Local anesthetics

Local anesthetics

Local anesthetics

Classification

1.      Natural: cocaine

2.      Synthetic nitrogenous compounds

a.       Derivatives of para-aminobenzoid acid

i. Freely soluble: procaine, amethocaine

ii. Poorly soluble: benzocaine, orthocaine

b.      Derivatives of acetanilide: lignocaine

c.       Quinolone derivaties: cinchocaine

d.      Acridine derivates: bucricaine

3.      Synthetic non-nitrogenous compounds; Benzyl alcohol, propanediol

4.      Misc drugs with local action: clove oil, phenol, chlorpromazine, certain antihistaminics ex: diphenhydramine

Mechanism of Action

The application of local anesthetic to nerve, that is actively conducting impulses will inhibit inward migration of Na⁺.This elevates threshold for electrical excitation, reduces rate of rise of action potential, slows propagation of impulse, and if drug concentration is high, completely blocks conduction. The local anesthetics interfere with process fundamental to generation of action potential, namely, the large, transient voltage-dependent rise in permeability of membrane to Na⁺.

Physiological basis for local anesthetic action is known, the precise molecular nature of process is not completely clear.

Almost all local anesthetics can exist as either uncharged base or as cation. The uncharged base is important for penetration to site of action, and charged form of molecule is required at site of action.

The cation forms of local anesthetics appear to be required for binding to specific sites in or near Na⁺ channels. The presence of local anesthetic at these sites interferes with normal passage of Na⁺ through cell membrane by stopping a conformational change in subunits of voltage-gated Na⁺ channel.

These permanently charged molecules cannot penetrate to receptor sites. Nerves that are rapidly depolarizing are inherently susceptible to effects of local anesthetics. This is termed frequency-dependent blockade and occurs because, the local anesthetics get to their receptor sites only when Na⁺ channel is open (depolarizing).

Schematic diagram of Mechanism of action of Local Anesthetics is shown below

Adverse Effects

i.           CNS stimulation characterized by restlessness, disorientation, tremors, and at times clonic convulsions. Continued exposure to high concentrations results in general CNS depression; death occurs from respiratory failure secondary to medullary depression. Treatment requires ventilatory assistance and drugs to control seizures. The ultra–short-acting barbiturates and benzodiazepine derivatives, diazepam, are effective in controlling these seizures. Respiratory stimulants are not effective. CNS manifestations generally occur before cardiopulmonary collapse.

ii.         Cardiac toxicity is result of drug induced depression of cardiac conduction (e.g., atrioventricular block, intraventricular conduction block) and systemic vasodilation.These effects may progress to severe hypotension and cardiac arrest.

iii.       Allergic reactions, such as red and itchy eczematoid dermatitis or vesiculation. True allergic manifestations have been reported with procaine. The amides are essentially free of allergic properties, but suspected allergic phenomena may be caused by methylparaben, a parahydroxybenzoic acid derivative used as an antibacterial preservative in multiple-dose vials and dental cartridges. Esters should be avoided in favor of an amide, when patient has history of allergy to PABA-containing preparation i.e., cosmetics or sunscreens.

Lidocaine

Lidocaine hydrochloride (Xylocaine) is most commonly used local anesthetic. It is well tolerated, and in addition to its use in infiltration and regional nerve blocks, it is commonly used for spinal and topical anesthesia and as an antiarrhythmic agent. Lidocaine has more rapidly occurring, more intense and more prolonged duration of action than does procaine.

Clinical Uses

A.    Topical Anesthesia

a.       It is used on mucous membranes in nose, mouth, tracheobronchial tree, and urethra.The vasoconstriction produced by some local anesthetics, cocaine especially, in nose by preventing bleeding and inducing tissue shrinkage.

b.      It permits many diagnostic procedures in awake patient, and when it is combined with infiltration techniques, excellent anesthesia may be obtained for many surgical procedures in eye and nose.

B.     Infiltration (i.e., injection of local anesthetics under skin) of surgical site provides adequate anesthesia if contiguous structures are not stimulated. Onset is rapid, the surgical procedures can proceed with little delay. Minimally effective concentrations should be used, especially in extensive procedures, to avoid toxicity from overdosage.

C.     Regional Block, a form of anesthesia that includes spinal and epidural anesthesia, involves injection near a nerve or nerve plexus proximal to surgical site. It provides excellent anesthesia. Brachial plexus block is used for upper extremity. Individual blocks of sciatic, femoral, and obturator nerves can be used for lower extremity. An amount that is close to maximally tolerated dose is required to produce blockade of a major extremity.

D.    Spinal Anesthesia (subarachnoid block) produces extensive and profound anesthesia with minimum amount of drug. The local anesthetic solution is introduced directly into spinal fluid, where the nerves are not protected by perineurium. This produces, in effect, a temporary cord transection such that no impulses are transmitted beyond the level that is anesthetized. Procedures as high as upper-abdominal surgery can be performed under spinal anesthesia. The sites of action of spinal anesthesia are the spinal nerve roots, spinal ganglia, and spinal cord.

E.     Lumbar epidural anesthesia affects same area of body as does spinal anesthesia. The drug is deposited outside dura. This method requires a much larger amount of drug. This procedure makes segmental anesthesia possible, whereby the anesthetized area is bordered caudally and cephalad by unaffected dermatomes and myotomes. The site of anesthetic action is on nerves as they leave intervertebral foramina. Effective drug concentrations may be found in spinal fluid, gains entrance through arachnoid villi. It is useful in obstetrics. Excellent analgesia occurs and the patient remains awake.Analgesia by epidural route can be provided for labor and delivery or for cesarean section.

F.      Caudal Anesthesia-In caudal form of extradural anesthesia, agent is introduced through sacral hiatus above coccyx. It is applicable to perineal and rectal procedures. Anesthetization of higher anatomical levels is not easily obtained, because required injection volume can be excessive. Although caudal anesthesia has been used extensively in obstetrics, lumbar epidural blockade is now used because of lower dose of drug required; in addition, sacral segments are spared until their anesthesia is required for delivery.

G.    Control of Cardiac Arrhythmias-Procainamide and lidocaine are primary drugs for treating cardiac arrhythmias. Since lidocaine has a short duration of action, it is common to administer it by continuous infusion. Procainamide, because of its amide linkage, has longer action than does its precursor, procaine. Orally active analogues of local anesthetics (e.g., mexiletine) also used as antiarrhythmics

Procaine

Procaine hydrochloride is readily hydrolyzed by plasma cholinesterase, although hepatic metabolism also occurs.

·                        Its use is confined to infiltration anesthesia and occasionally for diagnostic nerve blocks. This is because of its low potency, slow onset, and short duration of action. While its toxicity is fairly low, it is hydrolyzed in vivo to produce para-aminobenzoic acid, which inhibits the action of sulfonamides. Thus, large doses should not be administered to patients taking sulfonamide drugs.

·                        It is not effective topically but is employed for infiltration, nerve block, and spinal anesthesia. It has slow onset and short (1hour) duration of action.

·                        All concentrations can be combined with epinephrine.

·                        It is available in dental cartridges with phenylephrine as asoconstrictor.

Spinal anaesthesia

Spinal anesthesia is type of regional anesthesia that involves injection of local anesthetic drug into subarachnoid space of spinal cord, usually at level of second lumbar vertebra. There is loss of feeling (anesthesia) and movement in the lower extremities, lower abdomen, and perineum.

Complication of Spinal anaesthesia

1.      Respiratory paralysis

2.      Hypertension

3.      Headache

4.      Cauda equine syndrome

5.      Septic meningitis and

6.      Nausea and vomiting.