Pharmacology 22 (General Anesthetics)

Front 1

what general anesthetic is a gas?

Back 1

nitrous oxide

Front 2

isoflurane

Back 2

general anesthetic (volatile liquid)

Front 3

desflurane

Back 3

general anesthetic (volatile liquid)

Front 4

sevoflurane

Back 4

general anesthetic (volatile liquid)

Front 5

stage I of anesthesia

Back 5

"analgesia"

- analgesia
- amnesia
- euphoria

Front 6

stage II of anesthesia

Back 6

"Excitement"

- excitement
- delirium
- combative behavior
**like a bad nightmare**

Front 7

stage III of anesthesia

Back 7

"Surgical Anesthesia"

- unconsciousness
- regular respiration
- decreasing eye movement

Front 8

stage IV of anesthesia

Back 8

"Medullary Depression" = OD

- respiratory arrest
- cardiac depression and arrest
- no eye movement

Front 9

list the stages of anesthesia experienced by a patient as they are being put under for and then awakening from a surgery

Back 9

Stage I: Analgesia
Stage II: Excitement
Stage III: Surgical Anesthesia
surgery performed and anesthetic stopped
Stage II: Excitement
Stage I: Analgesia

Front 10

definition of general anesthetic

Back 10

drug which causes analgesia, amnesia, loss of consciousness, inhibition of sensory and autonomic reflexes, and skeletal muscle relaxation

Front 11

why is it important that general anesthetics inhibit autonomic reflexes?

Back 11

prevents the patient's blood pressure and heart rate from changing when an incision is made

Front 12

what is the advantage to quick induction with general anesthetics?

Back 12

with fast induction, the patient passes rapidly through the undesirable "excitement" phase (stage II) of anesthesia

Front 13

define induction, as it pertains to anesthesia

Back 13

rate of onset of anesthesia

(how quickly alveolar partial pressure of an anesthetic equilibrates with inspired partial pressure of the anesthetic)

**initially, the inspired partial pressure is much greater than the alveolar partial pressure**

Front 14

define maintenance of anesthesia

Back 14

maintaining constant alveolar partial pressure of anesthetic at therapeutic levels

**during maintenance, inspired partial pressure of the anesthetic will be equal to the alveolar partial pressure of that anesthetic**

Front 15

define recovery from anesthesia

Back 15

rate of decline of alveolar partial pressure of an anesthetic

**when a surgery is finished and a patient is being weaned from anesthesia, the alveolar partial pressure must decrease from therapeutic levels to zero**

Front 16

define partial pressure

Back 16

the partial pressure of a gas in a mixture of gases is the portion of the total pressure (760 mmHg) that is supplied by a particular gas

Front 17

why are neuromuscular blocking drugs often used in addition to anesthetics?

Back 17

often used to cause flaccidity of muscle, which enables the anesthesiologist to decrease the dose of general anesthetic required

**especially useful when working in highly muscular areas, like the abdominal cavity**

Front 18

what is the main difference between a low-flow anesthetic machine and a high-flow anesthetic machine?

Back 18

a low-flow system has a carbon dioxide absorber, whereas the high-flow system doesn't

Front 19

blood/gas partition coefficient

Back 19

ratio describing distribution of a gas between two phases (gas and blood) at equilibrium; i.e. ratio of gas dissolved in a given volume of solvent to the amount of free gas that would occupy the same volume of space

determines the rate of induction

Front 20

what inactive reservoir must be saturated before anesthetic equilibrium can be achieved?

Back 20

proteins in the blood

lipophilicity determines how quickly alveolar partial pressure equilibrates with arterial partial pressure of an anesthetic, b/c lipophilic anesthetics must bind to proteins and fill this reservoir before the partial pressure of the anesthetic in the blood can equilibrate with its partial pressure in the alveoli

Front 21

what are the three main categories of anesthetics classified based on blood solubility?

Back 21

soluble - high (double-digit) blood/gas partition coefficient - slow induction rate

intermediate - single-digit blood/gas partition coefficient - intermediate induction rate

poorly soluble - blood/gas partition coefficient of about 0.5 - rapid rate of induction

Front 22

what anesthetic is in the intermediate solubility classification of anesthetics?

Back 22

isoflurane

blood/gas partition coefficient of 1.4

intermediate rate of induction

Front 23

what anesthetics are in the poorly soluble classification of anesthetics?

Back 23

anesthetic (blood/gas partition coefficient)
nitrous oxide (0.47)
desflurane (0.45)
sevoflurane (0.65)

poorly soluble, therefore rate of induction is very rapid

Front 24

what is indicated by a high blood/gas partition coefficient? what does this mean for general anesthetics?

Back 24

high lipophilicity

because of high lipophilicity, the general anesthetics will seek out lipophilic portions of the blood (e.g. proteins)

Front 25

what is the active fraction of an inhaled anesthetic?

Back 25

the portion of anesthetic that exerts a partial pressure

portion of anesthetic dissolved in the water of plasma after the lipophilic portions of the blood (proteins) have been saturated

Front 26

what is the effect of lipophilicity on rate of induction of general anesthetics?

Back 26

high lipophilicity -> saturates proteins (inactive reservoir) -> Part equilibrates with Palv -> slow induction

low lipophilicity -> only small amt goes to lipophilic portions of blood -> Part equilibrates with Palv -> rapid rate of induction

Front 27

what are the stages in the equilibration of the partial pressure of an anesthetic that is inspired with the partial pressure of that anesthetic in the brain?

Back 27

1) alveolar partial pressure of an anesthetic equilibrates with inspired partial pressure of the anesthetic
2) arterial partial pressure equilibrates with alveolar partial pressure
3) arterial partial pressure equilibrates with brain partial pressure

Front 28

describe the equilibration of alveolar partial pressure of an anesthetic with the inspired partial pressure of the anesthetic

Back 28

the particular anesthetic used plays a large role

loading dose can be used for a few minutes to decrease the time required for this equilibration

Front 29

describe the equilibration of arterial partial pressure of an anesthetic with the alveolar partial pressure of the anesthetic

Back 29

takes about ten seconds for the blood in lung capillaries to reach the capillaries of the systemic circulation

this equilibration occurs very quickly

Front 30

describe the equilibration of arterial partial pressure of an anesthetic with the brain partial pressure of the anesthetic

Back 30

particular anesthetic used plays little/no role on rime required

this equilibration occurs pretty quickly regardless of which anesthetic is used

since all general anesthetics are somewhat lipophilic, they cross the blood-brain barrier readily

Front 31

what is the only way to increase the speed of recovery from a general anesthetic?

Back 31

agents with a quick induction have a quick recovery

advantage to a quick recovery is that the patient passes through phase II (excitement phase) quickly

Front 32

minimum alveolar concentration (MAC)

Back 32

minimum concentration (partial pressure) of anesthetic necessary to prevent movement in response to surgical skin incision in 50% of patients (measure of potency of inhaled anesthetic)

1.3xMAC is used during surgery to prevent movement in 95% of patients

Front 33

what is the most potent inhaled anesthetic?

Back 33

methoxyflurane (1MAC = 0.16% of atmospheric pressure)

Front 34

what is the least potent inhaled anesthetic?

Back 34

nitrous oxide (fills any empty cavity b/c it is a gas where other anesthetics are volatile liquids)

1MAC = 101% of atmospheric pressure
can only go to 80%, therefore nitrous oxide is an incomplete anesthetic

Front 35

how is MAC determined for mixtures of inhaled anesthetics?

Back 35

MAC = minimum alveolar concentration
MACs are additive for the different anesthetics used
(e.g. 0.5MAC N2O + 0.5MAC halothane = 1.0MAC)

Front 36

what is the advantage of mixing anesthetics?

Back 36

reduces the side effects due to each drug

Front 37

what is the effect of temperature on minimum alveolar concentration for inhaled general anesthetics?

Back 37

at lower temperatures, the MAC is lower (patient is more sensitive to general anesthetics)

at higher temperatures, the MAC is higher

Front 38

what is the effect of age on minimum alveolar concentration for inhaled general anesthetics?

Back 38

as a patient gets older, the MAC decreases (elderly patients are more sensitive to general anesthetics than are young patients)

Front 39

what is the effect of SNS/CNS altering drugs on the minimum alveolar concentration for inhaled general anesthetics?

Back 39

pt with a blood-alcohol content of 0.2% requires a lower dose of general anesthetic

chronic alcoholic without alcohol for a couple days requires a higher dose of general anesthetic

patient on CNS-depressing drugs requires lower dose of general anesthetics

patient on CNS-stimulating drugs requires higher dose of general anesthetics

Front 40

what is the effect of barometric pressure on minimum alveolar concentration for inhaled general anesthetics?

Back 40

decreased barometric pressure results in increased MAC

Front 41

what factors have no effect on the minimum alveolar concentration for inhaled general anesthetics?

Back 41

1) duration of administration (length of surgery)
2) biotransformation (more drug is required, but MAC remains same)
3) gender
4) blood pressure
5) arterial oxygenation
6) level of ventilation
7) hemoglobin concentration (anemia doesn't affect MAC)

Front 42

what is the Meyer-Overton theory of anesthesia?

Back 42

developed in 1900

states that anesthetic dissolves in lipid membrane, causes expansion, and subsequently the reversible inhibition of synaptic transmission

changes the properties of the cell membrane rather than using a receptor

states that anesthetics increase the affinity of the GABA receptor for GABA and inhibit the excitatory (glutamate) receptors

Front 43

how can the minimum alveolar concentration of an inhaled general anesthetic be predicted?

Back 43

MAC x (oil/gas partition coefficient) = 1.3

can fit a logarithmic scale line very well, thus MAC is actually the partial pressure required to generate a particular concentration of anesthetic in a lipophilic medium (i.e. lipid bilayers of CNS)

Front 44

what is the antagonist to general anesthetics?

Back 44

since general anesthetics' effects aren't receptor-mediated, there is no antagonist to them

Front 45

what is the effect of general anesthetics on the minute ventilation?

Back 45

decreases tidal volume, which consequently decreases minute ventilation

Front 46

what is the effect of general anesthetics on the respiratory rate?

Back 46

increases the respiratory rate

Front 47

what is the effect of general anesthetics on the arterial PCO2?

Back 47

increases arterial PCO2, leading to undesirable CV effects (changes TPR and CO)

Front 48

what is the effect of general anesthetics on the ventilatory response to carbon dioxide?

Back 48

with increasing PaCO2, the minute ventilation increases in a linear manner (plot of minute ventilation vs. PaCO2); the effect of general anesthetics is to decrease the slope of this line, so that the increase in minute ventilation is less than that seen with a comparable increase in PaCO2 without general anesthetics

Front 49

what is the effect of general anesthetics on the ventilatory response to hypoxemia?

Back 49

general anesthetics abolish the ventilatory response to hypoxemia; usually the minute ventilation increases as a result of low PaO2 (curves up after a certain partial pressure), but with general anesthetics the minute ventilation remains constant regardless of how low the PaO2 gets

Front 50

what is the only general anesthetic that doesn't increase PaCO2?

Back 50

nitrous oxide (N2O)

advantage - can be used in combination with other general anesthetics to give anesthesia without causing the undesirable CV effects (changing TPR and CO)

Front 51

for what reasons can nitrous oxide be used in combination with other general anesthetics?

Back 51

1) decrease hypercapnea caused by other GAs
2) improve hypotension caused by other GAs

Front 52

what is the only general anesthetic that doesn't decrease blood pressure?

Back 52

nitrous oxide (it can be used in combination with other general anesthetics in order to decrease the hypotensive effects of the other general anesthetics)

all others decrease TPR
sevoflurane decreases CO

Front 53

what are the effects of general anesthetics on the CNS? why is this undesirable?

Back 53

general anesthetics cause an increase in cerebral blood flow

undesirable b/c intracranial tumors cause increasing pressures within a closed vault (skull) and if more blood is flushed into the skull, intracranial pressure rises to a dangerous level

Front 54

what is the general anesthetic of choice for patients with high intracranial pressure (patients with tumors)?

Back 54

isoflurane

b/c it doesn't cause as extensive elevation of intracranial pressure as the rest of the inhaled general anesthetics

Front 55

what is the effect of general anesthetics on the kidneys?

Back 55

general anesthetics decrease renal blood flow, but usually this isn't clinically significant because it doesn't cause any pathology

Front 56

why is nitrous oxide combined with a narcotic (fentanyl) to be used as a general anesthetic?

Back 56

the narcotic doesn't affect blood pressure or cardiac output

Front 57

why is anesthetic metabolism important?

Back 57

can have toxic effects on the kidneys and liver

Front 58

what factors influence the extent of biotransformation of inhaled general anesthetics?

Back 58

1) enzyme activity - genetic factors/enzyme inducers may determine an individual's ability to metabolize the compound

2) substrrate availability - poorly soluble anesthetics (low blood/gas partition coefficient) leave little substrate available for metabolism; these anesthetics are exhaled rapidly

Front 59

halothane-associated hepatic dysfunction

Back 59

rare dysfunction (1/30,000 pts treated), but is associated with high mortality

profile of affected patient:
middle-aged obese
female fever then jaundice
repeated exposure

unknown mechanism - reactive intermediates attach to liver cell membranes and exert toxic effects

Front 60

what patients should not be given halothane?

Back 60

a) morbidly obese
b) repeated exposure
c) liver disease
d) enzyme induction

Front 61

biotransformation of methoxyflurane

Back 61

very soluble drug (high oil/gas partition coefficient), so about 50% of the absorbed dose is metabolized

transformation frees up fluoride and increases serum concentration, causing neprotoxicity

never use methoxyflurane, but the important thing is that general anesthetics are metabolized and cause problems (e.g. the nephrotoxicity)

Front 62

biotransformation of isoflurane

Back 62

chemically and pharmacologically similar to enflurane

metabolism is minimal (about 0.17%)

Front 63

biotransformation of sevoflurane

Back 63

though it has a low blood/gas partition coefficient, a surprisingly large amount (3% of dose) is metabolized; this causes significant amounts of fluoride buildup in the blood during long surgeries

Front 64

why would you not want to use sevoflurane in long surgeries?

Back 64

though it has a very low blood/gas partition coefficient, a surprisingly large amount (3%) is metabolized, which causes significant amounts of fluoride to build up in the blood during long surgeries

Front 65

biotransformation of desflurane

Back 65

essentially no metabolism (0.02%)

Front 66

why are IV anesthetics used, in general?

Back 66

used for induction, so that you can skip phase 2 (excitement phase; nightmare)

Front 67

what is the most commonly used ultra-short-acting barbiturate as a general anesthetic?

Back 67

thiopental

crosses the blood-brain barrier and establishes a brain:plasma equilibrium within 1 minute because of high lipid solubility

Front 68

why are barbiturates (thiopental) ultra-short-acting general anesthetics?

Back 68

they rapidly diffuse out of the brain and other highly vascular tissues and are redistributed to muscle, fat, and eventually all body tissues

Front 69

thiopental

Back 69

ultra-short-acting barbiturate

used as an IV general anesthetic for induction

rapid redistribution causes this to be very short acting

Front 70

propofol

Back 70

drug of choice as an IV general anesthetic agent; great for inducing anesthesia

smaller doses widely used for sedation in ICU

oil at room temperature, supplied as an emulsion

more rapid emergence from anesthesia than with thiopental; also characterized by minimal postoperative confusion

Front 71

what are the advantages of propofol over thiopental as IV general anesthetics?

Back 71

more rapid emergence from anesthesia with propofol than with thiopental

minimal postoperative confusion associated with propofol

Front 72

etomidate

Back 72

IV general anesthetic used to induce anesthesia; also used in combination with succinyl choline for intubation in code situations

increases available GABA receptors, perhaps by displacing an endogenous GABA inhibitor

causes minimal respiratory and cardiovascular depression

Front 73

malignant hyperthermia

Back 73

dangerous increase in body temperature brought on by the use of anesthetics
- mainly determined by genetic predisposition of the patient
- caused by calcium leak from the SR of skeletal muscle causing massive contractions and heat production

Tx: dantrolene (stabilizes the SR membrane without interfering with action potentials - acts like a calcium channel blocker)

Front 74

propofol

Back 74

drug of choice as an IV general anesthetic agent; great for inducing anesthesia

smaller doses widely used for sedation in ICU

oil at room temperature, supplied as an emulsion

more rapid emergence from anesthesia than with thiopental; also characterized by minimal postoperative confusion

Front 75

dantrolene

Back 75

essentially a calcium-channel blocker, though it doesn't bind to the calcium channels; stabilizes the SR membrane without interfering with action potentials

used as a Tx for malignant hyperthermia

Front 76

what are the advantages of propofol over thiopental as IV general anesthetics?

Back 76

more rapid emergence from anesthesia with propofol than with thiopental

minimal postoperative confusion associated with propofol

Front 77

etomidate

Back 77

IV general anesthetic used to induce anesthesia; also used in combination with succinyl choline for intubation in code situations

increases available GABA receptors, perhaps by displacing an endogenous GABA inhibitor

causes minimal respiratory and cardiovascular depression

Front 78

malignant hyperthermia

Back 78

dangerous increase in body temperature brought on by the use of anesthetics
- mainly determined by genetic predisposition of the patient
- caused by calcium leak from the SR of skeletal muscle causing massive contractions and heat production

Tx: dantrolene (stabilizes the SR membrane without interfering with action potentials - acts like a calcium channel blocker)

Front 79

dantrolene

Back 79

essentially a calcium-channel blocker, though it doesn't bind to the calcium channels; stabilizes the SR membrane without interfering with action potentials

used as a Tx for malignant hyperthermia

Front 80

propofol

Back 80

drug of choice as an IV general anesthetic agent; great for inducing anesthesia

smaller doses widely used for sedation in ICU

oil at room temperature, supplied as an emulsion

more rapid emergence from anesthesia than with thiopental; also characterized by minimal postoperative confusion

Front 81

what are the advantages of propofol over thiopental as IV general anesthetics?

Back 81

more rapid emergence from anesthesia with propofol than with thiopental

minimal postoperative confusion associated with propofol

Front 82

etomidate

Back 82

IV general anesthetic used to induce anesthesia; also used in combination with succinyl choline for intubation in code situations

increases available GABA receptors, perhaps by displacing an endogenous GABA inhibitor

causes minimal respiratory and cardiovascular depression

Front 83

malignant hyperthermia

Back 83

dangerous increase in body temperature brought on by the use of anesthetics
- mainly determined by genetic predisposition of the patient
- caused by calcium leak from the SR of skeletal muscle causing massive contractions and heat production

Tx: dantrolene (stabilizes the SR membrane without interfering with action potentials - acts like a calcium channel blocker)

Front 84

propofol

Back 84

drug of choice as an IV general anesthetic agent; great for inducing anesthesia

smaller doses widely used for sedation in ICU

oil at room temperature, supplied as an emulsion

more rapid emergence from anesthesia than with thiopental; also characterized by minimal postoperative confusion

Front 85

what are the advantages of propofol over thiopental as IV general anesthetics?

Back 85

more rapid emergence from anesthesia with propofol than with thiopental

minimal postoperative confusion associated with propofol

Front 86

etomidate

Back 86

IV general anesthetic used to induce anesthesia; also used in combination with succinyl choline for intubation in code situations

increases available GABA receptors, perhaps by displacing an endogenous GABA inhibitor

causes minimal respiratory and cardiovascular depression

Front 87

dantrolene

Back 87

essentially a calcium-channel blocker, though it doesn't bind to the calcium channels; stabilizes the SR membrane without interfering with action potentials

used as a Tx for malignant hyperthermia

Front 88

malignant hyperthermia

Back 88

dangerous increase in body temperature brought on by the use of anesthetics
- mainly determined by genetic predisposition of the patient
- caused by calcium leak from the SR of skeletal muscle causing massive contractions and heat production

Tx: dantrolene (stabilizes the SR membrane without interfering with action potentials - acts like a calcium channel blocker)

Front 89

dantrolene

Back 89

essentially a calcium-channel blocker, though it doesn't bind to the calcium channels; stabilizes the SR membrane without interfering with action potentials

used as a Tx for malignant hyperthermia

Front 90

use of opiates with regards to general anesthetics

Back 90

used as a premedication for sedation and analgesia

Front 91

use of benzodiazepines in regards to general anesthetics

Back 91

used as a premedication for their anxiolytic effects
e.g. diazepam, lorazepam

additionally, midazolam causes amnesia in 20% of patients

Front 92

usefulness of antimuscarinics in general anesthetics

Back 92

e.g. atropine, glycopyrrolate

general anesthetics increase mucous secretions in lungs and causes patients to wake up with a dry mouth - antimuscarinics combat these effects

Front 93

midazolam

Back 93

benzodiazepine

useful as a premedication for general anesthetics for anxiolytic effects; also causes amnesia in 20% of patients

Front 94

atropine

Back 94

antimuscarinic

useful with general anesthetics to block mucous secretion in the lungs that is caused by the general anesthetics