Local anesthetics pharmacology

local anaesthesia is defined as a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings

Or an inhibition of the conduction process in peripheral nerves; no loss of consciousness occurs
Local anesthetics interfere with the excitation process in the nerve membrane in one or more of the following ways:
1) Altering the basic resting potential of the nerve membrane
2) Altering the threshold potential (firing level)
3) Decreasing the rate of depolarization*
4) Prolonging the rate of repolarization

1. Local Anesthesia Dr. Chavan P.R. Pharm D

2. Definition a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings Or an inhibition of the conduction process in peripheral nerves; no loss of consciousness occurs

3. Properties of Local Anesthetics: Not irritating to the tissue No permanent alteration of nerve structure Systemic toxicity should be low Effective whether injected or applied topically Time of onset of anesthesia should be as short as possible Duration of action must be long enough to complete the procedure but not so long as to require an extended recovery Should be stable in solution and easily biotransformed Should not cause allergic reactions Should be sterile or capable of being sterilized by use of heat

4. Classification

5. Mode and Site of Action of Local Anesthetics Local anesthetics interfere with the excitation process in the nerve membrane in one or more of the following ways: 1) Altering the basic resting potential of the nerve membrane 2) Altering the threshold potential (firing level) 3) Decreasing the rate of depolarization* 4) Prolonging the rate of repolarization

6. Activity

7. Mechanism of Action of Local Anesthetics 1) Displacement of calcium ions from the sodium channel receptor site 2) Binding of the local anesthetic molecule to this receptor site 3) Blockade of the sodium channel 4) Decrease in sodium conductance 5) Depression of the rate of electrical depolarization 6) Failure to achieve the threshold potential level (firing level) 7) Lack of development of propagated action potentials 8) Conduction blockade

8. Actions CNS Cocaine is a powerful CNS stimulant causing in sequence euphoria—excitement—mental confusion— restlessness—tremor and twitching of muscles— convulsions—unconsciousness—respiratory depression—death

9. C.V.S. Heart- decrease automaticity, excitability, contractility, conductivity and prolong effective refractory period (ERP). Blood vessels - fall in BP Cocaine has sympathomimetic property; increases sympathetic tone, causes local vasoconstriction, marked rise in BP and tachycardia.

10. Pharmacokinetics Soluble surface anaesthetics ( lidocaine , tetracaine ) are rapidly absorbed from mucous membranes and abraded areas, but absorption from intact skin is minimal Rate of absorption depends on the blood flow to the area of application or injection . LAs are rapidly but temporarily bound to tissues, especially nerves, at the site of injection.

11. Precautions and interactions Before injecting the LA, aspirate lightly to avoid intravascular injection. Inject the LA slowly and take care not to exceed the maximum safe dose, especially in children. Propranolol (probably other β blockers also) may reduce metabolism of lidocaine and other amide LAs by reducing hepatic blood flow. Vasoconstrictor (adrenaline) containing LA should be avoided for patients with ischaemic heart disease, cardiac arrhythmia, thyrotoxicosis , uncontrolled hypertension, and those receiving β blockers (rise in BP can occur due to unopposed α action) or tricyclic antidepressants (uptake blockade and potentiation of Adr ).

12. Uses and techniques Surface anaesthesia Infiltration anaesthesia - used for minor operations, e.g. incisions, excisions, hydrocele , herniorrhaphy Conduction block - field block- used in herniorrhaphy , appendicectomy , dental procedures, scalp stitching, operations on forearms and legs, - nerve block- used for tooth extraction, operations on eye, limbs, abdominal wall, fracture setting, trauma to ribs, neuralgias, persistent hiccup

13. Spinal anaesthesia Epidural anaesthesia - thoracic, lumbar, caudal Intravenous regional anaesthesia (Intravascular infiltration anaesthesia )- upper limb and for orthopedic procedures.

14. Complications of spinal anasthesia Respiratory paralysis Hypotension Headache Cauda equina syndrome Septic meningitis

15. Cocaine Obtained from erythroxylon coca Rapidly absorbed from buccal mucous membrane First used for ocular anaesthesia in 1884. Never be injected; it is a protoplasmic poison and causes tissue necrosis. Produces prominent CNS stimulation Not producing significant tolerance on repeated use

16. Stimulates vagal centre→bradycardia ; vasomotor centre→rise in BP; vomiting centre→nausea and vomiting; temperature regulating centre→pyrexia Blocks uptake of NA and adr into adrenergic nerve endings Local vasoconstriction, tachycardia, rise in BP and mydriasis Only indication - ocular anaesthesia .

17. Lidocaine ( Lignocaine ) Versatile LA Injected around a nerve it blocks conduction within 3 min Anaesthesia is more intense and longer lasting. Used for surface application, infiltration, nerve block, epidural, spinal and intravenous regional block anaesthesia Overdose causes muscle twitching, convulsions, cardiac arrhythmias, fall in BP, coma and respiratory arrest Popular antiarrhythmic

18. Prilocaine Does not cause vasodilatation at the site of infiltration Lower CNS toxicity due to larger volume of distribution Methaemoglobinaemia Use - infiltration, nerve block and intravenous regional anaesthesia .

19. Eutectic lidocaine / prilocaine Alternative to lidocaine infiltration Applied under occlusive dressing for 1 hr before i.V . Cannulation , split skin graft harvesting and other superficial procedures

20. Bupivacaine Potent and long-acting amidelinked LA Use- infiltration, nerve block, epidural and spinal anaesthesia of long duration Very popular in obstetrics and for postoperative pain relief by continuous epidural infusion. Prolong qtc interval and induce ventricular tachycardia or cardiac depression—should not be used for intravenous regional analgesia. 0.75% bupivacaine – contraindicated due to development of cardiac arrest

21. Ropivacaine A newer bupivacaine congener, Equally long acting but less cardiotoxic Blocks aδ and C fibres more completely than aβ fibres which control motor function. Epidural ropivacaine is being used for relief of postoperative and labour pain For nerve blocks

22. Dibucaine ( Cinchocaine ) Most potent, most toxic and longest acting LA Surface anaesthetic on less delicate mucous membranes (anal canal). Spinal anaesthesia use get reduced

23. Benoxinate Good surface anaesthetic for the eye Has little irritancy 0.4% solution- used for T onometry without causing mydriasis or corneal damage.

24. Benzocaine and Butylaminobenzoate ( Butamben ) long-lasting anaesthesia without systemic toxicity Use- lozenges for stomatitis , sore throat; as dusting powder/ointment on wounds/ulcerated surfaces and as suppository for anorectal lesions Both are PABA derivative—can antagonize sulfonamides locally.

25. Oxethazaine A potent topical anaesthetic , Unique in ionizing to a very small extent even at low ph values Effective in anaesthetising gastric mucosa despite acidity of the medium Swallowed along with antacids it affords symptomatic relief in gastritis, drug induced gastric irritation, gastroesophageal reflux and heartburn of pregnancy. Doses exceeding 100 mg/day may produce dizziness and drowsiness

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