Sedatives and hypnotic agents
77 Questions
9 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary mechanism of propofol metabolism?

  • Reductive pathways
  • Oxidation by CYP450 hepatic enzymes (correct)
  • Glucuronidation
  • Sulfation

    • What is the characteristic of propofol that allows it to be used in patients with hepatic or renal dysfunction?

  • Dose-dependent elimination
  • High protein binding
  • Induction of CYP450 enzymes
  • Dysfunction of hepatic or renal systems does not negatively impair propofol (correct)

    • What is the benefit of using propofol for general anesthesia maintenance?

  • Increased risk of postoperative nausea and vomiting
  • Increased risk of respiratory depression
  • Prolonged recovery time
  • Minimal PONV and prompt awakening (correct)

    • What is the effect of propofol on bronchomotor tone in healthy and asthmatic patients?

    <p>Bronchodilation</p> Signup and view all the answers

    What is the effect of high doses of propofol and barbiturates on EEG activity?

    <p>Burst suppression</p> Signup and view all the answers

    What is the mechanism of decreased systemic blood pressure caused by propofol?

    <p>Decreased SVR and decreased CO</p> Signup and view all the answers

    What is the effect of propofol on intracranial pressure?

    <p>Decreased ICP</p> Signup and view all the answers

    What is the effect of propofol on pharyngeal contractile force?

    <p>Decreased pharyngeal contractile force</p> Signup and view all the answers

    What is the effect of propofol on cerebral autoregulation in response to changes in CO2?

    <p>Preserved cerebral autoregulation</p> Signup and view all the answers

    What is the primary mechanism of action of neuraxial neostigmine in producing analgesia?

    <p>Stimulation of muscarinic cholinergic receptors to produce analgesia</p> Signup and view all the answers

    What is a significant advantage of dexmedetomidine over clonidine?

    <p>Higher receptor affinity and selectivity for α2 receptors with a shorter duration of action</p> Signup and view all the answers

    What is a major side effect of epidural dexmedetomidine in cesarean sections?

    <p>Hypotension and bradycardia</p> Signup and view all the answers

    What is the benefit of using epidural dexmedetomidine in cesarean sections?

    <p>All of the above</p> Signup and view all the answers

    What is the primary mechanism by which benzodiazepines interact with GABA receptors?

    <p>By binding between the alpha and gamma subunit to increase the affinity of the receptor for GABA</p> Signup and view all the answers

    What is the result of increased chloride conductance in post-synaptic cells following benzodiazepine binding?

    <p>Hyperpolarization of the post-synaptic cell membrane</p> Signup and view all the answers

    What is a characteristic of the effects of benzodiazepines on adenosine degradation?

    <p>They decrease adenosine degradation, leading to increased cardioprotection</p> Signup and view all the answers

    What is a potential side effect of benzodiazepines when combined with other CNS depressants?

    <p>Loss of coordination and diminished cognitive function</p> Signup and view all the answers

    What is a characteristic of etomidate's effect on the cardiovascular system?

    <p>It has minimal changes in heart rate, stroke volume, or cardiac output</p> Signup and view all the answers

    What is a effect of etomidate on hepatic and renal function?

    <p>It has little impact on hepatic and renal function</p> Signup and view all the answers

    What is the effect of baclofen on neuronal transmission in the cerebral cortex, basal ganglia, thalamus, cerebellum, and spinal cord?

    <p>Suppression via agonism of GABA-B receptor</p> Signup and view all the answers

    What is the primary mechanism of action of ketorolac?

    <p>Cyclo-oxygenase inhibition to decrease prostaglandins</p> Signup and view all the answers

    What is the effect of magnesium sulfate on NMDA receptors?

    <p>Antagonizing calcium - inhibition</p> Signup and view all the answers

    What is the functional role of glutamate at the spinal cord level?

    <p>Excitatory</p> Signup and view all the answers

    What is the therapeutic use of intrathecal baclofen?

    <p>Treatment of pain associated with MS, CRPS type I, and low back pain</p> Signup and view all the answers

    What is the primary concern with the use of magnesium sulfate?

    <p>Neurotoxicity</p> Signup and view all the answers

    What is the effect of baclofen on electrolyte movement resulting in hyperpolarization and inhibition of glutamate and substance P?

    <p>Increase potassium conductance</p> Signup and view all the answers

    Which of the following neurotransmitters are inhibitory at the spinal cord level?

    <p>GABA and glycine</p> Signup and view all the answers

    What is Aquavan?

    <p>A more potent and soluble formulation of propofol with a larger Vd</p> Signup and view all the answers

    What is the mechanism of action of propofol?

    <p>Allosteric GABA-A agonist (a-b site) and modulates glycine receptors</p> Signup and view all the answers

    What are GABA receptors?

    <p>Ligand-gated chloride channels</p> Signup and view all the answers

    What is the result of propofol's high lipid solubility?

    <p>Fast onset and large Vd</p> Signup and view all the answers

    What is unique about the clearance of propofol?

    <p>Its clearance exceeds its hepatic blood flow</p> Signup and view all the answers

    What is unique about the context sensitive half time of propofol?

    <p>It is relatively unaffected by the duration of infusion - 40 mins after 8 hour infusion</p> Signup and view all the answers

    What characteristics make propofol neuroprotective?

    <p>Dose-dependent decrease in CRMO2 and thus CBF and ICP</p> Signup and view all the answers

    Which of the following are beneficial side effects of propofol?

    <p>Antiemetic</p> Signup and view all the answers

    What are the clinical manifestations of PRIS?

    <p>Metabolic acidosis, rhabdomyolysis, hyperkalemia, lipidemia, and cardiac dysfunction</p> Signup and view all the answers

    Which patient population tends to be affected by propofol-related infusion syndrome (PRIS)?

    <p>Critically ill children</p> Signup and view all the answers

    How does propofol have antioxidant properties?

    <p>Propofol's phenolic hydroxyl group scavenges free radicals</p> Signup and view all the answers

    How do propofol and etomidate enhance the affinity of GABA for GABAA?

    <p>They allosterically modulate the GABAA receptor to increase its affinity for GABA</p> Signup and view all the answers

    What is commonly observed after etomidate injection?

    <p>Myoclonus</p> Signup and view all the answers

    Etomidate has a longer CSHT than propofol

    <p>True</p> Signup and view all the answers

    How are propofol and etomidate metabolized?

    <p>Propofol - oxidation by hepatic enzymes</p> Signup and view all the answers

    What is a common side effect of etomidate?

    <p>Adrenal cortical suppression - dose-dependent inhibition of cholesterol to cortisol</p> Signup and view all the answers

    What effect does etomidate have on the respiratory system?

    <p>decreased Vt and increased RR</p> Signup and view all the answers

    Where do benzodiazepines bind on the GABA-A receptor?

    <p>Between the alpha and gamma subunit</p> Signup and view all the answers

    What is common amongst all benzodiazepines?

    <p>Highly protein bound to albumin and highly lipid soluble</p> Signup and view all the answers

    What effect do benzodiazepines have on opioids?

    <p>They decrease the analgesia of opioids</p> Signup and view all the answers

    What is unique about the solubility of midazolam?

    <p>It is water soluble at low pH but lipid soluble at physiologic pH</p> Signup and view all the answers

    What are the CNS effects of propofol?

    <p>Decreased CMRO2 with preserved cerebral vascular response to CO2</p> Signup and view all the answers

    What are the respiratory effects of propofol?

    <p>Ventilatory depressant and decreased swallowing reflex</p> Signup and view all the answers

    What effect does propofol have on the cardiovascular system?

    <p>Decreases CO (negative inotropy) and SVR (smooth muscle relaxation)</p> Signup and view all the answers

    CSHT in midazolam infusions reflect the duration of infusion

    <p>True</p> Signup and view all the answers

    Why has midazolam replaced diazepam in clinical anesthesia? (select 2)

    <p>Midazolam has a more rapid onset of action with a short duration</p> Signup and view all the answers

    What is unique about the duration of action for diazepam?

    <p>Its duration of action is a reflection of metabolism and elimination rather than redistribution</p> Signup and view all the answers

    What effect does diazepam have on the cardiovascular system?

    <p>Has minimal effects, similar to sleep</p> Signup and view all the answers

    What is the drug of choice for delirium tremens?

    <p>Diazepam</p> Signup and view all the answers

    Which benzodiazepine is more potent than midazolam or diazepam?

    <p>Lorazepam</p> Signup and view all the answers

    Ativan is ____ lipid soluble with a ___ onset than Versed

    <p>less, slower</p> Signup and view all the answers

    Why is Ativan not typically used in anesthesia induction?

    <p>Because of its long duration of action</p> Signup and view all the answers

    What is remimazolam?

    <p>An ultrashort-acting benzodiazepine that is metabolized by non-specific tissue esterases</p> Signup and view all the answers

    What is the mechanism of action of flumazenil?

    <p>Competitive antagonist of GABA receptors</p> Signup and view all the answers

    What is a precaution when administering flumazenil?

    <p>Using it in patients with seizure disorders</p> Signup and view all the answers

    What is the main difference in the mechanism of action between benzodiazepines and barbiturates?

    <p>Barbiturates increase the duration of opening of CL channels</p> Signup and view all the answers

    High doses of which sedative drug class can directly activate the GABA-A receptor?

    <p>Barbiturates</p> Signup and view all the answers

    What compound do thiobarbiturates have?

    <p>Sulfur</p> Signup and view all the answers

    What are the benefits of propofol compared to barbiturates?

    <p>Rapid onset and rapid awakening due to rapid distribution</p> Signup and view all the answers

    Which of the following anesthetics is thought to possess 'neuroprotective' properties and can be used for cerebral protection during incomplete brain ischemia?

    <p>Thiopental</p> Signup and view all the answers

    What is the mechanism of action of ketamine?

    <p>NMDA antagonist - Binds to the NMDA receptor to inhibit glutamate activation</p> Signup and view all the answers

    Ketamine is a racemic mixture. Which isomer is associated with faster clearance and more analgesia?

    <p>S(+) isomer</p> Signup and view all the answers

    How does ketamine produce sedation?

    <p>through a dissociative mechanism rather than CNS depression</p> Signup and view all the answers

    What are the cardiovascular effects of ketamine?

    <p>Increased heart rate, blood pressure, cardiac output, and peripheral vascular resistance</p> Signup and view all the answers

    How is ketamine metabolized?

    <p>Hepatically by CYP2B6 and CYP3A4 to normketamine, an active metabolite</p> Signup and view all the answers

    What precautions should be taken when using ketamine?

    <p>All of the above</p> Signup and view all the answers

    Ketamine possesses anticonvulsant activity

    <p>True</p> Signup and view all the answers

    Ketamine is a potent cerebral vasodilator.

    <p>True</p> Signup and view all the answers

    What is the mechanism of action of dexmedetomidine?

    <p>A highly selective alpha-2 agonist that inhibits activity in the locus ceruleus</p> Signup and view all the answers

    What are some potential side effects of dexmedetomidine?

    <p>Decreased plasma catecholamine supply, which may cause hypotension and bradycardia</p> Signup and view all the answers

    Study Notes

    Propofol

    • Propofol is taken up by lungs and then distributed to fat
    • Clearance exceeds hepatic blood flow, and volume of distribution (Vd) is very large
    • Pulmonary uptake is significant, and it is metabolized by CYP450 hepatic enzymes via oxidation
    • Conjugated to water-soluble metabolites and excreted by kidneys
    • Dysfunction of hepatic or renal systems does not significantly impair propofol

    Clinical Applications

    • Induction drug of choice for anesthesia: 1.5-2.5 mg/kg, with children needing larger doses and geriatrics needing smaller doses
    • Sedation: 25-100 mcg/kg/min, with prolonged infusion in pediatric patients leading to metabolic acidosis, lipemic plasma, bradycardia, and heart failure
    • Maintenance: 100-300 mcg/kg/min, often combined with a short-acting opioid or inhalation agent, and associated with minimal PONV and prompt awakening

    Side Effects

    • Reduced PONV
    • Antipruritic and anticonvulsant activity
    • Attenuation of bronchoconstriction in healthy and asthmatic patients, resulting in bronchodilation
    • Synergistic with other CNS depressants, e.g., synthetic opioids
    • Decreases CMRO2, CBF, ICP, and preserves cerebral autoregulation in response to changes in CO2
    • High doses produce burst suppression, and cortical SEE potentials are not significantly affected
    • Amnestic effects are similar to Versed

    Cardiovascular Effects

    • Decreases systemic BP due to decreased SVR and CO
    • Decreased SVR is due to relaxation of vascular smooth muscle and inhibition of sympathetic vasoconstriction
    • Decreased CO is due to negative inotropic effect and inhibition of the trans-sarcolemnal calcium influx
    • No change in HR, but CV effects are potentiated in hypovolemia, elderly, and LV dysfunction
    • Effects are reversed by laryngosenephrine, which stimulates and can reverse the decreased BP/SVR and CO effects

    Respiratory Effects

    • Dose-dependent depression of RR and Vt, and central depressant response to hypoxemia
    • Apnea frequently occurs, and respiratory effects are potentiated by opioids
    • Hypoxic pulmonary vasoconstriction remains intact, but decreases pharyngeal contractile force, relaxing muscles in the pharynx that keep the airway open

    Other Effects

    • Hepatic and renal function rarely affected
    • Lowers IOP during induction and intubation
    • No effects on coagulation and platelet function
    • Does not produce seizure activity, has anticonvulsant properties, and enhances SSE potential monitoring
    • Carries a significant abuse potential, supports bacterial growth, and increases frequency of excitatory spikes

    Benzodiazepines

    • Provide anxiolysis, sedation, anticonvulsant actions, spinal cord-mediated relaxation, and anterograde amnesia
    • GABA receptors concentrated in CNS
    • Mechanism of action involves binding between the alpha and gamma subunit to increase the affinity of the receptor for GABA, resulting in increased chloride conductance and hyperpolarization of the post-synaptic cell membrane
    • Ceiling effect and low toxicity, with differences in onset and duration of action reflecting differences in potency, lipid solubility, and pharmacokinetics
    • All are highly protein bound to albumin and highly lipid soluble, with a decrease in adenosine degradation having cardioprotective effects
    • Side effects include fatigue and drowsiness, loss of coordination and diminished cognitive function, profound amnesia, and synergistic effects with other CNS depressants

    Dexmedetomidine

    • A selective α2 receptor agonist with higher receptor affinity and selectivity for α2 receptors than clonidine
    • Fewer hemodynamic systemic effects, with intrathecal dose: 3 ug, and no neurotoxicity reported for intrathecal or epidural administration
    • Major side effects are bradycardia and hypotension

    Epidural Dex

    • Prolongs neuraxial sensory and motor blockade, decreases intraoperative anesthetic requirements, and improves postoperative analgesia
    • Decreases heart rate and BP in C-sections, with a black box warning for hypotension and bradycardia in C-sections

    Neuraxial Neostigmine

    • Inhibits acetylcholinesterase and prevents the metabolism of acetylcholine, with analgesic effects due to stimulation of muscarinic cholinergic receptors
    • Prolongs analgesia and minimal side effects with intrathecal (10-100 ug) or epidural (100-200 ug) use, and approved for treatment of neuropathic pain
    • Side effects include dizziness, confusion, ataxia, abnormal gait, memory impairment, and suicidal ideation

    Baclofen

    • A GABA-B receptor agonist suppressing neuronal transmission in the cerebral cortex, basal ganglia, thalamus, cerebellum, and spinal cord
    • Actions at laminae II & III, increasing potassium conductance and inhibiting calcium conductance, resulting in hyperpolarization and inhibition of glutamate and substance P release
    • Intrathecal baclofen is effective in treating pain with MS, CRPS type I, and low back pain

    Ketorolac

    • A cyclo-oxygenase inhibitor, with COX1 and COX2 facilitating production of prostaglandins leading to hyperalgesia and allodynia after injury
    • Intrathecal ketorolac appears to have little analgesia benefit

    Magnesium Sulfate

    • Acts on NMDA receptors by regulating calcium influx into cells, with magnesium being the natural antagonist to calcium
    • Does have some analgesic effect when administered intrathecally or in the epidural space, but animal studies have reported neurotoxicity, and human safety is not proven

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    Sedatives and Non-opioids.docx

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser