local anaesthetics

others capable of LA: ice, CO2 snow,ethylchloride spray [systemic ADRs: propranolol, chlorpromazine, H1antagonists, quinine]

LA safe,preferred in minor/restricted area surgery in cooperative[even though ill] pt retaining consciousness,vital functions.
MOA: state dependent blocking [rapidly firing neurons/high freq stimulus but not resting nerve with closed Na ch/ propagating AP with high Ca+2] of peripheral nerve impulse in both sensory[analgesia] & motor[paralysis] fibres [ionised form in low ICFpH]by binding to ICF part of activated[open] Na+ channel —> no Na+ influx/deplz/AP —> stabilizing the ch in inactivated state.
ADRs:
high doses cause CNS initial stimulation(from inh of inh neurones) [esp COCAINE :euphoria, allays fatigue, tremor, twitch, convulsions] later stimulation [unconscious, resp depr]. Rx:DZP.
N dose of LIDOCAINE causes drowsiness also.
N dose -CVSdepr [decr HR & BP] except COCAINE /w sympthmimetic -incr HR & BP.
high dose incr QTc –>arrhyth [BUPIVOCAINE most cardiotoxic]
antiarrhyth -PROCAINAMIDE, LIDOCAINE.

link between hydrophilic & lipophilic parts of LA:

1. ester –> : PROCAINE, COCAINE, TETRACAINE[toxic], BENZOCAINE.
   • rapid plasma hydrolysis so short acting.
   • PABA release causes hypersensitivity [angioedema, brspasm, dermatitis, rash], cross reactivity with sulfanamide & other LAs.
   • unstable so ionizes in high ECFpH –> lipid insoluble[low potency, ion trap in gastric mm].
2. amide –> : LODOCAINE, BUPIVOCAINE[cardiotoxic], ROPIVOCAINE, DIBUCAINE.
   • slow liver metabolism so long acting.
   • no allergic rxn so used for nerve block & infiltration.
   • stable unionised in high ECFpH –> lipid soluble[high potency].

• low potency =only inj –> PROCAINE
• mod inj potency & duration [low potent SA] –> [COCAINE only SA], LIDOCAINE.
• high potent inj & long duration [mod SA] –> TETRACAINE, BUPIVOCAINE, ROPIVOCAINE, DIBUCAINE.
• high potent SA only [no absorp -no systemic toxicity]–> BENOXINATE, BENZOCAINE, BUTAMBEN, OXETHAZAINE.

COCAINE-

• use only as ocular SA
• not inj –> necrosis sloughing of cornea, conjunctival bv constr.
• high abuse since no tolerance dev for CNS stimulation[euphoria, endurance]
• sympth & vagal centre stimulation -incr HR, BP, temp, mydriasis, vomiting.

LIDOCAINE -most widely used & versatile

• low pKa[=low ICFpH] causes shift of equilibrium to unionised form so rapid onset=3min & mod potency 1-2hr duration.
• both SA[ear, nose, respT, anorectal] & inj[all]
• only LA on intact skin[graft, iv canulation] –> eutctic cream w/ PRILOCAINE emulsified at 25degC
• antiarrhyth

TETRACAINE -[toxic]

• high potent inj spinal.
• mod SA [eye ear, respT]

BUPIVACAINE -[cardiotoxic -no iv regional, so prefer ROPIVACAINE]

• high potent inj [infiltrate, nerve block, spinal, epidural]
• continuous epidural [no motor block, only analgesia & blood levels< tissues] –>vaginal delivery, postoperative pain relief.

DIBUCAINE -[most systemic toxicity]

• most potent, longest action –.SA delicate mm: anorectal [piles,fissures]

only as SA-[no absorption -no irritant/systemic ADRs]

1. BENOXINATE -eye for IOP topometry.
2. BENZOCAINE,BUTAMBEN -wounds/ulcer ointment, sore throat/ stomatitis lozeng, anoractal suppository.
3. OXETHAZINE -lipid soluble even at acidic pH [gastritis,GERD, IBS gastrocolic reflex & pyogenic abscess]

LIDOCAINE	iv REGIONAL [elevate & bandage limb, then tourniquet]
LIDOCAINE BUPIVOCAINE	INFILTRATION -incision, excision, hydrocele, herniorhaphy FIELD[diff N]/ NERVE[trunk/plexus] BLOCK -intercoastalN-rib, ulnar brachial femoral -fracture setting, trigem & sciatic -neuralgia last resort, lingual-tooth extract, phrenic-hiccup. EPIDURAL -[difficult but ADRs less] -T[thoracic, Uabd], L[Labd,pelvis, L], CAUDAL[pelvis, perinium]
TETRACAINE LIDOCAINE,BUPIVOCAINE,DIBUCAINE	spinal [L234] – low abd, pelvis (obstetric,prostrate), LL. ADRs: resp centre depr, decr sympth[decr BP & HR -Rx:ephidrine, mephentermine], skms paralysis decr Vreturn, caudaequina syndrome[incontinences], headache, meningitis inf.