer the duration of action.
How are amides and esters metabolised?
- hepatic and so is dependent on liver BF
- plasma cholinesterase
What is the pKa?
The pH at which you have 50% ionised form and 50% free base
Higher pKa than pH > more ionised
Low pKa > more free base
What is use dependence?
LAs have a greater affinity for channels that are active (opening often)
Means the ones that are opening and need blocking are being blocked
What LA to use for fast relief at post tibial nerve?
Fast onset of action
Bupivicaine for longer duration
- low potency
- low pKa so fast onset
- low protein binding so short duration of action
Ideal for short surgical procedures like dental or mole removal or IV
- highly soluble and potent
- high pKa so slower onset of action
- high protein binding - longer duration
Ideal for nerve blocks for analgesia
Topical to nose
Used in IV regional anaesthesia
Long duration of action
Has less cardiac toxicity compared to bupivicaine
How can LAs cause toxicity?
1. Allergic reactions - rare with amides
2. Dose dependent CNS toxicity
> peri-oral paraesthesia
3. Dose dependent cardiac toxicity
> heart block and VF (cardiac arrest)
> more likely with bupivicaine
What is the CC:CNS?
Accidentally get LA into a vein (trying to get a block into the nerve)
More likely to have CNS toxicity (seizure) first
Ratio of dose needed to produce a cardiac arrest compared to a seizure (want big)
Lignocaine = 7
Bupivacaine = 3
How are LAs applied topically to the skin?
EMLA - eutectic mixture of LAs
Mixture of lignocaine and prilocaine as an oil preparation that allows most to be free base and so is able to cross the skin (lipid base not aqueous)
Is used for insertion of an IV cannula in kids
How are LAs applied topically to mucus membranes?
> awake intubation
- Lignocaine spray and viscous preparations
> instrumentation of the nose, mouth, pharynx, urethra
What is soft tissue infiltration?
It is used for minor interventions like mole removal where you would use a fast acting short duration agent
Can also use it for post-op pain relief where you would use a slow acting long duration agent
2 types of nerve blocks?
Neuraxial and peripheral nerve blocks
How does a peripheral nerve block work?
The LA is infiltrated around a specific nerve usually under US guidance i.e. brachial plexus if operating on the arm
In a mixed nerve the smaller sensory fibres are more susceptible to the LA but the motor fibres can also be affected
Peripheral nerve blocks can also be used during surgery without a general anaesthetic or for post op pain relief
How does a neuraxial blockade work?
The LA is injected into the intrathecal space below L2 (termination of spinal cord - subarachnoid space/CSF)
Results in a profound distal motor and sensory blockade and so allows for major surgery like a hip/knee replacement, C section to occur in an awake patient