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Who is the father of anesthesia and what did he invent?
William T. Morton
Invented the ether dome which is administered as a mask during surgery.
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What are the four goals of anesthesia?
1. Anesthesia (make pt unaware of what is going on)
2. Akinesia (keep pt still during surgery)
3. Muscle relaxation (enables access through muscles to bones and body cavities during surgery)
4. Autonomic control (prevents dangerous surges in hemodynamics during surgery)
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What are the two major categories of anesthetics?
1. Inhalation (drugs dissolved in gas)
2. Intravenous (All depress the CNS)
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What does the ending "ane" mean?
Menas that they are short strings of carbons
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Nitrous oxide
inhalational anesthetic drug
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chloroform
inhalational anesthetic drug
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Haloethane
inhalational anesthetic drug
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Isoflurane
inhalational anesthetic drug
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Enflurane
inhalational anesthetic drug
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Methoxyflurane
inhalational anesthetic drug
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Desflurane
inhalational anesthetic drug
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Sevoflurane
inhalational anesthetic drug
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Thiopental (barbiturate)
Intravenous anesthetic drug
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Methohexital (barbiturate)
Intravenous anesthetic drug
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Propofol (Michael Jackson drug)
Intravenous anesthetic drug
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Ketamine (vetrinary anesthetic)
Intravenous anesthetic drug
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Diazepam (Valium)
Intravenous anesthetic drug
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Midazolam (benzodiazepine)
Intravenous anesthetic drug
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Etomidate
Intravenous anesthetic drug
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Fentanyl (analgesic narcotic, found in 50% of short procedure anesthetics)
Intravenous anesthetic drug
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What are the three processes of anesthesia?
1. Pre-medication
2. Induction
3. Maintenance
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Explain the pre-medication portion of the anesthesia process.
*Calm and relax pt with minimal effcts on breathing and cardiovascular function.
*Start with short acting benzodiazepine to relax pt
*Others: analgesics, muscle relaxants, beta blockers, antacids, H2 blockers
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Explain the induction portion of the anesthesia process.
*Usually induced with an intravenous drug very quickly
*Intubation followed by gaseous anesthetics
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Explain the maintenance portion of the anesthesia process.
gaseous anesthetics provide good control of depth
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What are the four stages of anesthesia?
1. Analgesia
2. More pronoiunced analgesia, anterograde and retrograde amnesia
3. Loss of reflexes, skeletal muscle relaxation
- 4. Respiratory and cardiac depression
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In which stage of anesthesia is there loss of consciousness (cannot stay awake no matter what?
Stage 2
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Which stage of anesthesia is a good reference for when you should be preforming surgery?
Stage 3
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What are the four planes within stage 3 of anesthesia?
Plane 1: eyes moist, pupils mitotic
Plane 2: eyes dry, pupils mid dilated
Plane 3: loss of corneal reflex-->tested to know if you are at a good place to preform surgery
Plane 4: maximal pupoil dilation, apnea-->must support respiratory and cardiac systems at this stage. have gone too far to perform surgery at this plane
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What is the CNS target of analgesia?
Spinal cord and cortex
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What is the CNS target of amnesia?
Cortex, hippocampus
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What is the CNS target of loss of consciousness?
Brainstem, cortex, hypothalamus, RAS
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What is the CNS target of loss of reflexes?
Spinal cord
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What is the CNS target of skeletal muscle relaxation?
Spinal cord
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Describe the effects of general anesthetic drugs based on this graph.
1. As you increase concentration of drug or increase the time it is inhaled, you will see an increase in the number of patients that do not respond and are not able to form memories.
2. Some effects happen at lower concentrations of a drug than others
3. Dose response curve changes over time
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What is the prototype anesthetic drug?
Diethyl ether (very flammable)
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How are the derivatives of ether similar?
All have same basic skeleton, just added various halogens to make it less flammable.
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Name the derivatives of diethyl ether.
- 1. Halothane
- 2. Isoflurane
- 3. Enflurane
- 4. Methoxyflurane
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Between 1840 and 1850 which inhalation anesthetics were around?
chloroform, ether, and NO were around for recreation
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Between 1951 and 1990 which inhalation anesthetics were around?
halothane, still used in operating rooms today
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Between 1991 and 2003 which inhalation anesthetics were around?
Propofol
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What are the two important determinants of how drug levels in the brain are determined?
1. Partial pressure
2. Lipid solubility
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What is partial pressure?
Concentration of a gas in a mixture of gases (O2)
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Describe lipid solubility.
1. Measured by blood/gas partition coefficient--> usually an oil to water ratio
2. Solubility of gasious drugs when exposed to blood-> degree to which it dissolved in blood determines blood and brain concentration
3. Determines onset of effects--rate at which levels build up
4. Deteremines blood (and brain) levels of drug
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What is the Meyer-Overton equation?
for a general anesthetic drug, the partition coefficiet is inversely proportional to anesthetic potency
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What is this graph about inhalational anesthtic potency show?
x-axis: scale goes from 1-1000 (1000 times more soluble in a different substance)
y-axis: 1 = 100% of inspired gas would be gas of interest
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Explain the solubility in blood and effect latency chart of NO vs. Haloethane.
*NO has low oil/gas ratio
*Halothane has high oil/gas ratio
*NO sees blood compartment as very small (lipid insoluble)
*Halothane perceives blood compartment as very large (lipid soluble) and it must be filled up (high dosage) to have an anesthetic effect in brain
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What happns to the onset of effects and the recovery rates as the partition coefficient increases?
they are both slower
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What is minimal alveolar concentration?
Concentration of gas you need in alveoli you ned to have an ansethetic effect
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Which inhaled anesthetics have rapid onset and recovery?
1. Nitrous Oxide
2. Desflurane (has poor onset)
3. Sevoflurane
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Which inhaled anesthetics have medium onset and recovery?
1. Isoflurane
2. Enflurane
3. Halothane
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Which inhaled anesthetics have slow onset and recovery?
1. Methoxyflurane
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How are the partition coefficient, minimal alveolar concentration, onset and recovery all related in the inhaled anesthetic drugs?
The more rapid the onset/recovery is, the lower the partition coefficeint and the higher the minimal alveolar concentration is.
(Remember: when everything is high/rapid the only thing that is low is the partition coefficient......when everything is low/slow the only thing that is high is the partition coefficient)
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What is the mechanism of action of inhalational anesthetics?
*Specific and non-specific actions on neuronal activity
*Direct and indirect effects on various types of ion channels
*Binding sites on ion channel proteins
*Binding sites of cell membrane lipids
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Describe the general interactions with ion channels in inhaled anesthetics.
Action potential opens the pre but the presence of durg molecules do not allow for conduction, so it is inhibited (anesthetized).
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Name each hypothesis for binding of inhalational anesthetics.
1. Lock and Key
2. Protein dynamics
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What is the lock and key hypothesis?
Molecules bind within and around protein and cause a conformational change of the globular protein that closes the pore.
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What is the protein dynamics hypothesis?
*Inhaled general anesthetic drugs may not cuase conformational changes in ion channels or transmitter receptors
*Flexible loops on protein are impinged upon by neurotransmitter molecule and the pore closes
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Name 5 adverse side effects of inhaled anesthetics.
1. Respiratory and cardiac depression
2. Hypotension
3. Some increase in skeletal muscle tone
4. Diabetes insipidus (hypoglycemic reaction from methoxyflurane)
5. Hepatotoxicity - circulating environmental halothane caused severe liver damage to OR docs due to poor regulation of drug (is tightly regulated now)
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Do intravenous anesthetics induce rapid or slow state of unconsciousness?
Rapid
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What is potency correlated with?
Lipid solubility
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What type of neurotransmission do intravenous anesthettics enhance?
GABA (inhibitory) neurotransmission
(45% of synapses in the brain utilize GABA as their neurotransmitter while another 45% of synapses in the brain utilize Gluatmate which is an excitatory neurotransmitter)
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What type of clinical settings are intravenous anesthetics used in?
Multiple clinical settings (anesthesia, insomnia, anxiety, epilepsy)
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Are intravenous anesthetics good muscle relaxants?
yes
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What are the two most common drug classes of intravenous anesthetics?
1. Benzodiazepines
2. Barbiturates
**Benzodiazepines have almost completely replaced barbiturates in use
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Which intravenous anesthetics have the shortest and longest half lives?
*Thiopental has SHORTEST half life of 10-12 minutes
*Diazepam has LONGEST half life of 20-40 hours followed by propofol which has a half life of 5-10 hours.
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As far as respiratory and cardiac depression of intravenous anesthetics which of these drugs has a large safety margin and which one has a small safety margin?
*Benzodiazepines: large safety margin
*Barbiturates: small safety margin
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Name three adverse side effects of intravenous anesthetics.
1. Respiratory and cardiac depression
2. Hypotension
3. Pharmacogenetics
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Describe adverse side effects of intravenous anesthetics interms of pharmacogenetics (idiosyncratic reactions)?
- 1. Malignant hyperthermia (succinylcholine)
- *Certain polymorphisms in calcium channels that make some people very suceptible to succinylcholine.
- *Causes rise in body temperature, tachycardia, sweating, hallucinations
- --> there is now a screening for the known calcium channel mutation to prevent this reaction
2. Psychosis ( ketamine)
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Thiopental
Rapid onset
Rapid recovery
Barbiturate; induction; cardiovascular depression
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Methohexital
Medium onset
Slow recovery
Barbiturate; maintenance of anesthesia
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Propofol
Rapid onset
Rapid recovery
Induction and maintenance; lowers BP; replacing barbiturate
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Ketamine
Medium onset
Medium recovery
NMDA antagonist; cardiac stimulant; increase blood flow; glutamate receptor
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Diazepam
Medium onset
Slow recovery
Benzodiazepine; conscious sedation; slower recovery
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Midazolam
Slow onset
Slow recovery
Benzodiazepine; sedation; marked amnesia (commonly found in date rape drugs)
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Etomidate
Rapid onset
Medium recovery
Cardiac stabilizer/ skeletal muscle activator
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Compare and contrast general anesthetics therapeutic considerations.
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