Local Anesthetics

Local Anesthesia

List major groups of local anesthetics

Describe the MOBlock of the nerve impulses by LA

Discuss the relation between pH, pKa & the speed of onset of LA

List different approaches of LA

List the factors that determine the susceptibility of nerve fibers to blockade

List the major adverse effects of LA

Anesthesia

General anesthesia

Local anesthesia:

1. Surface- bronchial tree and cornea

2. Infiltrative-in regions

3. Field block

4. Regional nerve block

5. Bier’s block: IV regional anesthesia: prilocaine in limbs

6. Spinal anesthesia- for pelvic surgery

Local Anesthesia

Transmission of sensory is blocked from a local area of body to the CNS by blocking the Na channels of excitatory membranes.

Small & superficial parts are anesthetized

Indications: in dental procedure, skin biopsies, stitching up at cut, etc (t1/2: shorter)

C/I at areas of sensitive parts.

Form: injection, spray, & ointment or lotions

Regional anesthesia

Block sensation in the particular region of body [lower 1/2 of body, eyes, arms & legs]

The route of administrations: For

A. Lower half of the body: Spinal, caudal or epidural

B. Hand : median nerve block, ulna nerve block; radial nerve block

C. Finger anesthesia: metacarpal nerve block, digital nerve block

D. Foot & toe anesthesia: posterior & anterior ankle block, toe block

E. Facial anesthesia: blocking of 5^th cranial nerve, Supra-orbital nerve, Infra-orbital nerve, Mental nerve, etc.

Classification

I.  Esters:

 (i) Long acting: Tetracaine

 (ii) Medium acting: Cocaine

 (iii) Short acting: Procaine

 (iv) Surface- active: Benzocaine, cocaine

II. Amides:

 (i) Long acting: Bupivacaine, ropicaine

 (ii) Medium acting: lidocaine

Chemical Aspects

Esters or amides are simple benzene derivatives

All carry at least one amine function [weak bases- charged through a proton]

The pH of different tissues: the physiologic 7.4 [lowered in infected tissues (6.4)]

The degree of ionization of the drug are variable. The pKa of most LA is in between 8.0 & 9.0 (except benzocaine)

Variations in pH: significant effects on the proportion of ionized to non-ionized drug.

Pharmacokinetics

Many shorter-acting LA:

Absorbed from the injection site.

The duration of LA is limited unless blood flow to the area is reduced i.e. vascular constriction (alpha agonist) except cocaine

Longer acting (bupivacaine, ropicaine, tetracaine): < dependent on epinephrine

Surface activity is a property of only a few LA: cocaine, benzocaine, etc.

Metabolism

Esters: By plasma & tissue AChE & may be rapid [Procaine & chlor-procaine with long (1-2 h)]

Amides: Hydrolyzed in liver (2-6 h). Bupivacaine & rovivacaine- longest

Liver dysfunction- increase t1/2-beta

Mode of Actions

Block Na channel- block conduction of AP Gain to access to their Rptrs from the cytoplasm or  membrane

Lipid soluble form reaches effective I/C rapidly > the ionized form. In the axon the ionized form >> effective

Uncharged agent, the first reaches receptor site & charged causes the effects

The affinity of receptor site within Na channel for LA is function of receptor site within the Na channel [binding more readily to open or inactivated channels]

Thus , follows the rules of use & potential dependence.

Effects

Nerves: The smaller fibers are more easily blocked. The myelinated nerves > unmyelinited one

 - The pain fibers are blocked easily > others

Others: Class-I anti-arrhythmic agents, most weak blocker of  NM transmission [no clinical applications]

Cocaine elevates the mood [NE,DA, etc]

Adverse drug reactions

CNS effects:

 - Light headaches, sedation, restlessness, nystagmus, & tonic-clonic seizure (give Large dose Benzodiazepine).   

CVS: All LA are vasodilators except cocaine.

 - Heart block (preexisting heart disease)

 - Bupivacaine: arrhythmias, HPN [IV]

 - Ropicaine [long acting]: less cardio toxic

Cocaine: HTN, hemorrhage, arrhythmias, myocardial infarction

Prilocaine [o-tobuidine]: metHbnemia

High concentrated: local neurotoxic action- histological damage (difficult)

Allergy: rare

Treatment of toxicity

Severe toxicity: Symptomatic T/T

For seizures- diazepam or short acting barbiturate (thiopental)

Hyperventilation- with oxygen

For violent convulsive activity- NMJ blocker

For cardiovascular toxicity (bupivacaine over dose)- very difficult to treat.

Eutectic mixture of LA

For tropical effect on intact skin for needling procedures

Eutectic mixture of LA [mixture of bases of prilocaine or lidocaine] cream

Absorption is very slow & is applied under an occlusive dressing for at least 1 hour.

Tetracaine gel 4% is > effective than EMLA cream and enables pain free venepuncture 30 m after application.

Spinal Anesthesia

Lidocaine (1.5-5%) or tetracaine (0.25-0.5%) in 10% glucose (hyperbaric solution) into L2-L3 sub-arachnoid space

For performing surgical procedure on lower abdomen, pelvis and lower limbs

AE:

Severe headache, nausea & vomiting,

Hypotension

Respiratory arrest (rarely)

Septic meningitis

Cauda equina syndrome

C/I: HPN, hypovolemia, sepsis at the site vertebral deformities, children, etc.

Role of adrenaline with lidocaine

The effect of a lidocaine is terminated by its removal of site of application.

Adrenaline reduces local blood flow, slows the rate of absorption of LA

Prolongs lidocaine effect (double 1-2 hrs)

Reduces its systemic toxicity (HR, BP, etc)

Dosage: adrenaline 1:200,000 or 1:80,000

Contraindication of adrenaline: in

Fingers, toe, nose, genitals, etc.

For obvious anatomical reasons, blood supply may be cut off by intense vasoconstriction so that the organ may be damaged or lost.