• facilitate GABA neurotransmission
  • although many anesthetics enhance GABA function, they do so with different mechanisms
• augment glycine transmission

• inhibit glutamate channels (both do NMDA) (kainate for nitrous oxide only)

• minimum alveolar concentration
  • definition: renders 50% of subjects exposed to noxious stimuli immobile
  • mild anesthesia: 0.3
  • amnesia: 0.5
  • dose response relationship (STEEP)
    • 1.1 MAC: 95% of patients immobile to noxious stimuli
    • 1.3 MAC: blunted symp. responses to surgery and 99% of patients immobile
    • 2 MAC: lethal
  • different agents expressed as MAC equivalents are typically additive

• anestheisa is produced by changes in the physical properties of cell membranes
  • leading to reduced neuroexcitabliity
  • proof Meyeer Overton correlation
• problem- doesnt explain how proposed disturbances of lipid bilayer would produce reduced neuroexcitability
  • see breakdown in relationship with ketamine (hydrophilic)
  • some anesthetics exhibit stereoselectivity
    • usually both enantiomers have different anesthetic potencies that cant be explained by nonselective interaction with lipid membrane

• binds to specific site on GABA channel
• augments GABA responses by increasing length of time chloride channels remains open

• enhance GABA efficacy by increasing affinity of GABA for its binding site on GABA_A receptors

• in the midst of our excitatory stimulation, instead reaching threshold in our post synaptic cell, we do not reach the needed excitatory potential

• transfer lungs to arterial blood depends on solubility (if higher protein binding, solubility greater)
• agents with low solubiility have low partition coefficients
  • when anesthetics with low solubility diffuses from the lungs into the blood relatively few molecules are required to raise partial pressure and arterial pressure rises quickly (quicker to reach equilibrium)
• conversely, anesthetics with high solubility more molecules need to dissolve before partial pressure increases (slower to reach equilibrium)

• low solubility in blood
• reaches arterial partial pressure and equilibirum very quickly and has faster induction

• high solubility
• reaches equilibrium slowly
• not useful for rapid induction

• speed of induction inversely proportional to solubility of agent in blood (blood:gas partition)

• if you have low solubility, elimination will occur rapidly

• low blood:gas partition coefficient
• low fat:blood partition coefficient (we dont want anesthetic to be dissolved in fat)
• low MAC numbers
  • we want to provide oxygen to our patients (if you got 90% MAC, you can only give them 10% oxygen)
• we want no metabolism (inert)

• 1 MAC = 0.75%
• blood:gas coefficient relatively high, so induction in slow
• induction = 2-4%
• 0.5-1.5% maintenance
• soluble in fat
• unflammable, volatile colorless liquid, light sensitive

• advantages
  • nonflammable
  • moderately potent
  • smooth induction
• disadvantages
  • resp. is rapid and shallow, decreasing ventilation and increases CO₂ tension
  • hypotentsion (due to direct myocardial depression)
  • bradycardia, transient arrhythmias
  • halothane hepatitis (immune response evoking hepatic necrosis, fever, nausea, rash vomitting)

• colorless, volatile, sweet odor
• MAC = 1.7%
• blood:gas parition relatively high, so slow induction
• induction: 4%
• maintenance: 1.5-3% (1.7 x 1.3)

• advantages
  • no bradycardia seen with halothane
  • skeletal muscle relaxation maybe adequate
• disadvantages
  • CV depression (due to decrease contractility)
  • seizures (no permanent damage)
  • uterine muscle relaxants

• most commonly used inhal. anesthetics in US
• 1 MAC = 1.4%
• blood gas partition: relatively low, so somewhat fast induction
• induction 3%
• maintentance 1.5-2.5%
• smooth rapid induction

• advantage
  • CO maintained
  • systemic vessels dilate causing small decrease in bp
  • arrhythmias uncommon
  • potent coronary vasodil.
  • no hepatic or renal toxicity
• disadv.
  • mor pungent than halothane
  • progressive resp. depression

• nonflammable, nonirritating
• MAC 2%
• blood gas: relatively low, so very fast induction

• advantages
  • no arrhythmias
  • used for outpatient anesthesia (rapid recovery profile)
  • not iritating to airway
  • induction concentrations 2-4%
• disadvantages- some reports of toxicity

• MAC 6%
• blood:gas coefficient low, so very fast induction
• very fast emergence/recovery (usually does not exceed 5-10 minutes)
• maintenance: 6-8%

• advantage
  • useful for outpatient surgery (rapid onset and recovery)
  • not very soluble in fat
• disadvantage
  • irritating to airway (cough, salivation, bronchospasm)
  • low volatility (requires use of specially heated vaporizer)
  • may evoke tachycardia

• sweet odor
• blood gas coefficient high, so slow induction and slow recovery
• MAC: 0.16%
• highly soluble in rubber

• advantages
  • very potent
  • does not relax uterus
  • non irritation
• disadvantages
  • extensive metabolism
  • may produce renal failure and nephrotoxicity

• MAC: 105% (cant use in induction or maintenance cause we cant give 105% to a patient)
• blood gas coefficient is very low, so it is rapid induction and emergence
• function- analgesic
• solution- 70-80% NO and the remaining oxygen and nitrogen

• advantages
  • noninflammable
  • nonirritation
  • powerful analgesic
  • rapid induction/recovery
  • little toxicity
  • analgesia before anesthesia
• disadvantage
  • weak agent
  • hypoxia may occur upon discontinuation (100% oxygen rather than air should be administered)
  • closed air spaces may expand (nitrous oxide exchange with nitrogen)
  • CI: pneumothorax, obstructed middle ear, emboli, obstructed loop bowel, intraocular air bubble, intracranial air

• rapid onset (seconds)
• rapid awakenings (minutes)
• danger of OD due to irrevocability of IV injection
• redistribution determines DOA

• Propofol
• barbituates: sodium thiopental
• etomidate
• ketamine

• CNS and visceral organs
• high blood flow and low capaicity (equil 4-8 minutes)

• moderate flow and high capacity (equilibrates in 1-2 hrs)

• low flow and high capaicty
• equilibrium in 10-20 hrs

• low flow and low capacity
• ex: bone, cartilage, ligaments

• advantages
  • milk of amnesia- looks like milk and produces a hypnotic and forgetful rest
  • rapid and smooth induction
  • little accumulation
  • rapid metabolism and recovery
• disadvantages
  • not water soluble
  • no antagonist
  • no analgesia
  • cardioresp. depression
  • can elicit pain upon initial injection

• advantages
  • antagonists available
  • smooth onset
  • anterograde amnesia
  • CV stability (used for patients at risk for hypotension)
• disadvantages
  • pain on injection
  • no analgesia
  • accumulates, slowing recovery

• advantages
  • analgesia
  • no respiratory depression (may increase bp)
  • produce hypnotic state (dissociative anesthesia)
• disadvantages
  • increase muscle tone and incidence of involuntary movement
  • hallucinations
  • adverse effects are less common in children
    • consider for kids

• benzodiazepines
• antihistamines
• antiemetics
• opioids
• antimuscarinics
• muslce relaxants

• advantages
  • smooth and rapid induction
  • little post anesthetic excitement or vomitting
  • water soluble
• disadvantages
  • resp. and CV depression
  • no antagonist
  • slow recovery
  • no analgesia

• trauma victims
• elderly
• those with cardioresp. diseases

due to hypotensive effets (regardless of what anesthetic it is)

• reduce anxiety
• induce amnesia
• ex: midazolam, diazepam

• use diphenhydramine
• prevent allergic reactions
• some sedation

• ondansetrone (5HT₃ antagonist)
• reduce postsurgical nausea and vomitting
• prevent aspiration of stomach contents

• ex: fenatyl, morphine
• provide analgesia

• examples: atropine, scopolamine
• amnesia
• prevent bradycardia
• prevent fluid secretion

• ex: pancuronium
• facilitates intubation