Combinations of drugs to accomplish what one anesthetic cannot do alone

Combinations of drugs to accomplish what one

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Combinations of drugs to accomplish what one anesthetic cannot do alone Combination of drugs lowers drug doses of each → safer anesthesia and closer to “perfect” anesthesia Perfect anesthesia (per Dr. Nicholson’s POV) produces… Reversible “sleep” (not really sleep because pt does not get the same feeling of being rested) Analgesia Suppresses reflexes Muscle relaxation Amnesia Does NOT suppress respiratory and CV function Inexpensive and easy to admin Injectable Anesthetics Advantages Disadvantages Minimal equipment (less complex) “Direct” CNS access Wide variety of agents and techniques Recovery dependent on uncontrollable factors Individual variation in drug response Potential for drug “accumulation” Common Dose-Dependent Characteristics of Sedatives/Anesthetics Desirable effects (note: analgesia is NOT on the list!) Immobility Hypnosis Amnesia AEs CV depression (hypotension, + myocardial sensitization (changes in electrical current)) Respiratory depression Hypothermia N/V Drug Therapeutic Indications Sedative/Anesthetic Characteristics PK AEs/CIs GABAergic Agents Benzodiazepines - Conscious sedation (for short dx procedures) - Anesthetic induction - Pre-anesthetic - Schedule IV - GABA A positive modulator - Minimal respiratory and CV depression - CYP450 metabolism → potential DDIs with CYP3A4 inhibitors (i.e. erythromycin, grapefruit juice, antiretrovirals) - CNS depression (dose dependent) - Residual sedation - Anterograde amnesia - Paradoxical stimulation Neurology Exam 3 Study Guide | Page 23
sedative - Relatively high therapeutic index (compared to barbs) - No analgesic properties - Al have similar AEs, primary difference is in duration of action Midazolam : water soluble vehicle, greatest potency Lorazepam and Diazepam: non-water soluble → incompatible with many drugs; IV line should be adequately flushed - Many are converted to active metabolites which determines duration of action Midazolam : rapid onset, short acting Lorazepam : intermediate-acting Diazepam : long-acting (more common in children) - Apnea, respiratory depression (not at sedative doses) - Pregnancy category D or X - DDIs: PK interactions and additive CNS depression - Abuse liability - Tolerance (cross tolerance with GABA A sedative hypnotics) - Physical dependence but withdrawal typically non-life threatening Flumazenil - Reversal of benzodiazepine overdose - Reversal of short-acting benzodiazepine sedation Competitive antagonist of benzodiazepines Short acting - Precipitates withdrawal - Stimulatory characteristics on its own → seizures, nausea, and excitation Barbiturates - Anesthetic induction - Moderate to deep sedation combined with analgesic - Longer acting compounds for anticonvulsant effects - Schedule II-IV - GABA A receptor positive modulators - Very alkaline → very irritating to tissues if injected outside of vein - Very good at producing anesthesia - Poor analgesic agent - Low therapeutic index - Primary difference b/w compounds is duration of action Ultra short acting: thiamylal and methohexital b/c highly

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