LOCAL ANESTHESIA Ester Local Anesthetics Cocaine n Benzocaine
LOCAL ANESTHESIA
Ester Local Anesthetics Cocaine n Benzocaine n Procaine n Tetracaine n Chloroprocaine n
Amide Local Anesthetics Lidocaine n Mepivacaine n Prilocaine n Bupivacaine n Etidocaine n Articaine n
Metabolism of Amide Local Anesthetics n n Biotransformation by hepatic microsomal enzyme system Drugs may increase metabolism via enzyme induction Liver disease may decrease metabolism via decreased functional tissue Decreased metabolism secondary to decreased hepatic blood flow
Metabolism of Ester Local Anesthetics Hydrolyzed by plasma cholinesterase n Factors which may lead to decreased plasma esterase activity n – Liver dz—decreased protein synthesis – Pregnancy—decreased pseudocholinesterase activity – Atypical pseudocholinesterase
Excretion of Local Anesthetics Active metabolites excreted by kidney n Severe renal disease may result in accumulation of active metabolites and produce toxicity n
Local Anesthetics: p. Ka vs. Onset of Action AGENT Mepivacaine Lidocaine Articaine Etidocaine Prilocaine Bupivacaine Procaine p. Ka 7. 7 7. 8 7. 9 8. 1 9. 1 ONSET (MIN) 2 -4 min 2 -4 min 5 -8 min 14 -18 min
Local Anesthetics: Protein Binding vs. Duration Bupivacaine RELATIVE PROTEIN BINDING 95 Etidocaine 94 LONG Mepivacaine 75 MODERATE Lidocaine 65 MODERATE Prilocaine 55 MODERATE Procaine 5 SHORT AGENT DURATION LONG
Manufacturers’ Recommended Dose AGENT Lidocaine +Epinephrine Mepivacaine+/- Vaso Prilocaine +/- Epi Articaine + Epi Bupivacaine + Epi ADULT ABSOLUTE DOSE MAXIMUM (mg/lb) (mg) 2 300 3 500 3 400 3. 6 400 3. 2 500 0. 6 90
Local Anesthetics: Adverse Effects Central Nervous System n Cardiovascular System n Respiratory System n Local Toxicity (skeletal muscle) n
Local Anesthetics: CNS Effects n Anticonvulsant Properties – Procaine, lidocaine, mepivacaine n n Low dose; 1 -4. 5 ug/ml CNS depression; preconvulsant – 4. 5 -7 ug/ml n CNS depression; tonic-clonic seizures – 7. 5 -10 ug/ml n Generalized CNS depression – >10 ug/ml
Preconvulsant: Signs and Symptoms (4. 5 -7 ug/ml) n SIGNS – – Slurred speech Shivering Muscular twitching Tremor in muscles of face and distal extremities n SYMPTOMS – Numbness of tongue and circumoral region – Warm, flushed feeling of skin – Pleasant dream-like state – Generalized lightheadedness – Dizziness – Visual and auditory disturbances – Disorientation
Local Anesthetics: Pa. CO 2 vs. Convulsant Threshold (Cats) AGENT Procaine Pa. CO 2 (25 -40 torr) 35 Pa. CO 2 (68 -81 torr) 17 Prilocaine 22 12 Mepivacaine 18 10 Lidocaine 15 7 Bupivacaine 5 2. 5
Local Anesthetics: CV Effects n Decreased electrical excitability, conduction rate and force of myocardial contraction (1. 8 -5 ug/ml) –. 5 -2 ug/ml—normal blood level following intraoral injection (no CV effects) – 5 -10 ug/ml—myocardial depression and peripheral vasodilation – >10 ug/ml—massive peripheral vasodilation, intensive myocardial depression, arrest
Local Anesthetics: Drug Interactions Tricyclic antidepressants n Cocaine n Beta-adrenergic blocking agents n Phenothiazines n – alpha blocking effect
Local Anesthetic Toxicity: Interaction w/ Opioids Redrawn from Moore & Goodson, Anesth Prog 32: 129 (1985)
Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults. Hersh E, et al. JADA; 139 August 2008; 1080 -1093 n Objective – To determine the efficacy of soft tissue reversal – Phentolamine mesylate n Non-selective alpha-adrenergic blocking agent used for the treatment of HTN associated with pheo. – 1. 7 ml carpule with 0. 4 mg phentolamine mesylate n Methods – Four different locals with epi utilized – All injections resulted in soft tissue anesthesia to the lower/upper lip – 244 subjects
Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults. Hersh E, et al. JADA; 139 August 2008; 1080 -1093 n Methods – Randomized to phentolamine or sham injection – Subjective analysis of numbness q 5 min and function testing (speech, drooling, etc)
Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults. Hersh E, et al. JADA; 139 August 2008; 1080 -1093 n Results – Tongue function n n Phentolamine group; 60 min Sham group; 125 minutes – Lower lip n n Phentolamine group; 70 min Sham group; 155 min – Upper lip n Phentolamine group; 50 min Sham group; 133 min n Not significant between the two groups n – Vital sign changes and adverse events
Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults. Hersh E, et al. JADA; 139 August 2008; 1080 -1093 n Conclusions – “. . . safe and efficacious in reducing the duration of soft tissue anesthesia and function” n Studies have also found the drug to be safe and efficacious in children 6 -12 – Children 4 -6 were not included secondary to poor historians in determining level of soft tissue anesthesia, but the drug was found to be safe with no adverse events
ANALYSIS OF N 2 O/O 2 SEDATION
N 2 O/O 2 ADVANTAGES… n Analgesia: variable – 20% = 15 mg morphine n Sedation – Calm, relaxed, and tolerant n Amnestic – Passage of time becomes unclear n Rapid Onset – Clinical effects < 30 seconds, peak effects < 5 minutes
N 2 O/O 2 ADVANTAGES… n Titration – Sedation depth is easily controlled n Recovery – Complete recovery in < 3 -5 minutes n In combination – Sophrology, distraction techniques, premedication, local anesthesia
DISADVANTAGES N 2 O/O 2… n Weak anesthetic – MAC 104 -105% n Air space expansion – N 2 O is 35 times as soluble as N 2 n Diffusion hypoxia – HA, N/V, and lethargy n Need for cooperative patient
Contraindications to N 2 O/O 2 sedation… n Absolute – Respiratory tract infection – Craniofacial deformity n Relative – – Severe emotional and behavior problems Clinically significant COPD Pregnancy Drugs: potentiating effects of N 2 O/O 2
Properties of N 2 O… n Manufacturing – NH 4 NO 3 N 2 O + 2 H 2 O 99. 5 -99. 9% pure – Major contaminant is nitrogen – Sweet smelling and nonflammable – Will support combustion in the proper concentration
Properties of N 2 O… n Stored as a liquefied compressed gas – Full cylinder = 95% liquid, 5% vapor 35 times more soluble than N 2 n Stable, does not react with soda lime, anesthetic drugs, or metal anesthesia equipment n
PHARMACOLOGY OF NITROUS OXIDE
Pharmacokinetics N 2 O… n Relatively insoluble in blood – Quick onset n N 2 O replaces N 2 – 35 times more soluble than N 2 – Rigid body spaces—increase pressure – Non-rigid spaces—increase volume
Pharmacokinetics N 2 O… n Tissue concentrations – – – n Gas solubility Blood flow to tissue Conc. of gas in arterial blood Factors for elimination of N 2 O – Same as uptake factors – Diffusion hypoxia n Metabolism – N 2 O not metabolized – 99% eliminated through lungs
Central Nervous System… Mechanism of action: unknown n Cerebral cortex: depression of all forms of sensation. Memory and concentration minimally affected n Cerebellar functions: ataxia and uncoordinated movements, nystagmus n Chronic exposure n Pneumocephalus n
Hematopoietic System… n Megaloblastic bone marrow changes: primarily seen with abuse cases
Drug Reactions/Interactions No reported allergies to N 2 O in 150 years of use n Drug interaction: no direct interactions reported, but may enhance other CNS depressants n
OCCUPATIONAL EXPOSURE
History of Controversial Literature… Vaisman 1967 n Cohen et al 1970 n Bruce, Bach, and Arbit 1970 n – OSHA standards n Clark 1995
Specific Biologic Issues and Health Concerns
Biochemical and Metabolic … n Inactivation of Vit. B 12 – Enzyme Systems Blocked n Methionine synthase n Methylmalonyl-Co. A mutase n Leucine 2, 3 -aminomutase – Studies and clinical significance
Health Concerns… n Nunn et al – Deoxyuridine Supression Test—detects early signs of inactivation of the enzyme methionine synthase n No alteration if this enzyme occurred in anesthetists exposed to between 150 -400 ppm
Health Concerns… Because of the demands for folic acid during organogenesis (first trimester) postponement of N 2 O sedation is recommended. n Pregnant females employed in a setting using N 2 O– important to know the exposure levels of N 2 O n – Safe use of scavenging systems.
Health Concerns… n Abuse: chronic—MS like symptoms and myloneuropathies – – – Paresthesia of extremities Loss of dexterity Loss of balance Muscle weakness in legs Gait ataxia Impotence
Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery. A Randomized Controlled Trial Myles P, Leslie K et al Anesth. 2007; 107: 221 -31 n 3, 187 patients scheduled for GA for abdominal procedure – One group received 70% nitrous and 30% oxygen with anesthetic – One group received 80% oxygen and 20% nitrogen with anesthetic n End-points included: N/V, complications, arousal, quality of recovery, etc
Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery. A Randomized Controlled Trial Myles P, Leslie K et al Anesth. 2007; 107: 221 -31 n Results – Nitrous group had a lower incidence of major complications and N/V – No difference in length of hospital stay – Shorter time spent in ICU n Conclusions – Avoidance of nitrous oxide and concomitant increase in oxygen decreased the incidence of complications after major surgery
CONTROL OF OCCUPATIONAL EXPOSURE
Detection and Monitoring Establish base-line and monitor exposure n Limit legal liability n Techniques of monitoring n – Infrared spectrophotometry – Time-weighted average dosimetry
Dosimetry Devices
ADA Recommendations… Monitor office with N 2 O analyzer n Use scavenging mask n Vent gases outside of building n Minimize patient conversation n Test equipment for leaks monthly n Employ air sweep ventilation n Achieve levels of < 50 ppm n
Sexual Phenomena with N 2 O… n n n Euphoric effects associated with N 2 O: hallucinations, visualizations, auditory illusions, and sexual stimulation Legal and personal consequences Common sense approach to N 2 O administration – Concentration < 50%, – 3 rd person, – No suggestive language
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