Ophthalmic Anesthetics

local anesthetics

• do not produce unconsciousness

• effect is restricted to the site of admin

• advantages:

  • completely reversible

  • rapid recovery

  • less residual effects

  • no post-op confusion

  • no significant systemic effect

• risks:

  • not complete

  • requires time

  • slower than general

topical

• applied to the surface of skin, mucosal tissue

• non-absorbable form is preferred

• examples:

  • benzocaine (most often used)

  • proparacaine

  • tetracaine

• applications:

  • sunburn

  • rash

  • irritation of mucous membranes, mouth, throat, tracheobronchial tree, esophagus, rectum, nose, cornea, urinary tract

transdermal

drug applied to skin w/ the intention that it will penetrate into tissues

infiltration

• injection directly into an area, allowed to diffuse

• usually given with epi as a vasoconstrictor

• employed during suturing wounds or dental surgery

peripheral nerve block

injected near a nerve root → anesthesia in distribution of nerve

central nerve block (epidural)

b/t vertebrae & dura mater (usually at the level of intervertebral disk b/t L2 & 3

synthetic, poorly water soluble, weakly basic

describe the structural features of local anesthetics

lipophilic aromatic ring, linkage site, intermediate alkyl chain, hydrophilic ionizable amine

describe the general structure of local anesthetics

lipophilic aromatic ring

structural feature of LA that are essential for anesthetic activity, increase lipid solubility, & increase potency & duration of action

ester linkage

structural feature of LA that is unstable & rapidly hydrolyzed; most commonly used topical anesthetics

amide linkage

structural feature of LA that is very stabilized & metabolized in liver; most injectable anesthetics

cocaine, proparacaine, procaine, chloroprocaine, tetracaine, benoxinate, benzocaine

what are the ester link LAs?

plasma & tissue cholinesterases

where are ester link anesthetics hydrolyzed?

lidocaine, mepivacaine, bupivacaine, etidocaine, prilocaine, ropivacaine, articaine

what are the amide link LAs?

P450 systems in liver

where are amide link anesthetics metabolized?

pH of tissue, pKa, lipid solubility, concentration, protein binding, time of diffusion, nerve morphology & length of nerve, addition of vasoconstrictors

what are some factors that affect onset, potency, & duration of local anesthetics?

increases, shortens

a lower pKa _______ (increases/decreases) tissue penetration, which (shortens/lengthens) the onset of action of LA

closer to pH

pKa that is ________ optimizes penetration of LA

decrease, lengthen

inflammation in extracellular space may _______ (increase/decrease) pH & _________ (shorten/lengthen) onset of action of LA

lengthened

onset of action of LA is ______ (shortened/lengthened) in areas with increased tissue or nerve sheath size

high, increase

LA with _____ (low/high) partition coefficients that _______ (increase/decrease) lipophilic properties easily pass into the lipid nerve membrane

vascular absorption, decreases, decreases

vasodilation promotes _________, _________ (decreases/increases) local drug absorption & ___________ (decreases/increases) potency

epinephrine, sodium bicarbonate

the addition of ________ or ___________ with LA increases pH, which increases non-ionized particles (more lipid soluble)

lengthens, decreasing

addition of epinephrine w/ LA _____ (shortens/lengthens) duration of action by vasoconstriction & ________ (increasing/decreasing) systemic absorption

degree of protein binding

what is the primary determining factor of duration of action of LA?

increased

high protein binding of LA = _______ (increased/decreased) duration of action

increased

increasing pH of LA = ______ (increased/decreased) duration of action

less than 10min

general onset of action of procaine

30-45min

duration of action of procaine

w/in 10min

onset of action for injectable amide LAs

lidocaine, mepivacaine or prilocaine, etidocaine, bupivacaine

list the injectable amide LAs in order from shortest duration of action to longest duration of action

dizziness, auditory/visual disturbances, drowsiness, disorientation, talkativeness, nervousness, restlessness, dysarthria, convulsions, apnea, respiratory arrest

list some of the CNS toxicity effects of injectable LAs

HTN, tachycardia, hypotension, bradycardia, arrhythmia, cardiac arrest

list some of the cardiac toxicity effects of injectable LAs

rapid onset, effective for reasonable duration, no effect on pupil/accommodation/IOP, not affected by other drugs, comfortable application, no interference w/ healing processes, non-toxic locally or systemically

ideal properties of topical anesthetics

corneal anesthesia, evaluation of abrasions, Schirmer’s testing, electroretinography, CL fitting, conjunctival procedures, paracentesis of AC

what are some common clinical uses of topical LAs?

proparacaine, tetracaine, benoxinate, chloroprocaine, lidocaine,

what are the most commonly used topical anesthetics?

less than 30s

the most commonly used topical anesthetics have an onset of _______

15-30min

the duration of action for the most commonly used topical anesthetics is ______

tetracaine

(AK-T-Taine, Altacaine, Opticaine, Pontocaine, Tetcaine, Tetravisc)

• concentration: 0.5% sol

• advantages:

  • rare localized allergic rxn

  • rarely have cross-sensitivity to proparacaine

• disadvantages:

  • moderate stinging upon installation

  • produces corneal cell membrane damage, loss of microvilli, & desquamation of superficial epithelial cells

• pregnancy category: C

• preservative: 0.4% chlorobutanol

proparacaine

(AK-Taine, Alcaine, Ocu-Caine, Ophthaine, Ophthetic, Parcaine)

• general purpose topical anesthetic

• concentration: 0.5% sol

• advantages:

  • little to no stinging, burning, or conjunctival redness

  • localized allergic rxn is rare

• disadvantages:

  • doesn’t penetrate cornea or conjunctiva as well

  • corneal thickness instability can occur for ~5min after instillation

• pregnancy category: C

• preservative: 0.01% BAK

proparacaine + fluorescein sodium

(Fluoracaine, Flucaine)

• general purpose topical anesthetic

• concentration: 0.5% sol + 0.25% NaFl

• preservative: 0.1% thimerosal

• advantages:

  • little to no stinging, burning, or conjunctival redness

  • localized allergic rxn is rare

• disadvantages:

  • doesn’t penetrate cornea or conjunctiva as well

  • corneal thickness instability can occur for ~5min after instillation

• pregnancy category: C

benoxinate + fluorescein sodium

(Altafluor, Flurate, Fluress, Flurox)

• only commercially available in combo w/ vital dye

• primary use is for applanation tonometry

• concentration: 0.4% sol + 0.25% NaFl

• advantages:

  • stings less than tetracaine

  • produces less epithelial desquamation than proparacaine

  • localized allergic rxn is rare

  • no apparent cross-sensitivity to proparacaine

• disadvantages:

  • stings more than proparacaine

  • corneal thickness instability can occur for ~5min after installation

• pregnancy category: C

• preservative: 1.0% chlorobutanol

benoxinate + fluorexon disodium

• only commercially available in combo w/ vital dye

• primary use is for applanation tonometry

• concentration: 0.4% sol + 0.35% fluorexon disodium

• advantages:

  • stings less than tetracaine

  • produces less epithelial desquamation than proparacaine

  • localized allergic rxn is rare

  • no apparent cross-sensitivity to proparacaine

  • less likely to stain soft CLs

• disadvantages:

  • stings more than proparacaine

  • corneal thickness instability can occur for ~5min after installation

• pregnancy category: C

• preservative: 0.5% chlorobutanol

lidocaine

(Akten)

• intended to be used in any ocular procedure that requires a topical anesthetic agent

• concentration: 3.5% single unit dose gel

• dosage: 2gtts prior to procedure

• advantages:

  • can be used in pt w/ ester sensitivity

• disadvantages:

  • expensive

• pregnancy category: B

• preservatives: none

chloroprocaine

(Iheezo)

• ester anesthetic indicated for ocular surface anesthesia

• concentration: 3% single unit dose gel

• dosage: 3gtts prior to procedure

• preservatives: none

• pregnancy/lactation/child usage:

  • no adequate studies

transient burning & stinging, vasodilation, decreased TBUT, decreased reflexive tearing/blinking, corneal edema, slowed epithelial healing, epithelial desquamation, allergic rxns, superior punctate keratitis

ocular toxicity side effects of LAs

slowed epithelial wound healing, epithelial erosions, stromal edema, diminished duration of anesthesia, severe keratitis, corneal opacification, corneal scarring, corneal perforation

SE of repeated use of topical LAs

yellowish, white, dense, stromal ring surrounding primary disease, chronic non-healing epithelial defects

SE of self-administration of topical LAs

ocular hypersensitivity

• side effect of LAs

• uncommon

• mainly w/ ester groups

• clinical presentation:

  • conjunctival hypermia & chemosis

  • eyelid swelling

  • tearing

  • itching

• occurs 5-10min after instillation

• tx:

  • topical decongestants & cold compresses

ester

hypersensitivity rxns w/ LA are typically w/ what group?

systemic hypersensitivity

• side effect of LAs

• type 1 allergic rxn in <1% of adverse LA rxns

• not life threatening

• clinical presentation:

  • angioneurotic edema

  • uticaria

  • bronchospasm

  • hypotension

• tx:

  • systemic antihistamines

  • bronchodilators

  • epinephrine

hypersensitivity, liver disease, concomitant meds, dry eye testing, perforating ocular injury, cultures, caution in CV disease/asthma/hypothyroidism

what are some contraindications of LA

non-use-dependent

the hydrophobic pathway of LA is said to be __________

use-dependent

the hydrophilic pathway of LA is said to be ________

increases

as the AP frequency increases, the sodium channel is opening & closing & more LA molecules can get into the channels & block

the depth of LA channel block ________ with increasing AP frequency. why?

non-ionized LA crosses cell membranes & blocks channel from w/in cell membrane

describe the non-use dependent/hydrophobic/lipophilic pathway of LA

ionized forms must get into the cell via the open Na channels & then can block the channel

describe the use-dependent/hydrophilic pathway of LA

increases, more

in tears (neutral or alkaline environment), uncharged LA _______ & ______ anesthetic can enter the nerve cell membrane

increases, less

in the state of infections, the pH environment is more acidic, which means that ionized drug ______ & there is ______ of an LA effect