Pharmacology From PPT Flashcards
What are anticholinergics used for in combination with anticholinesterase drugs?
To prevent the parasympathomimetic side effects of anticholinesterase drugs
These side effects include bradycardia, arrhythmias, hypotension, bronchoconstriction, hypersalivation, diarrhea, and increased postoperative nausea and vomiting. (THINK ANTI-SLUD FOR ANTICHOLINERGIC DRUG & DUMBBELLS FOR ANTI-CHOLINERASTERSE DRUG)
What are the key characteristics of glycopyrrolate?
A quaternary ammonium compound with no central nervous system effects and less initial tachycardia
Glycopyrrolate can be administered first or mixed in the same syringe with neostigmine.
How is atropine metabolized and excreted?
Metabolized by the liver and excreted unchanged in urine, expired air, and feces.
What is the onset time of glycopyrrolate when administered intravenously?
1 minute
Onset time for intramuscular and subcutaneous administration is 15 to 30 minutes.
What is the recommended dose of glycopyrrolate?
10-20 mcg/kg
What is the primary pharmacological action of ephedrine?
Stimulates both alpha and beta receptors and causes the release of endogenous catecholamines.
What is the duration of action for ephedrine?
15 minutes to 1.5 hours
Duration depends on the dose administered.
What are the clinical applications of phenylephrine?
Used topically to prevent nosebleeds and reduce bleeding during ENT surgery, and as a mydriatic in ophthalmology.
What is the onset of action for intravenous phenylephrine?
Immediate
Duration ranges from 5 to 20 minutes.
What is esmolol’s elimination half-life?
Approximately 9 minutes
What is the recommended IV loading dose of esmolol?
500 mcg/kg
What is the primary use of metoprolol?
For its beta-blocking effects in managing myocardial infarction, angina, and hypertension.
What is the typical oral dosage range for metoprolol?
50-200 mg in one or two doses
What is the unique property of labetalol compared to other beta-blockers?
It possesses an alpha-blocking component along with beta-blockade.
What is the usual IV dose of labetalol?
0.25 mg/kg
What are the three anticholinergics used in anesthesia practice?
- Atropine
- Scopolamine
- Glycopyrrolate
What is the typical IV dose of atropine for increasing heart rate during anesthesia?
0.4 to 0.6 mg
What is the clinical duration of action for a scopolamine patch?
3 days
What is the primary mechanism of action for cefazolin? What does it treat?
Time-dependent killing; target common pathogens like Staphylococcus aureus and enteric gram- negative bacilli
Cefazolin is a β-lactam antibiotic.
What is the usual adult dosage of cefazolin for surgical procedures?
2g IV
When should parenteral prophylactic antimicrobials like cefazolin be administered?
As a single IV dose within 60 minutes before incision.
What is the recommended dose of dexamethasone for PONV prevention?
4 mg IV after anesthesia induction
What is ondansetron primarily used for?
As an antiemetic, more effective for vomiting than nausea.
What is the standard dose of ondansetron?
4 mg IV at the end of the procedure
What is the role of neurokinin 1 receptor antagonists like aprepitant?
Suppressing activity at the NST to prevent emesis.
What is the duration of action for palonosetron?
44 hours
What is the IV dose range for droperidol?
0.625 to 1.25 mg IV
What are NK-1 receptor antagonists?
Aprepitant (Emend), fosaprepitant, netupitant/palonosetron (Akynzeo), and rolapitant (Varubi)
They suppress activity at the NST, where vagal afferents from the GI tract converge with inputs from the brain that initiate emesis.
Which NK-1 receptor antagonist is FDA-approved for PONV?
Aprepitant
Others are approved for CINV.
What is a notable feature of rolapitant?
Long half-life
This makes it effective for PONV.
What side effects may droperidol cause?
Extrapyramidal side effects
It is contraindicated in Parkinson’s disease.
Why has the usage of droperidol decreased in the U.S.?
FDA warnings about QT interval prolongation
This raised safety concerns.
What is the antiemetic dose range for haloperidol?
1-2 mg
It has antiemetic properties at low doses.
What is the primary mechanism of transdermal scopolamine?
Blocking cholinergic impulses
It prevents nausea and vomiting.
What are common side effects of transdermal scopolamine?
Sedation, blurred vision, dizziness, dry mouth
These side effects can affect patient comfort.
What is the role of midazolam in antiemetic therapy?
Significant antiemetic effect
It decreases dopamine’s emetic effect in the chemoreceptor trigger zone. decreases serotonin release by binding to the GABA receptor complex.
What is the effective dose of metoclopramide for antiemetic effect?
Greater than 20 mg
It has a mild dopamine receptor blocking effect.
What limits the effectiveness of metoclopramide during surgery?
Short half-life of 30-45 minutes
This limits its utility if administered at the beginning of surgery.
What is recommended for patients at moderate to high risk for PONV?
Multimodal PONV and PONV prophylaxis
Combination therapy is advised.
What should be considered for children at moderate or high risk for PONV?
Combination therapy using a 5-HT3 antagonist and a second drug
This approach enhances prophylaxis effectiveness.
What should be done if PONV occurs within 6 hours postoperatively?
Do not give a repeat dose of the prophylactic antiemetic
Rescue therapy should be from a different therapeutic class.
What is the purpose of the Induction Phase in anesthesia?
Achieve a state of unconsciousness and prepare the patient for surgery.
This phase is crucial for ensuring that the patient is adequately anesthetized before surgical procedures begin.
What processes are involved in the Induction Phase?
Administering anesthetic agents, either intravenously or via inhalation.
The choice of method depends on various factors including the patient’s condition and the type of surgery.
What is monitored during the Induction Phase?
Close observation of vital signs to ensure adequate anesthesia depth.
Vital signs include heart rate, blood pressure, and respiratory rate.
What are the challenges faced during the Induction Phase?
Managing potential complications like hypotension or airway obstruction.
These complications can arise from the anesthetic agents used or the patient’s pre-existing conditions.
What is the goal of the Maintenance Phase in anesthesia?
Maintain a steady state of anesthesia and ensure patient comfort and safety.
This phase is critical for the duration of the surgical procedure.
What techniques are used during the Maintenance Phase?
Adjusting anesthetic dosage and using a combination of agents for optimal effect.
The combination helps in achieving effective anesthesia while minimizing side effects.
What is the objective of the Emergence Phase?
Safely bring the patient out of anesthesia.
This phase marks the transition from unconsciousness to alertness.
What process occurs during the Emergence Phase?
Gradual reduction of anesthetic agents, allowing the patient to regain consciousness.
This process must be carefully managed to avoid complications.
What challenges are faced during the Emergence Phase?
Managing airway and ensuring pain control while avoiding complications like nausea or delirium.
These challenges require careful monitoring and intervention.
What kind of care is provided post-anesthesia?
Providing care in the recovery room, assessing for return of reflexes, and ensuring patient stability.
Post-anesthesia care is crucial for monitoring the patient’s recovery from anesthesia.
What is the chemical structure of Dexmedetomidine?
Dexmedetomidine hydrochloride is the S-enantiomer of medetomidine, chemically described as (-) -4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole monohydrochloride.
What are the solubility and pKa of Dexmedetomidine?
Dexmedetomidine is freely soluble in water, with a pKa of 7.1.
What is the partition coefficient of Dexmedetomidine?
The partition coefficient (n-octanol/water) at pH 7.4 is 2.89.
What is the onset and duration of action for Dexmedetomidine?
Onset of action with loading infusion is 10 to 20 minutes, and the duration of action after the infusion is stopped is 10 to 30 minutes.
What is the IV dosage range for Dexmedetomidine?
Dexmedetomidine exhibits linear kinetics in the dosage range of 0.2 to 0.7 µg/kg/hour when administered by intravenous infusion for up to 24 hours.
What is the loading dose for Dexmedetomidine?
The loading dose is 1 µg/kg infused over 10 minutes followed by maintenance infusions of 0.2 to 0.7 µg/kg/hour.
What are the common uses of Dexmedetomidine?
Dexmedetomidine is widely used for sedation in critical care and for nonintubated patients requiring sedation for short-term surgical procedures.
What are the CNS effects of Dexmedetomidine?
Dexmedetomidine produces dose-dependent sedation resembling natural sleep without causing respiratory depression.
What are the cardiovascular effects of Dexmedetomidine?
The main cardiovascular effects are hypotension and bradycardia, occasionally transient hypertension with rapid initial loading doses.
What is a unique respiratory advantage of Dexmedetomidine?
Respirations are maintained, with normal brain respiratory responsiveness to CO2 and preserved airway patency.
What are the respiratory effects of dexmedetomidine?
Dexmedetomidine maintains respirations and normal brain respiratory responsiveness to CO2. Airway patency and reflexes are present or only slightly diminished. It completely blocked histamine-induced bronchoconstriction in dogs and appears beneficial in decreasing airway reactivity in patients with chronic obstructive pulmonary disease or asthma.
What are the other effects of dexmedetomidine?
Dexmedetomidine has a mild diuretic effect mediated via a2-receptor stimulation. It also exhibits renal, gastroprotective, and anti-inflammatory effects. It is thought to decrease the incidence of emergence delirium after general anesthesia in pediatric patients.
How does dexmedetomidine affect neurologic monitoring?
Dexmedetomidine does not interfere with neurologic monitoring, making it suitable for procedures requiring wake-up tests and does not change cerebral metabolism. Its effects on intracranial pressure are not clinically significant.
What are the cardiovascular effects of dexmedetomidine?
The main cardiovascular effects of dexmedetomidine are hypotension and bradycardia, resulting from CNS a-receptor stimulation and systemic vasodilation. Transient profound hypertension can occur when using certain drugs to treat dexmedetomidine-induced bradycardia in children.
What are the key points for clinical use of dexmedetomidine?
• Dexmedetomidine is an az-receptor agonist that results in central sympatholysis.
• Dexmedetomidine sedation allows for an arousable patient to ascertain neurologic status.
• Dexmedetomidine does not interfere with neurologic monitoring.
• Hypotension and bradycardia are the most frequent cardiovascular adverse effects.
• Respirations are maintained.
• It may reduce postoperative agitation and emergence reactions.
What is Etomidate?
Etomidate is a carboxylated imidazole derivative, synthesized in 1965 and introduced to European anesthesia practice in 1972. It has two isomers, but only the (+) isomer possesses hypnotic properties.
What is the pharmaceutical preparation of Etomidate?
Etomidate is supplied as a 2-mg/ml preparation, containing 35% propylene glycol as a solvent. It has a pH of 8.1 and a pKa of 4.2.
What are the pharmacodynamics of Etomidate?
Etomidate produces dose-dependent CNS depression within one arm-brain circulation time, decreases cerebral blood flow and cerebral metabolic rate of oxygen consumption, acts as a GABA-mimetic, and does not release histamine.
How is Etomidate metabolized?
Etomidate is rapidly metabolized in the liver by hepatic microsomal enzymes and plasma esterases, primarily through ester hydrolysis, forming inactive carboxylic acid metabolites.
What is the excretion and half-life of Etomidate?
Approximately 10% of the drug is excreted unchanged in the urine. The terminal half-life is 2 to 5 hours, and awakening typically occurs 5 to 15 minutes after bolus administration.
What are the uses of Etomidate?
Etomidate is primarily used in compromised patients where the use of other intravenous anesthetics may be problematic. Its major advantage is minimal cardiorespiratory depression.
What is the typical induction dose of Etomidate?
The induction dose of Etomidate is typically 0.2-0.3 mg/kg.
What are the CNS effects of Etomidate?
Etomidate produces dose-dependent CNS depression, decreases cerebral blood flow, and affects electroencephalogram (EEG) patterns and auditory evoked potentials (AEPs).
What are the cardiovascular effects of Etomidate?
Etomidate offers hemodynamic stability upon induction, making it a preferred choice in patients with compensated heart conditions. It does not significantly affect cardiac dysrhythmias.
What are the respiratory effects of Etomidate?
Etomidate causes dose-dependent respiratory depression, but to a lesser extent than propofol. It may cause brief periods of apnea following induction.
What are the adverse effects of Etomidate?
Etomidate can cause pain on injection, thrombophlebitis, nausea, and vomiting. The current formulation containing propylene glycol results in burning and pain on injection in up to 90% of patients. The incidence of subsequent venous sequelae up to 7 days postoperatively is 50%. Myoclonia during onset is common with etomidate use.
How does Etomidate affect steroid production?
Etomidate inhibits the enzyme 11ß-hydroxylase, essential in the production of corticosteroids and mineralocorticoids, leading to clinically significant reductions in steroid production even with a single dose.
What are the contraindications for Etomidate?
Etomidate is contraindicated in patients with known sensitivity, adrenal suppression, and acute porphyrias.
How does Etomidate contribute to cardiovascular stability?
Etomidate contributes to cardiovascular stability by acting as an agonist at a1B-adrenoceptors, mediating an increase in blood pressure. This effect helps maintain myocardial oxygen supply and demand balance.
What are the key points for Etomidate?
Etomidate is used in compromised patients when the use of other intravenous anesthetics may be problematic. The major advantage of etomidate is minimal cardiorespiratory depression. Etomidate reduces intracranial pressure, cerebral blood flow, and CMRO2. The mechanism of action of etomidate appears to be GABA-mimetic. Involuntary movements or myoclonia during onset is common. Etomidate frequently causes burning on injection. Etomidate increases postoperative nausea and vomiting. The induction dose is 0.2-0.3 mg/kg.
How does Ketamine affect opioid-induced analgesia?
Ketamine enhances opioid-induced analgesia and prevents hyperalgesia.
What is the primary pathway for Ketamine metabolism?
The primary pathway for ketamine metabolism by the cytochrome P-450 system is demethylation to form the metabolite norketamine.
How is norketamine further metabolized?
Hydroxylation of norketamine occurs at one of two positions in the cyclohexone ring to form hydronorketamine metabolites.
What is the elimination route for Ketamine metabolites?
These metabolites form a glucuronide derivative via conjugation, producing a more water-soluble compound that is eliminated primarily via renal excretion.
What are the uses of Ketamine?
Ketamine is used for induction of anesthesia, especially in high-risk patients, and is effective in obstetric and pediatric anesthesia, as well as for analgesia in combination with other agents.
What systemic effects does Ketamine have on the CNS?
Ketamine produces a dissociative state of anesthesia, characterized by catalepsy, open eyes, reactive pupils, intact corneal reflexes, and horizontal nystagmus.
What cardiovascular effects does Ketamine have?
Ketamine acts as a circulatory stimulant, increasing systemic blood pressure, heart rate, cardiac contractility and output, and central venous pressure.
What other systemic effects does Ketamine have?
Ketamine increases cerebral blood flow, cerebral metabolic rate, and intracranial pressure. It is a moderate analgesic with a preference for skin, bone, and joint pain.
What are the bronchodilatory effects of Ketamine?
Ketamine is a potent bronchodilator, preserving airway reflexes and increasing secretions. It maintains respirations and airway reflexes, although initial apnea may occur with high doses and rapid administration.
What are emergence phenomena associated with Ketamine?
Emergence phenomena, including vivid dreams, floating sensations, and delirium, can occur after ketamine administration. These are more common in adults than children and are reduced by benzodiazepine or other sedative administration.
How is Ketamine used in obstetrics and pediatrics?
Ketamine is used in obstetrics for analgesia or anesthesia. It is highly lipid-soluble and readily crosses the placenta, producing rapid anesthesia without compromising uterine tone, uterine blood flow, or neonatal status at delivery.
What is the controversy regarding anesthetic neurotoxicity and Ketamine?
There is a controversy regarding anesthetic neurotoxicity caused by ketamine. Neuroapoptosis has been noted in several animal models when ketamine is used in the developing brain, with implications for human use still being researched.
What are the intraocular effects of Ketamine?
Ketamine usually increases intraocular pressure (IOP), but the effect appears to be dose-dependent. It blocks oculocardiac reflex-induced arrhythmias better than propofol during sevoflurane anesthesia for strabismus surgery.
What is the premedication dosage for Ketamine?
A benzodiazepine such as midazolam is administered if patient status allows. An antisialagogue may also be given to decrease secretions.
What is the maintenance dosage for Ketamine?
Ketamine 15-45 mcg/kg/min (1-3 mg/min) by continuous IV infusion or 0.5-1.0 mg/kg supplemental IV doses as needed.
What are the induction doses of ketamine?
Ketamine 2-4 mg/kg IV, or 4-6 mg/kg IM (oral dose is 10 mg/kg).
What are the sedation and analgesia doses of ketamine?
Ketamine 0.2-0.8 mg/kg IV (over 2-3 min) followed by a continuous ketamine infusion (5-20 mcg/kg/min). 10-20 mg may produce preemptive analgesia.
What is the site of action of ketamine?
The NMDA receptor, where it inhibits glutamate as a noncompetitive antagonist.
What type of anesthetic state does ketamine produce?
Ketamine produces an anesthetic state referred to as dissociative anesthesia.
What is the onset of effect for ketamine compared to other induction drugs?
The onset of effect is relatively slow compared to other induction drugs (2-5 min).
What effect does ketamine have on cerebral perfusion pressure?
Ketamine produces a rise in cerebral perfusion pressure.
What are the respiratory effects of ketamine?
Ketamine is a bronchodilator, preserves airway reflexes, and increases secretions.
What type of sympathomimetic action does ketamine have?
Ketamine is an indirect sympathomimetic, releasing catecholamines, which accounts for the cardiac stimulation and bronchodilation.
What is the analgesic property of ketamine?
Ketamine is a moderate analgesic and is used preoperatively as an analgesic.
What is the chemical structure of Propofol?
Propofol is a 2,6-diisopropylphenol.
What is the composition of the Propofol lipid emulsion?
It consists of 10% soybean oil, 2.25% glycerol, and 1.2% purified egg lecithin.
What is the pH range and pKa of Propofol?
The pH of Propofol ranges from 7 to 8.5, and its pKa is 11.
What is a key concern regarding Propofol’s pharmaceutics?
Propofol’s unique vehicle is particularly susceptible to bacterial contamination.
What preservative is used in the original trade product Diprivan?
Diprivan contains disodium edetate (EDTA) as a preservative.
What do generic forms of Propofol contain as preservatives?
They contain sodium metabisulfite or benzyl alcohol, depending on the manufacturer.
How does Propofol exert its pharmacodynamic effects?
It interacts with the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the GABA_A glycoprotein receptor complex.
What is the onset time for Propofol after an intravenous bolus dose?
Rapid distribution occurs within 2 to 4 minutes.
What is the elimination half-life of Propofol?
The elimination half-life is 1 to 2 hours.
What is the typical induction dose of Propofol?
The induction dose is typically 1-2 mg/kg.
What are the maintenance infusion rates for Propofol?
The maintenance infusion is 100-200 µg/kg/min.
What systemic effect does Propofol have on the CNS?
It produces a rapid and pleasant loss of consciousness and reduces cerebral blood flow.
What cardiovascular effects can Propofol cause?
It usually results in a mild to moderate transient decrease in blood pressure.
What respiratory effects are associated with Propofol?
Propofol causes transient respiratory depression, commonly leading to apnea.
In what scenarios is Propofol used?
It is used for induction of general anesthesia, intravenous sedation, and in electroconvulsive therapy (ECT).
What is the neuroprotective role of Propofol?
Propofol might play an important role in multimodal neuroprotection, including the preservation of cerebral perfusion, temperature control, prevention of infections, and tight glycemic control. However, its role as a clinical neuroprotectant is not definitively established, as studies in both animals and humans have been inconsistent.
How does Propofol affect seizure duration during ECT?
Propofol is known to reduce the duration of seizures induced during electroconvulsive therapy (ECT) compared to barbiturates. This reduction in seizure duration does not appear to decrease the efficacy of ECT.
What effects does Propofol have on myoclonia and intraocular pressure?
Propofol may induce myoclonia, spontaneous excitatory movements due to selective disinhibition of subcortical centers. Adequate dosing may prevent these movements. It also decreases intraocular pressure.
What are the implications of Propofol use in obstetrics?
Propofol easily crosses the placental barrier due to its high lipid solubility. It can cause sedative effects in the neonate when used for cesarean delivery, and lower Apgar scores have been noted. Its antiemetic effects may be advantageous in obstetric patients.
What are the contraindications and precautions for Propofol?
Propofol should not be used in patients with known hypersensitivity to propofol or its components, or in those with disorders of lipid metabolism. New generic formulations containing sodium metabisulfite should not be used in sulfite-sensitive patients.
What is Propofol Infusion Syndrome?
This is a serious condition associated with the use of propofol, especially in higher doses or prolonged infusions. Symptoms include metabolic acidosis, hyperkalemia, lipidemia disorders, hepatomegaly, and elevated liver transaminases.
What are the key points for Propofol anesthesia?
Propofol is the most commonly used intravenous anesthetic as an induction drug and for sedation. Respiratory effects include transient respiratory depression or apnea, depending on dose. Although not a bronchodilator, safe use in asthmatics has been well established. Propofol is unique among induction agents in that it exhibits mild anti-emetic properties. It has a rapid onset and emergence after bolus or continuous infusions of the drug. Patients emerge with a mild euphoria followed by rapid dissipation of the sedative effects. Propofol reduces cerebral blood flow, CMRO2, and ICP. It decreases blood pressure, cardiac output, and systemic vascular resistance to a greater extent than etomidate at equipotent doses. The induction dose is 1-2 mg/kg followed by a maintenance infusion of 100-200 mcg/kg/min. Conscious sedation doses are 25-75 mcg/kg/min.
What are the pharmacodynamic effects of Midazolam?
Midazolam produces dose-dependent CNS depressant effects, ranging from anxiolysis to sedation, sleep, and anesthesia at high doses. It also has anticonvulsant effects, amnesia, and muscle-relaxing properties.
How does Midazolam affect seizure activity?
Midazolam increases the threshold to local anesthetic-induced seizure activity and produces anterograde amnesia.
What is the pharmacokinetic profile of Midazolam?
Midazolam exhibits a higher clearance rate compared to other benzodiazepines, making it shorter-acting. Its pharmacokinetic profile is influenced by factors such as age, gender, obesity, race, and hepatic and renal status.
How are the pharmacologic effects of Midazolam terminated?
The pharmacologic effects of midazolam are primarily terminated by redistribution out of the CNS.
What are the common uses of Midazolam?
Midazolam is commonly used for preoperative medication due to its rapid onset, short duration, and half-life. It is ideal as a preoperative anxiolytic, sedative, and amnestic.
What are the CNS effects of Midazolam?
Midazolam produces dose-dependent CNS depressant effects, including anxiolysis, sedation, sleep, and anesthesia at high doses. It also has anticonvulsant effects and produces anterograde amnesia.
What are the cardiovascular effects of Midazolam?
In clinical doses, midazolam has minimal cardiovascular effects. A decrease in blood pressure may be seen when combined with opioids, especially in patients with heart disease or the elderly.
What are the respiratory effects of Midazolam?
Midazolam produces dose-dependent respiratory depression and is the most respiratory depressing among benzodiazepines. Increased respiratory depression and apnea are possible when combined with other CNS depressants.
What are the most common adverse effects of midazolam?
The most common adverse effects of midazolam are unexpected respiratory depression and oversedation.
What condition should midazolam be avoided in?
Midazolam should be avoided in patients with acute porphyrias.
What is flumazenil?
Flumazenil is the sole benzodiazepine antagonist available in the United States.
How does flumazenil work?
Flumazenil is a competitive antagonist with a high affinity for the receptor site, producing prompt and effective reversal of benzodiazepine effects.
What is the onset and duration of action of flumazenil?
Flumazenil’s onset is 1 to 2 minutes, and its duration of action is 45 to 90 minutes.
What are the pharmacologic effects of midazolam when combined with fentanyl?
Midazolam produces synergistic CNS, cardiovascular, and respiratory effects when combined with fentanyl.
What cardiovascular effects can midazolam cause?
Midazolam has minimal cardiovascular effects in clinical doses but may cause a decrease in blood pressure when given with opioids, particularly in patients with heart disease or the elderly.
How does midazolam compare to other benzodiazepines in terms of respiratory depression?
Midazolam is the most respiratory depressing among benzodiazepines, and increased respiratory depression and apnea are possible when combined with other CNS depressants.
What is the induction dose of Etomidate?
0.2-0.3 mg/kg
What is the induction dose of Propofol?
1-2 mg/kg
What is the induction dose of Dexmedetomidine?
1 mcg/kg infused over 10 min followed by 0.2-0.7 mcg/kg/hr
What is the induction dose of Midazolam?
0.1-0.2 mg/kg
What are the central nervous system effects of opioids?
Opioids inhibit the ascending transmission of nociception information from the spinal cord dorsal horn and activate pain control pathways descending from the midbrain. They have minimal effects on electroencephalographic and evoked-potential activity, allowing for neurophysiologic monitoring during opioid anesthetic techniques.
How do opioids affect respiratory function?
Opioids produce dose-dependent respiratory depression by affecting mu and delta receptors in the brainstem’s respiratory centers. They reduce responsiveness to carbon dioxide and oxygen levels, leading to a shift in the CO2 response curve for respiration.
What effect do opioids have on pupils?
Opioids cause miosis (pinpoint pupils), especially under general anesthesia due to high doses of potent opiates. This effect is produced by opiate depression of inhibitory GABA interneurons, leading to stimulation of the Edinger-Westphal nucleus.
What are the antitussive effects of opioids?
Opioids suppress cough via a depressant effect on the cough center in the medulla.
How do opioids induce nausea and vomiting?
Opioids elicit nausea and vomiting by stimulating the chemoreceptor trigger zone in the medulla’s area postrema. Serotonin type 3 (5-HT3) and dopamine type 2 (D2) receptors are involved in this process.
What are the cardiac effects of opioids?
Opioids typically result in bradycardia with little effect on blood pressure in healthy patients, due to medullary vagal stimulation. They induce dose-dependent peripheral vasodilation.
What effect do opioids have on skeletal muscles?
Opioids can cause skeletal muscle rigidity.
What is a common side effect of neuraxial morphine?
Generalized itching is common with neuraxial morphine and can be treated with antihistamines or opiate receptor partial agonists or antagonists.
How do opioids affect the gastrointestinal system?
Opioids affect the gastrointestinal system, including constipation and urinary retention.
What are the endocrine effects of opioids?
Opioids have hormonal effects, including the release of vasopressin and inhibition of stress-induced release of corticotropin and gonadotropins.
How can opioids be administered for pain control?
Opioids can be administered intrathecally or epidurally for pain control. Side effects with spinal administration are similar to systemic administration, but pruritus and urinary retention occur more frequently. Respiratory depression is a serious complication associated with neuraxial opioids.
What is Morphine?
Morphine is a naturally occurring opioid and the prototype for opioid agonists, primarily used for moderate to severe pain relief.
What type of pain is Morphine more effective at relieving?
Morphine is more effective in relieving continuous dull pain than sharp intermittent pain.
What are the administration routes for Morphine?
Morphine can be administered intramuscularly, intravenously, subcutaneously, orally, intrathecally, and epidurally.
What is the effect sequence when Morphine is administered intravenously?
Sedation occurs first, followed by analgesia. Sedation should not be considered an indicator of appropriate analgesia.
What is the lipophilicity and onset characteristic of Morphine?
Morphine is among the least lipophilic opioids, resulting in slow penetration of biologic membranes and a slower onset.
How does Morphine metabolize in the liver?
Morphine undergoes phase 2 glucuronide conjugation at the 3 and 6 positions.
What is the active metabolite of Morphine and its effect?
The active metabolite is morphine-6-glucuronide (M6G), which can prolong therapeutic effects and may lead to excessive sedation in renal failure patients.
What is the potency of M6G compared to Morphine?
M6G is more potent than the parent drug within the CNS, while morphine-3-glucuronide (M3G) is inactive.
What is the dosing information for Morphine?
IV dose is 0.05 to 0.15 mg/kg, with an onset of 20 minutes, peak effect at 30-60 minutes, and duration of 4 to 5 hours.
What is the active metabolite of Morphine and its effect?
The active metabolite is morphine-6-glucuronide (M6G), which can prolong therapeutic effects and may lead to excessive sedation in renal failure patients.
What is Fentanyl?
Fentanyl is the most widely used opioid analgesic in anesthesia, known for its profound dose-dependent analgesia, ventilatory depression, and sedation.
What is the duration of action for a single dose of Fentanyl?
The duration of action for a single administered dose of Fentanyl is approximately 20-40 minutes.
How is the action of a single dose of Fentanyl terminated?
The action of a single dose is terminated by redistribution.
What allows for rapid tissue uptake of Fentanyl?
Fentanyl’s high lipid solubility allows for rapid tissue uptake.
How does Fentanyl metabolize?
Fentanyl is metabolized by N-dealkylation and hydroxylation to inactive metabolites that are eliminated in urine and bile.
What affects Fentanyl elimination?
Fentanyl elimination is prolonged in the elderly and neonates.
What is the prototypic application of Fentanyl?
Fentanyl is the prototypic opioid for transdermal application.
What are the benefits of transdermal administration of Fentanyl?
Transdermal administration does not require cooperation from the patient, avoids first-phase hepatic metabolism, and does not produce discomfort.
What is the delivery rate of current transdermal Fentanyl formulations?
Current formulations permit delivery of 25 to 100 mcg/hour for 24 to 72 hours.
How long does the transdermal Fentanyl patch provide a constant plasma concentration?
The transdermal Fentanyl patch provides a relatively constant plasma concentration for 72 hours.
What are some uses of Fentanyl besides intravenous during surgery?
Fentanyl has many other uses, including intrathecal, epidural, and postoperative PCA intravenous use.
What is the peak plasma concentration time for Fentanyl transdermal patches?
Fentanyl transdermal patches deliver 75 to 100 mcg/hour, resulting in peak plasma concentrations in approximately 18 hours.
What is Alfentanil?
Alfentanil is an opioid analgesic with a more rapid onset of action and shorter duration than Fentanyl, despite being less lipid-soluble.
What is the pharmacokinetics of Alfentanil?
The high nonionized fraction (90%) of Alfentanil at physiological pH and its small volume of distribution increase the amount of drug available for binding in the brain.
How is Alfentanil metabolized?
Alfentanil is metabolized in the liver by oxidative N-dealkylation and O-demethylation in the cytochrome P-450 system. The inactive metabolites are excreted in the urine.
What are the clinical uses and variability of Alfentanil?
Alfentanil is effective epidurally, but its duration of analgesia is short, which has limited its popularity. There is significant patient-to-patient variability in response to Alfentanil.
What drug interactions are associated with Alfentanil?
Erythromycin has been shown to prolong the metabolism of Alfentanil and interact with it to produce clinical symptoms of prolonged respiratory depression and sedation.
What is Hydromorphone?
Hydromorphone is a semisynthetic opioid derived from morphine, known for its high potency and used in pain management.
What is the onset of action for Hydromorphone when administered intravenously?
The onset of action is 15 to 30 minutes.
What is the peak effect time for Hydromorphone when given IV?
The peak effect occurs between 30 to 90 minutes.
What is the duration of action for Hydromorphone?
The duration of action is 4 to 5 hours.
What is the half-life of Hydromorphone?
The half-life is approximately 1 to 3 hours.
What is the recommended dose of Hydromorphone?
The recommended dose is 0.01 to 0.02 mg/kg.
Why is Hydromorphone recommended for patients with renal failure?
It is recommended due to the lack of any known active metabolites, making it a safer option compared to other opioids.
How does Hydromorphone compare to Morphine in terms of analgesia and side effects?
Studies demonstrate similar analgesia and side effect profiles between parenteral Hydromorphone and Morphine.
What is Meperidine?
Meperidine is a synthetic mu receptor agonist, structurally similar to atropine, and possesses an antispasmodic effect similar to atropine. It is used for its analgesic properties.
How is Meperidine metabolized?
After demethylation in the liver, Meperidine is partially metabolized to normeperidine, which is half as analgesic as Meperidine but lowers the seizure threshold and induces CNS excitability.
What is the elimination half-life of normeperidine compared to Meperidine?
The elimination half-life of normeperidine is significantly longer than that of Meperidine.
What are the clinical considerations for Meperidine use?
Accumulation of normeperidine can lead to CNS excitation characterized by tremors, muscle twitches, and seizures. Limitations on Meperidine use should be considered in patients with renal failure, the elderly, and for chronic use in cancer patients who may require high doses.
What drug interactions are associated with Meperidine?
Significant drug interactions can occur between Meperidine and first-generation monoamine oxidase (MAO)-inhibiting drugs, leading to hyperthermia, seizures, and death.
How is Meperidine used in shivering?
Meperidine is effective in reducing shivering from diverse causes, including general and epidural anesthesia. This effect appears to result from kappa receptor stimulation, reducing visible shivering and the accompanying increase in oxygen consumption.
What is Remifentanil?
Remifentanil is an opioid used in anesthesia known for its rapid onset, ultrashort duration, titratability, and simple metabolism.
What are the pharmacological properties of Remifentanil?
Remifentanil is a moderately lipophilic, piperidine-derived opioid with an ester link that allows for rapid metabolism by blood and tissue esterases.
What are the pharmacokinetics of Remifentanil?
Remifentanil has a small volume of distribution (Vd) and an elimination half-life of 8 to 20 minutes. It is metabolized by hydrolysis to a less active compound.
What is the clinical use of Remifentanil?
Remifentanil has a short duration of action, precise and rapid titratable effect, and noncumulative effects, leading to rapid recovery after discontinuation.
What precautions should be taken with Remifentanil?
Bolus dosing in the preoperative or postoperative care unit is not recommended due to potential respiratory depression and muscle rigidity.
How potent is Alfentanil compared to morphine?
Approximately 10-25 times more potent than morphine.
How potent is Fentanyl compared to morphine?
About 50-100 times more potent than morphine.
How potent is Hydromorphone compared to morphine?
Roughly 5-7 times stronger than morphine.
How potent is Meperidine compared to morphine?
Generally considered less potent than morphine, with a ratio of about 1:10 (meperidine to morphine).
How potent is Remifentanil compared to morphine?
Extremely potent, with estimates ranging from 100-200 times more potent than morphine.
How potent is Sufentanil compared to morphine?
Around 500-1000 times more potent than morphine.
How potent is Alfentanil compared to Fentanyl?
Approximately 1/5 to 1/10 as potent as fentanyl.
How potent is Hydromorphone compared to Fentanyl?
Around 1/10 to 1/20 as potent as fentanyl.
How potent is Meperidine compared to Fentanyl?
Significantly less potent than fentanyl, approximately 1/75 to 1/100 as potent.
How potent is Morphine compared to Fentanyl?
Generally considered to be about 1/50 to 1/100 as potent as fentanyl.
How does Remifentanil compare to Fentanyl in potency?
Roughly equivalent to fentanyl in potency, though it has a much shorter duration of action.
How potent is Sufentanil compared to Fentanyl?
About 5 to 10 times more potent than fentanyl.
What is Buprenorphine?
A potent partial agonist opioid that binds mainly to the mu receptors.
What is the duration of action for Buprenorphine?
Approximately 8 hours, due to its slow dissociation from the receptor.
How does Buprenorphine affect respiratory depression?
Exhibits a ceiling effect where an increase in dose does not increase respiratory depression.
What is the gastrointestinal effect of Buprenorphine?
Minimal effect on GI motility and smooth muscle sphincter tone.
What are the uses of Buprenorphine?
Commonly used in opioid use disorder treatment plans and for moderate to severe cancer pain through a transdermal system.
What is Butorphanol?
A highly lipophilic opioid, acting as an agonist at kappa receptors and a weak antagonist at mu receptors.
How does Butorphanol compare to morphine in terms of analgesia?
Can produce more analgesia than morphine but has a ceiling effect for respiratory depression below that of mu-agonists.
What are the uses of Butorphanol?
Used for the treatment of migraine headaches and postoperative pain, and has been studied for epidural use.
What is Nalbuphine?
Acts as both an agonist and an antagonist at opioid receptors, with analgesic response equal to that of morphine.
What are the effects of Nalbuphine?
Provides an agonist effect at kappa receptors and an antagonist effect at mu receptors.
How does Nalbuphine affect respiratory depression?
Demonstrates a ceiling effect for respiratory depression and difficulty with reversal using naloxone.
What are the uses of Nalbuphine?
Used to antagonize pruritus induced by epidural and intrathecal morphine and effectively antagonizes fentanyl-induced respiratory depression without producing adverse circulatory changes.
What is the ceiling effect for respiratory depression of Buprenorphine and Nalbuphine?
Buprenorphine and Nalbuphine exhibit a ceiling effect for respiratory depression.
Butorphanol’s ceiling effect is below that of n-agonists.
What is the receptor affinity of Buprenorphine?
Buprenorphine has a high affinity for mu receptors.
Butorphanol acts as an agonist at kappa receptors and a weak antagonist at mu receptors, while Nalbuphine provides an agonist effect at kappa receptors and an antagonist effect at mu receptors.
What are the clinical uses of Buprenorphine?
Buprenorphine is used in opioid use disorder treatment and for cancer pain.
Butorphanol is used for migraine and postoperative pain, and Nalbuphine is used for antagonizing pruritus and respiratory depression induced by other opioids.
What is Naloxone?
An oxymorphone derivative, Naloxone is a pure opioid antagonist.
What is the action of Naloxone?
It blocks opioid receptor sites, reversing respiratory depression and opioid analgesia through competitive antagonism at mu, kappa, and delta receptors.
What is the duration of action of Naloxone?
The duration of action of Naloxone is less than that of most opioid agonists, which can allow the return of respiratory depression in some patients treated with Naloxone.
What is the use of Naloxone?
Naloxone may antagonize intrinsic analgesic systems and can reverse the side effects of epidural opioids while preserving some analgesic effects.
What is Naltrexone?
Naltrexone has antagonist and receptor-binding properties similar to those of Naloxone but with higher oral efficacy and longer duration of action.
What is the metabolism of Naltrexone?
It produces an active metabolite with a half-life even longer than that of Naltrexone.
What is the duration of action of Naltrexone?
Approximately 24 hours.
What is the use of Naltrexone?
Routinely used in alcohol use disorder programs and administered to patients addicted to opioids to prevent the euphoric effects of opioids.
What is Nalmefene?
Structurally similar to Naloxone, Nalmefene is a long-acting parenteral opioid antagonist.
What is the duration of action of Nalmefene?
It has an elimination half-life of approximately 10 hours and a duration of action of 8 hours when given in usual doses.
What is the use of Nalmefene?
Primarily used in alcohol use disorder programs. In acute opioid overdose, it is recommended that 0.5 to 1.6 mg be given intravenously.
What is Naloxone?
An oxymorphone derivative, Naloxone is a pure opioid antagonist.
What is the action of Naloxone?
It blocks opioid receptor sites, reversing respiratory depression and opioid analgesia through competitive antagonism at mu, kappa, and delta receptors.
What is the duration of action of Naloxone?
The duration of action of Naloxone is less than that of most opioid agonists, which can allow the return of respiratory depression in some patients treated with Naloxone.
What is the use of Naloxone?
Naloxone may antagonize intrinsic analgesic systems and can reverse the side effects of epidural opioids while preserving some analgesic effects.
What is Naltrexone?
Naltrexone has antagonist and receptor-binding properties similar to those of Naloxone but with higher oral efficacy and longer duration of action.
What is the metabolism of Naltrexone?
It produces an active metabolite with a half-life even longer than that of Naltrexone.
What is the duration of action of Naltrexone?
Approximately 24 hours.
What is the use of Naltrexone?
Routinely used in alcohol use disorder programs and administered to patients addicted to opioids to prevent the euphoric effects of opioids.
What is Nalmefene?
Structurally similar to Naloxone, Nalmefene is a long-acting parenteral opioid antagonist.
What is the duration of action of Nalmefene?
It has an elimination half-life of approximately 10 hours and a duration of action of 8 hours when given in usual doses.
What is the use of Nalmefene?
Primarily used in alcohol use disorder programs. In acute opioid overdose, it is recommended that 0.5 to 1.6 mg be given intravenously.
What is the duration of action for Naloxone compared to Naltrexone and Nalmefene?
Naloxone has the shortest duration of action, while Naltrexone and Nalmefene have longer durations.
What is the primary use of Naloxone?
Naloxone is primarily used for the emergency treatment of opioid overdose.
What are Naltrexone and Nalmefene used for?
Naltrexone and Nalmefene are used in alcohol use disorder programs.
What contributes to the longer duration of action of Naltrexone?
Naltrexone produces an active metabolite contributing to its longer duration of action.
What is the reason for Nalmefene’s longer action?
Nalmefene’s longer action is due to its inherent pharmacokinetic properties.
What is Ketorolac?
An intravenous nonsteroidal anti-inflammatory drug (NSAID) used for mild to moderate pain.
How is Ketorolac administered?
Can be administered via both intramuscular and intravenous routes.
What are the advantages of Ketorolac over opioids?
Primary advantages include a lack of significant GI and cardiovascular side effects.
Who should avoid using Ketorolac?
Atopic or asthmatic patients, the elderly, patients with renal or GI dysfunction, or bleeding disorders.
What is Ibuprofen?
An intravenous formulation of Ibuprofen (Caldolor) available as an analgesic and antipyretic.
What are the clinical effects of Ibuprofen?
Similar to Ketorolac.
What is the usual dosage for Ibuprofen?
400 to 800 mg intravenously over 30 minutes, with an onset of 30 minutes and a duration of 4 to 6 hours.
What is Acetaminophen?
An intravenous analgesic and antipyretic drug for use in both adults and children over 2 years old.
What is the opiate-sparing effect of Acetaminophen?
Significant opiate-sparing effect.
What is the dosage of Acetaminophen for patients over 13 years old?
1000 mg infused over 15 minutes.
What is the dosage of Acetaminophen for children?
15 mg/kg.
What are the side effects of Acetaminophen?
Rare, but hepatotoxicity is a concern with doses less than 4000 mg/day.
What is the mechanism of action for Ketorolac and Ibuprofen?
Both Ketorolac and Ibuprofen are NSAIDs and work by inhibiting cyclooxygenase enzymes.
What is the mechanism of action for Acetaminophen?
Acetaminophen’s mechanism is less clear but is believed to involve central inhibition of prostaglandin synthesis.
What are the analgesic properties of Ketorolac and Ibuprofen?
Ketorolac and Ibuprofen are effective for mild to moderate pain.
What is Acetaminophen used for?
Acetaminophen is used for mild pain and fever.
What side effects are associated with Ketorolac and Ibuprofen?
Ketorolac and Ibuprofen can have gastrointestinal and cardiovascular side effects.
What are the side effects of Acetaminophen?
Acetaminophen is generally safer but can cause hepatotoxicity at high doses.
What factors affect Inspiratory Concentration (FI)?
- Fresh Gas Flow Rate: A higher fresh gas flow rate leads to a closer match between the inspired gas concentration and the fresh gas concentration.
- Breathing System Volume: A smaller breathing system volume helps in achieving a concentration closer to the set value on the vaporizer.
- Circuit Absorption: Lower absorption by the machine or breathing circuit also helps in maintaining the inspired gas concentration closer to the fresh gas concentration.
What factors affect Alveolar Concentration (FA)?
- Uptake: Anesthetic agents are taken up by the pulmonary circulation during induction, causing alveolar concentrations to lag behind inspired concentrations.
- Solubility in Blood: Insoluble agents like nitrous oxide are taken up less avidly by the blood compared to more soluble agents like sevoflurane, affecting the rate at which alveolar concentration rises and achieves a steady state.
- Alveolar Blood Flow/Cardiac Output: An increase in cardiac output increases anesthetic uptake, slowing the rise in alveolar partial pressure and delaying induction.
- Partial Pressure Difference: The gradient between alveolar gas and venous blood, which depends on tissue uptake, also affects the uptake of anesthetic by the pulmonary circulation.
What is Ventilation/Perfusion Mismatch?
It refers to the discrepancy between alveolar and arterial anesthetic partial pressures, often due to venous admixture, alveolar dead space, and nonuniform alveolar gas distribution.
How does Ventilation/Perfusion Mismatch affect arterial concentration?
It increases the alveolar-arterial difference, leading to an increase in alveolar partial pressure and a decrease in arterial partial pressure.
What is the Concentration Effect?
Increasing the inspired concentration raises both the alveolar concentration and its rate of rise, particularly significant with nitrous oxide.
What is the primary route for the elimination of inhalation anesthetics?
The primary route is through the alveolar membrane, especially significant for nitrous oxide.
What is recommended after discontinuing nitrous oxide?
Administer 100% oxygen for 5 to 10 minutes to prevent diffusion hypoxia.
How does biotransformation affect anesthetic elimination?
It generally accounts for a minimal increase in the rate of decline of alveolar partial pressure but has a greater impact on soluble anesthetics like methoxyflurane.
Why does halothane eliminate faster than isoflurane?
Halothane undergoes greater biotransformation compared to isoflurane, despite its higher solubility.
What factors speed up recovery from anesthesia?
Factors include elimination of rebreathing, high fresh gas flows, low anesthetic-circuit volume, low absorption by the anesthetic circuit, decreased solubility, high cerebral blood flow, and increased ventilation.
What is Ventilation/Perfusion Mismatch?
It refers to the discrepancy between alveolar and arterial anesthetic partial pressures, often due to venous admixture, alveolar dead space, and nonuniform alveolar gas distribution.
How does Ventilation/Perfusion Mismatch affect arterial concentration?
It increases the alveolar-arterial difference, leading to an increase in alveolar partial pressure and a decrease in arterial partial pressure.
What is the Concentration Effect?
Increasing the inspired concentration raises both the alveolar concentration and its rate of rise, particularly significant with nitrous oxide.
What is the primary route for the elimination of inhalation anesthetics?
The primary route is through the alveolar membrane, especially significant for nitrous oxide.
What is recommended after discontinuing nitrous oxide?
Administer 100% oxygen for 5 to 10 minutes to prevent diffusion hypoxia.
How does biotransformation affect anesthetic elimination?
It generally accounts for a minimal increase in the rate of decline of alveolar partial pressure but has a greater impact on soluble anesthetics like methoxyflurane.
Why does halothane eliminate faster than isoflurane?
Halothane undergoes greater biotransformation compared to isoflurane, despite its higher solubility.
What factors speed up recovery from anesthesia?
Factors include elimination of rebreathing, high fresh gas flows, low anesthetic-circuit volume, low absorption by the anesthetic circuit, decreased solubility, high cerebral blood flow, and increased ventilation.
What is diffusion hypoxia?
Diffusion hypoxia is a condition that can occur due to the rapid elimination of nitrous oxide from the body.
How is nitrous oxide eliminated from the body?
Nitrous oxide is eliminated quickly from the body through the alveolar membrane.
What effect does the rapid elimination of nitrous oxide have on recovery from anesthesia?
The rapid elimination of nitrous oxide speeds up recovery from anesthesia.
What happens to oxygen and carbon dioxide concentrations during the rapid exhalation of nitrous oxide?
There is a dilution of oxygen (O2) and carbon dioxide (CO2) concentrations in the alveolar gas.
What can the dilution of gases during nitrous oxide exhalation lead to?
The dilution can lead to a relative state of hypoxia.
How can diffusion hypoxia be prevented?
To prevent diffusion hypoxia, it is recommended to administer 100% oxygen for 5 to 10 minutes after discontinuing nitrous oxide.
What is the purpose of administering 100% oxygen after nitrous oxide?
Administering 100% oxygen helps to maintain adequate oxygen levels in the alveoli and bloodstream.
How does the administration of 100% oxygen counteract N2O?
It counteracts the dilution effect caused by the rapid exit of nitrous oxide.
What are the physical properties of nitrous oxide?
Nitrous oxide is a gas at room temperature and ambient pressure, and can be kept as a liquid under pressure. It is relatively inexpensive but raises safety concerns.
What are the safety concerns associated with nitrous oxide?
Nitrous oxide has raised safety concerns, leading to interest in alternatives like xenon. It is an NMDA receptor antagonist and has environmental impacts, including ozone depletion and greenhouse effects.
What are the cardiovascular effects of nitrous oxide?
Nitrous oxide stimulates the sympathetic nervous system, masking its direct myocardial depressant effects. In patients with coronary artery disease or severe hypovolemia, myocardial depression may be unmasked.
How does nitrous oxide affect respiratory function?
Nitrous oxide increases respiratory rate and decreases tidal volume due to CNS stimulation, with minimal change in minute ventilation and resting arterial pCO2. It significantly depresses the hypoxic drive.
What are the cerebral effects of nitrous oxide?
Nitrous oxide increases cerebral blood flow (CBF) and cerebral blood volume, mildly elevating intracranial pressure and increasing cerebral oxygen consumption. It provides analgesia at concentrations below MAC for various procedures.
What are the neuromuscular and systemic effects of nitrous oxide?
Nitrous oxide does not provide significant muscle relaxation and can cause skeletal muscle rigidity at high concentrations. It decreases kidney blood flow and glomerular filtration rate, and may reduce hepatic blood flow.
What is the biotransformation and toxicity of nitrous oxide?
Nitrous oxide is primarily eliminated by exhalation, with less than 0.01% undergoing reductive metabolism in the gastrointestinal tract. It can irreversibly oxidize the cobalt atom in vitamin B12, inhibiting vitamin B12 dependent enzymes.
How does nitrous oxide interact with other drugs?
Nitrous oxide is often used in combination with more potent volatile agents, reducing their required concentrations.
What are the contraindications for using nitrous oxide?
Nitrous oxide is contraindicated in conditions where rapid diffusion into air-containing cavities can be hazardous, such as pneumothorax, bowel distention, or intracranial air.
What is Minimum Alveolar Concentration (MAC)?
MAC is defined as the alveolar concentration of an inhaled anesthetic that prevents movement in 50% of patients in response to a standardized stimulus, such as a surgical incision.
What is the utility of MAC?
MAC reflects the partial pressure of the anesthetic in the brain, allows for comparisons of potency between different anesthetic agents, and serves as a standard for experimental evaluations.
What are the limitations of MAC?
MAC is a median value and has limited utility in managing individual patients, especially during periods of rapidly changing alveolar concentrations, such as during induction and emergence from anesthesia.
How do MAC values for combinations of anesthetic agents behave?
The MAC values for combinations of anesthetic agents are roughly additive.
Can you provide an example of MAC additivity?
A mixture of 0.5 MAC of nitrous oxide and 0.5 MAC of isoflurane produces a similar effect in suppressing movement in response to surgical incision as 1.0 MAC of isoflurane alone.
Is the degree of myocardial depression equivalent at the same MAC for different agents?
No, the degree of myocardial depression may not be equivalent at the same MAC for different agents.
Can you provide an example of variability in myocardial depression?
0.5 MAC of halothane causes more myocardial depression than 0.5 MAC of nitrous oxide.
What are MAC multiples and their clinical application?
MAC multiples are clinically useful if the concentration-response curves of the compared anesthetics are parallel, nearly linear, and continuous.
What is the approximate MAC value to prevent movement in 95% of patients?
Approximately 1.3 MAC of any volatile anesthetic prevents movement in about 95% of patients, approximating the EC95.
What MAC concentration is associated with awakening from anesthesia?
A concentration of 0.3 to 0.4 MAC is associated with awakening from anesthesia when the inhaled drug is the sole anesthetic agent.
What factors influence MAC?
MAC can be altered by various physiological and pharmacological variables.
How does age affect MAC?
There is a 6% decrease in MAC per decade of age, regardless of the volatile anesthetic.
What factors do not significantly affect MAC?
MAC is relatively unaffected by species, sex, or duration of anesthesia.
Is MAC altered after spinal cord transection in rats?
No, MAC is not altered after spinal cord transection in rats, suggesting that the site of anesthetic inhibition of motor responses may be in the spinal cord.
MAC for nitrous oxide
104
MAC for Isoflurane
1.17 (per table)
MAC for desflurane
6
MAC for sevoflurane
2
Isoflurane - Cardiovascular Effects
Dilates coronary arteries, with potential myocardial depression unmasked in certain patients.
Isoflurane - Respiratory Effects
Causes respiratory depression with less pronounced tachypnea and is a good bronchodilator.
Isoflurane - Cerebral Effects
Increases cerebral blood flow (CBF) and intracranial pressure at concentrations >1 MAC.
Isoflurane - Neuromuscular Effects
Provides muscle relaxation.
Isoflurane - Renal and Hepatic Effects
Decreases renal blood flow and may reduce total hepatic blood flow, but maintains hepatic oxygen supply.
Isoflurane - Biotransformation and Toxicity
Metabolized to trifluoroacetic acid; limited oxidative metabolism minimizes hepatic dysfunction risk.
Isoflurane - Contraindications and Drug Interactions
No unique contraindications; potentiates nondepolarizing neuromuscular blocking agents (NMBAs).
Desflurane - Cardiovascular Effects
Similar to isoflurane, with a decline in systemic vascular resistance and arterial blood pressure.
Desflurane - Respiratory Effects
Airway irritant.
Desflurane - Cerebral Effects
Increases CBF and intracranial pressure; cerebral vasculature remains responsive to Paco2 changes.
Desflurane - Neuromuscular Effects
Associated with a dose-dependent decrease in response to peripheral nerve stimulation.
Desflurane - Renal and Hepatic Effects
Does not cause significant nephrotoxic effects; hepatic function tests generally unaffected.
Desflurane - Biotransformation and Toxicity
Undergoes minimal metabolism; degraded by desiccated CO2 absorbent into carbon monoxide.
Desflurane - Contraindications and Drug Interactions
Shares contraindications with other volatile anesthetics; potentiates NMBAs.
What are the cardiovascular effects of Sevoflurane?
Mildly depresses myocardial contractility; causes a slight decline in systemic vascular resistance and arterial blood pressure.
What are the respiratory effects of Sevoflurane?
Depresses respiration and reverses bronchospasm similarly to isoflurane.
What are the cerebral effects of Sevoflurane?
Causes slight increases in CBF and intracranial pressure; high concentrations may impair CBF autoregulation.
What are the neuromuscular effects of Sevoflurane?
Produces adequate muscle relaxation for intubation.
What are the renal and hepatic effects of Sevoflurane?
Slightly decreases renal blood flow; maintains total hepatic blood flow and oxygen delivery.
How is Sevoflurane metabolized?
Metabolized at a rate lower than halothane but higher than isoflurane or desflurane; can be degraded into nephrotoxic compound A and hydrogen fluoride.
What are the contraindications and drug interactions of Sevoflurane?
Similar contraindications to other volatile anesthetics; potentiates NMBAs without sensitizing the heart to catecholamine-induced arrhythmias.
What are the cardiovascular effects of the three main inhalation anesthetics?
All three anesthetics have similar effects on the cardiovascular system, primarily causing a decrease in systemic vascular resistance and arterial blood pressure.
What are the respiratory effects of Isoflurane and Desflurane?
Isoflurane and sevoflurane both depress respiration and act as bronchodilators. Desflurane is an airway irritant.
What are the cerebral effects of the three main inhalation anesthetics?
All increase CBF and intracranial pressure, with sevoflurane and desflurane having similar effects on CBF autoregulation.
What are the neuromuscular effects of Isoflurane and Desflurane?
Isoflurane and sevoflurane provide muscle relaxation, while desflurane decreases response to peripheral nerve stimulation.
What are the renal and hepatic effects of Isoflurane and Desflurane?
Isoflurane and sevoflurane have similar effects on renal and hepatic systems, while desflurane is noted for minimal nephrotoxic effects.
How are the three main inhalation anesthetics metabolized?
Isoflurane has limited oxidative metabolism, desflurane undergoes minimal metabolism, and sevoflurane has a higher rate of metabolism with potential nephrotoxic byproducts.
What are the contraindications and drug interactions of the three main inhalation anesthetics?
All three anesthetics share similar contraindications and potentiate NMBAs.
What is the Single Twitch test?
Involves a single supramaximal electrical stimulus ranging from 0.1-1.0 Hz. It requires a baseline before drug administration and is generally used as a qualitative assessment.
What does the Train-of-Four (TOF) test consist of?
Consists of four twitches at 2 Hz every 0.5 sec for 2 sec. It reflects blockade from 70-100% and is useful during onset, maintenance, and emergence of neuromuscular blockade.
What is the Double-Burst Stimulation (DBS) test?
Involves two short bursts of 50-Hz tetanus separated by 0.75 sec. It’s similar to TOF and may be easier to detect fade than with TOF.
What does the Tetanus test generally consist of?
Generally consists of rapid delivery of a 30-, 50-, or 100-Hz stimulus for 5 sec. It should be used sparingly for deep block assessment as it can be painful.
What is the Posttetanic Count (PTC) test?
Involves 50-Hz tetanus for 5 sec, a 3-sec pause, then single twitches of 1 Hz.
What is the preferred monitoring site for neuromuscular blockade?
Ulnar Nerve: Preferred for determining the level of neuromuscular blockade (NMB). It’s usually accessible and convenient. The response at the ulnar nerve is best for measuring recovery.
What alternative monitoring site is used when access to the arm is not practical?
Facial Nerves: Used when access to the arm is not practical. The facial nerve monitoring generally involves the orbicularis oculi muscle around the eye or the corrugator supercilii that moves the eyebrow.
What is the minimum tidal volume necessary for neuromuscular function?
At least 5mL/kg is necessary but insensitive as an indicator of neuromuscular function.
What does Single-Twitch Strength indicate?
Should be qualitatively as strong as baseline, indicating 75-80% receptor occupancy.
What does a TOF test with no palpable fade suggest?
No palpable fade suggests 70-75% receptor occupancy. It’s uncomfortable but more sensitive as an indicator of recovery than single twitch.
What is Train-of-Four (TOF)?
TOF involves delivering four separate stimuli at a frequency of 2 Hz every 0.5 seconds for a total duration of 2 seconds. It is used to approximate the degree or percent of paralysis present, being most sensitive between 70% and 100% paralysis.
What does TOF Ratio (TOFR) measure?
The size of the fourth twitch (T4) is compared to the first twitch (T1), referred to as the TOFR.
What does the disappearance of T4 indicate?
The disappearance of T4 represents a block of 75% to 80%.
What does the absence of T4 and T3 indicate?
The absence of T4 and T3 indicates an 80% to 85% block.
What does it suggest when T4, T3, and T2 are absent?
When T4, T3, and T2 are absent, it suggests a 90% to 95% neuromuscular blockade (NMB).
What indicates 100% paralysis in TOF?
100% paralysis is achieved when no responses can be elicited.
What is the clinical application of TOF?
TOF is useful during the onset, maintenance, and emergence from neuromuscular blockade.
Why is TOFR important in reversing neuromuscular blockade?
The TOFR is crucial for guiding the reversal of neuromuscular blockade. A TOFR of 0.9 should be the standard attained, as even small degrees of residual block can increase the incidence of adverse respiratory events.
What is the timing for reversal when there is only one response to TOF stimulation?
When there is only one response to TOF stimulation, successful reversal may take as long as 30 minutes.
How long does recovery usually take with a TOF count of two or three responses?
With a TOF count of two or three responses, recovery usually takes 4 to 15 minutes after intermediate-acting drugs.
What is the recovery time after the fourth twitch of TOF returns with neostigmine?
Adequate recovery can be achieved within 5 minutes of reversal with neostigmine or 2 to 3 minutes after using edrophonium.
Why is TOF monitoring significant in clinical practice?
TOF monitoring is significant in avoiding residual paralysis and ensuring patient safety, particularly in higher-risk or elderly patients.
What complications can arise from residual block in the post-anesthesia care unit (PACU)?
Even small degrees of residual block can lead to complications like hypoxia, hypercarbia, atelectasis, and airway obstruction in the PACU.
What is the chemical structure of succinylcholine?
Succinylcholine is formed by the joining of two acetylcholine (ACh) molecules. Its chemical formula is C14H30N204.
What type of structure does succinylcholine have?
Succinylcholine contains a quaternary ammonium structure, making it water-soluble in the body.
Does succinylcholine pass the blood-brain barrier?
No, succinylcholine does not pass the blood-brain barrier and has no direct central nervous system (CNS) effects.
How does succinylcholine act on receptors?
Succinylcholine mimics the action of ACh by depolarizing the motor endplate.
Does succinylcholine act on ganglionic nicotinic receptors?
No, succinylcholine does not act on ganglionic nicotinic receptors but may cause bradycardia by acting on cardiac cholinergic muscarinic receptors.
What are the effects of succinylcholine on muscle receptors?
It leads to initial stimulation of cholinergic receptors, followed by desensitization, resulting in less drug needed at the receptor site to produce neuromuscular block.
What is the onset time for succinylcholine?
Succinylcholine has an extremely rapid onset, with effects usually within 3 minutes after administration.
What is the plasma half-life of succinylcholine?
The plasma half-life is 2 to 4 minutes, with a clinical duration of 5 to 10 minutes.
How is succinylcholine metabolized?
It is hydrolyzed by plasma cholinesterases into succinylmonocholine and choline, and further into succinic acid and choline.
What is the recommended dosage of succinylcholine for intubation?
A bolus of 0.5 to 1.5 mg/kg is recommended for adequate adult paralysis and relaxation for intubation.
What is the effective dose for 95% of the population (ED95) of succinylcholine?
The ED95 is approximately 0.30 mg/kg.
What are the central nervous system effects of succinylcholine?
It does not pass the blood-brain barrier and has no direct CNS effects, but may indirectly increase intracranial pressure (ICP).
What cardiovascular effects can succinylcholine cause?
It can cause slight tachycardia or bradycardia, especially in children or with repeat dosing in adults.
How is succinylcholine metabolized in the hepatic system?
It is metabolized by plasma cholinesterase produced in the liver.
Can succinylcholine be used in patients with renal disease?
Yes, it can be used if preoperative potassium levels are normal, but it is contraindicated in patients with elevated preoperative potassium levels.
How does succinylcholine affect elderly patients?
Onset may be slightly prolonged due to slower circulation time, and reduced plasma cholinesterase levels may allow for reduced dosage.
What is the recommended dose of succinylcholine for obese patients?
The recommended dose is 1.0 mg/kg based on total body weight.
How should succinylcholine be used in children?
It should be used only in emergency situations for children under 8 years old, not for routine intubation.
What is a risk associated with using succinylcholine in children with undiagnosed skeletal muscle myopathy?
There is a risk of cardiac arrest from hyperkalemic rhabdomyolysis.
What are the common side effects of succinylcholine?
Myalgias and fasciculations, particularly in the face, trunk, neck, and shoulders, are common after administration. Small doses of nondepolarizing muscle relaxants or pretreatment with sodium channel blockers or NSAIDs may prevent myalgia.
What is a significant risk associated with succinylcholine?
Hyperkalemia, which results in a transient increase in serum potassium levels, can be profound in patients with burn injuries or underlying muscle disorders.
In which condition is succinylcholine absolutely contraindicated?
Malignant Hyperthermia (MH), a pharmacogenetic skeletal muscle disorder, is a contraindication for succinylcholine.
What genetic variants affect the response to succinylcholine?
Pseudocholinesterase variants can result in a prolonged response and apnea. Notable variants include fluoride-resistant (F), silent (S), and K variants.
What cardiac effect can succinylcholine have?
Succinylcholine may cause bradycardia, especially in children or with repeat dosing in adults.
How does succinylcholine affect intracranial pressure?
It indirectly increases intracranial pressure (ICP), raising concerns for its use in neurosurgical procedures or patients with brain pathology.
What is a Phase II block?
A Phase II block, also known as a desensitization block, is a specific type of neuromuscular block that occurs with large doses of depolarizing neuromuscular blocking agents (NMBAs), such as succinylcholine.
What is the mechanism of action of Phase I block?
In Phase I, depolarizing NMBAs mimic acetylcholine (ACh) at the neuromuscular junction, leading to depolarization of the muscle membrane and muscle paralysis.
What characterizes the transition to Phase II block?
With prolonged exposure to high doses of depolarizing agents, the muscle membrane starts to repolarize but becomes less responsive to acetylcholine, characterizing the Phase II block.
What is a key characteristic of Phase II block regarding twitch response?
Phase II block shows a fade in response to tetanic or train-of-four (TOF) stimulation, unlike Phase I block which shows no fade.
Can Phase II blocks be reversed?
Yes, Phase II blocks can often be reversed with anticholinesterase drugs, which is not the case with Phase I blocks.
Why is it important to identify a Phase II block?
It is important for anesthesia providers to recognize a Phase II block because its management differs from a Phase I block, with the presence of fade in response to TOF stimulation being a key indicator.
How can a Phase II block be treated?
If a Phase II block is identified, it can often be treated with anticholinesterase drugs, similar to the treatment of a block induced by nondepolarizing NMBAs.
What is a key strategy for preventing Phase II block?
To prevent the development of a Phase II block, careful dosing of depolarizing agents is crucial, avoiding excessive or repeated doses of drugs like succinylcholine.
What is Rocuronium Bromide?
Rocuronium bromide is a monoquaternary aminosteroid neuromuscular blocker.
What is the chemical designation of Rocuronium Bromide?
1-(17B-(acetyloxy)-3a-hydroxy-2B-(4-morpholinyl)-5a-androstan-16ß-yll-1-(2-propenyl) pyrrolidinium bromide.
What is the pH and preservative status of Rocuronium Bromide formulation?
Formulated with a pH adjusted to 4.0 and contains no preservative.
How long is Rocuronium Bromide stable at room temperature?
It is stable at room temperature for up to 30 days.
How does Rocuronium Bromide act in the body?
It competes with acetylcholine for binding to nicotinic receptors at the motor endplate, leading to muscle relaxation.
What is the duration of action for Rocuronium Bromide?
In usual ED95 doses, it lasts 30 to 60 minutes.
What is the onset time of Rocuronium Bromide?
The onset time is dose-dependent.
What is the primary method of elimination for Rocuronium Bromide?
Biliary elimination of unchanged drug is the primary method.
What percentage of Rocuronium Bromide elimination is due to renal excretion?
Renal excretion accounts for 33% of elimination.
What is the elimination half-life of Rocuronium Bromide?
The elimination half-life is 60 to 120 minutes.
What is the primary use of Rocuronium Bromide?
Primarily used as a nondepolarizing neuromuscular blocker in anesthesia.
What is the intubating dose range for Rocuronium Bromide?
Doses ranging from 0.6 to 1.2 mg/kg provide good to excellent intubating conditions within 45 to 90 seconds.
What are the cardiovascular effects of Rocuronium Bromide?
It has no significant cardiac effects at clinical doses and does not result in histamine release.
How is Rocuronium Bromide affected by hepatic disease?
Its duration of action is prolonged in patients with hepatic disease.
How does renal status affect Rocuronium Bromide?
A small portion of the drug is excreted unchanged in the urine, leading to a prolonged elimination half-life in patients with renal disease.
What is the effect of aging on rocuronium in elderly patients?
The onset times of rocuronium are generally delayed in elderly patients due to slower circulation times and other kinetic changes associated with aging. The dosing interval and duration of action are prolonged due to decreased hepatic and renal clearance and an increased volume of distribution.
What special considerations are there for using rocuronium in obese patients?
The use of rocuronium in obese patients requires special clinical considerations due to their higher risk for gastroesophageal reflux disease and pulmonary aspiration. The duration of action is prolonged likely due to a decrease in elimination.
How is rocuronium metabolized?
Rocuronium undergoes deacetylation via the liver. Its plasma levels follow a three-compartment open model, resulting in extensive redistribution after intravenous injection.
What is the elimination half-life of rocuronium?
The elimination half-life of rocuronium is 60 to 120 minutes, with variations in children (38.3 minutes), normal adults (56 minutes), and elderly persons (137 minutes).
What is the priming technique in the use of rocuronium?
The priming technique involves giving 10% of the calculated intubating dose prior to inducing anesthesia, followed by the remaining dose after 1 to 3 minutes. This speeds the onset by valuable seconds.
What is the protein binding percentage of rocuronium?
Rocuronium is approximately 46% bound to human plasma proteins, which is somewhat less than other neuromuscular blockers. This decreased binding may lead to a slightly more rapid onset.
What is Vecuronium Bromide?
Vecuronium bromide is a monoquaternary aminosteroid neuromuscular blocker developed from pancuronium.
How was Vecuronium Bromide developed?
It was developed by altering the steroid nucleus from a bisquaternary to a monoquaternary compound.
What are the properties of Vecuronium Bromide?
Vecuronium is more lipophilic than pancuronium but remains predominantly hydrophilic.
What is the chemical designation of Vecuronium?
Vecuronium is chemically designated as piperidinium.
What is the action of Vecuronium?
Vecuronium acts by competing with acetylcholine for binding to nicotinic receptors at the motor endplate, leading to muscle relaxation.
How potent is Vecuronium compared to Pancuronium?
Vecuronium is 1.5 times more potent than pancuronium.
What is the onset of action for Vecuronium?
The induction dose of vecuronium is 0.1 mg/kg, producing maximum suppression of muscle twitch within 3 minutes.
How does the onset of Vecuronium vary?
The onset varies with the concurrent anesthetic administered and is inversely proportional to the dose.
What is the duration of action for Vecuronium?
The duration of action varies with the type of anesthetic and the dose administered.
What is the typical administration method for Vecuronium?
Vecuronium is administered intravenously.
What are the cardiovascular effects of Vecuronium?
Vecuronium has no significant cardiac effects at clinical doses and does not cause histamine release.
How is Vecuronium eliminated from the body?
Vecuronium is eliminated via hepatic and renal mechanisms.
What percentage of Vecuronium is recovered unchanged in urine?
Only 20% to 30% of the administered dose is recovered unchanged in the urine within 24 hours.
How does Vecuronium affect elderly patients?
Onset times are generally delayed in the elderly due to slower circulation and other kinetic changes.
What is the effect of hepatic disease on Vecuronium?
In patients with hepatic disease, the elimination half-life of vecuronium is prolonged, resulting in a longer duration of action.
What is the metabolism process of Vecuronium Bromide?
Vecuronium undergoes elimination via a three-compartment model and is more lipophilic than other agents in its class. A major portion of the dose (40%-80%) is taken up by the liver and excreted in bile.
What is the elimination half-life of Vecuronium?
The elimination half-life of Vecuronium ranges from 51 to 90 minutes in healthy adults. Total clearance has been reported from 3 to 5.6 mL/kg/min.
What is the duration of action for Vecuronium?
The duration of Vecuronium is 36.2 ± 6.4 minutes after a dose of 0.1 mg/kg in patients undergoing intravenous anesthesia. The time from 25% twitch recovery to 75% twitch recovery at this dose was 11 to 12 minutes, and the overall duration was 30 to 45 minutes.
How does hepatic disease affect the use of Vecuronium?
Vecuronium is metabolized in the liver and has been administered to patients with hepatic disease. In patients with cirrhosis, the elimination half-life was prolonged approximately 60%, resulting in a longer duration of action.
What is Cisatracurium Besylate?
Cisatracurium besylate (Nimbex) is a nondepolarizing muscle relaxant, three times more potent than atracurium with a slower onset of action.
What is the chemical structure of Cisatracurium?
It is the most notable of the 10 stereoisomers of atracurium.
What is the formulation of Cisatracurium?
Cisatracurium is available as a sterile, nonpyrogenic aqueous solution in various vial sizes with a pH of 3.25 to 3.65 and a concentration of 2 mg/mL (10 mg/mL in the 20-mL vial for convenience).
How does Cisatracurium act pharmacodynamically?
Cisatracurium acts as a nondepolarizing muscle relaxant by competing with acetylcholine for binding to nicotinic receptors at the motor endplate.
What are the pharmacokinetics of Cisatracurium?
Cisatracurium undergoes ester hydrolysis catalyzed by nonspecific esterases into a quaternary alcohol and a quaternary acid, which are excreted primarily in bile and urine.
What makes Cisatracurium suitable for patients with renal or hepatic impairment?
Cisatracurium’s elimination is nonorgan-dependent, making it a suitable choice for patients with renal or hepatic impairment.
What are the uses of Cisatracurium?
It is used in anesthesia for muscle relaxation, particularly advantageous in settings where cardiovascular stability is essential and in patients with ARDS.
What is the typical intubating dose of Cisatracurium?
The typical intubating dose of Cisatracurium is 0.1 mg/kg.
What are the cardiovascular effects of Cisatracurium?
Cisatracurium maintains cardiovascular stability and does not cause histamine release, avoiding hypotension and tachycardia associated with other muscle relaxants.
How does Cisatracurium affect elderly patients?
The kinetics of cisatracurium are not significantly changed in elderly patients, making it a reliable agent in this population.
Why is Cisatracurium preferred in obese patients?
Cisatracurium is preferred in obese patients due to its lack of histamine release and reliable kinetics, with dosing recommended at ideal body weight.
What is the primary elimination method for Cisatracurium?
Cisatracurium undergoes Hofmann elimination, which is pH and temperature-dependent, accounting for 77% of total body clearance.
What percentage of total body clearance of Cisatracurium is due to nonspecific esterases?
Nonspecific esterases are responsible for 23% of total body clearance.
What percentage of organ-dependent clearance of Cisatracurium occurs through renal pathways?
16% of organ-dependent clearance occurs through renal pathways.
What is the half-life of Cisatracurium?
The half-life of cisatracurium is approximately 26 to 36 minutes.
How does pediatric use of Cisatracurium differ from adult use?
Several differences exist among neonates, infants, and children in relation to their response to neuromuscular blocking agents (NMBAs).
The neuromuscular junction is incomplete at delivery and continues to mature throughout infancy.
How does sensitivity to neuromuscular blocking agents change in children?
The sensitivity to any relaxant may change from birth through childhood.
What is the chemical structure of Atracurium Besylate?
It is classified as a benzylisoquinoline.
What is the formulation stability of Atracurium?
Atracurium loses potency at the rate of 6% per year when refrigerated at 5°C and approximately 5% per month at room temperature. Its recommended unrefrigerated shelf life is 14 days.
What is the action of Atracurium?
Atracurium is a competitive bisquaternary neuromuscular blocker, highly selective in action, and degradable without renal or hepatic intervention.
What is the ED95 of Atracurium?
The ED95 of Atracurium is 0.10 to 0.25 mg/kg.
What is the onset time of Atracurium?
Atracurium has an onset time that is inversely proportional to dosage, ranging from 1.2 to 2.8 minutes.
What is the duration of action for Atracurium?
On average, as an intermediate relaxant, the duration of action is 30 to 60 minutes.
How does Atracurium undergo elimination?
Atracurium undergoes Hofmann elimination, a temperature- and pH-dependent breakdown, and ester hydrolysis catalyzed by nonspecific esterases.
What are the primary excretion routes for Atracurium metabolites?
These metabolites are excreted primarily in bile and urine.
What are the uses of Atracurium?
It is used as a competitive bisquaternary neuromuscular blocker in anesthesia, suitable for patients with liver and kidney diseases.
What is the administration dosage for Atracurium?
The dosage is adjusted based on the patient’s condition and the desired level of muscle relaxation.
What systemic effects can Atracurium have on the cardiovascular system?
Atracurium can cause histamine release, which may produce hypotension and tachycardia.
How does Atracurium affect patients with hepatic and renal diseases?
The pharmacokinetics of Atracurium in these patients show no differences in plasma elimination half-lives compared to nonimpaired subjects.
How does aging affect the duration of Atracurium in elderly patients?
The duration of Atracurium is not affected by aging, making it predictable in the elderly population.
What is the effect of Atracurium in obese patients?
The use of Atracurium in obese patients does not demonstrate a difference in recovery indices or times compared with normal weight patients.
What is the pharmacokinetics of atracurium in patients with hepatic and renal disease?
The pharmacokinetics of atracurium in patients with hepatic and renal disease show no differences in plasma elimination half-lives compared to nonimpaired control subjects. This indicates that atracurium is suitable for use in patients with liver and kidney diseases.
What cardiovascular effects can atracurium cause?
Atracurium can cause histamine release, leading to hypotension and tachycardia. This release is associated with decreases in blood pressure and increases in heart rate at usual clinical doses.
How does atracurium affect pediatric patients?
There are differences in the response to neuromuscular blocking agents (NMBAs) among neonates, infants, and children compared to adults. The neuromuscular junction in neonates is incomplete at delivery and matures throughout infancy, affecting sensitivity to relaxants from birth through childhood.
What is required for prophylaxis against histamine release caused by atracurium?
Prophylaxis against histamine release requires the administration of both H1 (antihistamines)and H2 (Pepcid/ -dine)receptor blockers to mitigate all receptor responses elicited by endogenous histamine release.
What is the importance of reversal in clinical practice?
Complete and effective reversal of muscle relaxants is crucial. Incomplete reversal can lead to significant challenges, including postoperative residual paralysis.
What is the most commonly used anticholinesterase agent for reversal?
Neostigmine is the most commonly used anticholinesterase agent for reversal.
What is an alternative to neostigmine and when is it used?
Edrophonium may be used for faster onset or if there are shortages of neostigmine, but its efficacy is less than neostigmine.
What is the historical relevance of pyridostigmine?
Pyridostigmine is largely historical and rarely used.
What is the recommended TOF count for edrophonium administration?
The degree of spontaneous recovery from neuromuscular block at the time of edrophonium administration should be at least a TOF count of 4.
What should be considered when using neostigmine?
Neostigmine does not reverse deep NMB and should be used cautiously to avoid incomplete reversal or false belief in safe return of muscular function.
What is the role of sugammadex in reversal?
Sugammadex is known for its high efficacy and emphasizes the need for quantitative monitoring of residual blockade at the end of a procedure.
What guides dose selection for sugammadex reversal?
Assessment of TOF, and if no response, the PTC (Post-Tetanic Count), guide dose selection for sugammadex reversal.
What factors influence postoperative residual neuromuscular blockade?
Several factors influence the incidence of postoperative residual NMB, including the type of anesthesia used, type and dose of NMBD administered, type and dose of anticholinesterase reversal drug, duration of anesthesia, use of neuromuscular monitoring, and patient factors.
What are Cholinesterase Inhibitors (AChEl)?
Cholinesterase Inhibitors primarily act due to their structural relationship and interaction with acetylcholinesterase (AChE), a protein that hydrolyzes acetylcholine (ACh) molecules.
How do Edrophonium and Neostigmine interact with AChE?
Edrophonium and neostigmine contain an ionized center that combines at the active center or a site removed from the active center of AChE.
What is Edrophonium?
Edrophonium is a reversible inhibitor of cholinesterase that electrostatically attaches to the anionic site of AChE and is stabilized by hydrogen bonding at the esteratic site.
What is the duration of action of Edrophonium?
Edrophonium has a shorter duration of action than compounds that form a bond.
What is Neostigmine?
Neostigmine is a carbamic acid ester of alcohol that forms a carbamyl-ester complex at the esteratic site of cholinesterase.
How does the drug-enzyme complex of Neostigmine behave?
The drug-enzyme complex of Neostigmine degrades similarly to the ACh-cholinesterase complex, leaving AChE unable to hydrolyze ACh.
What are the pharmacokinetic differences between Edrophonium and Neostigmine?
Edrophonium binds reversibly to the negatively charged enzyme site, while Neostigmine forms a more stable carbamylated enzyme, leading to differing pharmacokinetic profiles.
What is the lipid solubility of Edrophonium and Neostigmine?
Both are quaternary ammonium compounds with poor lipid solubility, limiting their penetration through lipid barriers.
What is the clinical application of Cholinesterase Inhibitors?
Cholinesterase inhibitors are used to reverse neuromuscular blockade by increasing the concentration of endogenous ACh around cholinoreceptors.
How do Cholinesterase Inhibitors affect neuromuscular blockers?
They increase the likelihood that ACh will reoccupy the receptor site once occupied by the neuromuscular blocker and prolong the time ACh remains in the cleft.
What is Neostigmine?
Neostigmine is a carbamic acid ester of alcohol that contains a quaternary or tertiary ammonium group.
What is the mechanism of action of Neostigmine?
Neostigmine forms a carbamyl-ester complex at the esteratic site of cholinesterase, preventing the hydrolysis of acetylcholine.
How is Neostigmine eliminated from the body?
Approximately 50% is eliminated by glomerular filtration, while the other 50% is hydrolyzed by plasma esterases and hepatic metabolism.
What are the metabolites of Neostigmine?
The metabolites are 3-hydroxyphenyltrimethyl ammonium (3-OH PPM) and conjugated 3-OH PPM, which have about one-tenth the activity of the parent compound.
What is the elimination half-life of Neostigmine?
The elimination half-life is 70 to 80 minutes, increasing to 181 to 183 minutes in anephric patients.
What is the clinical application of Neostigmine?
Neostigmine is used to reverse neuromuscular blockade by increasing the concentration of endogenous acetylcholine around cholinoreceptors.
What are the potential side effects of Neostigmine?
It may increase the incidence of postoperative nausea and vomiting.
What is the dose range for Neostigmine?
The dose range is 25-75 mcg/kg.
What is the onset and duration of Neostigmine?
Onset is 5-15 minutes, and duration is 45-90 minutes.
What caution should be taken when administering Neostigmine?
Neostigmine should not be administered to patients with deep neuromuscular blockade to avoid incomplete reversal.
What is the biological activity of Sugammadex?
Sugammadex is biologically inactive and shows a linear dose relationship up to 8.0 mg/kg.
What is the clearance rate of Sugammadex?
The clearance of Sugammadex is approximately 120 L/min.
What is the volume of distribution for Sugammadex?
The volume of distribution of Sugammadex is 18 L.
What is the elimination half-life of Sugammadex?
The elimination half-life of Sugammadex is 2.3 hours.
How much of an administered dose of Sugammadex is eliminated in urine within 24 hours?
Up to 80% of an administered dose of Sugammadex is eliminated in the urine within 24 hours.
Does Sugammadex bind to plasma proteins or erythrocytes?
Sugammadex does not bind to plasma proteins or erythrocytes.
In which patients should Sugammadex be avoided?
Sugammadex should be avoided in patients with significant renal disease.
What is the dosage range for Sugammadex?
The dosage of Sugammadex varies from 2 to 16 mg/kg depending on the depth of blockade at the time of reversal.
What is the recommended dose of Sugammadex if spontaneous recovery has reached the reappearance of the second twitch?
A dose of 2 mg/kg is recommended.
What is the recommended dose of Sugammadex if there are no twitch responses to TOF stimulation?
A dose of 4 mg/kg is recommended if spontaneous recovery of the twitch response has reached 1 to 2 PTC.
What is the recommended dose of Sugammadex for rapid reversal after rocuronium administration?
A dose of 16 mg/kg is recommended if there is a clinical need to reverse NMB soon after administration of a single dose of 1.2 mg/kg of rocuronium.
What are the common adverse effects of Sugammadex?
Common adverse effects include nausea, vomiting, allergy, hypertension, and headache.
What serious allergic reaction has been reported with Sugammadex?
Anaphylaxis has been reported, which initially delayed FDA approval.
What is the incidence of hypersensitivity reactions to Sugammadex?
Hypersensitivity to Sugammadex appears to be relatively low, with only 15 cases reported in a recent review.
When do most anaphylactic reactions to Sugammadex occur?
Most anaphylactic reactions were evident within the first 4 minutes after administration.
How were cardiovascular collapses treated in cases of anaphylaxis from Sugammadex?
Cardiovascular collapse was treated successfully with fluid resuscitation and epinephrine therapy.
What effect does Sugammadex have on oral contraceptives?
Sugammadex binds oral contraceptives, and women of childbearing age should use alternative contraceptive methods for 1 week after exposure.
