Stoelting Study 4

Front 1

2. What type of chemical structure is propofol?

Back 1

2. Propofol is a lipid-soluble isopropyl phenol formulated as an emulsion. The current fonnulation consists of 1 % propofol, soybean oil, glycerol, and purified egg phosphatide.

Front 2

3. What is the mechanism of action of propofol?

Back 2

3. The mechanism by which propofol exerts its effects is not fully understood, but it appears to be in part via the gamma-aminobutyric acid (GAB A) activated chloride ion channel. Evidence suggests that propofol may interact with the GABA receptor and maintain it in an activated state for a prolonged period, thereby resulting in greater inhibitory effects on synaptic transmission. Propofol may also inhibit the NMDA subtype of the glutamate receptor. (58; 2SI)

Front 3

4. How is propofol cleared from the plasma?

Back 3

4. Propofol is cleared rapidly from the plasma through both redistribution t( inactive tissue sites and rapid metabolism by the liver. (:

Front 4

5. What degree of metabolism does propofol undergo? How should the dose of propofol be altered when administered to patients with liver dysfunction?

Back 4

5. Propofol is extensively metabolized by the liver to inactive, water-soluble metabolites, which are then excreted in the urine. Less than 1 % of propofol administered is excreted unchanged in the urine. The metabolism of propofol is extremely rapid. Patients with liver dysfunction appear to rapidly metabolize propofol as well, lending some proof that extrahepatic sites of metabolism exist. This has been further supported by evidence of metabolism during the anhepatic phase of liver transplantation.

Front 5

6. What is the context-sensitive half-time of propofol relative to other intravenous anesthetics? What is the effect-site equilibration time of propofol relative to other intravenous anesthetics?

Back 5

6. The context-sensitive half-time refers to the time required to pass for the concentration of a particular drug to reach 50% of its peak plasma concentration after the discontinuation of its administration as a continuous intravenous infusion for a given duration. The context-sensitive half-time of a drug depends mostly on the drug's lipid solubility and clearance mechanisms. The continuous infusion of propofol rarely results in cumulative drug effects. After the continuous administration of propofol for several days for sedation in the intensive care unit the discontinuation of the infusion resulted in the rapid recovery to consciousness. The lack of cumulative effects of propofol illustrates that the context-sensitive half-time of propofol is short.

Front 6

7. How does the emergence from a propofol anesthetic or propcfol induction differ from the emergence seen with the other induction agents?

Back 6

7. After the administration of propofol, patients experience a rapid return to consciousness with minimal residual central nervous system effects. Patients who are to undergo brief procedures or outpatient surgical patients may espedally benefit from the rapid wake-up associated with propofol anesthesia. Propofol also tends to result in the patient awakening with a general state of well-being and mild euphoria. Patient excitement has also been observed. Hallucinations and sexual fantasies have been reported to have occurred in association with the administration of propofol.

Front 7

8. How readily does propofol cross the placenta? What effects does it have on the neonate when administered to a parturient?

Back 7

8. Propofol readily crosses the placenta, but it has minimal effects on the neonate Jecause it is rapidly cleared from the neonatal circulation. (60)

Front 8

9. How does propofol affect the cardiovascular system?

Back 8

9. The administration of an induction dose of propofol results in a decrease in systolic blood pressure by 25% to 40% and a decrease in cardiac output by about 15%. These effects of propofol appear to be due to both direct myocardial depression and vasodilation, which are dose dependent. The cardiovascular effects produced by propofol are similar to, but more pronounced than, those 'j produced by barbiturates. Unlike the barbiturates, the heart rate is usually unchanged with the administration of propofol. Propofol may selectively decrease sympathetic nervous system activity more than parasympathetic nervous system activity.

Front 9

10. How does propofol affect ventilation?

Back 9

10. The administration of an induction dose of propofol (1.5 to 2.5 mglkg) almost always results in apnea through a dose-dependent depression of ventilation in a manner similar to, but more prolonged than, that of thiopental. The apnea that results appears to last for 30 seconds or greater and is followed by a return of ventilation that is characterized by rapid, shallow breathing such that the minute ventilation is significantly decreased for up to 4 minutes. (60; 252-253)

Front 10

11. How does propofol affect the central nervous system?

Back 10

11. The administration of propofol results in decreases in intracranial pressure, cerebral blood flow, and cerebral metabolic oxygen requirements in a dosedependent manner. In patients with an elevated intracranial pressure the administration of propofol may be accompanied by undesirable decreases in the cerebral perfusion pressure, however.

Front 11

12. How does propofol affect the seizure threshold?

Back 11

12. The effects of propofol on the seizure threshold are controversial. The administration of propofol has resulted in seizures and opisthotonos and has been used to facilitate the mapping of seizure foci. Propofol has also been used to treat seizures. High doses of propofol can result in burst suppression on the elecrroencephalogram

Front 12

13. What is the relationship between propofol and nausea and vomiting?

Back 12

13. Propofol appears to have a significant antiemetic effect, given the low incidence of nausea and vomiting in patients who have received a propofol anesthetic. In addition, propofol administered in subhypnotic doses of 10 to 15 mg has successfully treated both postoperative nausea and vomiting and nausea in patients receiving chemotherapy.

Front 13

14. How is propofol administered for sedation?

Back 13

14. Propofol may be administered for sedation through a continuous intravenous infusion at a rate of 25 to 100 f.Lglkglmin. At these doses propofol will provide sedation and amnesia without hypnosis. I

Front 14

15. How is propofol administered for maintenance anesthesia?

Back 14

15. Propofol may be administered for maintenance anesthesia through a continuous Intravenous infusion at a rate of 100 to 200 j.Lglkglmin. The clinician may use signs of light anesthesia such as hypertension, tachycardia, diaphoresis, or skeletal muscle movement as indicators for the need to increase the infusion rate of propofol. For procedures lasting more than 2 hours, the use of propofol for maintenance anesthesia may not be cost effective.

Front 15

16. How can the pain associated with the intravenous injection of propofol be attenuated?

Back 15

16. The injection of propofol intravenously can cause pain in awake patients. The pain can be attenuated by using large veins for its administration, or with the prior administration of lidocaine at the injection site. Alternatively, lidocaine · may be mixed with the propofol for simultaneous infusion. (

Front 16

17. Why is asepsis important when handling propofol?

Back 16

17. Asepsis is important when handling propofol because the solvent for propofol, Intralipid, provides for a favorable culture medium for bacterial growth. Ethylenediaminetetraacetic acid has been added to the propofol formulation in the United States in an attempt to suppress bacterial growth. (

Front 17

18. Which patients may be at risk for a life-threatening allergic reaction to propofol?

Back 17

18. Patients at risk for a life-threatening allergic reaction to propofol are those with a history of atopy or allergy to other drugs that also contain a phenyl nucleus or isopropyl group. Anaphylactoid reactions to the propofol itself and separate from the lipid emulsion have been reported.

Front 18

.9. Name some of the barbiturates. From what chemical compound are they derived?

Back 18

19. Thiopental is the most commonly used barbiturate in the practice of anesthesia. Other barbiturates include secobarbital, pentobarbital, thiamylal, and methohexital. The barbiturate compounds are a derivative of barbituric acid. Structural alterations ot: two of the carbon atoms of barbituric acid result in the barbiturates used in clinical practice. Historically, the barbiturates had been classified as short-acting or long-acting agents. This method of classification is no longer used because of the erroneous implication that the duration of action is predictable for a given agent

Front 19

20. What is the mechanism of action of barbiturates?

Back 19

20. The mechanism of action of barbiturates is based on their ability to enhance : and mimic the action of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system. GABA is the main inhibitory neurotransmitter in the central nervous system. Barbiturates bind to the GABA receptor and increase the duration of activity of the GABA receptor, such that the chloride ion influx into the cells is prolonged. The chloride ion hyperpolarizes the cell and inhibits postsynaptic neurons. At higher concentrations the chloride ion channel may be stimulated by the barbiturate alone even in the absence of GABP

Front 20

21. How are barbiturates cleared from the plasma?

Back 20

21. Barbiturates are cleared from the plasma primarily through its rapid redistribution to inactive tissue sites after its administration as a bolus.

Front 21

22. What degree of metabolism do barbiturates undergo?

Back 21

22. Barbiturates are eliminated from the body through hepatic metabolism. Less than 1 % of the drug is excreted unchanged by the kidneys. (

Front 22

23. What is the context-sensitive half-time of barbiturates relative to other intravenous anesthetics? What is the effect-site equilibration time of barbiturates relative to other intravenous anesthetics?

Back 22

23. Barbiturates are most often used for the intravenous induction of general anesthesia. Maximal brain uptake and onset of effect takes place within 30 I seconds after the rapid intravenous injection of a barbiturate. Rapid awakening follows the administration of an induction dose of a barbiturate secondary to the rapid redistribution of these drugs. This accounts for the short effect-site equilibration time for these agents. The duration of action of barbiturates after its intravenous injection is dictated by its redistribution from the plasma to inactive sites. Large or repeated doses of the lipid-soluble barbiturates can result in saturation of the inactive sites. This may lead to the accumulation of drug and to prolonged effects of the usually short-acting drugs. The context-sensitive half-time of barbiturates is thus prolonged.

Front 23

25. How do barbiturates affect the arterial blood pressure?

Back 23

25. The administration of barbiturates typically results in a decrease in blood pressure by 10 to 20 mm Hg. This decrease in blood pressure primarily results from peripheral vasodilation. The vasodilation that accompanies the administration of barbiturates is due to a combination of depression of the vasomotor center in the medulla and a decrease in sympathetic nervous system 'I outflow from the central nervous system. Exaggerated blood pressure decreases lay be seen in patients who are hypertensive, whether or not they are being I treated by antihypertensives. The administration of barbiturates should also be undertaken with caution in patients who are dependent on the preload to the , heart to maintain cardiac output, as in patients with ischemic heart disease, ,ericardial tamponade, congestive heart failure, heart block, or hypovolemia.

Front 24

26. How do barbiturates affect the heart rate?

Back 24

26. The administration of barbiturates results in an increase in heart rate. This increase in heart rate is thought to be due to a baroreceptor-mediated reflex response to the decrease in blood pressure caused by the administration of the barbiturate. The increase in heart rate may increase myocardial oxygen requirements during a time when significant decreases in blood pressure may decrease coronary artery blood flow as well. Given this, the administration of a barbiturate to patients with ischemic heart disease must be done with extreme caution. Although the administration of barbiturates typically results in an increase in heart rate, the cardiac output may be decreased. This is in part due to the direct myocardial contractile depression that results from the adrninistra- . tion of barbiturates. The effect of a decrease in cardiac output by barbiturates is not of such significance that it is frequently seen clinically, however.

Front 25

27. How do barbiturates affect ventilation?

Back 25

27. Barbiturates depress ventilation centrally by depressing the medullary ventilatory centers. This is manifest clinically as a decreased responsiveness to the ventilatory stimulatory effects of carbon dioxide. Depending on the dose administered, the patient will have a slow breathing rate and small tidal volumes to the extent that apnea follows. Typically, after an induction dose of barbiturate transient apnea will result and require controlled ventilation of the lungs. When spontaneous ventilation is resumed, it is again characterized by a slow breathing rate and small tidal volumes.

Front 26

28. How do barbiturates affect laryngeal and cough reflexes?

Back 26

28. Induction doses of thiopental alone do not reliably depress laryngeal and cough reflexes. Stimulation of the upper anway, as with the placement of an oral r~flexes. Stimulation of the upper airway, as with the placement of an oral is therefore recommended that adequate suppression of these reflexes be obmined before instrumenting the airway. This can be accomplished with increased doses of a barbiturate, by the administration of a neuromuscular blocking drug, or by the addition of another preoperative medicine, such as opioids, to augment the anesthetic effects of thiopental during stimulation of the upper airway.

Front 27

29. How do barbiturates affect the central nervous system? How do barbiturates affect an electroencephalogram?

Back 27

29. Barbiturates are potent cerebral vasoconstrictors. This results in a decrease in cerebral blood flow, a decrease in cerebral blood volume, a decrease in intracranial pressure, and a decrease in cerebral metabolic oxygen requirements. Barbiturates are also thought to depress the reticular activating system, which is believed to be important in maintaining wakefulness. Thiopental produces a dose-dependent depression of the electroencephalogram. A fiat electroencephalogram may be maintained with a continuous infusion of thiopental.

Examples of patients who may benefit from the administration of a barbiturate as an induction agent or as maintenance anesthesia include patients with space-occupying lesions or patients who have suffered head trauma

Front 28

30. How should thiopental be administered and dosed for cerebral protection in patients with persistently elevated intracranial pressures?

Back 28

30. In patients with persistently elevated intracranial pressures, barbiturates may be given intravenously in high doses to decrease the intracranial pressure. Barbiturates may offer some cerebral protection for patients with regional cerebral ischemia. Patients with global cerebral ischemia, such as from cardiac arrest, are not thought to derive any protection from the administration of barbiturates

Front 29

31. What are the various routes and methods for the administration of barbiturates in clinical anesthesia practice?

Back 29

31. There are various routes and methods for the administration of barbiturates in clinical anesthesia practice. For instance, the rapid intravenous administration of a bolus of barbiturate is indicated for a rapid sequence induction of anesthesia. The bolus of barbiturate should be immediately followed by the administration of succinylcholine or a nondepolarizing neuromuscular blocking drug to produce skeletal muscle paralysis and facilitate tracheal intubation under these conditions. Alternatively, small doses of intravenous thiopental, in the range of O. 5 to 1 mg/kg, may be administered to adult patients who have difficulty accepting the application of an anesthesia mask and/or the inhalation of a volatile anesthe

Front 30

32. What are some potential adverse complications of the injection of thiopental?

Back 30

32. Potential adverse complications of the injection of thiopental may result from accidental intra-arterial, subcutaneous, and even appropriate venous administration of thiopental. The accidental intra-arterial injection of barbiturates results in excruciating pain and intense vasoconstriction that can last for hours.

Front 31

33. What is the risk of a life-threatening allergic reaction to barbiturates?

Back 31

33. Life-threatening allergic reactions to barbiturates are rare. The risk has been estimated to be 1 in 30,000. I

Front 32

34. What type of structure is etomidate? What is its mechanism of action?

Back 32

34. Etomidate is an imidazole derivative. The mechanism by which etomidate exerts its effects is not completely understood. It appears that etornidate acts in part through agonist effects at the GABA receptor

Front 33

35. How is etomidate cleared from the plasma?

Back 33

S. The induction dose of etomidate is 0.3 mglkg. The administration of etomidate induction doses results in unconsciousness in less than 30 seconds. The duration of action of etomidate after an induction dose is very short, owing to its rapid clearance from the plasma through redistribution to inactive tissue sites.

Front 34

36. What degree of metabolism does etomidate undergo?

Back 34

36. Etomidate rapidly undergoes nearly complete ester hydrolysis to pharmacologically inactive metabolites by the liver, with less than 3% of the drug being excreted in the urine unchanged. (

Front 35

37. What is the context-sensitive half-time of etomidate relative to other intravenous anesthetics? What is the effect-site equilibration time of etomidate relative to other intravenous anesthetics?

Back 35

37. Like thiopental and propofol, etomidate is highly lipid soluble, which allows it to quickly cross the blood-brain barrier to exert its effects. This accounts for the short effect-site equilibration time for these agents. The context-sensitive half-time of etomidate may be prolonged if repeated or continuous doses of the drug result in saturation of the inactive sites. It is less likely than thiopental to accumulate and have prolonged effects, however.

Front 36

38. How does etomidate affect the cardiovascular system?

Back 36

38. The administration of etomidate provides cardiovascular stability in that induction doses of etomidate result in minimal changes in heart rate, mean arterial pressure, central venous pressure, stroke volume, or cardiac index. Minimal decreases in blood pressure may result from the administration of etomidate to hypovolemic patients. the cardiovascular stability associated with etomidate sets it apart from the other induction agents and is the basis for its usefulness as an induction agent in patients with limited cardiac reserve. When etomidate is administered to these patients it is important to realize that it does not have any analgesic effects. Supplemental agents need to be administered in conjunction with etcmidate to blunt the stimulatory effects of direct laryngoscopy.

Front 37

39. How does etomidate affect ventilation?

Back 37

39. The administration of etornidate alone appears to result in less depressant effects on ventilation than propofol or thiopental. The effects of etomidate on ventilation may be augmented when administered in combination with other anesthetics or opioids. (.

Front 38

40. How does etomidate affect the central nervous system?

Back 38

40. The administration of etomidate results in decreases in cerebral blood flow, intracranial pressure, and cerebral metabolic oxygen requirements. Etornidate has similar effects as barbiturates on the electroencephalogram as well, such that etomidate may be titrated to an isoelectric electroencephalogram to maximally decrease cerebral metabolic oxygen requirements. (t

Front 39

41. How does etornidate affect the seizure threshold?

Back 39

41. The administration of etomidate has been shown to increase the activity of seizure foci on an electroencephalogram. Etomidate is similar to methohexital in this regard. Its effects can be used intraoperatively to facilitate intraoperative mapping of seizure foci for surgical ablation. (

Front 40

42. What are the endocrine effects of etomidate?

Back 40

42. The administration of etomidate is associated with the suppression of adrenocortical function. The suppression of adrenocortical function may last for up to 8 to 20 hours after the induction dose of etomidate has been administered. The concern regarding this suppression of adrenocortical function is the potential for the adrenal cortex to be unresponsive to adrenocorticotropic hormone. Should the adrenal cortex be unresponsive to adrenocorticotropic hormone, desirable protective responses against the stresses that accompany the perioperative period may be prevented. No adverse outcomes have been shown to have occurred secondary to short-term adrenocortical suppression associated with the administration of etomidate, however.

Front 41

what are some potential negative effects associated with the administration of etomidate?

Back 41

43. Potential negative effects associated with the administration of etomidate include pain during intravenous injection, superficial thrombophlebitis, involuntary myoclonic movements, and an increased incidence of postoperative nausea and vomiting.

Front 42

44. What chemical compound is ketamine a derivative of? What is its mechanism of action?

Back 42

44. Ketamine is a derivative of phencyclidine. The administration of ketamine produces unconsciousness and analgesia that is dose related. The exact mechanism by which ketamine exerts its effects is unknown. Ketamine occupies some rusm oy Willcn KeUllIllne exens us errects IS unknown. Ketamine occupies some its analgesic effects. Ketamine also binds to the NMDA receptor, which is believed to mediate the general anesthetic actions of ketamine.

Front 43

45. How do patients appear clinically after an induction dose of ketamine?

Back 43

45. After an induction dose of ketamine the patient appears to be in a cataleptic state. The appearance of the patient may be characterized as eyes remaining h a slow nystagmic gaze; the maintenance of cough, swallow, and corneal reflexes; moderate dilation of the pupils; lacrimation; salivation; and an increase in skeletal muscle tone with apparently coordinated but purposeless ,ovements of the extremities. Induction doses of ketamine provide an intense analgesia and amnesia in patients despite the patient appearing as if he or she may be awake. (I

Front 44

46. What is the mechanism by which the effects of ketamine are terminated?

Back 44

46. The redistribution of highly lipid-soluble ketamine to inactive tissue sites allows for rapid awakening after the administration of a bolus of ketamine. Ketamine undergoes extensive hepatic metabolism to norketamine for its elimination. Norketamine has between 20% and 30% the potency of ketamine and may contribute to some of the delayed effects of ketamine when administered as a continuous infusion

Front 45

47. What are the induction doses for intravenous and intramuscular routes of administration of ketamine? What is the time of onset for the effect of ketamine subsequent to its administration?

Back 45

47. For the induction of anesthesia, the intravenous dose of ketamine is 1 to 2 mg! : kg, whereas the intramuscular dose is 5 to 10 mglkg. The induction of anesthesia after intravenous administration is achieved within 60 seconds. The induction of anesthesia after intramuscular administration is achieved within 2 to 4 minutes. Return of consciousness after an intravenous induction dose of ketamine usually requires 10 to 20 minutes, whereas full orientation may take 60 to 90 minutes. Ketamine may also be administered orally or rectally.

Front 46

48. How does ketamine affect the cardiovascular system?

Back 46

48. The administration of ketamine results in an increase in systemic blood pressure, pulmonary artery blood pressure, heart rate, and cardiac output The systemic blood pressure may increase by 20 to 40 mm Hg over the first 5 minutes after ' often sustained for over 10 minutes. The degree of hemodynamic change elicited often sustained for over 10 minutes. The degree of hemodynamic change elicited , by the administration of ketamine is not influenced by the dose of ketamine that is administered, but it can be blunted by the prior administration of barbiturates, benzodiazepines, opioids, or droperidol. These cardiovascular ef- 1 fects of ketamine are most likely mediated centrally through the activation of nervous system outflow. Endogenous norepinephrine release has been found to nervous system outflow. Endogenous norepinephrine release has been found to accompany the administration of ketamine. This property of ketamine may make it useful as an induction agent in hypovolemic patients in whom hemodynamic support is beneficial

Front 47

50. How does ketamine affect skeletal muscle tone? How does this affect the upper airway?

Back 47

50. Ketamine preserves and may even increase skeletal muscle tone. Patients have varying degrees of purposeful skeletal muscle movement and hypertonus after an induction dose of ketamine. The preservation of skeletal muscle tone results in maintenance of a patent upper airway and the preservation of cough and swallow reflexes. Despite this, airway protection by these reflexes against regurgitation or vomiting cannot be assumed. (

Front 48

51. How does ketamine affect the central nervous system?

Back 48

; 1. Ketarnine has excitatory effects on the central nervous system such that there are increases in cerebral metabolism, cerebral blood flow, intracranial pressure, and cerebral metabolic oxygen requirements associated with its administration.

Front 49

52. What does the emergence delirium associated with ketamine refer to? What is the incidence'? How can it be prevented,?

Back 49

52. The emergence after the administration of ketamine has been associated with a delirium, often referred to as an emergence delirium. The severity of the emergence delirium varies. The emergence delirium manifests as vivid dreaming, visual and auditory illusions, and a sense of floating outside the body. These sensations are often associated with confusion, excitement, and fear, and are unpleasant to the patient. The emergence delirium typically occurs in the first hour after emergence and persists for 1 to 3 hours. The incidence of emergence delirium with ketamine administration has been estimated to be up to 30%, and it is more likely to occur when ketamine is used as the sole anesthetic agent

Front 50

53. What are some common clinical uses of ketamine?

Back 50

53. Some common clinical uses of ketamine include its administration for the induction of anesthesia in hypovolemic patients, its intramuscular injection for the induction of anesthesia in children or in developmentally disabled patients who are difficult to manage, and for dressing changes and debridement procedures in bum patients. Small doses of ketamine may be titrated for its analgesic · effects.

Front 51

55. How common are allergic reactions to ketamine?

Back 51

55. Allergic reactions to ketamine are uncommon. (66)

Front 52

56. Name some of the commonly used benzodiazepines. What are some of the clinical effects and properties of benzodiazepines that make them useful in anesthesia practice?

Back 52

56. Benzodiazepines that are commonly used in the perioperative period include midazolam, diazepam, and lorazepam. The most common effects of benzodiazepines are their anxiolytic and sedative effects. When administered at higher doses, benzodiazepines may also produce unconsciousness. Other properties of benzodiazepines include anterograde amnesia, a lack of retrograde amnesia, minimal cardiopulmonary depression, anticonvulsant activity, and relative safety lllllllUlCU l.:aImOpUIIDonary aepresslOn, anticonvulsant activity, and relative safety preoperative medication, for intravenous sedation, for the intravenous induction of anesthesia, and for the suppression of seizure activity.

Front 53

57. What is the mechanism of action of benzodiazepines?

Back 53

57. Benzodiazepines exert their effects through their actions on the gamma-aminobutyric acid (GAB A) receptor. When GABA receptors are stimulated by the inhibitory neurotransmitter GAB A, a chloride ion channel opens, allowing chloride ions to flow into the cell. This results in hyperpolarization of the neuron and a resistance of the neuron to subsequent depolarization. Benzodiazepines enhance the effect of GABA by binding to subunits of the GABA receptor and maintaining the chloride channel open for a longer period of time.

Front 54

58. Where are benzodiazepine receptors located?

Back 54

58. Benzodiazepine receptors are located primarily on postsynaptic nerve endings n the central nervous system. 1 The greatest density of benzodiazepine receptors is in the cerebral cortex. The distribution of benzodiazepine receptors is consistent with the minimal cardiopulmonary effects of these drugs.

Front 55

59. How does midazolam compare with diazepam with regard to its affinity for the benzodiazepine receptor?

Back 55

59. Midazolam has almost two times the affinity for benzodiazepine receptors than diazepam, which is consistent with its greater potency. (,

Front 56

60. How does water-soluble midazolam cross the blood-brain barrier to gain access to the ceIiral nervous system?

Back 56

60. Midazolam is a hydrophilic drug. When midazolam is exposed to the pH of the blood it undergoes a change in its structure and becomes highly lipid soluble. This change in ~tructure allows it to cross the blood-brain barrier and gain access to the central nervous system.

Front 57

61. What is the effect-site equilibration time of benzodiazepines relative to other intravenous anesthetics? How do the context-sensitive half-times of the benzodiazepines compare?

Back 57

61. Benzodiazepines are highly lipid-soluble drugs. This allows them to gain rapid entrance into the central nervous system by crossing the blood-brain barrier, where they are able to exert their effects. Thus the effect-site equilibration time The duration of action of benzodiazepines is devendent on the redistribution of The duration of action of benzodiazepines is dependent on the redistribution of the drug from the brain to inactive tissue sites. A continuous infusion or prolongation of the drug effect, particularly for the benzodiazepines that have prolongation of the drug effect, particularly for the benzodiazepines that have active metabolites, whereas midazolam has no active metabolites. The contextactive metabolites, whereas midazolam has no active metabolites. The contextsensitive half-times for diazepun and lorazepam are prolonged when compared with that of midazolam

Front 58

62. How do benzodiazepines affect the cardiovascular system?

Back 58

62. Induction doses of midazolam may lead to decreases in systemic blood pressure that are greater than those seen with the induction dose of diazepam. This effect of midazolam may be particuarly pronounced in patients who are hypovolemic.The decrease in systemic blood pressure is believed to be due to decreases in systemic vascular resistance. (67

Front 59

63. How do benzodiazepines affect ventilation?

Back 59

63. In general, benzodiazepines alone produce dose-dependent ventilatory depressant effects. Apnea may occur with the rapid administration of induction doses of midazolam, particularly if an opioid has been used for premedicication

Front 60

64. How do benzodiazepines affect the central nervous system?

Back 60

54. Benzodiazepines decrease cerebral blood flow and cerebral metabolic oxygen quirements in a dose-dependent manner. This makes benzodiazepines safe for use in patients with space-occupying lesions, although the administration of benzodiazepines to patients with intracerebral pathologic processes may make '~:I subsequent neurologic evaluation of the patient difficult secondary to the potenlonged effects of these drugs

Front 61

,5. What are some clinical uses of benz~diazepines in anesthesia practice?

Back 61

55. Clinical uses of benzodiazepines in anesthesia practice include preoperative medication, intravenous sedation, the intravenous induction of anesthesia, and the suppression of seizure activity. (

Front 62

). How do midazolam and diazepam compare with regard to time of onset and degree of amnesia when administered for sedation?

Back 62

66. When administered for sedation, rnidazolam has a more rapid onset and produces a greater degree of amnesia than diazepam. The slow onset and greater luration of action of lorazepam limits its usefulness as a preoperative medication. All benzodiazepines may have prolonged and more pronounced sedative Teets in the elderly

Front 63

67. What are some advantages and disadvantages of benzodiazepines for use as induction agents?

Back 63

· The intravenous induction doses of midazolam and diazepam are 0.1 to 0.2 mg! kg and 0.2 to 0.3 mg/kg, respectively. The time of onset of midazolam is anywhere between 30 and 80 seconds, depending on the dose and premedication. The time of onset of midazolam is more rapid than the time of onset of diazepam, making it the benzodiazepine of choice for the induction of anesthesia. The speed of onset of both these agents can be facilitated by the prior administration of opioids.

Front 64

68. How can the effects of benzodiazepines be reversed?

Back 64

68. The effects of benzodiazepines can be reversed by a specific antagonist drug, fiumazenil. Flumazenil is a competitive antagonist that binds to the benzodiazepine receptor but has little intrinsic activity. Flumazenil should be titrated to effect by administering 0.2 mg intravenously every 60 seconds up to a total dose of 1 to 3 mg. Flumazenil binds tightly to the benzodiazepine receptor but is cleared rapidly from the plasma. '

Front 65

69. What organic solvent is used to dissolve diazepam into solution? What are some of the effects of this solvent?

Back 65

69. Propylene glycol is an organic solvent used to dissolve lipid soluble diazepam into solution. Propylene glycol is likely responsible for the unpredictable absorption of diazepam when administered intramuscularly. It is also responsible for the pain and possible subsequent thrombophlebitis experienced by patients on the intravenous injection of diazepam. (68; 229

Front 66

70. How common are allergic reactions to benzodiazepines

Back 66

70. Allergic reactions to benzodiazepines are extremely rare. (68)