Pharmacology of LA Flashcards
Provide a general overview of the pharmacodynamics of LA on the CNS and CVS
(D in pharmacodynamics = what drug does to body)
· Most LA’s are vasodilators. Cocaine is the only LA which is a vasoconstrictor
· CNS effects: Depresses the response, and can be an anticonvulsant at low levels. Conversely, at high levels it can cause a seizure
· CVS effects: Decreases excitability of myocardium, decreases conduction rate, decreases force of contraction
· Lignocaine (IV) has be used to treat some CVS issues, but it can cause hypotension
What are four factors involved in pharmacodynamics?
Absorption
Distribution
Metabolism
Excretion
Describe the absorption of LA
Absorption
• Vasodilation increases rate of absorption, decreases duration of anaesthesia and increases potential for overdose
• Rate also depends upon vascularity of site
• Absorbed poorly from GIT
• Very well absorbed trans-mucosally (but poorly from intact skin)
Describe the distribution of LA
Distribution
• LA distributed from the bloodstream to tissues
• More in highly perfused organs (brain, liver, kidneys etc)
• Less in elderly, medically compromised patients
• Elimination ½ life = time required for a 50% reduction of drug level in blood
Describe the metabolism of LA in terms of esters and amides
Metabolism
Esters
• Hydrolysed in the plasma by pseudocholinesterase
• Procaine is hydrolysed into para-aminobenzoic acid (PABA)
• PABA is an allergen
• People with defective pseudocholinesterase will not be able to metabolise ester local anaesthetics
Amides
• Primarily metabolised in the liver
• Improper liver function and hepatic perfusion can affect blood levels and toxicity
• Prilocaine metabolite, orthotoluidine, if left to accumulate, can produce methaemoglobinaemia
• Prilocaine has some extra-hepatic metabolism (in the lungs)
• Articaine primarily metabolised by tissue and plasma cholinesterases (95%); the rest in the liver
Describe the excretion of LA
Excretion
• Both esters and amides are excreted via kidneys with minute amounts being eliminated as the parent compound
Describe the metabolism of lignocaine
in terms of:
- Site
- Enzyme/ process
Site:
Liver
Enzyme/ Process:
De-ethylation via CYP 450 amidase
Describe the metabolism of prilocaine
in terms of:
- Site
- Enzyme/ process
Site:
Liver/ kidneys/ lungs
Enzyme/ process:
De-ethylation via CYP 450 amidase
Describe the metabolism of articaine
in terms of:
- Site
- Enzyme/ process
Site:
Plasma
Enzyme/ process:
Carboxyesterase/ cholinestrase
Glucuronic acid conjugation
Describe the metabolism of bupivacaine
in terms of:
- Site
- Enzyme/ process
Site:
Liver
Enzyme/ process:
Carboxyesterase/ cholinestrase
Glucuronic acid conjugation
Describe the metabolism of procaine
in terms of:
- Site
- Enzyme/ process
Site:
Plasma
Enzyme/ process:
Carboxyesterase/ cholinestrase
Describe the pharmacokinetics of local anaesthetics on the body
· Pharmacokinetics is what the body does to the drugs
· Since the drugs are mainly excreted via kidneys, significant renal impairment can increase the potential for toxicity
List and describe 5 factors that affect dose levels of LA
- Presence of vasoconstrictor = high doses allowed
- Site of injection = Morphology of tissues E.g. palatal tissues vs pterygomandibular space
- Procedure: Depth of anaesthesia required eg extraction vs small restoration
- Age (young and old)
- Medical status = Kidney, liver disease
List the maximum recommended doses for different anaesthetics:
Lignocaine
Articaine
Bupivacaine
Prilocaine
Mevipacaine
Procaine
Lignocaine
- W/ adrenaline: 7mg/kg
- Without: 4mg/kg plain
Articaine
- W/ adrenaline: 7mg/kg
- Without: 4mg/kg plain
Bupivacaine
- 2 mg/ kg
Prilocaine
- W/ felypressin: 9mg/ kg
- Without: 4mg/kg plain
Mevipacaine
- 6.6 mg/ kg
Procaine
- 10 mg/ kg
If you have a 2.2 ml cartridge of a 2% solution, how much LA is in it?
If you have a 2.2 ml cartridge of a 4% solution, how much LA is in it?
44mg
88mg
