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Millers Anesthesia > Intravenous Anesthetics > Flashcards

Intravenous Anesthetics Flashcards

1
Q

Since its introduction in the …, propofol has become the most used IV hypnotic today.

Propofol is one of a group of … that are highly lipid soluble and are insoluble in an aqueous solution.

The formulation most used is that of 1% propofol, 10% soybean oil, and 1.2% … added as emulsifier, with 2.25% of glycerol as a tonicity-adjusting agent, and sodium hydroxide to change the pH.
Following concerns regarding microbial growth in the emulsion, … was added for its bacteriostatic activities.

A

1970s

alkylphenols

purified egg phospholipid

EDTA

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2
Q

Propofol metabolization

A

Propofol is oxidized to 1,4-diisopropyl quinol in the liver.
Propofol and 1,4-diisopropyl quinol are conjugated with glucuronic acid to propofol-1-glucuronide, quinol-1- glucuronide, and quinol-4-glucuronide, which then may be excreted by the kidneys.

Because clearance of propofol (>1.5 L/min) exceeds hepatic blood flow, extrahepatic metabolism may occur.
The most important extrahepatic site for propofol metabolism is the kidney. Renal metabolism of propofol accounts for up to 30% of propofol clearance, whichexplains the rapid clearance of propofol, which exceeds liver blood flow. The lungs also may play a role in the extrahepatic propofol metabolism

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3
Q

Propofol is known as a … inhibitor

A

CYP3A4

  • A short-term exposure to propofol at a blood concentration of 3 μg/mL already reduces the CYP3A4 activity by about 37%
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4
Q

The context-sensitive half-time for propofol for infusions of up to 8 hours is less than …

Because the required decrease in concentration for awakening after anesthesia or sedation with propofol is generally …%, recovery from propofol remains rapid even after prolonged infusion

A

40 minutes

less than 50

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5
Q

Patients aged 80 years or older generally need …% of the propofol dose of patients aged 20 years old to target the same level of sedation or hypnosis

A

50

  • Elderly individuals have decreased clearance rates and a smaller central compartment volume. Both may be the result of a reduced
    cardiac output. Because of this and because of an increased
    sensitivity, elderly individuals need lower doses.
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6
Q

In clinical practice, no significant propofol dose adjustment is required in case of hepatic disease

T or F

A

T

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7
Q

In the presence of sedative concentrations of propofol, plasma midazolam concentrations …%

A

increased by 27

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8
Q

Coadministration of propofol increased remifentanil concentrations via …

A

both a decrease in the central volume of distribution and distributional clearance of remifentanil by 41% and elimination clearance by 15%

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9
Q

The hypnotic action of propofol is mostly mediated by enhancing … through its binding to …subunit of GABAA receptor.

Sites on the … subunit of the transmembrane domains are crucial for the hypnotic action of propofol.

The … subunit subtypes also seem to contribute to modulating
the effects of propofol on the GABA receptor

A

γ-aminobutyric acid (GABA)-induced chloride current

the β-

β1-subunit, β2-subunit, and β3-

α-subunit and γ2-

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10
Q

Propofol results also in widespread inhibition of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor through modulation of sodium channel gating, an action that also may contribute to the drug’s CNS effects

T or F

A

T

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11
Q

The sense of well-being in patients with propofol is related to

A

the increase in dopamine concentrations in the nucleus accumbens (a phenomenon noted with drugs of abuse and pleasure-seeking behavior)

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12
Q

Propofol’s antiemetic action may be explained by

A

the decrease in serotonin levels it produces in the area postrema, probably through its action on GABA receptors

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13
Q

The onset of hypnosis after a dose of 2.5 mg/kg is rapid (one arm–brain circulation), with a peak effect seen at …

The median effective dose (ED50) of propofol for loss of consciousness is … after a bolus.

The duration of hypnosis is dose-dependent, being … after 2 to 2.5 mg/kg.

A

90 to 100 seconds

1 to 1.5 mg/kg

5 to 10 minutes

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14
Q

Rapid infusion rates of propofol produce burst suppression at blood propofol concentrations higher than …

A

8 μg/mL

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15
Q

Why do infants need higher doses of propofol

A

Children exhibit a relatively larger central compartment and therefore need a higher dose to assure a similar blood-drug concentration. In addition, the rapid clearance of propofol in children requires a larger maintenance dose as well

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16
Q

How does propofol affect intracranial presusre?

A

Propofol decreases intracranial pressure (ICP) in patients with either normal or increased ICP.
The decrease in ICP (30% to 50%) is associated with significant decreases in cerebral perfusion pressure (CPP)

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17
Q

How does propofol affect intraocular pressure?

A

Propofol acutely reduces intraocular pressure by 30% to 40%. Compared with thiopental, propofol produces a larger decrease
in intraocular pressure and is more effective in preventing an increase in intraocular pressure secondary to succinylcholine and endotracheal intubation

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18
Q

Does propofol have neuroprotective effects?

A

The neuroprotective effects of propofol remain controversial. Current evidence indicates that propofol can protect neurons against ischemic injury caused by excitotoxicity, but neuroprotection may be sustained only if the ischemic insult is relatively mild and is not sustained after a prolonged recovery period. Prolonged propofol sedation in children is associated with adverse neurologic sequelae

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19
Q

Propofol induces bronchoconstriction in patients with chronic obstructive pulmonary disease

T or F

A

F

Propofol induces bronchodilation in patients with chronic obstructive pulmonary disease

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20
Q

How does propofol affect hypoxic pulmonary vasoconstriction?

A

Propofol potentiates hypoxic pulmonary vasoconstriction, an effect
caused by inhibition of K(+) (ATP)-mediated pulmonary
vasodilatation

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21
Q

Propofol is a vasodilator due to …

The mechanism of this activity is a combination of a direct effect on …

A

a reduction in sympathetic activity

intracellular smooth muscle calcium mobilization, inhibition of prostacyclin synthesis in endothelial cells, reduction in angiotensin II–elicited calcium entry, activation of K adenosine triphosphate channels, and stimulation of nitric oxide

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22
Q

Propofol, similar to thiopental, enhance neuromuscular blockade produced by neuromuscular blocking drugs

T or F

A

F

Propofol, similar to thiopental, does not enhance neuromuscular blockade produced by neuromuscular blocking drugs

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23
Q

Propofol inhibits phagocytosis and killing of …

A

Staphylococcus aureus and Escherichia coli

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24
Q

The administration of propofol is associated with the development of pancreatitis, which may be related to

A

hypertriglyceridemia or or idiosyncratic drug reaction

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25
Q

Physiologic characteristics that best determine the appropriate dose to induce anesthesia are age, …, and central blood volume

A

lean body mass

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26
Q

The induction dose needs to be reduced in elderly patients and a dose of … mg/kg (with premedication) to … mg/kg (without premedication) is recommended for inducing anesthesia in patients older than …

A

1

1.75

60

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27
Q

Blood propofol concentrations … in the presence of hemorrhagic shock.

Shock results in … intercompartmental clearances and shock shifts the concentration effect relationship to the left, demonstrating
a 2.7-fold … in the effect-site concentration required to achieve 50% of the maximal effect in the BIS

A

increase

slower

decrease

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28
Q

Describe the Propofol infusion syndrome

A

is a rare but lethal syndrome associated with infusion of propofol at 4 mg/kg/h or more for 48 hours or longer. Yet, cases have been reported with smaller dosage schemes given for only 3 hours.

It was first described in children, but subsequently has been observed in critically ill adults

The clinical features of propofol infusion syndrome are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit >10 mmol/
L−1), rhabdomyolysis, hyperlipidemia, and enlarged or fatty liver. Other features include cardiomyopathy with acute cardiac failure, skeletal myopathy, hyperkalemia, hepatomegaly, and lipemia.

The symptoms and signs are the result of muscle injury and of the release of intracellular toxic contents.

The major risk factors for its development are poor oxygen delivery, sepsis, serious cerebral injury, and large propofol dosage.

Predisposing factors for the propofol infusion syndrome are likely genetic disorders impairing fatty acid metabolism, such as medium-chain acyl CoA (MCAD) deficiency and low carbohydrate supply.

Because lipemia has been noted, a failure of hepatic lipid regulation, possibly related to poor oxygenation or a lack of glucose, may be
the cause. In some cases, an increasing lipemia was the first
indication of impending propofol infusion syndrome onset,
so lipemia is a sign

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29
Q

Barbiturates are hypnotically active drugs that are derivatives of … (2,4,6-trioxohexahydropyrimidine), a hypnotically inactive pyrimidine nucleus that is formed by the condensation of malonic acid and urea.

The two major classes of barbiturates are the … with either an … at position 2 or with a … in position 2, respectively.

A

barbituric acid

oxybarbiturates and thiobarbiturates

oxygen

sulfur

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30
Q

Barbiturates cannot be reconstituted with … solution or mixed with other acidic solutions, as a decrease in the alkalinity of
the solution can result in …

A

lactated Ringer

precipitation of the barbiturates as free acids

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31
Q

Examples of drugs that are not to be coadministered or mixed in solution with the barbiturates are …

A

atracurium, vecuronium, rocuronium, suxamethonium, alfentanil, sufentanil, dobutamine, dopamine, esketamine, and midazolam

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32
Q

The barbiturates (with the exception of …) are metabolized … .

The metabolites are almost all inactive, water-soluble, and excreted in …

A

phenobarbital

hepatically

the urine

  • Renal excretion accounts for 60% to 90% of phenobarbital excretion in an unchanged form
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33
Q

Which disease does contraindicate the use of barbiturates? Explain

A

The hepatic enzyme induction by barbiturates is the reason that they are not recommended for administration to patients with acute intermittent porphyria.
Barbiturates may precipitate an attack by stimulating γ-aminolevulinic acid synthetase, the enzyme responsible for the production of porphyrins

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34
Q

Describe a form to increase de renal excretion of phenobarbital

A

Aalkalinization of urine with bicarbonate

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35
Q

In which kinetics type thiopental is metabolized?

A

In usual doses (4-5 mg/kg), thiopental exhibits first-order kinetics (i.e., a constant fraction of drug is cleared from the body per unit time); however, at very high doses of thiopental (300-600 mg/kg) with receptor saturation, zero-order kinetics occur (i.e., a constant amount of drug is cleared per unit time)

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36
Q

Mechanism of action of barbiturates

A

The mechanisms of action of barbiturates on the CNS are largely unknown, with the exception of their action on the GABAA receptor. Perhaps the NMDA receptors are involved with the effects of barbiturates.

At low concentrations barbiturates enhance the effects of GABA,
decreasing the rate of dissociation of GABA from its receptor and increasing the duration of GABA-activated chloride ion channel openings. This enhancement of the action of GABA is likely responsible for the sedative-hypnotic effects of the barbiturates. At larger concentrations, the barbiturates activate the chloride channels directly, without the binding of GABA, acting as the agonist itself.

The second mechanism of action of barbiturates involves the inhibition of the synaptic transmission of excitatory neurotransmitters, such as glutamate and acetylcholine. The actions of the barbiturates to block excitatory CNS transmission are specific for synaptic ion channels. Thiopental, however, may exert GABA-independent effects on the glutaminergic-NMDA system

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37
Q

Clinically, patients awake from a single dose of thiopental … minutes after administration, as the drug is redistributed from highly
perfused CNS tissues to well-perfused lean tissues

A

5 to 10

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37
Q

The ventilatory pattern with thiopental induction has been
described as …

A

“double apnea,” that is an initial apnea of a few seconds occurring upon drug administration, succeeded by a few breaths of reasonably adequate tidal volume, which is followed by a more prolonged period of apnea, typically of approximately 25 seconds. This apnea occurs in at least 20% of cases

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37
Q

Cardiovascular depression from barbiturates is a result of …

A

central and peripheral (direct vascular and cardiac) effects.

The primary cardiovascular effect of a barbiturate during induction of anesthesia is peripheral vasodilation causing a pooling of blood in the venous system.

Mechanisms for the decrease in cardiac output include (1) direct negative inotropic action, due to a decrease of calcium influx into the cells, (2) decreased ventricular filling, due to increased capacitance, and (3) transiently decreased sympathetic outflow from the CNS

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38
Q

Heart rate changes after thiopental administration

A

The increase in heart rate (10% to 36%) that accompanies thiopental administration probably results from the baroreceptor-mediated sympathetic reflex stimulation of the heart in response to the decrease in output and pressure

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39
Q

Describe the side effects of injecting barbiturates

A

The side effects of injecting barbiturates include a garlic or onion taste (40% of patients), allergic reactions, local tissue irritation, and rarely, tissue necrosis.
Thiopental and thiamylal produce fewer excitatory symptoms with induction than methohexital, which produces cough, hiccups, tremors, and twitching.

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40
Q

Treatment of accidental arterial injection of barbiturates

A

(1) dilution of the drug by the administration of saline into the artery, (2) heparinization to prevent thrombosis
(3) brachial plexus block.

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41
Q

In human hepatocyte culture, phenobarbital acts as an inducer of the … enzymes

A

CYP2B6, CYP2C9, CYP2C19, and CYP3A4

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42
Q

Recommended Doses of Barbiturates for Anesthesia Induction and Maintenance

A

Thiopental:
- Drug Induction Dose (mg/kg)*: 3-4 mg/kg
- Onset (s): 10-30 s
- Intravenous Maintenance Infusion: 50-100 mg every 10-12min

Methohexital:
- Drug Induction Dose (mg/kg)*: 1-1.5 mg/kg
- Onset (s): 10-30 s
- Intravenous Maintenance Infusion: 20-40 mg every 4-7 min

43
Q

Research is ongoing to elucidate the neural mechanism of the reward-related effects of benzodiazepines. Reynolds and associates conclude in their findings that …subunit–containing GABAA receptors are implicated as key mediators of the reward-related effects of benzodiazepines

A

α2- and α3-

44
Q

Elimination half-life (h) of midazolam and diazepam

A

midazolam 1,7 - 3,5 h

diazepam 20 - 50 h

45
Q

Describe the metabolization of midazolam

A

Midazolam is metabolized by CYP3A4 and CYP3A5 to 1-hydroxymethylmidazolam (= α-hydroxymidazolam) and 4-hydroxymidazolam.175 These metabolites possess similar sedative activities compared to the parent compound and, when given over a longer time, these metabolites may accumulate.

The metabolites are cleared more rapidly than midazolam itself, making them of little concern in patients with normal hepatic and renal function. In patients with renal impairment, though, they can cause profound sedation

46
Q

Describe the metabolization of diazepam

A

Metabolism occurs in the liver and is mediated mainly by CYP2C19 and CYP3A4. This accounts for 80% of the biotransformation of diazepam.
The metabolite N-desmethyldiazepam has pharmacodynamic characteristics similar to those of diazepam, but has a much slower
elimination half-life extending to 200 hours. N-desmethyldiazepam
is further metabolized to oxazepam, which is also pharmacologically active

47
Q

All benzodiazepines have hypnotic, sedative, anxiolytic, amnesic, anticonvulsant, and centrally produced muscle-relaxing properties

T or F

A

T

48
Q

For use as a premedication for pediatric patients, midazolam is available in several preparations (including a formulation for intranasal administration in some countries) and well tolerated. The dose is effective from … mg/kg and produces sedation and anxiolysis in 10 to 20 minutes

A

0.025

49
Q

The usual induction dose of midazolam is …mg/kg in premedicated patients, and up to … in unpremedicated patients. The onset of anesthesia is within …

The half-time of equilibrium between the plasma concentration and the EEG effects is about …

A

0.1 to 0.2

0.3 mg/kg

30 to 60 seconds

2 to 3 minutes

50
Q

The amnesic period after an anesthetic dose of benzodiazepine is about …

A

1 to 2 hours

51
Q

Midazolan doesn’t contribute to the prevention of PONV.

T or F

A

F

Numerous studies have highlighted the role that benzodiazepines, and specifically midazolam, may play in the prevention of PONV. A recent meta-analysis on the effect of intravenous midazolam on PONV concludes a significant decrease in overall PONV and rescue antiemetic drug. Jung and colleagues found that in women undergoing middle ear surgery, IV midazolam, 0.075 mg/kg after induction of anesthesia, reduced the incidence of PONV and the need for rescue antiemetics with no difference from placebo in pain
intensity or drowsiness.

52
Q

The most significant side effect with midazolam is respiratory depression. The major side effects of lorazepam and diazepam in addition to respiratory depression are …

A

venous irritation and thrombophlebitis, problems related to aqueous insolubility and requisite solvents

53
Q

The plasma half-life of flumazenil is about …

A

1 hour

54
Q

Doses of flumazenil

A

Reversal of benzodiazepines: 0.2 mg repeated up to 3 mg

Diagnosis in coma: 0.5 mg repeated up to 1 mg

55
Q

Ketamine is a racemic mixture of the isomers R(-)-ketamine and S(+)-ketamine. It usually does not depress the cardiovascular and respiratory systems, but it does possess some of the adverse psychological effects found with the other phencyclidines.

The …isomer (Ketanest) is 3 to 4 times more potent as an analgesic with a faster clearance and recovery and with fewer psychomimetic side effects. Still, … produces — besides analgesia — psychotropic effects

A

S(+)

S(+)-ketamine

56
Q

Describe the metabolization ok ketamine

A

Ketamine is metabolized by hepatic microsomal enzymes. The major pathway involves N-demethylation to form norketamine (metabolite I), which is then hydroxylated to hydroxynorketamine, which is further conjugated to water-soluble glucuronide derivates and excreted in the urine. The activity of the principal metabolites of ketamine has not been well studied, but norketamine (metabolite I)
has significantly less (20%-30%) activity than the parent compound

57
Q

Elimination Half-Life (h) of Ketamine

A

2,5 - 2,8 h

58
Q

Patients anesthetized with ketamine have profound analgesia, but keep their eyes open and maintain many reflexes. Corneal, cough,
and swallow reflexes are present and have keep they protective effects

T or F

A

F

Patients anesthetized with ketamine have profound analgesia, but keep their eyes open and maintain many reflexes. Corneal, cough,
and swallow reflexes all may be present, but should not be assumed to be protective

59
Q

Bioavailability of ketamina via oral and via intranasal

A

The bioavailability via oral administration is 20% to 30%, and via the intranasal route is approximately 40% to 50%.

60
Q

Because ketamine has a low molecular weight, a pKa near the physiologic pH, and relatively high lipid solubility, it crosses the blood-brain barrier rapidly and has an onset of action within … of administration. The maximal effect occurs in about …

A

30 - 60 seconds

1 minute

61
Q

Signs that can be present after administration of ketamine

A

Pupils dilate moderately, and nystagmus occurs. Lacrimation and salivation are common, as is increased skeletal muscle tone, often with coordinated but seemingly purposeless movements of the
arms, legs, trunk, and head

62
Q

The duration of ketamine anesthesia after a single IV administration of a general anesthetic dose (2 mg/kg) is … ,and full orientation to person, place, and time occurs within …

A

10 to 15 minutes

15 to 30 minutes

63
Q

The … enantiomer enables quicker recovery (by a couple of minutes) than the racemic mixture.
This is due to …

A

S(+)

the smaller dose necessary to produce an equianesthetic effect and to the 10% faster hepatic biotransformation

64
Q

Mechanismo of action of ketamine

A

Ketamine acts at multiple receptors including the NMDAR, opioid receptors, and monoaminergic receptors.

At high ketamine concentrations, sigma opioid receptors are also affected, muscarinic receptors are blocked, and GABAergic neurotransmission is facilitated.

Its most important action is the inhibition of NMDAR-mediated
glutamergic input to the GABAergic system leading to a changing excitatory activity in the cortex and limbic system that in the end results in unconsciousness.

At the spinal cord level, ketamine has potent antinociceptive effects
on NMDAR and inhibits acetylcholine release

65
Q

The primary site of CNS action of ketamine seems to be the …

The drug selectively depresses neuronal function in …, while stimulating parts of the …

This process creates what is termed a …

A

thalamoneocortical projection system

parts of the cortex (especially association areas) and thalamus

limbic system, including the hippocampus

functional disorganization of nonspecific pathways in midbrain and thalamic areas

66
Q

ketamine effects on the perfusion and metabolic rate of the CNS

A

Ketamine increases cerebral metabolism, CBF, and ICP. Because of its excitatory CNS effects, which can be detected by generalized EEG development of theta wave activity and by petit mal seizure-like activity in the hippocampus, ketamine increases CMRO2. There is an increase in CBF, which appears higher than the increase in CMRO2 would mandate. With the increase in CBF and the generalized increase in sympathetic nervous system response, there is an
increase in ICP after ketamine.

67
Q

Describe the emergence reactions associated with ketamine

A

Ketamine, similar to other phencyclidines, produces undesirable psychological reactions, which occur during awakening from ketamine anesthesia and are termed emergence reactions. The common manifestations of these reactions, which vary in severity and classification, are vivid dreaming, extracorporeal experiences (sense of floating out of body), and illusions (misinterpretation of a real, external sensory experience). These incidents of dreaming
and illusion are often associated with excitement, confusion,
euphoria, and fear.

68
Q

Ketamine effects on the respiratory system

A

Ketamine has minimal effects on the central respiratory drive as reflected by an unaltered response to carbon dioxide. There can be a transient (1-3 minutes) decrease in minute ventilation after the bolus administration of an induction dose of ketamine (2 mg/kg intravenously). Unusually large doses can produce apnea, but this is seldom seen. With the use of adjuvant sedatives or anesthetic drugs, respiratory depression may become clinically significant.

Ketamine depresses ventilatory control in children especially with bolus doses. Ketamine is a bronchial smooth muscle relaxant.

A potential respiratory problem, especially in children, is the increased salivation that follows ketamine administration, which can be modulated by an anticholinergic drug such as atropine or
glycopyrolate

69
Q

Ketamine effects on the cardiovascular system

A

Ketamine increases arterial blood pressure, heart rate, and cardiac output in a biphasic manner. It produces a direct cardiodepressive, negative inotropic effect next to an indirect stimulatory effect due to activation of the sympathetic system. Ketamine causes the systemic release of catecholamines, inhibition of the vagal nerve, inhibition of norepinephrine reuptake at peripheral nerves and non-neuronal
tissues such as the myocardium, and norepinephrine release from sympathetic ganglia. Cardiodepression precedes stimulation after large-dose ketamine administration or occurs after repeated administrations when presynaptic catecholamine stores become depleted.

Whereas the cardiovascular stimulatory effects of ketamine generally are dominant, after termination of S-ketamine infusion, cardiovascular depression may become evident as cardiac output may decrease below pre-infusion values

70
Q

Uses and Doses of Ketamine

A

Induction of general anesthesia:
- 0.5-2 mg/kg IV
- 4-6 mg/kg IM

Maintenance of general anesthesia
- 0.5-1 mg/kg IV with N2O 50% in O2
- 15-45 μg/kg/min IV with N2O 50%-70% in O2
- 30-90 μg/kg/min IV without N2O

Sedation and analgesia
- 0.2-0.8 mg/kg IV over 2-3 min
- 2-4 mg/kg IM

Preemptive or preventive analgesia
0.15-0.25 mg/kg IV

71
Q

Because ketamine’s preservative—…— is neurotoxic, this formulation of ketamine for subarachnoid or epidural administration is contraindicated. S(+) ketamine is available in a preservative-free
solution. The FDA has not approved the use of intrathecal
or epidural ketamine

A

chlorobutanol

72
Q

Etomidate has a pKa of 4.2 and is hydrophobic at physiologic pH. To increase its solubility it is formulated as a 0.2% solution either in 35% …

A

propylene glycol

73
Q

Mechanism of action of etomidate

A

The primary action of etomidate on the CNS is through the GABAA receptor and results in hypnosis, which is achieved in one arm–brain circulation after a normal induction dose (0.3 mg/kg).

The mechanism by which etomidate produces hypnosis is almost exclusively through GABAA receptor facilitation. This includes two effects produced by different concentrations of etomidate:
- The first is the positive modulation of the GABAA receptor: activation of the receptor by agonists at concentrations associated
with clinical doses. A lower dose of GABA is required in the presence of etomidate to activate the GABAA receptor;
- The second action is called the direct activation or allosteric agonism. In supraclinical concentrations etomidate can directly, thus in absence of GABA, activate the GABAA receptor

74
Q

Etomidate effects on the respiratory system

A

Etomidate has less effect on ventilation than other anesthetics used to induce anesthesia. It does not induce histamine release in healthy patients or in patients with reactive airway disease. Ventilatory response to carbon dioxide is depressed by etomidate, but the ventilatory drive at any given carbon dioxide tension is greater than that following an equipotent dose of methohexital. Induction
with etomidate produces a brief period of hyperventilation, sometimes followed by a similarly brief period of apnea, which results in a slight (±15%) increase in PaCO2, but no change in the partial pressure of arterial oxygen (PaO2).

75
Q

The hemodynamic stability seen with etomidate is due to …

A

its lack of effect on the sympathetic nervous system and on
the function of the baroreceptor.
Etomidate acts as an agonist at alpha2-adrenoceptors, which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure

76
Q

Etomidate effects on the endocrine system

A

The specific endocrine effects manifested by etomidate are a dose-dependent reversible inhibition of the enzyme 11β-hydroxylase, which results in decreased biosynthesis of cortisol. The blockade of the cytochrome P450-dependent enzyme 11β-hydroxylase also results in decreased mineralocorticoid production and an increased
formation of intermediaries (11-deoxycorticosterone).

The etomidate concentrations associated with adrenal cortical suppression are less than 10 ng/mL, which are much lower than the concentrations needed for hypnosis (more than 200 ng/mL).

Etomidate is associated with suppression of adrenal steroidogenesis,
which can last up to 72 hours.

77
Q

Etomidate is most appropriate in patients with …

A

cardiovascular disease, reactive airway disease, intracranial hypertension, or any combination of disorders indicating the
need for an induction agent with limited or beneficial physiologic
side effects

78
Q

Etomdiate effects on the CNS perfusion

A

At a dose of 0.2 to 0.3 mg/kg, etomidate reduces CBF by 34% and CMRO2 by 45% without altering MAP. CPP is maintained or increased, and there is a beneficial net increase in the cerebral oxygen supply-to-demand ratio

79
Q

Induction of anesthesia with etomidate is an independent risk factor in the development of an emergence delirium
T or F

A

T

80
Q

Etomidate effects on seizures

A

Etomidate has been associated with grand mal seizures and produces increased EEG activity in epileptogenic foci. This feature has proven useful for intraoperative mapping of seizure foci before surgical ablation

81
Q

Although etomidate causes adrenal suppression, it should not be used as a therapeutic measure in cases of endogenous hypercortisolism

T or F

A

F

Etomidate has a special place in the treatment of endogenous hypercortisolemia. It is proven to be an effective parenteral treatment for this indication. In patients with unstable hemodynamics, patients with a sepsis, or patients with a psychosis, treatment should be performed under intensive care conditions

82
Q

Although etomidate provides stable hemodynamics and minimal respiratory depression, it is associated with several adverse effects when used for induction, including …

A

PONV, pain on injection, myoclonic movement, and hiccups.

OBS.: More recently, etomidate in a lipid emulsion was associated with an equal or an increased incidence of postoperative nausea compared with propofol. The lipid formulation of etomidate is associated with a much less frequent incidence of pain on injection, thrombophlebitis, and histamine release

83
Q

How to reduce the myoclonus caused by etomidate?

A

premedication with a hypnotic like midazolam or a small dose of magnesium 60 to 90 seconds before the induction dose of etomidate is given

84
Q

Dexmedetomidine is the …enantiomer of …

A

S

medetomidine

85
Q

Metabolismo of dexmedetomidene

A

Dexmedetomidine undergoes almost complete biotransformation
with very little unchanged dexmedetomidine excreted in urine and feces. Biotransformation involves both direct glucuronidation as well as cytochrome P450–mediated metabolism. The major metabolic pathways of dexmedetomidine are: direct N-glucuronidation to inactive metabolites, hydroxylation (mediated primarily by
CYP2A6), and N-methylation

86
Q

Which weight use to calculate de dexmedetomidine dose?

A

the bodyweight adjustment dosing that is currently applied is only justified in a non-obese population. For obese patients, fat-free mass may be more appropriate

87
Q

Dexmedetomidine dose adjustment in hepatic insufficiency

A

Child-Turcotte-Pugh class A and B: No dosage adjustment necessary

Child-Turcotte-Pugh class C: General anesthesia, ICU sedation: Use lowest end of the recommended dosage range; titrate to desired effect

  • From UpToDate
88
Q

The elimination half-life of dexmedetomidine is …, with a context-sensitive half-time ranging from … after a 10-minute infusion to … after an 8-hour infusion

A

2 to 3 hours

4 minutes

250 minutes

89
Q

Describe the different physiologic functions of α2 adrenoreceptors subtypes

A

α2A:
* Presynaptic feedback inhibition of norepinephrine release
* Hypotension
* Analgesia
* Sedation
* Inhibition of epileptic seizures

α2B:
* Hypertension
* Placental angiogenesis
* Hypertensive effect of etomidate
* Analgesic effect of nitrous oxide

α2C:
Feedback inhibition of adrenal
catecholamine release
* Analgesic effect of moxonidine
* Modulation of behavior

90
Q

The α2A adrenoreceptors are primarily distributed in …,
whereas α2B and α2C are in …

A

the periphery

the brain and spinal cord

91
Q

Postsynaptically located α2 adrenoreceptors in peripheral blood vessels produce …, whereas presynaptic α2 adrenoreceptors …, potentially attenuating the …

A

vasoconstriction

inhibit the release of norepinephrine

vasoconstriction

92
Q

The overall response to α2 adrenoreceptor agonists is related to
the stimulation of α2 adrenoreceptors located in …

These receptors are involved in the … effects of α2 adrenoreceptors

A

the CNS and spinal cord

sympatholysis, sedation, and antinociceptive

93
Q

The α2 agonists have the advantage that their effects are readily reversible by α2-adrenergic antagonists (e.g., …)

A

atipamezole

OBS.: Atipamezole is currently not approved for use in humans

94
Q

The α2 agonists produce their sedative-hypnotic effect by an action on α2 receptors in the … and an analgesic action at α2 receptors within the …

A

locus caeruleus

locus caeruleus and within the spinal cord

95
Q

Dexmedetomidine induces sedation through in a similar way to propofol

T or F

A

F

Dexmedetomidine induces sedation through different receptors than the sedative drugs propofol or benzodiazepines, which exert
their action through the GABA system. The sedative effect of dexmedetomidine acts through the endogenous sleep-promoting
pathways, generating natural sleep patterns. Dexmedetomidine has been shown to induce a non–rapid eye movement sleeping pattern (NREM)

96
Q

How does dexmedetomidine induce a non-REM sleeping pattern?

A

The stimulation of the locus caeruleus (LC) by dexmedetomidine releases the inhibition the LC has over the ventrolateral preoptic nucleus (VLPO). The VLPO subsequently releases γ-aminobutyric acid (GABA) onto the tuberomammillary nucleus (TMN). This inhibits the release of the arousal-promoting histamine on the cortex and forebrain, inducing the loss of consciousness

97
Q

Dexmedetomidine is associated with delirium

T or F

A

F

The number of patients experiencing delirium in the ICU is significantly lower when sedated with dexmedetomidine, compared to propofol or lorazepam, or midazolam

98
Q

The analgesic effect of the α2 agonists is mediated through stimulation of the α2C and α2A receptor in …, directly suppressing pain transmission by reducing the release of …

A

the dorsal horn

pronociceptive transmitters, substance P and glutamate, and hyperpolarization of interneurons

99
Q

Dexmedetomidine role in neurosurgery

A

Dexmedetomidine has been used in neurosurgical procedures involving neurophysiologic monitoring. Cortical evoked potentials, amplitudes, and latencies were minimally affected when using dexmedetomidine intraoperatively. It may also be suitable as an anesthetic adjunct during seizure surgery, since the epileptiform activity of seizure foci was not reduced by dexmedotomidine

100
Q

Dexmedetomidine effects on de cardiovascular system

A

Ebert and colleagues performed a study in volunteers using a target-controlled infusion system to provide increasing concentrations (0.7 to 15 ng/mL) of dexmedetomidine. The lowest two concentrations produced a decrease in MAP (13%) followed by progressive increase (12%). Increasing concentrations of dexmedetomidine also produce
progressive decreases in heart rate (maximum 29%) and cardiac output (35%).

The most commonly reported hemodynamic adverse reactions associated with dexmedetomidine in a phase III trial in 401 patients were hypotension (30%), hypertension (12%), and bradycardia (9%). The initial increase in arterial blood pressure is probably due to the vasoconstrictive effects of dexmedetomidine when stimulating peripheral α2 receptors.

101
Q

As a premedicant, dexmedetomidine, at IV doses of … given … minutes before surgery, seems efficacious, while minimizing the cardiovascular side effects of hypotension and bradycardia.

Dexmedetomidine has a high bioavailability when administered nasally or buccally. This improves compliance and absorption in younger children. A dose of … , … hour before surgery is safe
and effective

A

0.33 to 0.67 μg/kg

15

3 to 4 μg/kg

1

102
Q

A recent study shows that dexmedetomidine may be advantageous by improving the quality of emergence from general anaesthesia in avoiding coughing, agitation, hypertension, tachycardia, and shivering. This may be achieved by administration of dexmedetomidine … μg/kg intravenously at the end of surgery. Time to extubation is not prolonged.

A

1

103
Q

Dexmedetomidine increase salivation, intraocular pressure and the shivering threshold

T or F

A

F

Dexmedetomidine may produce dry mouth due to a decrease in salivation. Furthermore, dexmedetomidine decreases intraocular pressure and decreases the shivering threshold

104
Q

The use of neuroleptanesthesia has largely disappeared in modern
anesthetic practice. The primary use of droperidol in anesthesia has been as an … and to a lesser extent as a …

A

antiemetic

sedative and antipruritic (for pruritus secondary to opioid)

105
Q

Droperidol is a …, a fluorinated derivative of phenothiazines.
iT produces CNS depression, characterized by marked apparent tranquility and cataleptic immobility and are potent antiemetics. Droperidol is potent, and, similar to the others, it produces its action centrally at sites where … act.

In particular, droperidol results in a submaximal inhibition of the GABAA α1, β1, and γ2 acetylcholine receptors and full inhibition of α2 acetylcholine receptors. This submaximal inhibition of GABA receptors by droperidol may explain the … that may occur with its administration

A

butyrophenone

dopamine, norepinephrine, and serotonin

anxiety, dysphoria, and restlessness

106
Q

Similar to most antipsychotics, droperidol may …

A

prolong the QT interval by delaying myocardial repolarization and precipitating torsades de pointes

107
Q

Use of droperidol today in the perioperative period is largely restricted to its antiemetic and sedative effects. It is an effective
antiemetic; the dose for this use ranges from …

A

10 to 20 μg/kg IV (typically 0.6-1.25 mg for a 70-kg individual)

Millers Anesthesia (15 decks)

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