213 Questions
Which induction agent has distinct antiemetic properties?
Propofol
Which induction agent produces the greatest degree of hypotension and apnea?
Propofol
What is a significant disadvantage to the use of etomidate, particularly as an infusion?
Adrenal suppression
Which drug produces a dissociative state and has intrinsic analgesic properties?
Ketamine
Which of the following is a potential clinical feature of propofol infusion syndrome?
Severe, refractory bradycardia
What is a potential effect of propofol on the respiratory system?
Dose-dependent depression of ventilation
What is a potential effect of propofol on the cardiovascular system?
May suppress SVT
Which statement about fospropofol (AQUAVAN) is true?
It is a water-soluble prodrug rapidly metabolized by alkaline phosphatase in the blood and tissues.
What is a potential disadvantage of fospropofol (AQUAVAN)?
Delayed systemic appearance of propofol from hydrolysis
Which organ system effect may be observed during pediatric strabismus surgery with propofol anesthesia?
Increased incidence of the oculocardiac reflex
Which statement about propofol infusion syndrome is true?
It may lead to skeletal myopathy
What is a potential effect of propofol on the neuromuscular blockers?
No potentiation of the neuromuscular blockers
Which organ system effect may be observed with propofol administration in patients with COPD?
May produce bronchodilation in COPD patients
What is a potential recommendation for handling propofol?
Aseptic technique should be used when handling propofol
What is a potential effect of propofol on pain perception during injection?
Pain on injection
Which anesthetic agent is associated with a high incidence of bradycardia?
Dexmedetomidine
What is the dominant cardiovascular effect of ketamine in a patient with an intact autonomic nervous system?
Hypertension and tachycardia
What property is NOT included in the ideal anesthetic agent properties?
Long duration of action
Which anesthetic agent's mechanism of action involves increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane?
Propofol
Which anesthetic agent demonstrates rapid induction and more complete awakening than other induction agents?
Propofol
Which of the following is NOT a potential clinical feature of propofol infusion syndrome?
Increased incidence of the oculocardiac reflex
What is a potential effect of propofol on the neuromuscular blockers?
No effect on the neuromuscular blockers
Which anesthetic agent's mechanism of action involves increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane?
Propofol
What is a potential recommendation for handling propofol?
Discard opened ampule after 24 hours
Which organ system effect may be observed with propofol administration in patients with COPD?
Bronchodilation
What is a potential effect of propofol on pain perception during injection?
No pain on injection due to its unique formulation
What is a potential disadvantage of fospropofol (AQUAVAN)?
Delayed systemic appearance of propofol from hydrolysis
Which drug produces a dissociative state and has intrinsic analgesic properties?
Ketamine
Which statement about fospropofol (AQUAVAN) is true?
It is rapidly metabolized by alkaline phosphatase in the blood
What property is NOT included in the ideal anesthetic agent properties?
Potentiation of neuromuscular blockers
Which of the following is a potential dosing range for maintenance of anesthesia with propofol?
100-300 $μg/kg/min$
What is the recommended dosing for sedation with propofol?
25-100 $μg/kg/min$
In which population is a 25-50% reduction in propofol dose recommended?
Elderly
What is the typical bolus dose for postoperative nausea and vomiting (N/V) in PACU with propofol?
$10-15mg$
What is the dose of propofol recommended for effective treatment of neuraxial opioid-associated pruritis?
$10mg$
What percentage decrease in intraocular pressure can be expected with propofol induction?
30-40%
Which organ system effect may be observed following propofol administration in patients with COPD?
Arterial and venous vasodilation
What effect does propofol have on the tachycardic response to hypotension?
Blunted response
In which patient population is propofol-induced hypotension more common and exaggerated?
Hypovolemic patients
What is the approximate reduction in cerebral blood flow (CBF) that can be achieved with propofol?
30%
Which induction drug has been shown to provide cerebral protection following incomplete ischemia when titrated to EEG burst suppression?
Propofol
What is the potential mechanism underlying the neuroprotective activity of propofol?
Antioxidant activity and free radical scavenging
Which anesthetic agent's mechanism of action involves increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane?
Propofol
Which anesthetic agent is initially suspended in Cremaphor EL and now provided in an emulsion of propofol, soybean oil, glycerol, and purified egg phosphatide?
Propofol
Which anesthetic agent demonstrates rapid induction and more complete awakening than other induction agents?
Propofol
Which anesthetic agent's clearance exceeds hepatic blood flow and is eliminated by the kidneys with a prolonged half-life due to slow release from the peripheral compartment?
Propofol
Which anesthetic agent's pharmacokinetics are best described with a three-compartment model with very high clearance and a slow peripheral compartment?
Propofol
Which anesthetic agent is associated with a high incidence of bradycardia due to its inhibition of norepinephrine release from the locus coeruleus?
Propofol
What is the dosing range for maintenance of anesthesia with propofol?
100-300 μg/kg/min
Which population requires a 25-50% reduction in propofol dose?
Elderly
What is the recommended dosing for sedation with propofol?
25-100 μg/kg/min
In which condition is propofol as efficacious as ondansetron for reducing postoperative nausea and vomiting?
Chemotherapy related N/V
What is the effect of propofol on intraocular pressure (IOP)?
$30-40% decrease
What is the mechanism of propofol's anticonvulsant activity?
$\text{GABA receptors activation}$
What effect does propofol have on cerebral metabolic rate of oxygen (CMRO2)?
$\text{~40% decrease}$
Which organ system is directly affected by propofol-induced hypotension?
Cardiovascular system
In which patient population is propofol-induced hypotension more common and exaggerated?
Elderly patients
What is the primary mechanism behind the cardiovascular effects of propofol?
Vasodilation only
Which benzodiazepine has a slower onset than thiopental or propofol but provides reliable amnesia?
Midazolam
What is the primary route of clearance for midazolam?
Renal excretion
Which benzodiazepine is insoluble in water and undergoes hepatic oxidative reduction?
Diazepam
Which benzodiazepine has a lower lipid solubility resulting in delayed onset of CNS effects despite a higher affinity for GABA receptors?
Lorazepam
What are the principal pharmacologic effects of benzodiazepines?
Anxiolysis, sedation, anticonvulsant, skeletal muscle relaxation, and amnesia
Which new ultra-short acting benzodiazepine has been submitted for FDA approval and shows a rapid loss of consciousness and a short context-sensitive half-time compared to midazolam?
Remimazolam
What is the mechanism of action of etomidate?
Enhances the affinity of the GABAA receptor for GABA
What is the pharmacokinetic characteristic of etomidate?
Best described by a three compartment model with high clearance
What is a clinical use of etomidate?
Induction of anesthesia
What preparation change has essentially eliminated pain and venous irritation associated with etomidate administration?
Preparation in a lipid emulsion
What is the dominant cardiovascular effect of ketamine in a patient with an intact autonomic nervous system?
Hypertension and tachycardia
Which anesthetic agent's mechanism of action involves increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane?
Propofol
What is a potential effect of propofol on the neuromuscular blockers?
Potentiation
Which organ system effect may be observed during pediatric strabismus surgery with propofol anesthesia?
Respiratory depression
Which of the following is a potential clinical feature of propofol infusion syndrome?
Severe, refractory bradycardia
What is a potential recommendation for handling propofol?
Avoid rapid bolus administration
What is a potential disadvantage of fospropofol (AQUAVAN)?
Delayed systemic appearance of propofol from hydrolysis
Which anesthetic agent produces a dissociative state and has intrinsic analgesic properties?
Ketamine
What is the primary mechanism behind the cardiovascular effects of propofol?
May suppress SVT
What is a potential effect of propofol on the cardiovascular system?
Hypotension
What is a potential effect of propofol on the respiratory system?
$25-40%$ of apnea following induction
Which statement about fospropofol (AQUAVAN) is true?
It has a rapid onset of action similar to propofol
What is a potential recommendation for handling propofol?
$Aseptic$ technique
Which drug produces the greatest degree of hypotension and apnea among the listed induction agents?
Propofol
What is a potential effect of propofol on the tachycardic response to hypotension?
Tachycardic response to atropine attenuated during propofol anesthesia
What is a potential clinical feature of propofol infusion syndrome?
Hyperglycemia
Which anesthetic agent's mechanism of action involves increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane?
Propofol
What is a significant disadvantage to the use of etomidate, particularly as an infusion?
Adrenal suppression
What is a potential dosing range for maintenance of anesthesia with propofol?
$0.5-3.5 ext{mg/kg/hr}$
Which organ system effect may be observed with propofol administration in patients with COPD?
May produce bronchodilation in COPD patients
What is a potential effect of propofol on pain perception during injection?
Pain on injection
What is a potential clinical feature associated with fospropofol (AQUAVAN)?
Metabolic acidosis
What is the mechanism of action of etomidate?
Activates the GABAA receptor directly
What is a potential clinical use of etomidate?
Induction of anesthesia
What is a significant disadvantage to the use of propofol?
Potential for adrenocortical suppression
What is a potential side effect associated with etomidate administration?
Myoclonus
Which of the following is a potential contraindication for using etomidate as an anesthetic agent?
Reactive airways disease
What is a potential side effect of etomidate that may limit its use in certain patient populations?
Myoclonus
Which of the following is a potential advantage of using etomidate in patients with compromised cardiovascular function?
Minimal effects on baroreceptor function
Which potential adverse effect limits the use of etomidate in patients with a history of seizure disorder?
Activation of epileptogenic foci
What is the primary mechanism of action for benzodiazepines as anesthetic agents?
Activation of GABA receptors
What factor determines the drug effect of benzodiazepines?
Receptor occupancy
Which characteristic distinguishes midazolam from other benzodiazepines?
Substituted imidazole ring
What is a potential consequence of midazolam's hepatic oxidative hydroxylation?
Prolonged duration of action
What distinguishes methoxycarbonyletomidate (MOC) from etomidate?
Lower myoclonus incidence
What distinguishes carboetomidate from etomidate?
Greater adrenal suppression
What distinguishes carboetomidate from methoxycarbonyletomidate (MOC)?
Greater adrenal suppression
Which benzodiazepine has a slower onset than thiopental or propofol but provides reliable amnesia?
Midazolam
What is the primary route of clearance for midazolam?
Renal clearance
Which benzodiazepine is insoluble in water and undergoes hepatic oxidative reduction?
Diazepam
What is a potential effect of propofol on the cardiovascular system?
Decreased blood pressure
What is the approximate reduction in cerebral blood flow (CBF) that can be achieved with propofol?
~50%
Which anesthetic agent's mechanism of action involves increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane?
Propofol
Which anesthetic agent is beneficial for patients with compromised cardiovascular status, questionable intravascular volume status, and elevated ICP?
Etomidate
What effect does etomidate have on steroid synthesis?
It inhibits steroid synthesis
Which side effect is associated with etomidate?
Myoclonus
What is the primary mechanism of benzodiazepines' effect on GABAA receptors?
Enhanced receptor affinity for GABA
Which benzodiazepine has the highest clearance?
Midazolam
What distinguishes methoxycarbonyletomidate (MOC) from etomidate?
It has a different chemical structure
What is the primary route of clearance for midazolam?
Renal excretion
Which benzodiazepine has a slower onset than thiopental or propofol but provides reliable amnesia?
Lorazepam
What distinguishes diazepam from other benzodiazepines in terms of metabolism?
Hepatic oxidative reduction
What is the mechanism of action of flumazenil?
Benzodiazepine receptor ligand
What characteristic distinguishes midazolam from lorazepam and diazepam in terms of metabolism?
Greater hepatic clearance
What are the clinical uses of benzodiazepines?
Preoperative anxiolysis and IV sedation
What are the pharmacologic effects of benzodiazepines?
Anxiolysis, sedation, anticonvulsant, skeletal muscle relaxation, and amnesia effects
What distinguishes remimazolam from midazolam?
Ultra-short acting with rapid loss of consciousness compared to midazolam
What is the dosing recommendation for flumazenil for reversal of benzodiazepine effects?
3.0 mg total dose
What organ system effects are associated with propofol administration?
CNS, cardiovascular, respiratory, and musculoskeletal system effects
What is the mechanism of action of flumazenil?
Antagonizes the effects of benzodiazepines at the GABAA receptor complex
What is the primary mechanism of action of barbiturates at low concentrations?
Enhance effect of GABA
What was the first intravenous barbiturate introduced?
Somnifen
Which barbiturate became the preferred intravenous barbiturate due to its rapid onset, short duration, and lack of excitatory effects?
Thiopental
Who clinically used thiopental for the first time?
$Ralph$ Waters and John Lundy
What is a known use of flumazenil?
$Treatment$ of residual benzodiazepine-induced sedation
What is a characteristic feature of hexobarbital?
It saw a great deal of use in Europe, but not North America.
When was thiopental first used clinically?
1930s
What is the recommended dose of droperidol for antiemetic use?
10-20 μg/kg IV
What is the management approach for central anticholinergic syndrome induced by scopolamine?
Physostigmine 15-60 μg/kg IV repeated at 1-2 hour intervals
What is the primary current use of droperidol?
Antiemetic
What is the side effect associated with scopolamine administration that may interfere with drainage of aqueous humor?
Mydriasis and Cycloplegia
What is the potential treatment for failure of thermoregulatory sweating caused by scopolamine or atropine fever?
$Physostigmine$ $15-60$ $rac{ ext{μg}}{ ext{kg}}$ $IV$ repeated at $1-2$ hour intervals
What are the organ system effects of droperidol in terms of cardiovascular response?
Mild hypotension secondary to vasodilation with blockade of α2 receptors
What is the mechanism behind the CNS depression caused by droperidol?
Submaximal inhibition of GABAA receptors and full inhibition of α2 -acetylcholine receptors, producing an imbalance between dopamine and acetylcholine
What is a potential side effect associated with scopolamine administration that may lead to a wide range of symptoms from restlessness and hallucinations to somnolence and unconsciousness?
Central Anticholinergic Syndrome
What is the primary mechanism of action of dexmedetomidine?
Agonism at alpha2 adrenergic receptors
What is the primary site of analgesic action for dexmedetomidine?
Spinal cord
What is the half-life of dexmedetomidine?
$2-3$ hours
Which receptor does dexmedetomidine primarily agonize to produce hypotension and bradycardia?
Alpha2B adrenergic receptor
What is the recommended dosing for pre-procedure sedation with dexmedetomidine intravenously?
$0.33 - 0.67 μg/kg IV 15$ minutes pre-procedure
In which setting is dexmedetomidine a very useful tool for sedation during airway management?
$ ext{Difficult airway}$
What is the primary effect of dexmedetomidine when used as an adjunct to general anesthesia?
Reduces MAC of isoflurane by $35-50 ext{%}$
Which receptor does dexmedetomidine primarily agonize to produce vasoconstriction in the cerebral vessels?
Alpha1 adrenergic receptor
What is the primary effect of dexmedetomidine on the neuroendocrine stress response to surgery?
Decreased release of cortisol, vasopressin, epi, NE
What is the renal effect of dexmedetomidine?
Diuretic effect by opposing the action of vasopressin
What is the most common subtype of porphyria?
Acute intermittent porphyria
Which drug is NOT listed as a potential trigger for porphyria?
Droperidol
What is the primary mechanism of action for ketamine?
Inhibition of NMDA receptors
Which isomer of ketamine has approximately 4 times greater affinity for the phencyclidine binding site on NMDA receptor than the other?
S(+) ketamine
What effect may be observed with chronic dosing of ketamine?
Tolerance due to downregulation of NMDA receptors
What is a potential clinical use of ketamine at sub-anesthetic doses?
$0.2 - 0.5 mg/kg/hr$ infusion for analgesia
What organ system effect may be observed with ketamine use?
$Decreased intracranial pressure$
What is the primary route of clearance for ketamine?
Renal clearance
What is a potential side effect associated with ketamine use?
Respiratory depression
What preparation is ketamine supplied in?
1%, 5%, and 10%
Which receptor type does ketamine act as an antagonist at?
Muscarinic receptors
What is the approximate duration of action for thiopental?
6-8 minutes
What is the primary route of clearance for barbiturates like thiopental?
Hepatic clearance
Which effect has been observed at lower doses of methohexital in patients with existing seizure disorders?
Induction of seizure activity
What is the approximate percentage decrease in cerebral metabolic rate of oxygen (CMRO2) achievable with barbiturates?
~40-50%
Which cardiovascular effect is typically observed with barbiturates like thiopental?
Peripheral vasodilation with venous pooling
What is a potential respiratory effect of barbiturate induction?
Decreased tidal volume
Which receptor does ketamine primarily act on to induce sedation and hypnosis?
NMDA receptor
What is the approximate duration of action following a single induction dose of ketamine?
10-20 minutes
Which organ system effect may be observed with ketamine administration?
Increased systemic blood pressure
What is the primary mechanism behind the cardiovascular effects of dexmedetomidine?
Inhibition of vagal outflow
What is the primary route of clearance for dexmedetomidine?
$90 ext{%}$ renal excretion
Which organ system effect may be observed with dexmedetomidine administration?
$10-20 ext{ minutes}$ duration of action
What is a potential clinical use of dexmedetomidine?
Sedation in patients with acute bronchospasm
What are the potential side effects associated with ketamine use?
Increased ICP and emergence reactions
Which effect is NOT primarily associated with alpha-2A receptor stimulation by dexmedetomidine?
Vasoconstriction
What are the potential CNS effects associated with ketamine use?
Increased CMRO2
What is a potential concern when using ketamine for induction in patients with known coronary artery disease?
Increased myocardial work and MVO2
Which of the following is a potential trigger for Acute Intermittent Porphyria?
Ketamine
What are the primary symptoms of porphyria?
Pain and skin changes
Which sedative/hypnotic has a rapid onset of action and high lipid solubility?
Ketamine
Which ketamine isomer has greater affinity for the phencyclidine binding site on the NMDA receptor?
$S(+) ketamine$
What is the active metabolite produced when ketamine is metabolized by hepatic microsomal enzymes?
$Norketamine$
Which receptor does ketamine affect in addition to NMDA receptors?
$Opioid receptors$
What is a potential clinical use of ketamine at sub-anesthetic doses?
Analgesia for somatic pain
What are some contraindications for barbiturates?
Severe cardiovascular instability and respiratory obstruction without secured airway
What are some side effects associated with barbiturates?
Cardiovascular and respiratory side effects, with methohexital associated with excitatory phenomenon
What are some uses of barbiturates other than sedation?
Lethal injections and truth serum, also abused and known by various street names
Which of these drugs is a non-GABA agonist sedative/hypnotic?
Ketamine
Which of the following is a potential side effect of etomidate?
Excitatory activity
What is a potential benefit of using etomidate in patients with compromised cardiovascular function?
Minimal effects on the sympathetic nervous system
What is a potential limitation for using etomidate in patients with a history of seizure disorder?
Activation of epileptogenic foci
Which anesthetic agent has a much greater potency in inhibiting steroid synthesis than as a sedative-hypnotic?
Etomidate
What distinguishes methoxycarbonyletomidate (MOC) from etomidate?
Similar hypnotic potency and reduced adrenal suppression
What characteristic distinguishes midazolam from lorazepam and diazepam in terms of metabolism?
Hepatic oxidative hydroxylation and prolonged elimination in the elderly
What is the primary mechanism of action for benzodiazepines as anesthetic agents?
Increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane
What is a potential dosing range for maintenance of anesthesia with propofol?
2-3 mg/kg/hr
What is the primary current use of droperidol?
Treatment of nausea and vomiting
What is the approximate duration of amnesia and disorientation following return of consciousness caused by ketamine?
60-90 minutes
Which of the following is a potential side effect of ketamine's cardiovascular effects?
Increased heart rate
What is the primary mechanism of action of dexmedetomidine?
$\alpha2$ receptor agonism
What is a potential side effect of ketamine's respiratory effects?
Bronchoconstriction
What is the dosing range for ketamine used for induction of anesthesia?
$1-2 mg/kg$ IV
Which personality type may be more susceptible to emergence reactions caused by ketamine?
Type A personality type
What are the indications for ketamine induction?
Hemodynamic instability, active bronchospasm, lack of IV access
What is the primary effect of ketamine on cerebral metabolic rate of oxygen consumption (CMRO2)?
Increased CMRO2
Which receptor does dexmedetomidine primarily agonize to produce sympatholysis?
$\alpha2A$ receptor
What are the clinical uses of ketamine?
Postoperative sedation, analgesia, and induction of anesthesia
What is a potential side effect associated with ketamine administration?
Decreased platelet aggregation
What distinguishes dexmedetomidine from medetomidine?
Non-selective receptor agonism vs highly specific $\alpha2A$ receptor agonism
Study Notes
Anesthetic Agents: Properties, Mechanisms, and Clinical Uses
- Ketamine's dominant cardiovascular effect in a patient with an intact autonomic nervous system is hypertension and tachycardia
- Dexmedetomidine inhibits release of norepinephrine from the locus coeruleus and is associated with a high incidence of bradycardia
- Ideal anesthetic agent properties include drug compatibility, lack of pain on injection, rapid onset of hypnosis, and absence of postoperative complications
- Most commonly used induction agents include propofol, etomidate, ketamine, and barbiturates
- GABA agonist sedative-hypnotics include propofol, etomidate, benzodiazepines, and barbiturates
- Propofol's mechanism of action involves increasing duration of GABA-activated opening of chloride channels and hyperpolarizing the postsynaptic cell membrane
- Propofol is initially suspended in Cremaphor EL and now provided in an emulsion of propofol, soybean oil, glycerol, and purified egg phosphatide
- Propofol decreases the rate of dissociation of GABA from the GABAA receptor and increases the duration of GABA-activated opening of chloride channels
- Propofol's clearance exceeds hepatic blood flow and it is eliminated by the kidneys with a prolonged half-life due to slow release from the peripheral compartment
- Propofol's pharmacokinetics are best described with a three-compartment model with very high clearance and a slow peripheral compartment
- Clinical uses of propofol include rapid induction of anesthesia with dosing in healthy adults at 1.5-2.5 mg/kg for unconsciousness at 2-6 μg/ml
- Propofol demonstrates rapid induction and more complete awakening than other induction agents
Benzodiazepines: Pharmacokinetics and Clinical Uses
- Midazolam has a rapid metabolism via hepatic oxidative hydroxylation and is primarily cleared by the kidneys, with potential accumulation in renal insufficiency.
- Presence of drugs inhibiting cytochrome P-450 can delay midazolam metabolism, and its hepatic clearance is significantly greater than that of diazepam and lorazepam.
- Diazepam is insoluble in water, so it is dissolved in organic solvents, and it undergoes hepatic oxidative reduction, with prolonged elimination half-time in cirrhosis due to decreased protein binding and hepatic blood flow.
- Lorazepam is metabolized via hepatic glucuronidation to inactive metabolites, and its lower lipid solubility results in delayed onset of CNS effects despite a higher affinity for GABA receptors.
- Benzodiazepines are clinically used for preoperative anxiolysis, IV sedation, induction and maintenance, and other uses such as termination of seizure activity and management of delirium tremens.
- Midazolam dosing guidelines recommend 0.05-0.15 mg/kg for induction and 0.05 mg/kg maintenance, while lorazepam and diazepam have different dosing ranges for various indications.
- Midazolam has a slower onset than thiopental or propofol but provides reliable amnesia, and its dose and onset are affected by premedication, anesthetic agents, ASA classification, and patient characteristics.
- Benzodiazepines have five principal pharmacologic effects: anxiolysis, sedation, anticonvulsant, skeletal muscle relaxation, and amnesia.
- Benzodiazepines have organ system effects on the CNS, cardiovascular, respiratory, and musculoskeletal systems, with implications for intracranial compliance, seizure management, blood pressure, and respiratory depression.
- Remimazolam, a new ultra-short acting benzodiazepine, has been submitted for FDA approval and shows a rapid loss of consciousness and a short context-sensitive half-time compared to midazolam.
- Flumazenil is a benzodiazepine receptor ligand with high receptor affinity, minimal intrinsic effect, and rapid clearance by hepatic microsomal enzymes, used for reversal of residual benzodiazepine-induced sedation and suspected benzodiazepine overdose.
- Flumazenil is administered incrementally to a total dose of 3.0 mg for reversal of benzodiazepine effects, as it prevents or reverses all effects of other benzodiazepines in a dose-dependent manner.
Benzodiazepines: Pharmacokinetics and Clinical Uses
- Midazolam has a rapid metabolism via hepatic oxidative hydroxylation and is primarily cleared by the kidneys, with potential accumulation in renal insufficiency.
- Presence of drugs inhibiting cytochrome P-450 can delay midazolam metabolism, and its hepatic clearance is significantly greater than that of diazepam and lorazepam.
- Diazepam is insoluble in water, so it is dissolved in organic solvents, and it undergoes hepatic oxidative reduction, with prolonged elimination half-time in cirrhosis due to decreased protein binding and hepatic blood flow.
- Lorazepam is metabolized via hepatic glucuronidation to inactive metabolites, and its lower lipid solubility results in delayed onset of CNS effects despite a higher affinity for GABA receptors.
- Benzodiazepines are clinically used for preoperative anxiolysis, IV sedation, induction and maintenance, and other uses such as termination of seizure activity and management of delirium tremens.
- Midazolam dosing guidelines recommend 0.05-0.15 mg/kg for induction and 0.05 mg/kg maintenance, while lorazepam and diazepam have different dosing ranges for various indications.
- Midazolam has a slower onset than thiopental or propofol but provides reliable amnesia, and its dose and onset are affected by premedication, anesthetic agents, ASA classification, and patient characteristics.
- Benzodiazepines have five principal pharmacologic effects: anxiolysis, sedation, anticonvulsant, skeletal muscle relaxation, and amnesia.
- Benzodiazepines have organ system effects on the CNS, cardiovascular, respiratory, and musculoskeletal systems, with implications for intracranial compliance, seizure management, blood pressure, and respiratory depression.
- Remimazolam, a new ultra-short acting benzodiazepine, has been submitted for FDA approval and shows a rapid loss of consciousness and a short context-sensitive half-time compared to midazolam.
- Flumazenil is a benzodiazepine receptor ligand with high receptor affinity, minimal intrinsic effect, and rapid clearance by hepatic microsomal enzymes, used for reversal of residual benzodiazepine-induced sedation and suspected benzodiazepine overdose.
- Flumazenil is administered incrementally to a total dose of 3.0 mg for reversal of benzodiazepine effects, as it prevents or reverses all effects of other benzodiazepines in a dose-dependent manner.
Benzodiazepines: Pharmacokinetics and Clinical Uses
- Midazolam has a rapid metabolism via hepatic oxidative hydroxylation and is primarily cleared by the kidneys, with potential accumulation in renal insufficiency.
- Presence of drugs inhibiting cytochrome P-450 can delay midazolam metabolism, and its hepatic clearance is significantly greater than that of diazepam and lorazepam.
- Diazepam is insoluble in water, so it is dissolved in organic solvents, and it undergoes hepatic oxidative reduction, with prolonged elimination half-time in cirrhosis due to decreased protein binding and hepatic blood flow.
- Lorazepam is metabolized via hepatic glucuronidation to inactive metabolites, and its lower lipid solubility results in delayed onset of CNS effects despite a higher affinity for GABA receptors.
- Benzodiazepines are clinically used for preoperative anxiolysis, IV sedation, induction and maintenance, and other uses such as termination of seizure activity and management of delirium tremens.
- Midazolam dosing guidelines recommend 0.05-0.15 mg/kg for induction and 0.05 mg/kg maintenance, while lorazepam and diazepam have different dosing ranges for various indications.
- Midazolam has a slower onset than thiopental or propofol but provides reliable amnesia, and its dose and onset are affected by premedication, anesthetic agents, ASA classification, and patient characteristics.
- Benzodiazepines have five principal pharmacologic effects: anxiolysis, sedation, anticonvulsant, skeletal muscle relaxation, and amnesia.
- Benzodiazepines have organ system effects on the CNS, cardiovascular, respiratory, and musculoskeletal systems, with implications for intracranial compliance, seizure management, blood pressure, and respiratory depression.
- Remimazolam, a new ultra-short acting benzodiazepine, has been submitted for FDA approval and shows a rapid loss of consciousness and a short context-sensitive half-time compared to midazolam.
- Flumazenil is a benzodiazepine receptor ligand with high receptor affinity, minimal intrinsic effect, and rapid clearance by hepatic microsomal enzymes, used for reversal of residual benzodiazepine-induced sedation and suspected benzodiazepine overdose.
- Flumazenil is administered incrementally to a total dose of 3.0 mg for reversal of benzodiazepine effects, as it prevents or reverses all effects of other benzodiazepines in a dose-dependent manner.
Intravenous Anesthetic Agents: Etomidate and Benzodiazepines
- Etomidate has a dosage of 4 mg/kg and is beneficial for patients with compromised cardiovascular status, questionable intravascular volume status, elevated ICP, electroconvulsive therapy, mapping of epileptogenic foci, and maintenance of anesthesia.
- Etomidate may not be suitable for patients with a history of seizure disorder due to its activation of epileptogenic foci and amplification of SSEP signal.
- Etomidate has minimal effects on the sympathetic nervous system and baroreceptor function, making it useful in patients with poor cardiovascular function and settings where any reduction in blood pressure may be significant.
- Etomidate induces less depression of ventilation compared to other induction agents and is safe to use in patients with reactive airways disease.
- Etomidate has a much greater potency (20x) in inhibiting steroid synthesis than as a sedative-hypnotic, leading to suppression of adrenal steroidogenesis and cortisol production for up to 72 hours.
- Side effects of etomidate include excitatory activity, myoclonus, pain on injection, and high incidence of postoperative nausea and vomiting (PONV).
- Methoxycarbonyletomidate (MOC) and carboetomidate are potential etomidate derivatives with similar hypnotic potency and reduced adrenal suppression.
- Midazolam, a benzodiazepine, has a unique structure with a substituted imidazole ring and is lipid-soluble.
- Benzodiazepines enhance the affinity of the GABAA receptors for GABA, resulting in increased chloride conductance and hyperpolarization of the postsynaptic cell membrane.
- The drug effect of benzodiazepines is a function of receptor occupancy, with less than 20% occupancy leading to anxiolysis and over 60% leading to unconsciousness.
- Benzodiazepines are highly protein bound, with Lorazepam having slightly greater volume of distribution despite lower lipid solubility, and Midazolam having the highest clearance.
- Midazolam undergoes hepatic oxidative hydroxylation and has a rapid onset, short duration, and high hepatic clearance, with prolonged elimination in the elderly due to decreased hepatic blood flow and enzyme activity.
Ketamine and Dexmedetomidine: Pharmacology and Clinical Uses
- Ketamine dosed at 1-3 μg/kg/min IV infusion for postoperative sedation and analgesia
- Ketamine used for induction of anesthesia with dosing at 1-2 mg/kg IV and 4-8 mg/kg IM
- Indications for ketamine induction include hemodynamic instability, active bronchospasm, and lack of IV access
- Ketamine may produce amnesia and disorientation for 60-90 minutes following return of consciousness
- Ketamine's effects on the CNS include functional disorganization of midbrain and thalamic pathways
- Ketamine is associated with increased cerebral metabolic rate of oxygen consumption (CMRO2) and intracranial pressure (ICP)
- Ketamine may lead to emergence reactions in 10-30% of adults, with certain personality types being more susceptible
- Ketamine's cardiovascular effects include increased systemic blood pressure and heart rate
- Ketamine has minimal effect on respiratory drive and may cause increased salivation and bronchodilation
- Side effects of ketamine include emergence delirium and inhibition of platelet aggregation
- Dexmedetomidine is the S-enantiomer of medetomidine, a highly specific α2 receptor agonist
- Dexmedetomidine's mechanism of action includes sedation, sympatholysis, analgesia, and neuroprotection through α2 receptor agonism
Test your knowledge of anesthesia dosing variables with this quiz. Explore how different factors such as age, weight, and gender can impact the dosing of anesthesia for maintaining anesthesia and achieving rapid awakening.
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