Local anaesthetics

1. By
Rani I. Gurudasani
M.Pharm.

2. Local Anaesthetics
 Local Anaesthetics(LA) reversibly block the impulse conduction in any part of
nervous system & in all nerves including sensory & motor types.
 They provide a transient loss of sensation in a restricted region of the body
 LAs preferred for performing minor surgeries
 LAs neither produce loss of consciousness nor maintenance of vital functions
during the surgery.
 Nerve fibers which are Smaller in length are more sensitive than large fibers.

3. Local Anaesthetics
 Myelinated fibers are blocked earlier than un-myelinated fibers.
 Pain, temperature and touch sensation are blocked first, skeletal muscle tone is
lost latter on.
 These are weak bases-- partly ionized with acids--unionized parts is lipophilic
in nature and which helps the LA to penetrate into nerve membrane-- after
going inside the ionized part which is active at the receptor side
 LAs are basic in nature so -- they are action is strong at alkaline pH & less at
acidic pH -- unionized form is needed for its diffusion through axon membrane

4. Classification
1. Injectable anaesthetic
a. Low potency, short duration
 Procaine
 Chloroprocaine
b. Intermediate potency and duration
 Lidocaine (Lignocaine)
 Prilocaine
c. High potency, long duration
 Tetracaine (Amethocaine)
 Bupivacaine
 Ropivacaine
 Dibucaine (Cinchocaine)
2. Surface anaesthetic
a. Soluble b. Insoluble
Cocaine Benzocaine
Lidocaine Butylaminobenzoate(Butamben)
Tetracaine Oxethazaine
Benoxinate

5. Mechanism of action of LAs:
 LAs → block the voltage gated Na+ channels during depolarisation→ Na+ permeability
decreases → consequently nerve conduction is blocked.
 LAs interact with a receptor within the voltage sensitive Na+ channel and raise the
threshold of opening the channel.
 All local anaesthetics are membrane stabilizing drugs – slows down speed of Action
potential - ultimately stop Action potential generation
 Reversibly decrease the rate of depolarization and repolarization of excitable
membranes
 Act by inhibiting sodium influx through sodium-specific ion channels in the neuronal
cell, voltage-gated sodium channels
 When the influx of sodium is interrupted - action potential cannot rise and signal
conduction is inhibited.

6. Pharmacokinetics:
ABSORPTION:
 Orally: All LA are absorbed poorly except cocaine • Reason: High first pass metabolism
 Topically: Absorbed at different rates after application to mucous membranes.
 Injection: Uptake of LA after parentral administration depends on:
 I. Vascularity of the injection site and II. Vasoactivity of the drug.
DISTRIBUTION:
 When LAs enters the blood, then distributed to all tissues, like brain, liver, lungs, kidneys
& spleen have high levels of local anaesthetics.
 Due to their high level of perfusion. Skeletal muscle has the highest level because it has
the largest mass of tissue in the body.

7. Pharmacokinetics:
METABOLISM:
 PABA ( Paraaminobenzoic acid) metabolism : - LAs hydrolyzed in plasma
by enzyme pseudo cholinesterase.
 Primary site of metabolism: Liver • Prilocaine is metabolized in the liver
& lung
EXCRETION:
 Major excretory organ: Kidneys
 PROCAINE: Appear in urine as 90% PABA & 2% unchanged.
 COCAINE: Appear in urine as 10% unchanged.

8. Pharmacological Actions:
1. CNS:
 All LAs are capable of producing a sequence of stimulation followed by
depression.
 Cocaine is a powerful CNS stimulant causing in sequence
 euphoria—excitement—mental confusion—restlessness—tremor and twitching
of muscles— convulsions—unconsciousness—respiratory depression—death,
in a dose-dependent manner.
 Procaine and other synthetic LAs at Higher dose or accidental i.v. injection
produces CNS stimulation followed by depression.

9. Pharmacological Actions:
2. C.V.S.:
 Heart: LAs are cardiac depressants, but no significant effects are observed
at conventional doses. At high doses or on inadvertent i.v. injection, they
decrease automaticity, excitability, contractility, conductivity and increase
effective refractory period (ERP).
 Blood vessels: LAs tend to produce fall in BP. This is primarily due to
sympathetic blockade, but high concentrations, as obtained locally at the
site of injection, do cause direct relaxation of arteriolar smooth muscle.

10. Pharmacological Actions:
3. RESPIRATORY SYSTEM:
 DUAL EFFECTS:
 Non-overdose levels: Direct relaxant action on bronchial smooth muscle.
 Overdose levels: RESPIRATORY ARREST DEATH
4. LOCAL TISSUE TOXICITY:
 Longer acting LA produces more damage to skeletal muscle than shorter
acting LA.

11. Individual drugs
1. Procaine:
 It is the first synthetic local anaesthetic
 procaine penicillin injected i.m. acts for 24 hours due to slow absorption
from the site of injection.
 Metabolised-in Plasma by plasma pseudocholine esterases.
 Excretion- 2% unchanged, 90% -PABA, 8% diethyl aminoethanol in
urine.
 Drug of choice for intra-arterial injection and accidents.
 Not used now.

12. 2. Lidocaine (Lignocaine):
 It is currently the most widely used LA.
 It is a versatile LA, good both for surface application as well as injection and is available
in a variety of forms.
 Metabolised- Liver by microsomal fixed function oxidases to monoethyl glycerine and
xylidide
 Excretion –In Urine less than 10% unchanged.
 Anesthetic half-life is 1.6 hrs.
 Injected around a nerve it blocks conduction within 3 min, whereas procaine may take
15 min; also anaesthesia is more intense and longer lasting.
 Vasodilatation occurs in the injected area.

13. 2. Lidocaine (Lignocaine) cont….
 It is used for surface application, infiltration, nerve block, epidural, spinal
and intravenous regional block anaesthesia.
 In contrast to other LAs, early central effects of lidocaine are drowsiness,
mental clouding, altered taste and tinnitus are observed.
 Overdose: unconsciousness and respiratory arrest.
 Lidocaine is a popular antiarrhythmic.
 Adverse reactions- CNS stimulation then Depression

14. 3. Prilocain:
It is similar to lidocaine but does not cause
vasodilatation at the site of infiltration and has lower
CNS toxicity due to larger volume of distribution.

15. 4. Bupivacaine:
 Metabolism –Liver by Amidases
 Excretion by kidney (16% unchanged)
 Anesthetic half-life -2.7hrs
 A potent and long-acting amide linked LA: used for infiltration, nerve block,
epidural and spinal anaesthesia of long duration.
 A 0.25–0.5% solution injected epidurally produces adequate analgesia
without significant motor blockade.

16. Bupivacaine: cont..
 If given by IV route, then It may produce cardiac arrhythmia, hence not
given by IV route.
 Uses: pulpal anesthesia. (during root canal), Full mouth reconstruction,
management of post op pain, obstetrics (during delivery) and for
postoperative pain relief by continuous epidural infusion.
 Adverse effects: burning sensation at site of injecton, Contraindicated in
children

17. 5. Ropivacaine:
A newer bupivacaine congener, equallylong acting but less
cardiotoxic.
Continuous epidural ropivacaine is being used for relief of
postoperative and labour pain.

18. 6. Cocaine:
 It is a natural alkaloid from leaves of Erythroxylon coca.
 Cocaine is a good surface anaesthetic and is rapidly absorbed from buccal mucous
membrane.
 Cocaine produces prominent CNS stimulation with marked effect on mood and behaviour.
 Uses: Cocaine is used by health care professionals to temporarily numb the lining of the
mouth, nose, and throat (mucous membranes) before certain medical procedures.
 A.E.: drowsiness, confusion, hallucinations, mood swings.
 Cocaine should never be injected; it is a protoplasmic poison and causes tissue necrosis.
 Cocaine also stimulates vagal centre causes bradycardia;
 Stimulate vasomotor centre leads to rise in BP.

19. 7. Benoxinate:
It is a good surface anaesthetic for the eye; has little irritancy.
A 0.4% solution rapidly produces corneal anaesthesia sufficient
for tonometry without causing mydriasis or corneal damage.

20. 8. Benzocaine and Butylaminobenzoate
(Butamben)
 These drugs have very low aqueous solubility.
 These LAs are not significantly absorbed from mucous membranes or
abraded skin.
 They produce long-lasting anaesthesia without systemic toxicity.
 Uses: They are used as lozenges for stomatitis, sore throat; as dusting
powder/ointment on wounds/ulcerated surfaces and as suppository for
anorectal lesions.