Pharmacology of Dental LA Flashcards
What is in a cartridge?
- usually 2.2ml or 1.8ml
- anaesthetic agent
- vasoconstrictor
- stabiliser/preservative
- isotonic carrier medium - same concentration as tissue fluids
List some common preparations and their trade name:
Lidocaine and adrenaline - lignospan special
Mepivacaine - scandonest
Prilocaine and Felypressin - citanest
Prilocaine Plain (no vasoconstrictor) - citanest plain
Articaine and adrenaline - septanest
What is the general structure of a local anaesthetic agent?
- aromatic ring (lipophilic)
- intermediate chain
- hydrophilic tail
What determines the type of LA?
What are the two types and how are they distinguished?
Structure of intermediate chain determines type of LA
- ester - COO -
- amide - NHCO -
List examples of esters?
Which drugs are classified as amides?
- procaine and benzocaine
Amides: drugs by injection
- lidocaine
- prilocaine
- mepivacaine
- bupivacaine
- articaine
How do LAs work?
What are the two theories on how they actually work?
LA works to block action potentials by reversibly blocking NA+ channels
- Membrane expansion theory
- Specific receptor theory
What does the membrane expansion theory suggest?
- LA diffuses into axon membrane and expands membrane
- Prevents sodium channels opening, as they are squashed together
- Not likely
Explain the specific receptor theory:
- LA binds to the sodium channel (reversibly)
- Inactivates sodium channel, holding it shut
LA accesses Na+ channel from inside so:
- LA must pass through phospholipid membrane
- LA must be able to bind to Na channel
- hence the lipophilic and hydrophilic ends
Explain some dissociation and solubility LA properties:
- LA drugs poorly soluble in aqueous environment
- Exists in 2 states: uncharged lipid soluble - pass through axon membrane, charged - binds to sodium channel
Proportion of charged vs uncharged depends upon:
- pKA of the drug
- pH of the environment
If a drug has a low pKA, how does this affect it?
Low pH? What can cause low pH?
Low pKa:
- more uncharged drug
- passes through nerve membrane rapidly
Low pH results in a slow onset as there are more charged molecules and can lead to failure
Low pH can be due to inflammation and infection
What are protein binding LA properties?
Protein binding:
- increases duration
- provides a pool of LA
- drugs with high protein binding include bupivacaine and articaine
How is vasodilation a property of LA?
- all are vasodilators
- increases rate of systemic uptake
- least vasodilatory are prilocaine and mepivacaine (plain preparations with no vasoconstrictor)
What type of nerves are easier to block and lasts longest?
- C fibres are easiest (smallest and most commonly associated with pain)
- A-delta
- A-beta
- A-alpha are most difficult (largest)
Name the types of local anaesthetics:
- lidocaine - gold standard
- priloccaine - an alternative
- mepivacaine - an alternative - least vasodilatory
- bupivacaine - high protein binding –> long acting
- articaine - relatively new witha unique selling point: diffusability
What is absorption?
What does this depend on?
- uptake from site of deposition into bloodstream, loss of LA activity
Depends on:
- dose
- vasoactivity of LA
- vascularity of tissues
- vasodilator effect vs use of vasoconstrictor
Where can LA be distributed?
- unbound LA may enter any organ
- in particular, organs that are highly perfused: brain, liver, kidneys, placenta
How can LA affect other organs?
CNS: initial stimulation, depression of CNS with increasing dose
Peripheral vessels: vasodilation, overdose –> hypotension
Respiratory system: low doses - bronchodilation, high dise: CNS depression
Myocardium: reduces excitability and conductivity, used in acute cardiac care
These side effects only occur when you over-prescribe dose of LA
Where are LAs metabolised?
What are the half lives of lidocaine, prilocaine and articaine?
- amidases breakdown LA drugs in the liver
- important to recognise patients with liver disease as you must reduce dose of LA
Prilocaine is broken down in the lungs
Articaine is broken down in plasma
Half life of lidocaine and prilocaine - 1.6 hours
Articaine - 0.5 hours
Why do we use vasoconstrictors?
- increase speed of onset
- counteract vasodilatory effects of LA agent
- extend duration of anaesthesia
- improve depth of anaesthesia
- lower blood levels of LA
- reduces haemorrhage
What are the types of vasoconstrictors?
Adrenaline: sympathomimetic amines
- acts on alpha 1 receptors causing vasoconstriction
- concentration usually 1:80,000 = 12.5 micrograms/ml
- 2.2ml cartridge contains 27.5 micrograms
- requires a preservative to maintain shelf life
Felypressin: synthetic polypeptides
- 0.03 IU/ml = 0.54 micrograms/ml
- analogous to vasopressin
- works on venous side
- vasocontrictive potency is half that of adrenaline
- poor haemostasis compared to adrenaline
Is there any contra-indications of any vasoconstrictors in pregnancy?
Felypressin and pregnancy
- mild toxic effect
- theoretical risk of interfering woth placental circulation and uterine tone
- however dose used in dentistry is small: need ~100 cartridges to induce labour
- despite low risk, should avoid in pregnancy
What % anaesthetic is in Lidocaine hydrochloride?
- Vasoconstrictor?
- Preservative?
- Maximum Anaesthetic Dose?
- 2% = 20mg/ml (44mg in a 2.2ml cartridge)
- Vasoconstrictor: adrenaline, 1:80,000 = 12.5micrograms/ml
- Preservative: sodium or potassium metabisulphite
Maximum Anaesthetic Dose:
- 4.4mg/kg upto a maximum of 300mg = 6.8 cartridges!
How is maximum anaesthetic dose of 2% lidocaine and adrenaline calculated for a 70kg healthy adult?
Explain another way to work this out:
Are there any important points to note regarding maximum dose?
4.4mg/kg upto a max of 300mg
max dose = 70 x 4.4 = 308mg but max dose is 300mg
- 2.2ml cartridge contains 44mg
so: 300/44 = 6.8 cartridges - very rarely need more than 3 cartridges
Another way to calculate: a tenth of a cartridge per kg for healthy patients
e.g. cartridge for every 10kg of body weight up to a max of 6.8 cartridge
Once max dose reached, do not switch to another LA drug as it uses same metabolic pathways, resulting in a high level of anaesthetic in bloodstream!!
What is the concentration of anaesthetic in mepivacaine hydrochloride?
Vasoconstrictor?
Preservative?
Max Dose?
- 3% = 30mg/ml (66mg in a 2.2ml cartridge)
- No vasoconstrictor
- No preservative
Maximum anaesthetic dose:
- 4.4mg/kg (absolute max 300mg)
Concentration of Prilocaine?
Vasoconstrictor?
Preservative?
Maximum dose?
- 3% = 30mg/ml (66mg in a 2.2ml cartridge)
- vasoconstrictor: Felypressin - 0.03IU/ml = 0.54micrograms/ml
- No preservative
Maximum Anaesthetic Dose:
- 6mg/kg (absolute max 400mg)
What LA should you use for majority of procedures?
When should this not be used?
Lidocaine/Adrenaline should be used as it results in effective haemostasis, anaesthesia, and is safe.
Do not use if patient has:
- unstable angina
- severe cardiac dysrhythmia
- allergy to any components
Caution with other cardiac conditions
- avoid or reduce dose
When would you use prilocaine?
Mepivacaine?
Articaine?
Prilocaine:
- wish to avoid adrenaline
- preservative allergy
- avoid prilocaine in pregnancy
Mepivacaine:
- use as an alternative to prilocaine
- short acting
Articaine:
- USP: diffusability, especially through bone
- potential alternative to inferior alveolar blocks
What type of patients should you reduce dose of LA?
Are any drugs contraindicated with use of adrenaline?
- liver disease: impaired metabolism
- beta blockers
- calcium channel blockers
- drug abusers
Reduce dose or use alternative (prilocaine) in patients who take tricyclic antidepressants and mono-amine oxidase inhibitors as use of adrenaline was thought to be contraindicated
What are the main features of articaine?
- classified as an amide but contains an ester group (helps systemic safety)
- lipophilic component is a thiophene ring which increases lipid solubility (better diffusivity and imporves efficacy)
Concentration of articaine?
Vasoconstrictor?
Preservative?
Maximum Anaesthetic Dose?
When should this not be used?
- 4% - 40mg/ml (88mg in a 2.2ml cartridge)
- vasoconstrictor: adrenaline, 1:100,000 = 10micrograms/ml
- preservative: sodium metabisulphite
Maximum Anaesthetic Dose:
- 7mg/kg (upto a max of 300mg)
Do not use in children under 4 years
How is articaine metabolised?
- Plasma: plasma esterase enzymes break ester bonds and deactivate drug when enters bloodstream
- Liver: hepatic amidase enzymes break amide bond
- Elimination via kidneys
- rapid breakdown –> low systemic toxicity –> safe
- mothers should not breastfeed for 48 hours following anaesthesia as effects are unknown
What are the three things to consider whether you adopt something new/else?
What is special regarding articaine?
- Efficacy - is it as good as the others?
- Is it better than the others? Any USP?
- Is it safe?
Articaine USP:
- ability to diffuse through bone
- can achieve anaesthesia of lower posterior teeth by infiltration
What are the safety points of articaine?
- rapid metabolism (plasma and liver)
- high protein binding: less of drug free to float around body
- lower adrenaline concentrations - 1:100,000 or 1:200,000
- higher anaesthetic concentrations (4%)
- no serious adverse effects
What causes paraesthesia?
- physical trauma to nerve trunk
- not likely due to articaine itself as it has the lowest neurotoxicity when compared to other drugs at the same concentration
- likelihood of nerve damage following regional LA apears to be more likely when LA concentration is increased
What is the advise for articaine and IANB?
- IAN block dependent on technique, anatomy, not diffusability through bone
- avoid articaine for IAN block injections
- consider using it by infiltration for: failed IANB, supplementary IANB, as a potential alternative to IANB
