Pharmacology of local anaesthetics Flashcards
Define anaesthesia
Without feeling or sensation
Define local anaesthesia
Loss of feeling restricted to a particular region
When is local anaesthesia used?
To enable minor or major operative procedures to be carried out
To provide relief from prolonged severe pain
What can local anaesthesia be produced by?
- Local anaesthesia can be produced by:
- Cooling with ethyl chloride (block of neuronal conduction at 8-10°C)
- Pressure (used to reduce discomfort from injection in palatal tissue)
- Hypoxia
- Irreversible blockade (phenol ethanol, radiofrequency lesion)
- true local anesthetics
Give examples of irreversible blockers used as local anaesthetics
Phenol ethanol
Radiofrequency lesion
Describe true local anaesthetics
A substance applied to any nerve fibre in sufficient concentration will produce reversible blockade of axonal conduction without depolarisation
What is a local anaesthetic?
A local anaesthetic is a drug that causes reversible local anaesthesia and a loss of nociception (the neural processes of encoding and processing noxious stimuli)
Define nociception
The neural processes of encoding and processing noxious stimuli
How do local anaesthetics work?
They reversibly block impulse conduction along nerve axons and other excitable membranes that utilise sodium channels as the primary means of generating action potentials
What is the result of using local anaesthetics on specific nerve pathways?
Effects such as analgesia and paralysis can be achieved
Define analgesia
Loss of pain sensation
Loss of pain sensation
Loss of muscle power
Name some techniques local anaesthetics are used in?
- Topical application
- Subcutaneous injection
- Nerve block
- Epidural
- Intrathecal
Where is a topical anaesthetic applied?
Around the gums, cornea and skin prior to venipuncture
What is a Subcutaneous injection?
An infiltration anesthesia can be one or more injections
Where is a nerve block applied?
Around the nerve
Where is an epidural given?
Into the epidural space
Where is an intrathecal anesthetic given?
Into subarachnoid space
It is a form of spinal anesthesia
List some ideal properties of local anesthetic
- stable in solution, (requires no additive)
- non-irritating to tissues
- no permanent damage to nerves
- no systemic toxicity
- no allergic response
- potent
- rapid onset of action
- predictable duration of action
- Must be a sensory not a motor block
- Must have no active metabolites
On what day is the first recorded use of general anaesthetics?
October 16th 1846
What did Dr Karl koller notice?
That the end of his tongue went numb when he tasted cocaine
He then dropped some cocaine dissolved in water into his eye – noticed its tissue-numbing capabilities
What did Dr Koller demonstrate in 1884?
The potential for cocaine to be used as a local anaesthetic in eye surgery
What is Dr Kollers nick name?
Coca Koller
What replaced cocaine as a local anaesthetic and when?
In the 20th century, other agents such as lidocaine replaced cocaine as a local anaesthetic
What is the aromatic terminal of LA’s described as and why?
Lipophilic as is contains no positive or negative charges
Define lipophilic
Lipid soluble
Why is the aromatic terminal essential for LA’s?
In order for them to penetrate fatty tissues such as the lipid sheath of nerves in order to gain access to the nerve cell membranes to reach its site of action
What is the amino terminal in local anaesthetics described as?
Water soluble or hydrophilic
Why is solubility in water essential for LA’s?
- To allow for the dissolution in a solvent to permit injection
- To allow penetration through interstitial fluid allowing administration
How does the amide structure of articaine differ from other local anaesthetics?
The amide structure is similar but the molecular structure differs through the presence of a thiophene ring instead of a benzene ring
Name some ester linked agents
Cocaine
Procaine
Describe what cocaine does and when it was used?
It was first used in 1884,
It is a good penetrator
It is not used as much now as it is a drug of abuse,
It blocks sodium re uptake
What are the major disadvantages of cocaine?
Cocaine is an intense vasoconstrictor and has a potential to cause cardiovascular toxicity
Describe what procaine does and when it was used?
First used in 1905 as a nerve blocker
Has low potent and last for a short duration
Not used much now
Name the type of procaine given as an epidural during childbirth
2-chloroprocaine
Name some amide linked agents
- Lidocaine
- Prilocaine
- Mepivacaine
- Bupivacaine
- Ropivacaine
- Articaine
What does lidocaine do?
It is used as a vasodilator
It reduces cardiac excitability
Affects the central nervous system in large doses
Name the most commonly used amid linked LA used in dent?
Articaine
Name the ketone type agent we use as an LA
Dyclonine
What is dyclonine used as?
A liquid topical anaesthetic agent
Heat properties does dyclonine have
Has bactericidal and fungicidal properties
What is the pKa of most LAs and what does this mean?
Between 8.0 -9.0
This means at pH 7.4about 5 - 20% of the LA will be in the non ionised form
What does a pKa value indicate?
It is the acid dissociation constant
It indicates the pH at which the ionised and non ionised forms of the substance are at equal concentrations
Why must a high concentration of LA be administered?
As only a small fraction of LA molecules will reach the target site
Name some of the major determinant of how well the LA will penetrate the tissues
- Site of administration
- the lipid solubility of the drug
- The pKa of the drug
- Pathophysiological factors eg inflammation
What are sodium channels?
They are integral membrane proteins that form ion channels
These channels allow sodium ions to pass through the cells plasma membrane
What is the trigger for voltage gated sodium channels to open?
Voltage change
How do local anaesthetic drugs affect sodium channels?
They inhibit the influx of Na+ ions through ththe voltage gated sodium Channels
This means an action potential cannot be generated so conduction inhibited
What is an action potential?
It is a self regenerating wave of electrochemical activity that allow excitable cells to carry a signal over a distance
When are sodium channels closed?
When the channel is fully polarised
What happens as you increase the concentration of LA to thte nerve fibre?
- Threshold for excitation increases
- Impulse conduction slows
- Rate of the rise of the action potential declines
- Actionable potential amplitude decreases
- Ability to generate action potential is abolished
What is the sensitivity to inhibition by LAs a function of?
Nerve diameter
Myelination
Describe post ganglion is autonomic nerves
They have a small diameter and are unmyelinated
State the order of sensitivity to LA inhibition
Autonomic > warmth > pain> touch > pressure
Do sodium channels in the rested state or activated state have a higher affinity to LA?
Channels in the activated state
Which LA blocks only the sodium ion channels in their resting state?
Benzocaine
What is acidosis?
An increased acidity of the blood plasma
When does acidosis occur?
When arterial p( falls below 7.35
When does alkalosis occur?
When arterial pH is over 7.45
What does acidosis do?
It can partly reduce the action of LA
Why does acidosis reduce the action of LA?
Because most of the anaesthetic is ionised and therefore can not cross the cell membrane to reach the cytoplasmic facing site of action on the sodium channel
Local anaesthetic in which form can cross the cell membrane?
Only the non ionised for of LA can cross the cell membrane to reach the cytoplasmic facing site of action on the sodium channel
Describe characteristic of neurones that are more sensitive to blockage by LA
- Short axons
- Nerves which are not in their resting state
- Small myelinated nerves
- motor nerves are usually blocked first in large mixed nerves
What happens to the level of inhibition when there are long intervals between nerve impulses?
The level of inhibition of each impulse will be the same (tonic blockade)
What happens to the level of inhibition when there are short intervals between nerve impulses?
The level of inhibition increases with each impulse (phasic blockade)
Administration of LA at which side has the fastest absorption rate?
Intravenous
Administration of LA at which side has the slowest absorption rate?
Subcutaneous infiltration
List the sites we can administer LA from fastest to slowest absorption rate
- Intravenous
- Mucous membrane
- Intercostal block
- Causal block
- Epidural block
- Brachial plexus block
- Peripheral nerve block
- Subcutaneous infiltration
What us hypersensitivity a result of?
Anaphylactic reaction (allergic reaction) to LA
Hypersensitivity is associated with which toe of LA?
Esters and very rarely with amides
How can LA toxicity affect the CNS?
Initial effects are excitatory with involuntary muscle activity
Later effect is depressant which may lead to unconsciousness
How can LA toxicity affect the Heart?
Possible feduction in cardiac output may lead to circulatory collapse
(Rare)
What is a toxic effect of prilocaine and articaine?
Methaemoglobinaemia
What are some of the symptoms of Methaemoglobinaemia?
- Cyanosis
- Lethargy
- Respiratory distress which doesn’t respond to oxygen
What is the treatment for Methaemoglobinaemia?
Administer methylene blue intravenously 1-2mg/kg
Is Methaemoglobinaemia a concern in the dental practice?
No because we use small amounts of LA
What do vasoconstrictors do?
They restrict the diffusion of the LA away from the site of injection and thus allows the LA to stat at rhs site for longer producing a longer duration of action
Wh6 are LAs frequently given with vasoconstrictors?
To:
- prolong action
- reduce plasma levels (less risk of CNS effects?)
- ‘greater anaesthesia’ or reduced dose
- reduced operative haemorrhage
Which vasoconstrictors is usually used?
epinephrine (adrenaline) 1:200,000, or norepinephrine (noradrenaline) 1:100,000
When are vasoconstrictors not administered with LA?
when injected into extremities (fingers & toes) since, with a more limited circulation, there is a risk of tissue hypoxia
