Local anaesthetics

Local anaesthetics

·         Local anaesthetics are drugs that on topical application or local injection cause reversible loss of sensations in a restricted area of the body

·         It blocks generation and conduction of nerve impulse in the nerve

Properties of desirable local anaesthetics

·         It should be non-irritating to tissues.

·         It should cause reversible loss of sensation.

·         It should have good penetrating property into body tissues.

·         It should not cause structural damage to nerve or other tissues.

·         Its absorption should be slow and gradual.

·         It should have high potency so hat low concentration can be used.

·         It should have rapid but desirable duration of action

·         It should be sterilisable.               

·         Its pH should be near neutrality.

Classification

According to their chemical structure local anaesthetic can be classified into two groups,

1.       Ester linked local anaesthetic – Procaine, benzocaine, cocaine, amethocaine

2.       Amide linked local anaesthetic – Lignocaine, bupivacine, prilociane, mepivacaine.

Mechanism of action

·         Local anaesthetics block initiation and propagation of nerve impulse by preventing the voltage dependant sodium ion conduction.

·         Local anaesthetics are weak bases, on administration; the unionized form of drug traverses the nerve membrane to react with its site of action.

·         The axoplasm is in acidic state and the drug ionizes and approaches the receptor site, located within the intracellular region.

·         The Na+ channel have two gates, activation and inactivation gate.

·         In resting state the activation gate is closed and inactivation gate is located away from sodium channel.

·         In activate state i.e., at depolarization, the channel is open and sodium moves inward

·         During inactivated state, the inactivation gate is closed and sodium inflow ceases.

·         Binding of local anaesthetic to its receptor site stabilizes membrane in the inactivated state and reduces probability of channel opening.

·         In absence of local anaesthetic, channel returns to resting state and is again ready for opening.

Pharmacokinetics

·         Soluble surface anaesthetics (lidocaine) are rapidly absorbed from mucus membrane and abraded areas but absorption from intact skin is poor.

·         Procaine does not significantly penetrate mucus membrane

·         The absorbed local anaesthetic being lipophilic is widely distributed rapidly and enters highly perfused organs like brain, heart, liver and kidney followed by muscle and other viscera.

·         Ester linked local anaesthetic are rapidly hydrolyzed by plasma pseudocholinesterase and remaining by esterase in the liver.

·         Amide linked local anaesthetics are degraded only in the liver microsomes.

·         After oral ingestion both procaine and lidocaine have high first pass metabolism in the liver. Thus they are not active orally for antiarrythmic purpose.

Pharmacological actions

·         Any local anaesthetics infected or applied locally is ultimately absorbed and can produce systemic effects depending on the concentration attained in the plasma and tissues.

·         CNS: All are capable of producing a sequence of stimulation followed by depression. Cocaine is a powerful stimulant.

·         CVS: Local anaesthetics are cardiac depressants, but no significant effects are observed at conventional doses.

·         Procaine, procainamide and lidocaine are used as a classical antiarrythmic agent.

Adverse effects

·         Systemic toxicity on rapid intravenous injection is related to the intrinsic anaesthetic potency of local anaesthetics.

·         Toxicity after topical application or regional injection is influenced by relative rates of absorption and metabolism.

·         CNS: Dizziness, auditory and visual disturbances, mental confusion, tremors, twitches and finally convulsions and respiratory arrest.

·         CVS:  Bradicardia, hypotension, cardiac arrhythmia and vascular collapse.

·         Hypersensitivity reactions: Rashes, angioedema, dermatitis, asthma and rarely anaphylaxis occur. These are common with ester type local anaesthetics and cross reactivity is frequent among them, but not with amide local anaesthetics.

1. Ester linked local anaesthetic

Cocaine

·         It is a natural alkaloid from the leaves of Erythroxylon coca.

·         Good surface anaesthetic and is rapidly absorbed from the buccal mucosa.

·         It produces prominent CNS stimulation with marked effect on mood and behavior. It induces a sense of well being

·         Cocaine is one among the drugs of abuse, hence not used clinically.

Procaine

·         First synthetic local anaesthetic and it remained most widely used local anaesthetic till the introduction of lignocaine.

·         The advantage was it is free from liability to addiction.

·         Rapid rate of inactivation by plasma pseudocholinesterase reduces the risk of toxicity.

·         It is hydrolyzed to yield diethylaminoethanol and P-amino benzoic acid. The latter is responsible for the ability of procaine to antagonize the bacteriostatic action of sulfonamides.

·         Free of tissue irritation

·         It forms poorly soluble salt with benzyl penicillin (Procaine penicillin injection intramuscularly acts for 24 hrs due to slow absorption from the site of injection).

Amethocaine

·         More potent and more toxic

2. Amide linked local anaesthetic

Lignocaine (Lidocaine)

·         It is currently the most widely used local anaesthetics.

·         Good both for surface application as well as injection.

·         Anaesthesia is more intense and long lasting than procaine.

·         It is a popular antiarrythmic drug.

Prilocaine

·         Similar to lidocaine but less CNS toxicity.

·         One of its metabolite has potential to cause methaemoglobinemia.

Eutectic lidocaine / Prilocaine

·         Unique preparation which can anaesthetize intact skin after surface application

(Eutectic mixture refers to lowering of melting point of two solids when they are mixed)

Bupivacine

·         A potent and long acting amide linked local anaesthetic.

Clinical Uses

·         Epiduaral injection

·         Infiltration anaesthesia

·         Topical anaesthesia

·         Nerve blocks