Pharmacology of Local Anesthetics Flashcards
Local anesthetics act on
Every type of nerve ifber
Also on cardiac, skeletal muscle and brian
No damage ot nerve cell
Ideal local
Short onset wiht long duration but not too long
Chemical structures of local
Weakly basic with lipophilic aromatic raing
Intermediate ester or amide
Hydrophilic carbon chain bearing amino group
Either R or S
Channel vs ion carrier
Channel is defined pathway for ion transport when open
Carrier shuttles bac kand forth carrying ions across the membrane
Na channel structure
Larger alpha and 1 or 2 smaller beta
ALpha is site of ion conduction and binding
10 genes on 4 chromosomes
Local anesthetics MOA
Block permeability ot NA
Bind to internal membrane of sodium channel
Potential and gradeint unchanged
Only bind in open and inactive state
How does anesthetic get in
Uncharged passes through membrane…then binds hydrogen ion inside the cell to become charged
Why not use local on abscess
Acidic enviroment charges it and it can’t cross the mmebrane
Local anesthetics and AP
Decrease amplitude
Slow rate of depolarization
Increase threshold
Slow condcuiton
Inrease refractoyr period
Pharmacokinetics of locals
Enterb y direct injection or absorption (often with epinephrine to constrict BV)
Considerable first pass uptake in lung
Bind to alpha 1 glycoprotein and labumin
Distrivbution of local`
Alpha - rapidly into well perfused (brian. lung ,kidney, heart)
Beta - slower into less perfused (muscle and fat)
gGamma - clearance representing metab and excretion
Esters and amides metab
Esters - hydrolyzed in plasma by pseudocholinesterase into PABA
Amides metabolized in ER of hepatocytes…tertiary into secondary which hydrolyzed by amidases
Lipid solubility determines
POtency
Higher value is more potent
Amides>esters
Lipid:water partition coefficient
Also determines duration
Not related ot protein
Rapidity of onset realted to
pKa
Esters closer to 7.4 so faster
Ph=pKa+log(unionized/ionized)
Allergic reactions
More common in esters because of PABA
Most OTC anesthetics are
Esters because have quicker onset of action, less potent, and removed quikcer
CNS toxicity
More potent means more likelyto cause
Seizrues
Toxic effects wiht inreasing concentration
First - convulsion, nnumbness of tongue, etc.
Coma
Resp arrest
CVS depresison
How to correct seizrues
Benzodiazepine or propofol
CV toxocity
NEgative inotropic effect b/c calcium signaling
Automaticity - negative chronotropic
Ventriclar arrythmias
Bupivacaine exception
Dysrythmias seen more often
D isomer worse
Tx of cardiac toocity
Lipid emulsions
Effects on smooth muscle
Low concentrations - vasoconstriction
High concentrations - vasodilation (except cocaine)
Ropivacaine
Solely as S isomer so less cardiotoxic
