1. School of Pharmacy, University of Nizwa
Local Anesthetics
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-32
April 28, 2012

2. Original in the Royal College of Surgeons of England, London.
18th Century Surgery
Original in the Royal College of Surgeons of England, London.

3. William T.G. Morton’s Ether Inhaler
October 17, 1846: First public demonstration of the use of ether in anesthesia at Massachusetts General Hospital

4. Classic Stages of Anesthesia
Stage 1: Analgesia
decreased awareness of pain
Stage 2: Excitation
delirium & excitation, enhanced reflexes
Stage 3: Surgical Anesthesia
unconscious, no pain reflexes, regular respiration, BP is maintained
Stage 4: Medullary Depression
respiratory & CV depression requiring ventilation and pharmacologic support

5. Mechanisms of Action Enhanced GABA effect on GABAA Receptors
Inhaled anesthetics, Barbiturates
Block nicotinic receptor subtypes (analgesia)
Moderate to high concentrations of inhaled anesthetics
Activate K channels
Nitrous oxide, ketamine
Inhibit NMDA (glutamate) receptors

6. Local Anesthetics
Applied locally and block nerve conduction of sensory impulses from the periphery to the CNS
Abolish sensation in a limited area of the body without producing unconsciousness
Onset of action should be quick, and duration of action should be sufficient to allow time for the surgical procedure

7. Local Anesthetics: Mechanism of Action
Inhibit the inward migration of Na+
Elevates the threshold for electrical excitation, reduces the rate of rise of the action potential, and slows the propagation of the impulse

8. Local Anesthetics: Clinical Pharmacology
Useful route of administration
Topical (nasal, mucosal)
Infiltration (injection in the vicinity of peripheral nerve endings)
Injection into the epidural spaces surrounding the spinal cord
Intravenous regional anesthesia is used for short surgical procedure (<45 min)

9. Local Anesthetics
Lidocaine
Bupivacaine
Prilocaine
Cocaine
Benzocaine

10. Lidocaine Pharmacological Actions: Absorption, Fate, and Excretion:
Produces faster, longer lasting, and more extensive anesthesia than does an equal concentration of procaine
Absorption, Fate, and Excretion:
Absorbed rapidly after parenteral administration
Metabolized in the liver by CYPs enzymes
Excreted in the urine
Toxicity:
The side effects of high doses include drowsiness, tinnitus, and dizziness. As the dose increases, seizures, coma, and respiratory depression and arrest occur
Clinical Uses:
Wide range of clinical uses as a local anesthetic

11. Bupivacaine Pharmacological Actions: Toxicity:
Widely used amide local anesthetic
A potent agent capable of producing prolonged anesthesia
Long duration of action
Can be used to provide several days of effective analgesia
Toxicity:
Bupivacaine is more cardiotoxic than lidocaine
Bupivacaine-induced cardiac toxicity can be very difficult to treat

12. Prilocaine An intermediate-acting amino amide local anesthetic
Pharmacological profile similar to that of lidocaine
It is unique among the local anesthetics in its propensity to cause methemoglobinemia

13. Cocaine Cocaine remains useful as topical use
Toxicity prohibits its use as anesthesia
Cocaine has a rapid onset of action (1 minute) and a duration of up to 2 hours
Lower concentrations are used for the eye, while higher ones are used on the nasal and pharyngeal mucosa
Bradycardia, tachycardia and hypertension are associated with cocaine
Larger doses are directly depressant to the myocardium, and death results from cardiac failure
Over dosage leads to convulsions followed by CNS depression

14. Benzocaine
Used primarily for topical application to skin and mucous membranes
Its low aqueous solubility allows it to stay at the site of application for long periods
Its minimal rate of absorption after topical administration is associated with a low incidence of systemic toxicity