CNS Pharmacology

Local Anesthesia

1

2

Local AnesthesiaDefinition and ScopeHistory:

Nerve compression and refrigeration. Coca leaves used by the Incas.1860, Cocaine isolated.1884, Cocaine used in eye surgery and

dentistry, and then in nerve blocks.1903, Adrenaline added1905, Procaine then Lidocaine in 1943

3

local anesthesia refers to loss of sensation in a limitedregion of the body

• Direct drug delivery to target• Systemic circulation functions

to terminate effect.

Definition and Scope

3

Features of an Ideal LA

Rapid onset.Not irritating.Sufficient duration of action.Reversible effect.Low systemic toxicity.Proper physical properties: StabilityWater solubility.

4

Chemistry of LAAll LA have three structural domains:

Aromatic group: influences the hydrophobicity of the drug.

Amide or Ester linkage: influences the duration of action and toxicity of the drug.

Amine group: influences the rate of onset and potency of the drug.

5

7

6

Mechanism of Action of LA

Blockade of voltage-gated sodium channels from inside the channel.

7

10

8

9

10

Pharmacokinetics of LAAbsorption and Distribution:Dose.Site of injection.

Drug Tissue Binding.Vascularity (local blood flow).The use of vasoconstrictors( 50% prolongation of action and 30% reduction in blood levels).Physicochemical Properties.pH.

14

11

Mechanism of Action of LAProduce Differential Blockade: C--B -- AAutonomicPainColdWarmthTouchPressureMotor

12

13

Pharmacokinetics of LAMetabolism:

For ester –type LAs:Pseudocholinesterase ------ PABA---Allergenic.Very rapid, so short t1/2

For amide-type LAs:Liver metabolism by cytochrome P450 enzymes.

14

Routes of Administration of LATopical or Surface: Lidocaine and Tetracaine.Infiltration: Most LAsRegional Block:

Nerve Block: most LAsSpinal(Subarachnoid): Lidocaine, TetracaineLumbar Epidural: Lidocaine, BupivacaineCaudal.

Intravenous Extremity Block(Bier Block): Lidocaine, Tetracaine.

Systemic: Intravenous: Lidocaine for ventricular arrhythmias

15

16

Pharmacological and Toxicological Effects of LACardiac Effects:

Decreased excitability, conductivity, and contractility.

Vascular Effects:Usually vasodilation which will reduce

venous return and consequentlycardiac output.

Hypersensitivity Reactions:Usually with esters, due to PABA. Might also be due to the preservatives. Can cause allergic dermatitis or asthma.

17

Pharmacological and Toxicological Effects of LA

Central Effects:Can cross BBB due to small size.

Usually cause CNS stimulation.CNS depression occurs with high doses.

Neuromuscular & Ganglia:Can decrease ACh release.

Local Irritation.

18

Ester Local AnestheticsCocaine:

Medium potency, medium duration of action,mainly in ophthalmology, also topical, cardiotoxic

and euophoric. Procaine:

Short acting, used for infiltration and dental anesthesia

Benzocaine: Usually for topical use.

Chloroprocaine.Tetracaine:

Long acting, highly potent, used in spinal and topical anesthesia.

19

Amide Local AnestheticsLidocaine: Most commonly used.

Rapid onset,Most intense, Medium duration.

Bupivacaine: In obstetrics and postoperative anesthesia.

Long duration(24hrs).Levobupivacaine:

Is less toxic.

19

Amide Local AnestheticsArticaine: amino-amide anesthetics Has a thiophene. The modification of the

ring serves to enhance lipophilicity, and thus improve tissue penetration, while

Also contains an additional ester.

Inclusion of the ester leads to a shorter plasma half

20

Amide Local AnestheticsRopivacaineEtidocaineMepivacainePrilocaine:

Has some vasoconstrictor effect, no need to add epinephrine.

21

Topical AgentsEMLA:“Eutectic Mixture of Local Anesthetics”:

Mixture of lidocaine and prilocaine.Patch or cream.For children to reduce the pain of venipuncture, arterial cannulation, lumbar puncture, dental procedures, and skin graft donor site.

TAC:Tetracaine + Adrenaline + Cocaine.For repair of minor lacerations.