2. INTRODUCTION
LA are drugs which produce reversible blockade of
impulses along central and peripheral nerve pathways.
Autonomic nervous blockade , sensory anaesthesia
and skeletal muscle paralysis in the area innervated by
the affected nerve
Without loss of conciousness
3. HISTORY
1884-Koller introduced cocaine as first local
anaesthetic for use in ophthalmology
1885-Halstead recognised ability of cocaine to
interrupt nerve impulse conduction
1905- Ist synthetic local anaesthetic–procaine by
Einhorn
1943-lidocaine by Lofgren
5. Hydrophilic group-tertiary amine,such as diethylamine
Lipophilic group-unsaturated aromatic ring,such as
para aminobenzoicacid
Responsible for anesthetic activity
An ester(-CO-)or an amide(-NHC-)bond links the
hydrocarbon chain to lipophilic aromatic ring. This
forms the basis of classification of local anaesthetics.
9. PREPARATIONS OF LA
Most LA are bases that are poorly soluble.
Solubility is greatly increased by preparation of their
hydrochloride salts.
Dilute preparations are usually acidic (ph 4.0-5.5) and
contain a reducing agent (e.g. sodium metabisulphite)
to enhance the stability of added vasoconstrictors.
10. MECHANISM OF ACTION
Local anesthetic
↓
block voltage gated sodium channels
↓
no entry of sodium ions into the cell
↓
no depolarisation
↓
no generation of action potential
↓
no generation or conduction of nerve impulse
↓
local anesthesia
12. VOLTAGE GATED SODIUM CHANNEL
Transmembrane protein
Subunit – alpha and beta
Binds inactivated closed state –stabilize these
channels in this configuration and prevent their
change to rested closed and activated open in response
to nerve impulse
13. FREQUENCY DEPENDENT
BLOCKADE
Sodium channel tends to recover from LA induced
blockade between action potential. Additional
conduction blockade is developed each time sodium
channels open during action potential and LA gain
access to receptors only when channels are in activated
open state and bind more strongly to inactivated state
Resting nerve is less sensitive to LA than is a nerve that
has been repetitively stimulated.
14. Other sites
Voltage dependent potassium channel
Voltage dependent calcium channel
G-protein coupled receptors
16. MINIMUM EFFECTIVE
CONCENTRATION
Depends upon:
Diameter of nerve fibers: larger nerve fibre require
high concentration of LA.
pH ↑ →Cm ↓
Frequency of nerve stimulation: higher frequency
require – decreases Cm
Cm of motor fibres is approximately twice that of
sensory fibres
Despite an unchanged Cm,less LA is needed for
subarachnoid anesthesia than for epidural
17. CHANGES DURING PREGNANCY
Sensitivity increased.
Alteration in plasma protein binding characteristics of
bupivacaine may result in increased concentrations of
pharmacologically active unbound drug in the
parturients plasma.
18. pKa
It is ph at which LA is 50%ionized and 50% non ionized.
LA are weak bases that have pK values somewhat above
physiological ph. LA with pKs nearest to physiologic ph
have the most rapid onset of action.
<50% of LA exist in a lipid soluble nonionized form at
physiologic ph.
Acidosis (as in inlammation) favours ionization of drug.
Adding sodium bicarbonate to LA increases non ionized
form of drug leading to increased drug penetration into
cell and quicker onset of action.
20. ABSORPTION
The sysytemic absorption of LA is determined by
1.SITE OF INJECTION (vascularity)
Intravenous>Tracheal>Intercostal>Paracervical
>Caudal>Lumbar epidural>Brachial plexus>
Subarachnoid>Subcutaneous
2.SPECIFIC DRUG CHARACTERISTIC- Tendency to
produce vasodilator action of lidocaine results in
greater systemic absorption and short duration of
action.
21. 3.USE OF VASOCONTRICTOR:
Epinephrine (1:200,000)
Limits systemic absorption
Maintain drug concentration in vicinity of nerve
Reduce systemic toxicity
Contraindications of epinephrine-
Ring block of fingers,toes,penis,pinna
Retina
Halothane
Hyperthyroid
Hypertensives
i/v regional anesthesia or biers block
22. DISTRIBUTION
Highly perfused organs(brain , lungs ,liver ,kidney
,heart) followed by less perfused tissue(skeletal
muscle and gut)
High lipid solubility facilitate tissue uptake of drug
Plasma protein binding retain LA in blood
23. LUNG EXTRACTION
Lidocaine,bupivacaine and prilocaine
Pulmonary circulation will limit the concentration of
drug that reaches the systemic circulation for
distribution to the coronary and cerebral circulation.
For bupivacaine , the first pass pulmonary extraction
is dose dependent , suggesting that uptake becomes
saturated rapidly.
Propranolol impairs bupivacaine extraction by the
lungs.
24. PLACENTAL TRANSFER
Clinical significant transplacental transfer between
the mother and the fetus
Plasma protein binding influences the rate and degree
of diffusion
Fetal acidemia favours maternal to fetal transfer
Not esters
25. RENAL ELIMINATION AND CLEARANCE
< 5% renal excretion of unchanged drug due to poor
water solubility
cocaine 10-20%
Water soluble metabolites of LA, such as para-
aminobenzoic acid readily excreated in urine
26. METABOLISM
METABOLISM OF AMIDE LA:
liver microsomal enzymes P450
Rapid metabolism-Prilocaine
Intermediate – lidocaine and mepivacaine
Slowest-etidocaine , bupivacaine and ropivacaine
Slower metabolism and more systemic toxicity than esters.
lidocaine
↓
Monoethylglycinexylidide (80% activity of lidocaine for
protecting against cardiac dysrythmias)
↓
Xylidide(10% activity of lidocaine
Prilocaine → Orthotoluidine → methemoglobinemia
27. METABOLISM OF ESTER LA:
Plasma cholinestrase enzyme(exception cocain)
Most rapid-chloroprocaine
Intermediate-procaine
Slowest- tetracaine
PABA inactive metabolite –allergic reaction
Plasma cholinestrase activity decreased in-
liver disease,
increased BUN
parturients
patients treated with chemotherapeutic agents
28. ADVERSE EFFECTS OF LA
1. ALLERGIC REACTIONS:
PABA
Methylparaben
Cross sensitivity between LA reflects the common
metabolite
Occurrence of rash ,urticaria , and laryngeal edema
with or without hypotension and bronchospasm
29. 2.LOCAL ANESTHETIC SYSTEMIC TOXICITY:
Excess plasma concentration of drug
Accidental direct intravasvular injection -MC
The magnitude of this systemic absorption depends on
the (a)dose administered into tissues (b) vascularity of
injection site (c)presence of epinephrine in solution
(d) physicochemical property of drug.
Involves central nervous system and cardiovascular
system
Bupivacaine is more potent local anesthetic and
generates arrythmias at lower concentrations
compared with lidocaine and mepivacaine.
30. CNS TOXICITY:
prilocaine Lidocaine ,mepivacaine and
numbness of tongue and circumoral tissues
↓
Restlessness ,vertigo,tinnitus, and difficulty in
focussing
↓
Slurred speech and skeletal muscle twiching
↓
Tonic clonic seizures
↓
CNS depression accompanied by hypotension and
apnea
31. SELECTIVE CARDIAC TOXICITY:
Accidental IV injection of bupivacaine
↓
Protein binding gets saturated
↓
Leaving a significant amount of unbound drug
available for diffusion into the conducting system of
heart
↓
hypotension , cardiac dysrhythmia and
atrioventricular heart block
32. Pregnancy may increase sensitivity to cardiotoxic
effects of bupivacaine but not ropivacaine
Caution must be taken in the use of bupivacaine in
patients who are on antidysrhythmic drugs or other
cardiac drugs known to depress impulse propagation
Epinephrine and phenylephrine may increase
bupivacaine toxicity.
Cardiac resuscitation is more difficult after
bupivacaine induced cardiovascular collapse,acidosis.
33. TREATMENT OF LAST
Airway management ,circulatory support and
mechanism to remove local anesthetic at receptor site.
Ventilation of patients lung with oxygen
I/V administeration of midazolam or diazepam
Lipid emulsion- Initial bolus of 1.5ml/kg 20%lipid
emulsion followed by 0.25ml/kg/min of infusion,
continued for atleast 10 minutes after circulatory
stability is achieved
Epinephrine at a lower than typical dose during
resuscitation.
Avoid Calcium channel blockers and beta blockers
Cardiopulmonary bypass
35. TRANSIENT NEUROLOGICAL SYMPTOMS:
Moderate to severe pain in lower back , buttock and
posterior thighs
Appears within 6-36 hrs of complete recovery from
block
Sensory and motor examination normal
Complete recovery with in 1-7 days
Maximum risk with intrathecal lidocaine
36. ANTERIOR SPINAL ARTERY SYNDROME:
Lower extremity paresis with a variable sensory deficit
Etiology-thrombosis or spasm of anterior spinal artery
, hypotension ,vasoconstrictor drugs
Advanced age , peripheral vascular disease may
predispose patient to development of ASA syndrome.
37. CAUDA EQUINA SYNDROME:
Diffuse injury across lumbosacral plexus producing
varying degree of sensory anesthesia ,bowel and
bladder sphincter dysfunction and paraplegia
Hyperbaric 5% lidocaine for continous spinal
anesthesia
Microcatheters during continous spinal anesthesia
38. 4. METHEMOGLOBINEMIA
Rare but life threatening complication
Decreased oxygen carrying capacity
Central cynosis occurs when methemoglobin exceeds
15%
May follow administeration of certain
drugs(prilocaine, benzocaine,nitroglycerine
,phenytoin ,sulphonidws ) or chemicals that cause
oxidation of hemoglobin to methemoglobin
Neonates are at greater risk.
39. Diagnosis - difference in calculated and measured
arterial saturation.
Confirmed by co-oximetry
Readily reversed by the administeration of methylene
blue 1-2 mg/kg IV over 5 min(total dose should not
exceed 7 -8 mg/kg
40. USES
1. TOPICAL OR SURFACE ANESTHESIA
Mucous membranes of nose , mouth ,
tracheobronchial tree , esophagus or genitourinary
tract.
Cocaine 4-10%,Tetracaine 1-2%,Lidocaine 2-4% are
most often used.
Nebulised lidocaine before fiberoptic laryngoscopy
and/ or brochoscopy and as treatment for patients
experiencing intractable coughing.
41. EUTACTIC MIXTURE OF LA(EMLA)
5% Lidocaine-prilocainecream (2.5%lidocaine and
2.5%prilocaine)
Diffuse through intact skin to block neuronal
transmission from dermal receptors.
1-2g of EMLA cream is applied per 10cm2 area of skin
and covered with occlusive dressing.
Effective in relieving the pain of venipuncture, arterial
cannulation, lumbar puncture and myringotomy in
children and adults
42. Factors affecting EMLA analgesia:
Skin blood flow
Epidermal and dermal thickness
Duration of application
Presence of skin pathology
contraindications:
Congenital or idiopathic methemoglobinemia
Mucous membranes
Skin wounds
Known h/o allergy to amides
Patient on certain dyshythmic drugs(mexiletine)
43. 2. LOCAL INFILTERATION
Extravascular placement of LA in the area to be
anesthetized
Lidocaine most commonly used
The duration of can be approximately doubled by
adding 1:2,00,000 epinephrine to the LA solution.
Epinephrine containing solutions should not be
injected tissues supplied by end arteries.
44. 3. PERIPHERAL NERVE BLOCK ANESTHESIA
Injecting LA into tissues surrounding individual
peripheral nerves or nerve plexuses such as brachial
plexus
Diffusion : outer surface(mantle) →center(core) of the
nerve along concentration gradient
Mantle fibers - proximal and core fibers- distal
So development of anesthesia- proximal to distal
Conduction blockade is inversely proportional to fibre
size.
Duration of anesthesia depends on the dose of LA, its
lipid solubility , its degree of protein binding, and
concomitant use of vasoconstrictor.
45. IV REGIONAL ANESTHESIA (BIER BLOCK)
The IV injection of LA solution in a vein of a torniquet
occluded limb
Lidocaine most commonly used.
Normal sensation and skeletal muscle tone return
promptly on release of torniquet, which allows the
blood flow to dilute the concentration of drug.
Bupivacaine and Etidocaine should never be used.
46. 4. EPIDURAL ANESTHESIA:
Diffusion across the dura to act on nerve roots and
the spinal cord and through the intervertebral
foramina producing multiple paravertebral nerve
block.
15-30 min delay in onset of sensory anesthesia after
placement of LA solutions in the epidural space
lidocaine, bupivacaine, ropivacaine
Addition of opioids to LA solutions results in
improved analgesia.
47. 5. SPINAL ANESTHESIA
Principal site of action –preganglionic fibres
Dosage of LA vary according to (a) height of the
patient (b) segmental level of anesthesia required (c)
duration of anesthesia required
