local anesthesia Flashcards
Na, Cl, K, HCO3: intra or extracellular higher?
Na: out
K: in
Cl: out
HCO3: out
Pain Threshold:
– The least experience of pain which a subject can recognize
• Pain Tolerance:
– The greatest level of pain which a subject is prepared to tolerate
when is pain tolerance highest? lowest?
highest: morning
lowest: late afternoon
axoplasm and axolemma
plasm: nn cyto
lemma; nn cell mem
electrochemical gradients for Na and K
both are into the nn, but K favors out due to concentration
AP basic diagram
Where do local anesthetics work?
nn membrane
SPECIFIC RECEPTOR theory
– Local anesthesia bind to specific receptor on the voltage gated Na channel
What about Myelinated Nerve Fibers?
conduction much faster with saltatory conduction possible (a-a and a-d fibers)
Myelinated Nerve Fibers
insulation from?
• Myelin sheath insulates axons electrically and pharmacologically
• Nodes of Ranvier=Sodium channel is abundance
Ensuring effective anesthesia on myleinated fibers
what must be blocked, length?
– 2 or 3 nodes needs to be blocked
– 8-10 mm length needed
How Local Anesthesia Work?
• Decrease permeability of ion channels to Na
• Nerve block by local anesthesia is a Non-depolarizing block
Basic Structure of Local
Anesthetics
EXCEPT BENZOCAINE
Active Forms of Local Anesthetics
exceptions?
hydrophobic/philic? exception?
what has weak LA properties?
• Majority are Tertiary amine, some esters
– Except prilocaine and hexylcaine ( 2nd amine)
• All local anesthetics are amphipathic except…benzocaine
• Antihistamine and anticholinergics have weak local anesthetic properties
2 Types of local anesthetics, hydrolysis?
– Amide
• Resist hydrolysis, excrete unchanged in urine
– Ester
• Readily hydrolyzed in aqueous solution
naming trick to local anesthetics
all amides have an i before -caine
benzocaine structure
Benzocaine doesn’t have hydrophilic group
Therefore, its not suitable for injection but nice topical !!
Dissociation of Local Anesthesia, equilibrium and shifts?
• Local Anesthesia are weak basic compounds
– They combine with acids to form local anesthetic salt (HCl)
• RNH+ ↔ RN + H+
– RNH+ ← RN + H+
Excess H+ (low pH), equilibrium shifts to the left RNH+
– RNH+ → RN + H+
Decrease of H+ (high pH), equilibrium shifts toward free base
• pKa
equation, rearranged to pH?
when pH=pKa?
(dissociation constant)
– Relative proportion of ionic form depends on pKa
Log(Base/acid) = pH - pKa
pH = Log(Base/acid) + pKa
When pH of solution = pKa, you have 50/50 RN/RNH+
Two Factors involved in the action of local anesthesia
– 1) Diffusion through nerve sheath
– 2) Binding at receptor site
diffusion and binding of local anesthesia
only free base can diffuse but only cationic form can bind receptor
Etidocaine example of diffusion and action
at 7.4 RN=25%
• Etidocaine @ normal tissue pH 7.4
– 25% free base (RN), 75% cation (RNH+) (RNH+ ↔ RN + H+)
• Let’s say we have 1000 molecules available
– 250 lipophilic RN WILL diffuse through membrane
• Once at intracellular level, 250 will re-equilibrate into
– 70 RN and 180 RNH+
• This process will continue until all gone
pKa influence on onset of action, why is benzocaine not injected?
– ↑ pKa translate to slow onset
• b/c few free base molecule available to diffuse
– ↓ pKa will have faster onset
• Remember, once intracellular, we need RNH+ to bind the receptor.
i.e. Benzocaine isn’t all that cool for injection purpose! (doesn’t form cation)
Clinical Implication: Extracellular pH and local anesthesia
Extracellular pH determines the ease for nerve blockade
• Inflamed or infected tissue is much more difficult to get
adequate anesthesia b/c lower pH or ↑H+ (shift to cation and less free base to diffuse)
Local Anesthetic Solution pH (injected and topical forms)
what is added to injected forms?
why are topical forms prepared this way?
• Keep low pH equates ↑effective shelf live of local anesthesia
• Most local anesthesia have pH 5.5 to 7
– Sodium bisulfite (antioxidant) is added with vasoconstrictor
– Slower onset with vasoconstrictor vs “plain”
• Most topical Anesthesia is prepared in more concentrated form compared to injectable local anesthesia (1% or 2 % lidocaine)
– This is due to poor buffering capacity of mucous membrane
barrriers to diffusion
• Endoneurium, Perineurium, Epinerium
• Perineurium is greatest barrier for diffusion
– Slower diffusion is dependent on the thickness
mantle and core fibers innervate?
• Mantle fiber tends to innervate proximal region (molars)
• Core fiber innervates more distal points (incisors)
Complete conduction blockade requires
– Volume and Concentration in correct region
What happens to injected drug?
Absorbed by nonneural tissue
– Diluted by interstitial fluid
– Removed by capillaries and lymphatic system
– For Ester-type: immediate enzymatic hydrolysis
lower pKa?
faster onset
greater lipid solubility effect?
more potent (rapid diffusion)
increased protein binding effect?
increased duration of action
Recovering from nerve block
– “reverse” of anesthetic induction pattern
– Intraneural concentration exceeds extraneural concentration, diffusion out
Recurrence of Immediate profound anesthesia
reduced concentration where?
what should be done?
– Reduced concentration at mantle fibers= reinjection
– Residual local + newly deposited supply = immediate profound anesthesia
Difficulty reestablish profound anesthesia when?
– Surgical procedure outlasts effectiveness of med
– Tachyphylaxis
Tachyphylaxis, factors?
– ↑ Tolerance to drug after repeated administration
• Factors
– Edema
– Localized hemorrhage
– Clot formation
– Transudation
– Hypernatremia
– ↓pH of the tissue
what do lipid solubility, pro binding and pKa influence?
