Local Anaesthesia Flashcards
(35 cards)
2 classes of LA
ester and amide LA
briefly explain the significance of electrical excitability
nerves and muscle cells have the ability to generate propagated AP for communication in the nervous system and initiation of mechanical activity in cardiac and striated muscles. ELECTRICAL EXCITABILITY -> PAIN and ALL SENSATIONS
Briefly explain the role of voltage gated sodium channels on electrical excitability
VG sodium channels at the cell membrane allow the influx of sodium ions and raises the cell potential triggering action potential. At a certain cell potential eg. +30mV, VGSC will close, potassium channels open allowing for potassium efflux and repolarisation
States of sodium channels?
- deactivated: gating mechanism and channel closed
- inactivated: gating mechanism closed
- closed: channel closed
- activated: gating mechanism and channel OPEN
MOA of LA
Stop axonal conduction by blocking sodium channels in the
axonal membrane when applied locally in appropriate
concentration prevent sodium ion entry slow down
or bring conduction to a halt
How does the chemical properties of LA affect it’s MOA?
LA exist in the ionised form at physiological pH with a minority in the basic form. The basic form enters the phospholipid bilayer and protonates before binding to the VGSC intracellularly.
What is the significance of the state of the LA?
The onset of the LA depends on the state of the LA at physiologic pH. If it is more basic, the LA molexules can pass through lipid bilayer to reach site of action
Which preferred states of VGSC do LAs strongly bind to?
inactivated (gating mechanism closed) and activated states
Describe the use dependency of LA
The depth of LA nerve block increases with action potential frequency because
LA molecules gain better access to the channel (LA’s efficacy increases in painful states) and have higher affinity for inactivated than deactivated channels
Define LA
LAs are non-selective modifiers of neuronal function. They will block AP in all accessible neurons.
How to achieve selectivity for LAs
Deliver LA to a limited area; limit blood supply to the area; reduce systemic spread
Factors affecting LA action
- lipid soluble drugs (hydrophobicity) more potent and act longer
- smaller nerve > bigger nerve
- high frequency of firing > low frequency of firing (sensory > motor)
- circumferential > deep
- myelination > non-myelinated
- pH dependency: critical in LA penetrance to site of action
LA potency is strongly pH dependent
Hierarchy of axons that are blocked
small myelinated axons > small non-myelinated axons > large myelinated axons
hence diameter of the axons determine potency of LA the most
What form of transmission is blocked first by LA?
nociceptive and sympathetic transmission blocked first
What are the 2 key traits to note when using ester vs amide type LA?
Ester type LA has a higher incidence of allergic reaction than amide type because of production of PABA metabolite (allergen).
Ester type LA is metabolised by plasma / tissue - non specific esterases present throughout the body while amide type LA is metabolised by hepatic enzymes only.
List 4 types of ester LA
- cocaine
- procaine
- tetracaine
- benzocaine
Short acting ester LA
Procaine
Long acting ester LA
Tetracaine
Surface use ester LA
Benzocaine
Examples of amide LAs (usually 4 syllables)
- lidocaine
- mepivacaine
- bupivacaine (CARDIOTOXICITY)
- etidocaine
- prilocaine
- ropivacaine
Medium acting amide LA
- lidocaine
- mepivacaine
- prilocaine
Long acting amide LA
- bupivacaine
- etidocaine
- ropivacaine
A patient with liver cirrhosis and is allergic to sunscreen. What type of LA do you use?
Amide type with careful dose adjustment and monitoring because of impaired metabolism of drugs hepatically.
Mode of absorption of LA
local with some systemic distribution determined by blood flow to site of action
