Local Anesthetics (LA) Flashcards
What does LA do?
Causes loss of sensation in a circumvented area of the body by blocking ap generation and propagation
Targets of LAs
Voltage gated sodium channels
- tetrodotoxin
- saxitixin
Blocks vgsc from extra cellular side
VGSC are inhibited by
LAs
Certain antiarrhythmics
Certain antiepleptics
- carbamazepine, lamotrigine, valproate, topiramate
Which nerves are the most sensitive to blocking?
Most sensitive:
- type c: dorsal root
- type c: sympathetic
Due to lack of myelination
Least sensitive Type a: alpha Type a: beta Type a: gamma and delta Due to heavy myelination
Medium sensitive
Type b due to light myelination
Order of disappearance of sensation
Pain Temp Touch Deep pressure Motor function
Chemical structure of LAs
Hydrophobic/lipophilic aromatic region
+
Ester or amide bond
+
Ionizable group hydrophilic/water soluble
Types of LAs
Procaine Cocaine Tetracaine Cinchocaine/dibucaine Lidocaine Prilocaine Buoivacaine Articaine Benzocaine Ax-314
Difference between protonated and non-protonated state
Protonated:
- NH+
- ionized
- hydrophilic
- acid
- poor membrane permeability
Non-protonated:
- N
- non-ionized
- lipophilic
- base
- penetrates axonal membranes and nerve sheets
LAs act in their cationic/charged form, but reach their site of action in non-ionic form
Chemical factors influencing LAs effect
- Free base/non-protonated: lipid soluble = tissue penetration
- cationic form: the most active unblocking VGSC
- on physiologic pH; primarily in cationic form
The lower the pka, the bigger the portion of the uncharged weak base at a given pH.
Inflamed tissues have lower pH, so the protonated fraction increases leading to difficulties for LAs to reach site of action giving decreased effect
Modes of administration
- Surface anesthesia
- nose, mouth, bronchial tree
- not effective for skin
- lidocaine, tetracaine,dibucaine, benzocaine - Infiltration anesthesia
- direct injection into tissue to reach nerve branches and terminals
- most drugs
- add vasoconstrictor (adrenaline/felypressin) - Intravenous regional anesthesia
- Injected distal to pressure cuff
- lidocaine,prilocaine - Nerve block anesthesia
- injected close to nerve trunks to produce loss of sensation peripheral.
- dentistry, survey, analgesia - Spinal anesthesia
- infected into subarachnoid space containing CSF - Epidural anesthesia
- injected into epidural space blocking spinal roots
- lidocaine, bupivacaine
Cocaine
Onset: medium Duration: medium Tissue penetration: good Half-life: 1h Unwanted effects: CV and CNS effects owing to block of amine uptake Note:rarely used, only as spray for URT
Procaine
Onset: medium Duration: short Tissue penetration: poor Half-life: <1h Unwanted effects: - CNS; restlessness, shivering, anxiety, convulsions followed by respiratory depression - CV; bradycardia, decreased CO, vasodilation Note: no longer used
Lidocaine
Onset: rapid
Duration: medium
Tissue penetration: good
Half-life: approx 2h
Unwanted effects:
- CNS; restlessness, shivering, anxiety (but not so common as for procaine)
-CV;bradycardia, decreased CO, vasodilation
Note: widely used LAs, can also be used to treat ventricular arrhythmia (not first choice)
Mepivacaine
Onset: rapid Duration: medium Tissue penetration: good Half-life: approx 2 h Unwanted effects: - CNS; restlessness, shivering, anxiety, - CV: bradycardia, decreased co Note: less vasodilation - may be administered without vasoconstriction
Tetracaine
Onset: very slow Duration: long Tissue penetration: moderate Half-life: approx 1 h Unwanted effects: -less tendency to cause CNS effects, - bradycardia, decreased co and vasodilation Note: mainly for spinal and corneal anesthetic
