Local anaesthetics (l)

Pharmacology lecture for MBBS students

1. DR RAHUL Local Anaesthetics 10/4/2013 RK 1

2. Definition of Anesthesia Anesthesia literally means “no sensation” Derived from the Greek verb for “to perceive” : Oliver Wendell Holmes, 1846 10/4/2013 RK 2

3. Local Anaesthesia L oss of sensory perceptions by reversibly inhibiting the propagation of signals along nerve pathways in a specific area of the body. LAs block generation and conduction of impulse at all parts of neurons where they come in contact. 10/4/2013 RK 3

4. History Cocaine : First local anaesthetic Discovered by German, Albert Niemann (1860) Isolated from the leaves of coca First clinical use in 1884 by Sigmund Freud and Karl Kollar in ophthalmology as a topical ointment 10/4/2013 RK 4

5. INJECTABLE Low potency & short duration Procaine Chloroprocaine Intermediate potency & duration Lignocaine Prilocaine High potency & long duration Tetracine Bupivacaine Ropivacaine SURFACE Soluble Cocaine Lignocaine Tetracaine Insoluble : Benzocaine CLASSIFICATION 10/4/2013 RK 5

6. General structure 10/4/2013 RK 6

7. Lignocaine Mepivicaine Prilocaine Bupivacaine More intense and longer lasting anaesthesia Cocaine Procaine Tetracaine Chlorprocaine Benzocaine Short DOA, less intense analgesia Types of Local Anaesthetics Esters Amides 10/4/2013 RK 7

8. These get metabolized in the liver to inactive agents Binding to amides is provided by alpha 1 glycoprotein in plama No allergies associated with amides Hydrolysed in the plasma by a pseudo cholinesterase One by-product of this reaction Para-Amino B enzoic Acid (PABA) A llergic reaction are associated with PABA Types of Local Anaesthetics Esters Amides 10/4/2013 RK 8

9. Mechanism of Action Inhibits sodium influx through sodium-specific ion channels in the nerve cytoplasm Sodium ions cannot flow in, so potassium ions cannot flow out, thereby preventing the depolarization of the nerve R ate of rise of AP and depolarisation decreases with increase in concentration of LAs To do this the anaesthetic molecules must actually enter through the cell membrane of the nerve. This is where the differences in the time of onset and duration of the various local anaesthetics lies. 10/4/2013 RK 9

10. 10/4/2013 RK 10

11. Factors that affect action of local anesthetics pH C ationic form binds to receptor site. The uncharged form penetrates membrane . Efficacy of drug can be changed by altering extracellular or intracellular pH 10/4/2013 RK 11

12. Factors that affect action of local anesthetic Lipophilicity M ain determinant of anesthetic potency. Compounds with high lipophilicity penetrate the nerve membrane easily. This means less molecules are needed to inhibit the blockade of sodium ions. This leads to enhanced potency. 10/4/2013 RK 12

13. Vasoconstrictors Blood absorbs the unused anesthetic. In order to slow down this process many anesthetics are administered with a vasoconstrictor. These constrict the vessel and slow down the absorption of the anesthetic, by allowing less blood to enter/leave the site 10/4/2013 RK 13

14. ADVANTAGES OF LIGNOCAINE ADRENALINE COMBINATION Decrease systemic toxicity (  uptake by up to 1/3) Prolong local anesthesia (by ~50%) Decrease local bleeding (improve visualization of surgical field DIS ADVANTAGES: Makes injection more painful Increases chances of local injury and necrosis. May raise BP and promote arrhythmias in susceptible individuals 10/4/2013 RK 14

15. Progression of local anesthesia Loss of: 1. Pain 2. Cold 3. Warmth 4. Touch 5. Deep pressure 6. Motor function 10/4/2013 RK 15

16. PHARMACOLOGICAL ACTIONS CNS : All can produce CNS stimulation followed by depression. Cocaine: Euphoria-excitement-mental Confusion-tremors-muscle Twitching-convulsions- Unconciousness -resp. Depression. Procaine, Lignocaine: safe at clinical doses CVS : Cardiac depressant at iv doses Antiarrhythmic action (procainamide) 10/4/2013 RK 16

17. Techniques of administration Topical Anesthesia Infiltration Conduction block Field block Nerve block Peridural Spinal anesthesia 10/4/2013 RK 17

18. Topical Anesthesia Done by the administering the anesthetic to mucous membranes or skin. Relieves itching, burning and surface pain, i.e. sunburns. 10/4/2013 RK 18

19. Infiltration Occurs by directly injecting a local anesthetic to block the nerve endings under the skin or in the subcutaneous tissue. Used mainly for surgeries, i.e. cavities being filled. 10/4/2013 RK 19

20. Conduction block 10/4/2013 RK 20

21. Epidural Anesthesia This is accomplished by injecting a local anesthetic into the peridural space, a covering of the spinal cord 10/4/2013 RK 21

22. Spinal anesthesia Here, the local anesthetic is injected into the subarachnoid space of the spinal cord 10/4/2013 RK 22

23. Toxicity CNS Toxicity: Systematic absorption can lead to excitement (tremors, shivering, convulsions), I f absorbed in even higher amounts can lead to depression (coma, respiratory arrest and death) Cardiovascular toxicity: If absorbed in excess systematically can lead to depression of the cardiovascular system Hypersensitivity : Rashes to anaphylaxis Local reactions: Combination with vasoconstrictor (combination should be avoided-feet, fingers, toes, pinna, penis) 10/4/2013 RK 23

24. 10/4/2013 RK 24

25. 10/4/2013 RK 25

26. 10/4/2013 RK 26

27. Thank you…. 10/4/2013 RK 27