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Pharm Exam 2
Set 2: General Anesthetics
88
Pharmacology
Graduate
10/21/2011

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Cards

Term
What was the first general anesthetic?
Definition
diethyl ether
Term
Function

general anesthesia
Definition
reversible depression of the CNS =>
1) unconsciousness
2) analgesia (pain killer)
3) amnesia
4) immobility
Term
What are the 2 classes of general anesthesia?
Definition
1) inhalation
2) intravenous
Term
def

balanced anesthesia
Definition
combination of inhaled & intravenous anesthesia to take advantage of the favorable properties of each agent while minimizing their adverse reactions
Term
What are the 2 theories of anesthesia?
Definition
1) Lipid theory (lipid soluble = potency)
2) protein theory
Term
def

MAC (minimum alveolar concentration)
Definition
measure of inhaled anesthetic potency - the alveolar concentration required to immobilize 50% of patients when exposed to a surgical incision
Term
What happens to MAC values when several anesthetics are used simultaneously?
Definition
additive
Term
What factors can make MAC vary among patients?
Definition
1) Age
2) EtOH
3) underlying disease
4) DDIs

(NOT affected by height, weight, sex)
Term
def

oil:gas partition coefficient
Definition
potency of an anesthetic
Term
Equation

Potency on anesthetic
Definition
P = 1/MAC
Term
What is the Unitary Theory of Anesthesia (lipid theory)?
Definition
Anesthetics work by changing membrane dimension &/or membrane state.

dimension: change volume of membrane
physical state: increase fluidity
Term
What is the protein theory of anesthesia?
Definition
anesthetic interacts directly with hydrophobic domain of any membrane protein
Term
What are the primary targets of general anesthestics (GAs)?
Definition
ligand-gated ion channels:
-GABA
-nAchR
-Glu
-5-HT3
-NMDA
Term
What are the 2 inhibitory receptors that GAs work on?

3 excitatory?
Definition
I: Glu & GABA
E: 5-HT3, NMDA, nAchR
Term
MOA

GA on inhibitory receptors (GABA & Glu)
Definition
potentiate the action of endogenous agonists (stabilizes open state) => decreased AP at post-synaptic neuron => more potent agonists (i.e. need less concentration of agonists to achieve maximum response - decrease EC50)
Term
MOA

GAs on excitatory receptors (5-HT3, NMDA, nAchR)
Definition
inhibits the action of endogenous agonists => no depolarization of post synaptic membrane => no AP (like adding a non-competitive antagonist, EC50 stays the same, but efficacy decreases)
Term
def

dual process model of anesthesia
Definition
1) inhibits excitatory receptors
2) ehances inhibitory receptors
Term
Why are GAs the most dangerous drugs in clinical use?
Definition
low safety margin & no antagonist
Term
What are the 2 types of inhaled GAs?
Definition
1) non-halogenated
2) halogenated
Term
What is the inhalation non-halogenated GA?
Definition
NO (gas)
Term
What are the 4 halogenated inhalation GAs?
Definition
(volatile liquid):
sevoflurane, isoflurane, halothane, desflurane
Term
What inhaled anesthetic has the highest MAC?
Definition
NO
Term
SOA

NO inhalation anesthetic
Definition
analgesic (only used alone in dental procedures)
Term
SOA

halothane inhalation anesthetic
Definition
induction in children
Term
SOA

isoflurane inhalation anesthetic
Definition
most widely used

induction/maintenance
Term
SOA

desflurane inhalation anesthetic
Definition
most widely used for outpatient surgery
Term
SOA

sevoflurane inhalation anesthetic
Definition
induction in children
outpatient surgery
Term
SE

inhaled anesthetic on cardiovascular system
Definition
decreased BP
Term
SE

inhaled anesthetic on resp. system
Definition
reduce or eliminate ventilatory drive & reflexes maintaining aairway patency (all except NO)
Term
SE

inhaled anesthetic on brain
Definition
increase cerebral blood flow => increased cerebral blood volume => increased ICP
Term
SE

inhaled anesthetic on kidney
Definition
decrease glomerular filtration rate & renal blood flow => increased filtration fraction
Term
SE

inhaled anesthetic on liver
Definition
concentration-dependent decrease in hepatic blood flow (15-45% reduction)
Term
def

malignant hyperthermia
Definition
autosomal dominant genetic disorder of skeletal muscle that occurs in susceptible individuals undergoing GA with volatile agents & muscle relaxants. An increase in free [Ca2+] in skeletal muscle => increase in anesthetic morbidity & mortality.
Term
Sx

malignant hyperthermia
Definition
rapid onset tachycardia & HTN
severe muscle rigidity
hyperthermia
hyperkalemia
acidosis
Term
Tx

malignant hyperthermia
Definition
dantrolene to prevent Ca2+ release from SR
Term
What factor determines rate of uptake of an anesthetic & its distribution throughout the body?
Definition
solubility in blood & body tissue
Term
How is solubility of inhalation anesthetics most commonly measured & expressed?
Definition
Blood:Gas partition coefficient
Term
def

blood:gas partition coefficient
Definition
main factor that determines the rate of induction & recovery from anesthesia (relative affinity for the blood compared to air)
Term
When will there be faster induction & recovery from a GA?
Definition
lower the blood:gas partition coefficient
Term
Why does a low blood:gas partition mean faster induction & recovery?
Definition
equilibriate faster since less has to be transferred via the lungs to the blood in order to achieve a given partial pressure
Term
What 2 inhaled anesthetics have a higher blood:gas partition coefficient?
Definition
halothane & isoflurane
Term
How does blood flow affect GA?
Definition
the greater the blood flow (perfusion), the faster the uptake of the anesthetic
Term
def

tissue capacity for a GA
Definition
volume of compartment & solubility of anesthetic in tissue
Term
What are the 3 groups of tissue based on their perfusion & capacity to take up anesthesia?
Definition
1) high flow, low capacity (brain, lung, heart, kidney)
2) medium flow, high capacity (skeletal muscles)
3) low flow, very high capacity (adipose tissue)
Term
Which tissue group has the fastest rise in partial pressure of the anesthetic?

slowest?
Definition
fast: high flow, low capacity
slow: slow flow, very high capacity
Term
How does % body fat affect uptake & distribution of a GA?
Definition
highlt lipid soluble dug + high body fat = slow recovery & patient remains drowsy
Term
What does the rate of the rise of anesthetic gas tension in arterial blood depend on?
Definition
rate & depth of ventilation

magnitude varies dependent on the blood:gas partition coefficient
Term
How do you increase the rate of onset of an inhaled anesthesia?
Definition
increase the ventilation rate (hyperventilation) due to increased concentrations of the agent
Term
What happens to the rate of induction of an inhaled anesthetic when pulmonary blood flow increases (i.e. increase in cardiac output)?
Definition
slows (effect is larger for more blood soluble gases)
Term
Why does increased pulmonary blood flow decrease the rate of induction of an inhaled anesthetic?
Definition
increased blood flow = larger volume of blood exposed to anesthetic => takes longer for anesthetic & blood to equilibrate
Term
How are inhaled anesthetics cleared from the body?
Definition
Major route: lungs
Minor route: some metabolism in liver
Term
How are inhaled anesthetics terminated?
Definition
redistribution from brain to the blood, down partial pressure gradient
Term
Is rate of recovery from inhaled anesthetics faster with a high or low blood:gas partition coefficient?
Definition
low
Term
What is rate of recovery from an inahled anesthetic proportional to?
Definition
duration under anesthesia. (the longer it's applied, the more anesthsia distributes to muscle groups & fat)
Term
Does hyper- or hypo- ventilation increase rate of recovery from an inhaled anesthetic?
Definition
hyperventilation
Term
Which inhaled anesthetic is the only one with a significant portion of it (~40%) metabolized?
Definition
halothane
Term
DO IV anesthetics have a more or less rapid rate of induction than inhaled anesthetics?

Why?
Definition
More rapid b/c they're more lipid soluble & easily cross the BBB
Term
Why are IV anesthetics often used for outpatient procedures?
Definition
rapid rate of recovery
Term
In balanced athesthesia, are IV anesthetics administered pre or post inhaled anesthetics?
Definition
pre, due to rapid onset & short duration of action
Term
Where is IV anesthetics trasported first via the vascular system?
Definition
heart => brain & highly vascularized tissues (peak within 1 min)
Term
Why is drug redistribution to adipose much later in IV anesthetics?
Definition
low blood flow to body fat
Term
How are IV anesthetics eliminated?
Definition
liver/plasma metabolism (NOT ventilation)
Term
What are the 4 IV anesthetics used?
Definition
1) Barbituates
2) Propofol
3) Etomidate
4) Ketamine
Term
What 3 barbituates are used as IV anesthestia?
Definition
1) Sodium Thiopental
2) Thiamylal
3) Methohexital
Term
Onset/Duration

barbituates
Definition
rapid onset(seconds)/ultra-short
Term
What is the most populat IV anesthetic?
Definition
Propofol
Term
Onset

Propofol
Definition
rapid (half time to blood-brain equilibriation is 1-3min)
Term
Why is propofol a good choice anesthetic for outpatient procedures?
Definition
rapid recovery
Term
SOA

propofol
Definition
outpatient procedures
critical care prolonged sedation
Term
Where is porpofol rapidly metabolized?
Definition
liver
Term
What IV anesthetic is the analog to PCP & produces dissociative anesthesia?
Definition
ketamine
Term
SE

ketamine
Definition
hallucinations
irrational behavior
dose-related cardiovascular stimulation (only IV anesthesia to do so)
Term
SOA

ketamine
Definition
induction & maintenance (usually in comination with a sedative)
Term
MOA

ketamine
Definition
noncompetitive antagonist of NMDA
Term
def

dissociative anesthesia
Definition
catatonia
amnesia
analgesia
w/o loss of consciousness
Term
Onset

ketamine
Definition
rapid-acting w/ profound analgesia
Term
Where is katamine metabolized?
Definition
liver
Term
For which patients is etomidate primarily used?

Why?
Definition
those @ risk for hypotenstion b/c does not cause significant cardiovascular or resp. depression
Term
What is usually co-administered with etomidate?

Why?
Definition
Lidocaine b/c high incidence of pain on injection
Term
SE

etomidate
Definition
post-op N/V
Term
Where is etomidate metabolized
Definition
extensively in plasma & liver to inactive metabolites
Term
What 2 drug types are used as adjuvants, but also have some anesthetic quality when administered IV?
Definition
1) benzodiazepines
2) opioids
Term
What are the 3 benzodiazepines used as an adjuvant to GA?
Definition
1) Diazepam
2) Lorazepam
3) Midazolam
Term
Why are benzos given as an adjuvant to GA?
Definition
anxiolytic & anterograde amnestic propeties
Term
SOA

benzos as an IV anesthetic
Definition
inoperative sedation
Term
What are the 2 opioids used as an adjuvant to GA?
Definition
1) morphine
2) fentanyl
Term
Why are opioids used an adjuvant to GA?
Definition
analgesia (poor amnestics)
Term
Duration

opioids
Definition
30-60 min
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