Local Anaesthesia Flashcards
What is a local anaesthetic ?
a drug or agent which reversibly blocks neuronal transmission in the applied region causing a temporary loss of sensation/pain, without affecting consciousness
What is a general anaesthetic?
a drug or agent which produces a loss of response to painful stimulation (analgesia) and a loss of reflexes (motor and autonomic) with a reversible loss of consciousness
What is an analgesic?
a drug or agent which relieves and prevents pain without a loss of consciousness
What is a sedative?
a drug or agent which reduces irritability, excitement or nervousness
Where is LA injected?
Near nerve branches innervating the small, specific area of the body near the surgical site
Briefly state some reasons why LA is clinically useful
temporary and rapid in action, completely reversible
sufficient potency to provide complete anaesthesia
sufficient in duration to complete procedure comfortably
not irritating to tissues
does not produce allergic reaction (hypoallergenic)
not addictive
low degree of systemic toxicity
high therapeutic ratio
What was the first naturally occurring local anaesthetic
cocaine
Found in coca leaves
Who was the first clinician to inject cocaine to perform a peripheral nerve block? When did this take place?
William Halsted (1884)
What does a low therapeutic index refer to ?
This is when there is a small difference between the therapeutic and toxic doses of a drug
Give an example of a toxic effect of cocaine
respiratory depression
There is a potential for abuse an addiction when using cocaine. Briefly state why this is the case
CNS stimulant, psychological dependence
crave drugs euphoric and stimulatory effects
What are the short term CNS effects of cocaine?
Mydriasis (dilated pupils)
headache
nausea
vomiting
muscle tremors
twitching
pseudohallucinations (cocaine bugs)
What are the long term CNS effects of cocaine?
Generalised seizures
hallucinations
gross muscle tremors and twitching
decreased responsiveness to stimuli
increased deep tendon reflexes
incontinence
What are effects of a cocaine overdose on the CNS?
Generalised convulsions
cerebral infarction and haemorrhage
pupils fixed and dilated
flaccid paralysis
loss of vital support functions
CNS depression
coma
What are the short term cardiovascular system effect of cocaine?
vasoconstriction
hypertension
tachycardia
pallor
What are the long term cardiovascular effects of cocaine?
cardiac dysrhythmias
hypertension
tachycardia
peripheral cyanosis
What is cyanosis?
blue/grey lips or skin; happens when there is not enough blood supply to these areas
What are effects of a cocaine overdose on the cardiovascular system?
aortic dissection
MI
cardial arrest
What are short term respiratory effects of cocaine?
increase in breathing rate and depth
What are long term respiratory effects of cocaine?
abnormally rapid breathing (tachypnoea)
shortness of breath/gasping (dypnoea)
irregular breathing pattern
What are the effects on a cocaine overdose of the respiratory system?
respiratory depression
respiratory failure
cyanosis (lack of oxygen)
gross pulmonary oedema
paralysis of respiration
What are the short term effect of cocaine on the body temperature?
elevation
What are the long term effects of cocaine on the body temperature?
sever hyperthermia
What is the effect of a cocaine overdose on the body temperature?
Severe hyperthermia
What are the short term behaviour effect of cocaine?
euphoria
elation
excitation
restlessness (increased motor activity)
Garrulousness (excessively talkative)
alert
energetic
strong
paranoia
What are the short term behaviour effect of cocaine?
social maladjustment
paranoia
depression
agitation
difficulties with emotion regulation and impulse control
violent or suicidal tendencies
What is the effect of a cocaine overdose on behaviour?
death
Synthetic local anaesthetics are broadly split into ________ and _______.
Esters
Amide
State a method that can be used to identify ester and amide local anaesthetics
Amides have an “i” in the prefix before the “caine” whilst esters do not
Name some examples of ester LA
Cocaine
Procaine
Tetracaine
Benzocaine
Give some examples of amide LA
Bupivacaine
Lidocaine (lignocaine)
Articaine (has an ester side-chain)
Prilocaine
Regarding the structure of amides and esters; they both contain an ________
aromatic ring
Ester LAs are metabolised by …
plasma esterases
Amide LAs are metabolised by…
hepatic enzymes
What does pharmacokinetics refer to ?
what the body does to the drug
ADME
What does pharmacodynamics refer to?
what the drug does to the body
Local anaesthetic drugs are classified as …
Weak bases
BH+ <—-> B + H+
B exists as the unionised form
At the physiological pH of 7.4, all local anaesthetics will exist in what form ?
more will be in the ionised form as opposed to the unionised from
What affects the proportions of ionised V unionised forms of LA at physiological pH 7.4?
The pKa
How much exist in ionised form
How much exist in unionised form
What percentage of lidocaine exists in the unionised form?
25%
What percentage of bupivacaine exists in the unionised form?
15%
Between lidocaine and bupivacaine, which one of these would reach their target site more quickly and why?
lidocaine reaches the target site more quickly and has a faster onset of action because more of it exists in the unionised form and thus can cross the membrane and reach the target site much quicker
Why would LA delivery be less effective in a patient with irreversible pulptitis?
“Hot tooth” will have infected/inflamed tissue; infected environments tend to have a lower (acidic) pH; this means that a greater proportion of LA will exist in the ionised form (BH+)
the ionised form is unable to penetrate the cell membrane and therefore is less effective
Areas of inflammation also have an increased body supply due to vasodilation and thus this might increase “wash-out” before it can reach the site of action on the neurone
What are the 4 principles of local anaesthetics?
Lipid solubility
Dissociation constant
Chemical linkage
Protein binding
Lipid solubility correlates to the _______ of LA
potency
The dissociation constant (pKa) correlates to the ___________.
time of onset
The chemical linkage correlates to the ___________ of LA
metabolism
Protein binding correlated to the ___________ of LA
duration
Briefly state why the potency (lipid solubility) of LA is important
greater lipid solubility enhances diffusion through neuronal coverings (myelin sheath) and the cell membrane, thus allowing lower milligram dosage
What is the importance of the pKa of LA
It determines the portion of an administered dose that exists in the lipid soluble, unionised form at given pH
LA with a lower pKa have a _________ proportion in the unionised form. What is the benefit of this
Greater proportion in unionised form
this leads to a quicker onset
Ester LAs are hydrolysed by …
plasma cholinesterases
The duration of action of LA is dependent on _________
Protein binding at the receptor site (Na channels)
A higher affinity for proteins means that the LA remains at the site of action for longer period of time
The affinity of LA for proteins at the receptor site (with sodium channels) corresponds to…
Their affinity for plasma proteins
if they bind tightly to plasma proteins then they will do the same at the receptor site
What is the effect of local anaesthetic on neurones?
They disrupt the ion channel function within the neuronal cell membrane.
Thus preventing the transmission of the neuronal action potential
What is the MOA of local anaesthetics?
Once the unionise form has diffused into the neuron
The ionised form then blocks the voltage gated Na+ channels via the open gate from the intracellular side of the membrane
It acts as a physical plug which repels positively charged Na+ (the ionised form is also positively charged)
Therefore blocks initiation and propagation of action potentials
When do LAs gain access to the voltage gated Na+ channel? What is the consequence of this on the depth of the block observed?
In its open state
Therefore, the depth of the block increasease with action potential firing
Use dependence
What is use dependence?
This is the selective inhibition of hyper active neurons while minimising the effects on normal neuronal activity
LA differentially blocks neurons. Nerve fibres associated with what sensory modality are blocked first?
Nerve fibres associated with pain are blocked before other sensory modalities such as touch, pressure and proprioception.
What nerve fibres are blocked first?
Adelta and fibres (nociception, temperature, touch)
blocked before Abeta fibres (touch, pressure and proprioception)
What other types of nerve fibres are blocked quicker?
myelinated nerve fibres are blocked unmyelinated
smal diameter nerve fibres are blocked before large diameter nerve fibres
- large diameter motor axons are relatively resistant
During dental treatment, what is the order of sensation loss?
pain, temperatue, touch, proprioception (pressure), skeletal muscle tone (motor)
This is the reason why you may still feel touch but not pain during dental treatment
When considering the site of injection, what should you take into account?
whether it is an area of high vascularity
an area of high vascularity will result in a greater uptake and high blood concentrations of the LA
consider systemic toxicity
What is the uptake of local anaesthetic from greatest to lowest
IV>tracheal>intercostal>caudal>paracervical>epidural>bracial>sciatic>subcutaneous
The peak blood concentrations of LA corresponds proportionally to …
the total dose administered
What doe of LA should be used for a planned treatment?
the lowest dosage that results in effective anaesthesia for that planned treatment
How can the maximum safe dose of LA be calculated ?
By multiplying the patients weight by the dosage factor
What does a higher dosage factor mean?
A higher dosage factor means a higher maximum safe dose
What is the maximum dosage of 2% lidocaine (dosage factor: 0.22) for a 57kg adult?
0.22ml/kg x 57kg= 12.54ml
1 cartridge= 2.2ml
12.54/2.2= 5.7 cartridges
Therefore; maximum number of safe cartridges for 2% lidocaine is 6 cartridges
What is the maximum dosage of 2% lidocaine (dosage factor 0.22kg/ml) for a 20kg child?
0.22ml/kg x 20kg= 4.4ml
4.4/2.2= 2
2 cartridges
What is the purpose of the addition of a vasoconstrictor to LA?
Most LAs have a direct vasodilator action
This increases the rate of absorption into systemic circulation which increases their potential toxicity
This reduces their LA action
vasoconstrictor keeps the LA at the site of action and limits their potential toxicity
Increasing their LA action
Give examples of vasoconstrictors used in LA
Adrenaline
Felypressin
What is the “gold standard” LA used in most dental procedures?
2% lidocaine 1: 80 000 epinephrine
Individual local anaesthetics exhibit different rates of absorption. Give an example of this
at the brachial plexus blockade lidocaine is absorbed faster than prilocaine
What kind of LA is absorbed at a slower rate ?
LA that is highly tissue bound are absorbed at a slower rate
Absorption of individual LAs is dependent on…
their intrinsic ability to cause vasodilation
Where are higher concentrations of local anaesthetics found during distribution?
In highly perfused organs such as kidneys, brain and heart
What tissue has the highest level of distribution of LA after absorption and why?
skeletal muscle
it has the largest mass of tissue in the body
Weak acids such as warfarin bind to what plasma protein?
Albumin
Weak bases such as lidocaine bind to which plasma proteins?
acidic glycoproteins
What is the advantage of drugs that have a higher affinity for plasma proteins?
they have a longer duration of action as only the free drug is available for metabolism
Patients with a pseudocholinesterase deficiency may experience ____________ due to __________
LA toxicity
due to slower metabolism of ester drugs
Some ester LA can be hydrolysed into _________. Give examples of LA that can be hydrolysed into this compound.
Paraaminobenzoic acid (PABA)
Procaine
Benzocaine
PABA is associated with _____________. What is the implication of this?
allergic reactions
Can become a medical emergency
What is an advantage of amide LA over ester LA?
They rarely cause allergic reactions
What is a contraindication for amide LA use?
liver dysfunction
this means that amide LAs will be slowly metabolised and this can lead to LA toxicity
Large doses of prilocaine can cause a condition known as _____________.
methhaemoglobinaemia
the metabolite of prilocaine causes methaemoglobin to be produced (oxygen delivery affected)
What are some signs/symptoms of methaemoglobinaemia?
Dyspnoea (shortness of breath)
Cyanosis (purple lips or extremeties?); due to lack of oxygen in these areas
PABA interferes with…
the antibacterial effect of sulphonamides
A hypersensitivity reaction to PABA can present as…
swelling of the tongue, throat and face
What is the onset of a PABA hypersensitivity reaction?
within 5 minutes
may be delayed for up to 40 minutes
What are the symptoms associated with 3-15% methaemoglobin levels?
slight discoloration (pale, grey) of the skin
What are the symptoms associated with 15-20% methaemoglobin levels?
cyanosis (patients are ususally asymptomatic)
What are the symptoms associated with 25-50% methaemoglobin levels?
headache
light headedness
weakness
confusion
palpitations
chest pain
What are the symptoms associated with 50-70% methaemoglobin levels?
abnormal cardiac rhythms
altered mental status
delirium
seizures
coma
profound acidosis
What are the symptoms associated with 70% methaemoglobin levels?
death
What forms/preparations are LAs available as?
solution for injection
sprays
creams
hel
LAs are prepared as ___________ for LA base to be stable in solution
hydrochloride salt
Give examples of topical anaesthesia
Lignocaine 5% gel, 10% spray
benzocaine 20% gel
EMLA (eutetic mixture of 2.5% lidocaine and 2.5% prilocaine)
What preservatives are found in LA?
0.1% sodium meta-bisulphite with or without a fungicide
multidose vials contain 1mg/ml of methyl para-hydroxybenzoate
What is an additive/adjuvant ?
increases the efficacy or potency of other drugs when given concurrently (at the same time)
What are the benefits of using adrenaline as a vasoconstrictor?
-reduces traumatic blood loss from the site via same mechanism
-minimise vasodilator action of LA
-decrease the rate at which the drug is removed from the site of action by absorption into systemic circulation
What is the purpose of the addition of bicarbonate to LA ?
more of the drug is present in the unionised for and thus this speeds up the onset of action
The addition of too much bicarbonate to LA can lead to ____________
the precipitation of the LA
The unionised form of LA is ______ soluble in water than the hydrochloride salt
less
When is lidocaine (xylocaine) use contraindicated?
when there is an amide allergy or increased adrenaline may be hazardous (heart conditions?)
What LA can be administered without a vasoconstrictor and why?
Mepivacaine (scandonest)
This is because it has less vasodilation effects
What LA is widely used because of the long duration of action?
Bupivacaine (marcaine)
What is the duration of plain lidocaine (without adrenaline) and lidocaine with adrenaline ?
10 minutes
1-2 hours
When is prilocaine (citanest) use indicated?
when adrenaline needs to be avoided
- pt may have severe hypertension or unstable cardiac rhythm
-prilocaine with or without felypressin
Why does articaine (septanest) have a short duration of action?
the chemical structure contains an amide linkage and an ester side chain; hydrolysis of the side chain in the plasma inactivates the drug
Which type of tissue is blocked by LA first, pulp or soft tissue ?
soft tissue is blocked first
Systemic toxicity of LA is ______ dependent
dose
What are some unwanted CNS effect of LA ?
Light-headedness
drowsiness
numbness of tongue
restlessness
parasthesia
dizziness
blurred vision
tinnitus
headache
nausea
vomiting
convulsions
muscle twitching
tremors
respiratory failure
unconsciousness
coma
What are some unwanted CVS effects of LA?
myocardial depression
peripheral vasodilation
hypotension
bradycardia
arrhythmias and cardiac arrest
What LA has a tendency for cardiotoxicity?
Bupivacaine
What LA has less of a tendency to cause CNS effects?
lidocaine
What are some potential LA complications ?
-Ischaemic necrosis of tissues and nerve damage may follow injections of LA
-vascular damage
-drug error
-needle breakage and dental cartridge failure
-no anaesthetic block; block failure
What can cause ischaemic necrosis of tissues and nerve damage following injections of LA?
irritating nature of solution
pressure from large volumes
constriction of vasculature by adrenaline
Give an example of vascular damage caused by LA
haematoma
Give another use of lidocaine drug (aside from anaesthetic agent)
used as an anti-arrhythmic at high doses in combination with other LA may cause myocardial depression or increase the risk of ventricular arrhythmias
There is an increased risk of methaemoglobinaemia with prilocaine is a patient is concomitant _____________
sulphonamide e.g. co-trimoxazole
There is an increased risk of ___________ if high doses of lidocaine are administered with antipsychotics that prolong the QT interval
ventricular arrhythmias
What effects do antivirals have on lidocaine ? Give examples of these antivirals
they increase plasma concentration of lidocaine and potentially increase cardiotoxicity
Fosamprenavir
Darunavir
Atazanavir
Lipinavir
Saquinavir
Lidocaine clearance is reduced by which beta-blockers?
propanolol
Possibly nadolol
Lidocaine in combination with beta-blockers can cause …
myocardial depression
What potential interaction can occur if diuretics such as acetazolamide is concurrently taken with lidocaine?
Acetazolamide causes hypokalemia (increased secretion of K+) which antagonised action of lidocaine
Hypokalemia antagonises action of lidocaine
Sedative, midazolam has been reported to cause a modest reduction in serum _________ levels but not _________ levels
lidocaine
mepivacaine
What LA uses felypressin vasoconstrictor?
prilocaine
What LA considerations must you make for patients who abuse cocaine?
avoid using LA containing adrenaline in patients who abuse cocaine unless certain they have not used in >24 hours
Cocaine and adrenaline have sympathomimetic effects. What does this mean?
combined use increases these effects and the risk of arrhythmias
What is the name of the new long-acting LA ?
Ropivacaine
an effective alternative to bupivacaine
Ropivacaine is an isomer of ____________ and is used mainly for _________ blocks
levobupivacaine
Mandibular nerve blocks
What are the advantages of ropivacaine ?
lowe cariovascular toxicity
no need for adrenaline to achieve prolonged duration
lowers the need of postoperative analgesics
What is the disadvantage of ropivacaine?
not available as dental cartridges
What is Opaqix ?
EMLA (eutectic mixture of 2.5 % lidocaine and 2.5% prilocaine)
What is the purpose of thermosetting agents in Opaqix ?
enables dispension as a liquid and change (in body tem) in periodontal pocket to a gel
What is the benefit of Opaqix having a pH of 7.5-8.0?
it is effective in inflamed and infected tissue
Contraindications for opaqix use include …
allergy to lidocaine, prilocaine or similar LA
congenital or idiopathic methaemoglobinaemia
Intranasal administration is suitable for what kinds of patients ?
patients anxious of needles
Give an example of LA administered intranasally
kovacaine mist nasal spray
What is phentolamine mesylate (OraVerse) ?
an injection which is the first and only local dental anaesthesia reversal agent
What is the function (use) of OraVerse?
reversal of soft tissue anaesthesia post dental procedure (e.g. numb lip or tongue)
this can help prevent injuries/symptoms associated with soft tissue parasthesia -self-inflicted injuries, uncontrolled drooling, perceied sense of altered appearance
What is the MOA of phentolamine mesylate?
increase diameter of blood vessels in the area
increase blood flow removes extra LA which can be metabolised and excreted by liver and kidneys
OraVerse is no suitable in what situations?
post-oral surgery where pain is anticipated
Briefly state correct administration techniques for OraVerse (phentolamine mesylate)
same injection site and technique as LA
1:1 cartridge ratio to LA
What is the maximum dose of OraVerse for adults?
2 cartiridges
What is the maximum dose of OraVerse for children?
<1 cartridge
