Local Anaesthetics. Local anesthetics (LA) Part 1: Basic facts Part 2: Clinical aspects. 1. Reversible. blockade of conduction in peripheral nerves

Transcription

1 Local Anaesthetics Part 1: Basic facts Part 2: Clinical aspects Local anesthetics (LA) 1. Reversible. blockade of conduction in peripheral nerves pain 2. Lowers myocardial excitability Treatment of arythmia 3. Inhibits epileptic seizures (CNS) 4. Reduces neuropathic pain* (New) 5. Anti-inflammatory* (New) Leif Olgart 1

2 Mile stones (LA) 1. Cocaine 1884, cornea; - toxic, addictive 2. Procaine 1905, synthetic 3. Lidocaine 1946; Löfgren chemically stable heat resistant rapid onset frequent onset Leif Olgart 2

3 Cocaine LA chemical structure & properties H 2 N C OO R N Ester type R 1 R 2 Cocaine Procaine Benzocaine Tetracaine Local anesthetic NHCO R N Amide type R 1 R 2 Lipophilic link hydrophilic Lidocaine Prilocaine Mepivacaine Bupivacaine* Ropivacaine*.... Leif Olgart 3

4 LA are weak bases, pka: LA LA -H + Uncharged Charged 50% ph 8 50% (pka = 8) Na + channels Paranodal jct protein K + channels Myelin sheat Layers of myelin Node of Ranvier Axon Nucleus 10% ph 7 90% ( ~ normal) 1% ph 6 99% (inflamed) Poor diffusion = Poor clinical effect Sensitive area Several types of Na + channels exist Their number and type change when the nerve is injured and during inflammation Leif Olgart 4

5 Saltatory propagation is blocked L.A. Na + in K + out Na + in K + out Impulse Nerve Action potential Myelinated nerve Rest potential Leif Olgart 5

6 Action mechanism of LA Sodium Channel state Depot LA + LA-H + Connective tissue LA + LA-H + (open) Nerve membrane LA + LA-H + Use-dependent Nerve block (closed) Leif Olgart 6

7 Extracellular Intracellular LA - Effect on different types of nerves If Low concentration Mixed nerve: Thin unmyelinated fibers blocked first 1.Vasoconstrictor fibers 2. Temperature fibers 3. Pain fibers (C-type, A -type) 4. Touch fibers (A type, myelinated) 5. Motor fibers (heavily myelinated = protection) Leif Olgart 7

8 Most LA are vasodilators Adjuncts Vasoconstrictors: Adrenaline Octapressin = increased blood flow = more absorption = longer latency = often failure = shorter duration Shorter latency Often success Longer duration Less toxic risks Lower dose Reduced bleeding Leif Olgart 8

9 Local conc in nerve Diffusion Nerve fiber Absorption Blood LA + vasoconstrictor Disadvantages with catecholamines (adrenaline) Tricyklic antidepressants ( not SSRI) Hyperthyroidism ( Graves disease, Mb Basedow) LA Time Ischaemia (fingers, toes, ears...) Leif Olgart 9

10 Sympathetic Nerve terminals TCA + Adrenaline Adrenaline Leif Olgart 10

11 Human incisor tooth Xylokain 2% + adrenalin 12.5 g/ml Citanest 3% + octapressin 0.54µg/ml LA - Distribution Rapid via blood to all organs Passes blood-brain barrier Pulpans blodflöde reduceras = sämre försvar mot preparationstrauma... Passes placenta (50% of mother blood level) Leif Olgart 11

12 LA Metabolism - Elimination Infiltration, upper jaw Ester type: Procaine Tetracaine Metabolised by esterases in blood Renal excretion Amide type: Lidocaine Prilocaine* etc... Metabolised in the liver Renal excretion no adrenaline adrenaline 5 g/ml Plasma articaine concentration-time curve after intraoral submucosal injection of 80 mg articaine n= 14, infiltration regio 15. Leif Olgart 12

13 Adrenaline? Chose alternatives: High blood pressure Heart problems (takykardi) Hyperthyreosis (Graves disease, Mb Basedow) Antidepressants Ishemia-risk LA - Adverse reactions 1. Allergic very unusual 2. Local (infection) 3. General Myocard depression, blood pressure fall Convulsions, muscle contractions Respiratory arrest Leif Olgart 13

14 Blood plasma conc g/ml 14 LA - Toxic effects on CNS Respir. depress. Convuls Initially - Circumoral numbness Dizzyness Difficulty in focussing, Tinnitus Pressure fall Myocard depress. Epilepsy treatment Arythmia treatment Neuropathy treatment mg/kg LA dose systemic local Excitation phase - Shivering, Muscle twitching Depression phase - Tremors, Generalised tonic-clonic convulsions Unconciousness Respiratory arrest Leif Olgart 14

15 LA Toxic effects on CVS Initially - Hypertension, Tachycardia during CNS excitation Intermediate Phase - Negative inotrope Decreased cardiac output Moderate hypotension Terminal Phase - Peripheral vasodilation Profound hypotension Sinus bradycardia Ventricular dysrhythmias Circulatory collaps Rädsla för tandbehandling Postoperativ smärta Undviker tandvård Rädsla Smärta Rädsla Smärtsam behandling Patologiska tillstånd Smärta Bra Bedövning LO Leif Olgart 15