General Anesthetics I & II Flashcards
The condition of general anesthesia incorporates what 3 properties, all desirable properties for patients undergoing surgery
analgesia, amnesia and loss of consciousness
Volatile general anesthetics are _______molecules with structures seemingly unrelated to one another
uncharged, nonpolar
In volatile general anesthetics the higher the
_______-, the more potent the general anesthetic
oil:water partition coefficient
An ideal general anesthetic would exhibit: _____
1) a rapid and smooth onset of action,
2) a rapid recovery from anesthesia upon termination of drug administration,
3) the drug would have a wide margin for safe use
the minimum alveolar concentration (MAC) of anesthetic that produces insensitivity to painful
stimulation has been measured for a variety of inhalational anesthetics, and is ______ proportional to potency
inversely
Because of the clearly demonstrated correlation of potency with lipid solubility, it is strongly
suspected that volatile anesthetics interact with ______ regions of proteins.
hydrophobic (lipophilic)
How do General anesthetics depress neuronal excitability in the CNS?
Through potentiation of GABA(A) receptor activity which increases the duration of inhibitory postsynaptic
potentials
The effects on action potential conduction occur largely
at doses above the ______ , and so conduction block is not believed to underlie anesthesia. Indeed, action potential conduction in the peripheral nervous system has been found to be normal in anesthetized patients.
clinical range
Because The hydrophobic protein pockets within which volatile anesthetics bind are not specific binding sites, (but pocket size does account for the size cut-off for volatile anesthetics), volatile anesthetics exert clinically-relevant effects only at concentrations much higher (i.e.______) than those needed for drugs with specific binding sites.
~1-100 mM
General anesthesia is characterized by _________, that is, a progressive loss of function from higher (e.g., cognition and consciousness) to lower (e.g., respiratory control) levels within the central nervous system.
descending depression
what are the 4 stages of anesthesia?
Stage I – analgesia
Stage II – excitement, delirium
Stage III – surgical anesthesia
Plane 1: regular, metronomic respirations
Plane 2: onset of muscular relaxation, fixed pupils
Plane 3: good muscular relaxation, depressed
excursion of intercostal muscles during respiration
Plane 4: diaphragmatic breathing only, dilated pupils
Stage IV – medullary paralysis
The rate at which an effective
concentration of anesthetic is reached in the brain depends upon five factors: ________
1) concentration of the anesthetic
in inspired air,
2) alveolar ventilation rate,
3) pulmonary blood flow (cardiac output)
4) blood:gas partition coefficient,
5) potency (oil:gas partition coefficient).
The maintenance stage of inhalation anesthesia is a steady state condition in which the anesthetic gas partial pressure in lung = ________
anesthetic gas partial pressure in blood = anesthetic gas partial pressure in body tissues
The blood:gas partition coefficient ____ is a measure of the solubility of anesthetic gas in blood.
(λ)
the rate of rise in partial pressure ratio is faster for a gas with ______ and slower for a gas with _______
low solubility (nitrous oxide), higher solubility (halothane)
The initial rise in arterial anesthetic gas concentration is slowed by increased ______
pulmonary flow (cardiac output).
The rate of uptake into body tissues depends upon what 3 things?
(1) anesthetic gas solubility in body tissues,
(2) tissue blood flow,
(3) partial pressures of anesthetic in blood
and in tissues.
anesthetic is ~equally soluble in blood and lean tissues, but anesthetic is substantially more soluble in _______
fatty tissue
Tissue blood flow determines the rate at which anesthetic gas is delivered to the tissue.
The higher the blood flow, the _______ the delivery of anesthetic. This is determined by cardiac output
faster
In early stages of anesthesia, the rate of uptake is ______ because this rate depends upon the difference in partial pressure between blood and tissue and this is initially large. As anesthesia develops, tissue levels of anesthetic rise, the difference in partial pressure gets smaller, and thus the rate of anesthetic uptake from blood into tissue _________.
rapid,
decreases.
In highly vascularized tissues such as brain, heart, kidney, liver and endocrine glands, Uptake rate into these tissues is _______because these tissues are very well perfused.
Thus uptake into body tissue as a whole is dominated initially by the rate of uptake into this ________
group.
very high (minutes), vessel-rich
From the point of view of solubility of inhalational anesthetics, body tissues can be organized into what three main groups?
1) vessel-rich
2) Muscle group
3) Fat group
Uptake into Muscle and skin occurs over _____. Uptake is slower into this tissue group because ________ is lower than in the vessel-rich group.
2-4 hours,
perfusion
Inhaled anesthetic uptake occurs very slowly in fatty tissue owing to what 2 reasons?
(i) the enormous amount of anesthetic that can be dissolved in fatty tissue,
(ii) the low perfusion.
The inverse of the ______ for a volatile anesthetic is the generally accepted means of estimating its potency.
MAC value (1/MAC)
Anesthetic potency is related to ________, which is the alveolar concentration that prevents gross skeletal muscle response to a standard painful stimulus (skin incision) in 50% of patients.
MAC (minimum alveolar anesthetic concentration)
The oil:gas partition coefficient provides an index of anesthetic ______, while the blood:gas partition coefficient relates to _______
potency,
anesthetic uptake and elimination kinetics.
Increased rate and depth of alveolar ventilation, _______ the rate of rise in arterial concentration of anesthetic.
increases
what is Diffusion hypoxia as it relates to nitric oxide
when anesthetic administration is terminated
Large N2O volume leaving blood expands lung and dilutes alveolar O2 -> hypoxia
what is the Concentration effect as it relates to nitric oxide?
1 liter/min of N20 taken up, owing to high inspired % (maybe 75%), Big anesthetic vol. taken out of lung into blood, sucks more N2O gas into lung
Thus, uptake rate is faster than predicted
what is the Second gas effect as it relates to nitric oxide?
It is like the concentration effect, but with 2 gaseous GAs (75% N2O, 1% halothane)
Huge volume uptake rate of N2O sucks more of both gases into lungs
Thus, uptake of halothane is increased over expected value alone
N2O cannot be used as a sole anesthetic agent. It is used in “balanced anesthesia”: N2O combined with
____________.
barbiturate + opioid
what are 3 adverse effects of halothane
(i) Respiratory and cardiovascular failure (arrhythmias)
(ii) Hepatotoxic
For 1/10,000, 2-5 days after anesthesia, fever, anorexia and nausea/vomiting
Death occurs in 50% of these patients
Repeated exposure to halothane significantly
increases the risk
(iii) Malignant hyperthermia and central core disease
what are the signs of Malignant hyperthermia?
muscle rigidity, and subsequently fever
what is malignant hyperthermia?
Inherited disorder, with mutations in ryanodine receptors in skeletal muscle
what is the Tx of Malignant hyperthermia
Ice water immersion, dantrolene to block RyR and relax muscle
Use IV anesthetic if family history indicates risk for malignant hyperthermia
what is the most widely used inhalational anesthetic?
Isoflurane
what are the advatages of isoflurane
Somewhat more potent
Less incidence of hepatotoxicity, renal toxicity
Little seizure propensity
what is a potential drawback of Isoflurane?
pungent odor can trigger coughing
Halothane until recently, was most widely used inhalational anesthetic, has _______ potency and is a ______ analgesic
Moderately to highly;
poor
Isoflurane has minimal direct _______ depression and is a good __________ relaxant
myocardial,
muscle
what is a drawback of Sevoflurane (Ultane )
chemically unstable, releases fluoride ions, which are toxic to kidneys
what is Sevoflurane?
Inhalational general anesthetic
In practice, use ______ of GA, supplemented with IV agents to maintain Stage III surgical anesthesia
0.8-1.2 MAC
Name the Anti-anxiety agents used preoperatively to ease induction or for sedative purposes
benzodiazepines - (diazepam (Valium®), midazolam, lorazepam)
Name the Induction agents used in surgery for rapid deep anesthesia (20 sec), avoiding excitation/delirium
propofol,
thiopental
name the Analgesics used for surgery
opioids: morphine, fentanyl (latter has advantageously short duration of action)
Name the Neuromuscular blockers used to relax skeletal muscle, particularly for abdominal surgeries
vecuronium,
tubocurarine,
succinylcholine
Name the Anticholinergic drugs that reduce GA-induced hypotension, bradycardia, and excess
salivary secretions that can choke patient during anesthesia
glycopyrrolate,
atropine,
scopolamine
Name an Anti-emetics used to reduce post-operative nausea and vomiting (common problem)
ondansetron (5-HT3–type serotonin receptor antagonist)
