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general anesthetics
CBN III
68
Medical
Graduate
02/08/2011

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Term
when was the first suggestion that N2O could produce general anesthesia?
Definition
~1800. it was tried first in 1845 and then successfully in 1846.
Term
what are the inhalation anesthetics?
Definition
*gas: N20 (nitrous oxide/ether) and *volatile liquids: desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane
Term
what are the IV anesthetics?
Definition
*ultrashort acting barbiturates: methohexital, thiamylal, and thiopental. *nonbarbiturates: etomidate and propofol. *dissociative agent: ketamine and phencyclidine. *neuroleptanalgesia: droperidol/fentanyl combo.
Term
what characterizes the the therapeutic index for general anesthetics?
Definition
it is low. circulatory arrest dose/general anesthetic dose = 3/1
Term
what are the stages of anesthesia?
Definition
1) analgesia 2) delirium 3) surgical anesthesia 4) medullary anesthesia
Term
what characterizes stage I of anesthesia?
Definition
analgesia, which begins w/administration of the anesthetic: depression of signal transmission in the RAS (general sensory) and dorsal horn cells (pain).
Term
what characterizes stage II of anesthesia?
Definition
delirium, which begins w/a loss of consciousness. depression of the cortex results in less inhibition of subcortical areas: disinhibition. this then can lead to hyperreflexia (violent muscular contractions), irregular respiration (apnea alternating w/hyperapnea [problematic w/inhalational anesthesia]), and vomiting (aspiration into the respiratory tract, can cause asphyxiation and postop pneumonia).
Term
what are stage I and II of anesthesia referred to as?
Definition
the induction period, in which the goal is to get to stage III as quickly as possible.
Term
what is stage III of anesthesia?
Definition
surgical anesthesia, which begins w/muscular relaxation and a return to a regular but lower respiratory rate and BP. there is a greater depression of the RAS and spinal cord.
Term
what is stage IV of anesthesia?
Definition
medullary paralysis, which begins w/ cessation of spontaneous respiration, depression of the pons and medulla, and ends w/circulatory failure.
Term
what characterizes uptake and distribution of general anesthetics? how does perfusion compare w/lipid content?
Definition
the objective is to get the pt from conscious to unconscious as rapidly and safely as possible. the perfusion rate is highest in the brain, then muscle, then adipose while lipid content is highest in the adipose, brain and then muscle.
Term
what is the loop bypassed in parenteral anesthesia which is present w/inhalation?
Definition
general anesthesia <-> inspired air <-> lungs <-> blood <-> brain/muscle/adipose
Term
what is the quickest way to achieve a maximum blood level w/general anesthesia?
Definition
IV
Term
what factors influence the transfer of inhalational GA's (general anesthetics)?
Definition
solubility (blood/gas partition coefficient means GA is more soluble in blood - *if high [NO2] it will move into tissues from blood slowly/if low [halothane] it will rapidly leave the blood for tissues), anesthetic concentration of inspired air (higher concentration = higher rate of transfer) and pulmonary ventilation (faster breaths and/or deeper breaths = faster transfer).
Term
what characterizes elimination of general anesthetics?
Definition
in general, recovery is slower than induction b/c these lipid soluble compounds are stored in fat. expired air is the major route of elimination for inhalational GA's (higher B/G P = longer recovery time). biotransformation is not a major factor. as duration of administration of GA increases, tissue stores increase and recovery takes longer.
Term
what is anesthetic potency determined by?
Definition
blood level and minimum alveolar concentration. MAC (only for inhalational GA) is a unit which refers to the *concentration of the drug in the alveolar space where 50% of patients do not feel the initial surgical incision and there is a very steep dose-response curve: 95% of pts do not feel incision at 1.1 MAC.
Term
why is the mechanism of GA likely not related to a specific receptor?
Definition
b/c drugs w/very different molecules all will still produce general anesthesia.
Term
what is the lipid solubility (myer-overton) GA theory?
Definition
this explains of access of GA to brain tissue but is not related to mechanism of action. no longer accepted.
Term
what is the interaction w/lipid component of bran cell membrane GA theory?
Definition
GA's interact with lipid molecules of cell membrane and shift the membrane to a disordered state = decreased Ca+/Na+ influx (hyperpolarization/decreased release of excitatory NTs). no longer accepted (one GA molecule interacting with one [or even two] lipid molecules is not sufficient to cause the shift).
Term
what is the interaction w/protein component of bran cell membrane GA theory?
Definition
in the same 5000 A^2 area of brain cell membrane is 1 protein molecule. therefore, one GA molecule could bind to this protein molecule & inactivate it; could interfere with operation of an ion channel. most likely one to be inactivated is the K+ channel = an increase in K+ efflux and hyperpolarization. this is the current theory for GA MOA.
Term
do GAs interact w/ the GABA-A receptor?
Definition
GAs may enhance the activity of the GABA-A receptor = increased influx of Cl- = hyperpolarization.
Term
what are 4 examples of pre-anesthetic medication and the reasoning for their used?
Definition
relief of anxiety (sed/hyp/BZDs will also enhance GA effect), decreased secretions (atropine > scopolamine), counteraction of bradycardia (atropone > scopalamine), and elevation of gastric pH (cimetidine, decreases lung scarring if vomiting occurs).
Term
what are the objectives of general anesthesia? how are they met?
Definition
rapid elimination of consciousness, skeletal muscle relaxation, and analgesia. since no single currently available GA can accomplish all of these objectives, general surgery is usually performed using two or more GA's and one or more adjunctive agents ('balanced anesthesia') including: an induction agent (rapid-acting GA), GA, and anesthetic adjuncts (skeletal muscle relaxants/opioids)
Term
what are problems w/biotransformed GAs?
Definition
pre-existing enzyme induction and obesity
Term
is NO2 (inhalation anesthetic) flammable or explosive?
Definition
no
Term
what is the effect of NO2 at 20% (80% O2)? (*know this*)
Definition
provides analgesia = morphine and drop in beta-endorphin levels.
Term
what is the effect of NO2 at 50% (50% O2)? (*know this*)
Definition
this is used in dental procedures, no significant respiratory depression.
Term
what is the effect of NO2 at 65% (35% O2)? (*know this*)
Definition
this is the highest concentration which will still provide adequate oxygenation (no hypoxia)
Term
what is the effect of NO2 at 80% (20% O2)? (*know this*)
Definition
most pts are unconscious (stage II). if pts have sickle cell they may go into a crisis at this level. (100% NO2 will still not get pts to stage III).
Term
what are the uses for NO2?
Definition
analgesic (dentistry, acute MI, first stage of labor) and induction of general anesthesia.
Term
what are advantages for NO2?
Definition
rapid and pleasant
Term
what are disadvantages for NO2?
Definition
not potent, inadequate skeletal muscle relaxation, and dreams of sexual assault (at > 50% conc)
Term
what characterizes acute NO2 toxicity?
Definition
fall = bone fracture and positional asphyxia
Term
what characterizes chronic NO2 toxicity?
Definition
loss of balance/ataxia, leg weakness, peripheral neuropathy and impotence
Term
what characterizes halothane (volatile liquid)?
Definition
this is rarely used, nonexplosive and nonflammable
Term
how potent is halothane?
Definition
1 MAC at .75% conc (high O2 to pt), B/G PC = 2.4
Term
how much of halothane is biotransformed?
Definition
15-20%
Term
what are the advantages of halothane?
Definition
nonexplosive, nonflammable, smooth/relatively rapid induction, bronchodilation, and relatively low incidence of toxicity
Term
what are the disadvantages of halothane?
Definition
poor analgesia, poor muscle relaxation, sensitization of the myocardium to catecholamines (any halogenated hydrocarbon can produce card. arrhythmias), hepatitis (not dose-related, possibly allergic, rare but fatal rxn can occur on repeated exposure), and (possibly severe) hypotension (decreased myocardial contractility [decreased entrance and interaction of Ca++ intracellularly] and decreased compensatory tachycardia)
Term
what characterizes the potency of methoxyflurane?
Definition
this is the most potent GA; 1 MAC = 0.16% (maintenance at 0.2 - 0.8%). B/G PC = 12; slow induction (20-30 minutes if used alone). provides more skeletal relaxation, more analgesia and less myocardial sensitization than halothane.
Term
what characterizes the biotransformation of methoxyflurane?
Definition
methoxyflurane is biotransformed 50-70%
Term
what ADRs are associated w/methoxyflurane?
Definition
it can result in flouride toxicity (>50 umol/L serum) which can remain elevated for days. the renal system may be damaged and Fl- diabetes insipidus may be incurred.
Term
what characterizes enflurane?
Definition
this volatile liquid has 1 MAC of 1.68% and a B/G PC of 1.9 (moderately fast induction). provides more skeletal relaxation, more analgesia and less myocardial sensitization than halothane. fluoride toxicity possible; less likely than with methoxyflurane. seizures may occur - but more likely if pre-existing condition.
Term
what characterizes isoflurane?
Definition
1 MAC = 1.4%, B/G PC = 1.4. more respiratory irritation on induction than halothane. very limited biotransformation, about .17%.
Term
what characterizes desflurane?
Definition
1 MAC = 1.4%, B/G PC = .42. biotransformation: .02%. induction of general anesthesia within 2 - 4 minutes but NOT recommended for this purpose due to high incidence of respiratory tract irritation (e.g., laryngospasm, coughing, increased secretions, breathholding, apnea)
Term
what characterizes sevoflurane?
Definition
low blood/gas solubility. no significant odor (good for peds). biotransformed into 2 metabolites: F- (rapidly eliminated b/c parent molecule rapidly cleared - less nephrotox than methoxyflurane) and HFIP (rapidly glucuronidated, low toxic potential)
Term
what are the more common volatile liquid GAs?
Definition
isoflurane, desflurane, and sevoflurane are the more common volatile liquid GA
Term
what characterizes thiopental (ultrashort-acting barbiturate)?
Definition
this is administered IV or infusion, anesthesia occurs w/in seconds, primary site of action: RAS. emergence from GA is rapid due to redistribution from brain to other tissues *not biotransformation (only about 15% per hour) but may be slow if IV infusion is prolonged. thiopental is stored in adipose tissue and slowly released.
Term
when is thiopental used?
Definition
induction of GA and as the sole GA for short procedures w/o significant pain.
Term
what are the advantages of thiopental?
Definition
easy to administer, rapid and pleasant induction
Term
what are the disadvantages of thiopental?
Definition
lack of moment-moment control, poor analgesia (may cause hyperalgesia), powerful respiratory depressant, and poor skeletal muscle relaxation
Term
what are contraindications w/thiopental?
Definition
pts w/porphyria may experience n/v, paralysis, or death.
Term
what characterizes etomidate (nonbarbiturate)?
Definition
this rapid-acting hypnotic has high lipid solubility and wide distribution, but is *not an analgesic. it has minimal effects on HR, CO, and peripheral circulation. etomidate is rapidly metabolized in the liver and primarily excreted in the kidneys.
Term
what uses are associated w/etomidate?
Definition
*induction of GA (onset in 1 min, effects persist 3-5 min), supplemental anesthesia during short operative procedures, and prolonged sedation of critically ill pts.
Term
what ADRs are associated w/etomidate?
Definition
transient venous pain on injection, myoclonic skeletal muscle movements after injection, hypotension/tachycardia/arrhythmias, hyperventilation/transient apnea/laryngospasm/hiccups, and post op n/v.
Term
what characterizes propofol (nonbarbiturate)?
Definition
propofol is prepared as a lipid/water emulsion which has wide and rapid distribution to highly perfused tissues (brain, heart, lungs, liver). hypnosis w/in 40 sec of IV administration and anesthesia w/in 1-3 min. there is some degree of analgetic activity.
Term
what is propofol used for?
Definition
continuous sedation in pts who are intubated or who are on mechanical ventilation (ICU), induction of general anesthesia and maintenance of general anesthesia (in balanced anesthesia).
Term
what is the advantage for propofol?
Definition
propofol is extensively metabolized into inactive metabolites (primarily
glucuronide) allowing rapid recovery from sedation or anesthesia. elimination t1/2: 300-700 min. pts are usually oriented and respond to verbal commands approx. 8 min. after infusion terminated.
Term
what ADRs are associated w/propofol?
Definition
pain at the injection site (rash/pruritus), clonic/myoclonic movements, seizures, rigidity, thrashing, confusion, delirium, hallucinations, hypersalivation, bronchospasm, cough, hyperventilation, green urine and urinary retention.
Term
what are cautions for propofol?
Definition
caution in pts w/increased intracranial pressure, not recommended for delivery (neonatal depression may occur), and some fatalities have been reported in pediatric pts being treated in the ICU for respiratory tract infections at high doses.
Term
what characterizes phencyclidine (dissociative agent)?
Definition
aka PCP, this has been withdrawn from human use due to hallucinations during emergence
Term
what characterizes ketamine (dissociative agent)?
Definition
related to PCP, this NMDA antagonist produces "dissociative amnesia" where pts exhibit catatonia, analgesia, and amnesia (eyes open, appear in a trance, unresponsive to pain/stimuli) due to action in the cerebral cortex and limbic system (occurs w/in 15 sec).
Term
what is the duration of the different effects due to ketamine?
Definition
unconsciousness: 10-15 min, analgesia: ~ 40 min, amnesia: 60-120 min
Term
what are the advantages w/ketamine?
Definition
strong analgesia, no significant respiratory depression, support of the CV (increased HR/BP), and reduced risk of psych ADRs (compared to PCP).
Term
what are the disadvantages w/ketamine?
Definition
prolonged retention in the body (stored in adipose tissue, traces appear in urine for weeks), psych ADRs upon emergence (nightmares, hallucinations, delirium, schizoid rxns - more common in 30 y/o+ pts, reduce w/conferring, diazepam and avoidance of tactile/verbal stimulation during emergence), and flashbacks (memory phenomenon - not ketamine retention)
Term
what are the uses of ketamine?
Definition
emergency sx, outpt procedure which requires GA, changes in burn dressings, and dx procedures in children
Term
what drugs interact w/GA agents?
Definition
*tetracyclines: increased risk of nephrotoxicity w/methyoxyflurane. *bacitracin, aminoglycosides, and polymixins: additive skeletal muscle paralysis w/neuromuscular blocking agents (non-depolarizing). *CNS depressants: acute - increased effect, chronic - possible increased effect at time of sx or tolerance. cigarette smokers: may require increased dose of GA due to enzyme induction.
Term
what is neuroleptanalgesia?
Definition
combination of an antipsychotic and opioid which allows: reduced initiative/emotions, some slowness in stimuli response, no effect on intelligence, no effect on coordination. droperidol+fentanyl is given for this as slow IV infusion for minor sx, dx procedures and changing of burn dressings.
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