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 5th 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.

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