Local Anesthetics

Weak Bases (pKa 8-9) thus are mostly ionized (BH+) at intracellular pH

Sufficient amount of non-ionized [B] form is available to diffuse through membrane

Most common if LA gets in systemics (amide) after regional anesthesia

CNS: Sleepiness, Visual/Auditory disturbances: *circumoral and tongue NUMBNESS is a bad sign*

CONVULSIONS

CV: can lead to arrythmias

Allergic Rxns: Mostly ester type due to PABA metabolite*

Vasoconstriction reduces diffusion of the drug from site of action - increased efficacy

Must beware in places of low perfusion (finger/toes) --> ischemia

Antagonizes LA effect: more rested channels

Potentiates LA effect: A depolarized membrane has more inactive channels (sites to bind)

Local Anesthetic - Ester thus short DOA

*Lacks Topical Activity*

Preparation available w/ or w/o Epinephrine

Metabolized to PABA which inhibits sulfonamides

Local Anesthetic - Ester

*Long acting but slow onset*
- often used for spinal anesthesia, also good on mucous membranes
combined with 10% dextrose to increase the sp gravity so it is heavier than spinal fluid

Local Anesthetic - Ester

*OTC Preparations*

Typically used to treat sunburn/minor burns

Local Anesthetic - amide (2 i's)

similar to lidocaine, *but should not be used in pt's with cardiac or respiratory disease*
*may produce METHEMOGLOBINEMIA* thus contraindicated in congenital methemoglobinemia
(methemoglobinemia can be reversed by methylene blue)

Local Anesthetic - amide

*Long DOA* - greater cardiotoxicity (broadens QRS) than other amides*

preferred for infiltration blocks and epidurals

Local Anesthetic - amide

Long acting, mild

S-isomer of bupivacaine --> less lipid soluble --> less adverse effects**

Must be non-ionized to diffuse through membrane --> become ionized intracellulary to bind Na+ channels

Bind primarily activated and inactivated (not resting) membrane voltage-gated sodium channels

*must bind intracellulary, thus must cross membrane*

Reversibly block AP

Inflammation lowers pH, increasing the ionized form of LA, making it less permeable to the membrane and DECREASING EFFICACY

BH+ --> B + H+
Local Anesthetics are weak bases:

[BH+]/[B] = 10^ (pKa - pH)

if pH is below pKA, the ionized drug will predominate

Ester-based drugs (1 i) are metabolized rapidly by pseudocholinesterase
(not hepatotoxic)

Amide-based (2 i's) are metabolized by liver p450
(potential for hepatotoxicity)

Local Anesthetic - prototype amide (2 i's) - P450 metabolism

Longer duration than procaine

Infiltration blocks and epidurals

OD results in SEIZURES - like other amides

(also used as an antiarrhythmic)

Short: Procaine, Chloroprocaine (esters)

Intermediate: Lidocaine, Mepivicaine, Prilocaine

Long: Tetracaine, Bupivacaine, Etidocaine, Ropivacaine

Decreases intracellular pH --> *increases intracellular drug concentration* by increasing the diffusion coefficient of non-ionized to ionized across the membrane, also the ionized form is active once inside the cell

Enhances*

Short-acting alkaloid
*only used for topical anesthesia of mucous membranes

*blocks the uptake of catecholamines --> sympathomimetic

Vasoconstriction actually aids in mucous membrane bleeding

Schedule II controlled substance*

Type C Fiber (Dorsal Root): unmyelinated - most sensitive to Local Anesthetics

LA also effect postganglionic sympathetic fibers

Type C Fiber (Dorsal Root): unmyelinated - most sensitive to Local Anesthetics

LA also effect postganglionic sympathetic fibers