General Anesthetics

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characteristics of general anesthesia

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unconsciousness, analgesia, amnesia, skeletal muscle relaxation, loss of reflexes

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inhaled anesthetics (classes)

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gas and volatile liquids

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IV anesthetics (classes)

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barbiturates, dissociative, opioids, benzodiazepines

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stages of anesthesia

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1.) analgesia: decreased awareness of pain, consciousness impaired but not lost
2.) disinhibition: delirious and excited; amnesia occurs, reflexes are enhanced, respiration is irregular; retching and incontinence may occur
3.) surgical anesthesia: patient is unconscious and has no pain reflexes; respiration is very regular and BP is maintained
4.) medullary depression: severe respiratory and cardiovascular depression that requires mechanical and pharmacologic support

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conscios sedation

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minor procedures- combine IV agents and local anesthetics
- profound analgesia with retention of patient's ability to maintain a patent airway and to respond to verbal commands

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general MOA of anesthetics

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increase threshold for firing of CNS neurons

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anesthetics that facilitate y-aminobutyric acid (GABA)-mediated inhibition at GABAa receptors

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inhaled anesthetics, barbiturates, benzodiazepines, etomidate, propofol

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ketamine MOA

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antagonizes the action of the excitatory neurotransmitter glutamic acid on NMDA receptor

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another MOA of inhaled anesthetics

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inhibit nicotinic acetylcholine receptor isoforms at moderate to high concentrations

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another "target" of inhaled anesthetics

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strychnine-sensitive glycine receptor

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temporal involvement of brain regions to general anesthetics

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inhibition of neurons involved in pain pathways earlier than those in midbrain reticular formation

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drugs with what type of blood:gas partition coefficient equilibrate more quickly

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low blood:gas partition coefficient

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partial pressure relation to blood levels

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high partial pressure of gas in lungs= more rapid achievement of anesthetic levels in the blood; administration of gas concentrations higher than those for maintenance of anesthesia

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ventilation relation

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greater the ventilation, more rapid the rise in alveolar and blood partial pressure of agent and onset of anesthesia

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pulmonary blood flow relation

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high pulmonary blood flows, gas partial pressure rises at a slower rate; speed of onset of anesthesia is reduced
- at low flow rates- onset is faster **circulatory shock- rate of onset faster

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AV concentration gradient effect

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-uptake of soluble anesthetics into highly perfused tissues may decrease gas tension in mixed venous blood
- can influence the rate of onset of anesthesia because equilibrium depends on difference in anesthetic tension b/w arterial and venous blood

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termination of anesthesia

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redistribution of drug from brain to blood and elimination through lungs

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blood: gas partition coefficient effect on termination of anesthesia

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recovery faster using agents with low blood: gas partition coefficients (low blood solubility) -NO

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hepatic metabolism

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halothan and mehtoxyflurane

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minimum alveolar anesthetic concentration

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MAC- alveolar concentration needed to eliminate the response to a standardized painful stimulus in 50% of patients

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CNS effects of inhaled anesthetics

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decrease brain metabolic rate
- reduce vascular resistance and increase cerebral blood flow
- increase in ICP
- spike and wave activity and muscle twitching (enflurane)

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CV effects of inhaled anesthetics

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- decrease arterial BP moderately
- enflurane and halothane- myocardial depressants that decrease CO

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inhaled anesthetics that cause peripheral vasodilation

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isoflurane, descflurane, sevoflurane

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halothane interaction with catecholamines

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sensitize myocardium to arrhythmogenic effects

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respiratory effects of inhaled anesthetics

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dose-dependent decrease in TV and minute ventilation--> increase in arterial CO2 tension
-decrease response to hypoxia

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pulmonary complication with desflurane

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- pulmonary irritant that may cause bronchospasm

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toxicity of inhaled anesthetics

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postoperative hepatitis with halothane in pts experiencing hypovolemic shock

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toxicity of methoxyflurane

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fluoride released by metabolism can cause renal insufficiency

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prolonged exposure to NO

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decreases methionine synthase activity and can lead to megaloblastic anemia

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when anesthetics are used together with neuromuscular blockers

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malignant hyperthemia; mutations in gene loci corresponding to ryanodine receptor

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treatment of malignant hyperthermia

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dantrolene

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barbiturates used for induction of anesthesia for short surgical procedures

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thipental and methohexitol

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termination of thiopental effecfts

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redistribution from brain to other highly perfused tissues; hepatic metabolism necessary for elimination

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barbiturates on respiratory and circulatory system

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depressants- depress cerebral blood flow and can decrease ICP

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benzodiazepam frequently used adjunctively with inhaled anesthetics and IV opioids

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midazolam

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duration of action of midazolam compared to thiopental

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onset of CNS effects is slower and has longer duration of action

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ketamine effects

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"dissociative amnesia"
- patient remains conscious but has marked catatonia, analgesia, and amnesia
- congener of PCP

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effect of ketamine on CV system

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stimulant- increase in ICP
- emergence reactions occur- disorientation, excitation, hallucinogens

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opioids as IV anesthetics

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morphine and fentanyl used with other CNS depressants- great for those who might not survive a full general anesthetic

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IV opioid effect on respiration

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- can cause chest wall rigidity and subsequent impaired ventilation
- reversed post-op with naloxone

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neuroleptanesthesia

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analgesia and amnesia produced when fentanyl is used with droperidol and NO

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two newer opioids used for induction of anesthesia

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alfentanil and remifentanil

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propofol rates of anesthetic induction

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as rapidly as IV barbiturates and recovery is more rapid

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propofol is commonly used when

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component of balanced anesthesia and as an anesthetic in outpatient surgery

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propofol on vascular resistance

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decreases vascular resistance- hypotension can result

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fospropofol

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water-soluble prodrug- rapidly broked down by alkaline phosphatase to form propofol
- more readily injectable

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etomidate

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imidazole derivative
- rapid induction with minimal change in cardiac function or respiratory rate and short duration of action
- not analgesic
- anesthesia in patients with limited cardiac or respiratory reserve

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SE of etomidatee

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- pain and myoclonus on injection and nausea post op
- prolonged may cause adrenal suppression