Anesthesia Review: Drug Interactions
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Questions and Answers

What is required before reproducing any part of the publication?

  • Notification to the editor of the book
  • Prior permission in writing from the publishers (correct)
  • A verbal agreement from the authors
  • A fee payment to the publishers

What should readers do to ensure they have the most accurate medical information?

  • Check information from the manufacturer of products (correct)
  • Rely solely on the information provided in the book
  • Consult the latest medical journals
  • Follow the practices described in older textbooks

What does the publisher state about their association with products mentioned in the book?

  • They have financial ties to some vendors
  • They author some of the products discussed
  • They are exclusively sponsored by specific brands
  • They are not associated with any product or vendor (correct)

What is the responsibility of practitioners in relation to the information provided in the book?

<p>To take all appropriate safety precautions (B)</p> Signup and view all the answers

What is implied by the statement about medical knowledge and practice?

<p>They are subject to constant change and require verification (B)</p> Signup and view all the answers

Which of the following is not mentioned as a part of the publisher's contact information?

<p>Fax number for manuscript submissions (D)</p> Signup and view all the answers

What should practitioners ensure before administering any products mentioned in the book?

<p>They are aware of all potential side effects and contraindications (A)</p> Signup and view all the answers

What caution does the publisher express regarding their liability?

<p>They cannot be held liable for any misuse of the material (C)</p> Signup and view all the answers

Which of the following drugs is an example of a high extraction ratio drug?

<p>Lidocaine (A)</p> Signup and view all the answers

What effect does Quinidine have on digoxin?

<p>Reduces Vd and clearance (A)</p> Signup and view all the answers

What type of pharmacodynamic interaction occurs when two drugs with similar mechanisms of action are combined?

<p>Additive Interaction (D)</p> Signup and view all the answers

Which combination is an example of an antagonistic interaction?

<p>Neostigmine + NDMR (A)</p> Signup and view all the answers

Which drug is known to inhibit CYP3A4 and significantly reduce the clearance of midazolam?

<p>Propofol (D)</p> Signup and view all the answers

In drugs with low extraction ratio, which metabolic activity is rate limiting?

<p>Enzyme induction (C)</p> Signup and view all the answers

What effect does sodium bicarbonate have on bupivacaine?

<p>It precipitates it. (B)</p> Signup and view all the answers

What is a characteristic of synergistic interactions?

<p>Yields a greater effect than the sum of individual effects (D)</p> Signup and view all the answers

Which of the following anesthetic combinations exemplifies an additive pharmacodynamic interaction?

<p>2 volatile anesthetics or N2O + VA (A)</p> Signup and view all the answers

Which combination of agents can lead to serotonin syndrome when used together?

<p>Meperidine and Epinephrine (A)</p> Signup and view all the answers

Which of the following is a drug with a low extraction ratio?

<p>Diazepam (A)</p> Signup and view all the answers

What is the effect of neostigmine on ester local anesthetics?

<p>It increases their action. (A)</p> Signup and view all the answers

What is one of the effects of reduced hepatic blood flow?

<p>Increased concentration of lidocaine (A)</p> Signup and view all the answers

What is a consequence of MAO inhibitors in relation to indirect sympathomimetics?

<p>They enhance their effects. (D)</p> Signup and view all the answers

Which enzyme is inhibited by etomidate, resulting in reduced synthesis of cortisol?

<p>Both B and C (D)</p> Signup and view all the answers

Which of the following is an enzyme inducer that can affect drug metabolism?

<p>Phenobarbitone (A)</p> Signup and view all the answers

What happens to the elimination of phenobarbital in acidic urine?

<p>It is increased due to ion trapping. (D)</p> Signup and view all the answers

What is the mechanism by which probenecid affects penicillin?

<p>It inhibits its secretion. (D)</p> Signup and view all the answers

Which food product can cause hypertensive crises due to tyramine when consumed with MAO inhibitors?

<p>Aged cottage cheese (B)</p> Signup and view all the answers

Which sympathomimetic agent's effects are enhanced by MAO inhibitors but only to a lesser extent?

<p>Norepinephrine (A)</p> Signup and view all the answers

What is a common consequence of prolonged propofol infusion exceeding 48 hours in pediatric patients?

<p>Hyperlipidemia (B)</p> Signup and view all the answers

Which condition is NOT associated with the risk factors for hyperkalemia?

<p>Fatty liver disease (C)</p> Signup and view all the answers

Which early marker would likely indicate complications from high dose propofol prior to renal failure?

<p>Unexplained metabolic acidosis (C)</p> Signup and view all the answers

What is a recommended prevention method to mitigate the effects of propofol infusion?

<p>Minimize duration of infusion (C)</p> Signup and view all the answers

Which substance is specifically mentioned as being avoided to prevent complications of hyperkalemia from propofol use?

<p>Additional lipids (A)</p> Signup and view all the answers

What crucial intervention should be taken immediately upon detection of complications from high-dose propofol?

<p>Stop the propofol infusion (C)</p> Signup and view all the answers

Which of the following best describes the pathophysiology of effects related to propofol in relation to cardiac function?

<p>Potential for sinus arrest and bradycardia (D)</p> Signup and view all the answers

What potential adverse effect is associated with catecholamines and corticosteroids in the setting of sedation?

<p>Increased myocardial oxygen demand (A)</p> Signup and view all the answers

What lab investigation might reveal the earliest signs of adverse effects from prolonged propofol infusion?

<p>Arterial blood gas (ABG) (D)</p> Signup and view all the answers

Which receptor does ketamine act upon to produce its bronchodilator effect?

<p>Muscarinic receptors (B)</p> Signup and view all the answers

Which is true regarding the potency of the S (+) isomer of ketamine compared to the R (–) isomer?

<p>The S (+) isomer is four times more potent in analgesia. (C)</p> Signup and view all the answers

What is the primary difference in the metabolism of the S (+) isomer compared to the R (–) isomer?

<p>The R (–) isomer undergoes more rapid hepatic biotransformation. (C)</p> Signup and view all the answers

Which statement correctly describes the emergence reactions of the two isomers?

<p>The S (+) isomer has a lower incidence of emergence reactions. (B)</p> Signup and view all the answers

What is the effect of ketamine on salivation as seen between its two isomers?

<p>The S (+) isomer causes less salivation than the R (–) isomer. (A)</p> Signup and view all the answers

What is a significant pharmacokinetic characteristic of ketamine?

<p>Ketamine has a rapid onset of action of 30-60 seconds. (C)</p> Signup and view all the answers

How does the S (+) isomer of ketamine affect EEG suppression compared to the R (–) isomer?

<p>The S (+) isomer is more potent in EEG suppression. (D)</p> Signup and view all the answers

Which statement describes the neurovascular effect of ketamine administration?

<p>Ketamine causes increased cerebral blood flow due to vasodilatation. (A)</p> Signup and view all the answers

Flashcards

Copyright

The exclusive legal right, given to the creator of a literary or artistic work, to reproduce, publish, and sell the work.

Disclaimer of Liability

A statement that the publisher and author(s) are not responsible for any harm caused by using the information in the book.

Professional Medical Services

Services provided by a trained medical professional.

Current Medical Information

The most up-to-date information about medical procedures and treatments.

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Safety Precautions

Steps taken to prevent injury or harm.

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Trade Names

Brand names used for products.

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Author's Views

The opinions and perspectives of the contributor(s) or author(s) in a book.

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Medical Knowledge

The information about medical procedures & treatments

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Sodium Bicarbonate and Bupivacaine

Sodium bicarbonate reduces the solubility of bupivacaine, causing it to precipitate out of solution.

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Sodium Bicarbonate and Catecholamines

Sodium bicarbonate inactivates catecholamines, such as epinephrine and norepinephrine.

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Neostigmine and Ester Local Anesthetics

Neostigmine enhances the action of ester local anesthetics, like procaine, cocaine, and tetracaine.

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Etomidate and Cortisol Synthesis

Etomidate inhibits the enzymes involved in cortisol and aldosterone synthesis, reducing their production.

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Enzyme Inducers

These drugs increase the activity of enzymes that break down other medications.

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Enzyme Inhibitors

These drugs slow down the activity of enzymes that break down other medications.

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MAO Inhibitors and Indirect Acting Sympathomimetics

MAO inhibitors increase the action of indirect acting sympathomimetics, leading to potential hypertensive crises.

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MAO Inhibitors and Tyramine

Tyramine, found in aged cheese and wine, interacts with MAO inhibitors to cause hypertensive crises.

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MAO Inhibitors and Direct Acting Sympathomimetics

MAO inhibitors increase the action of direct acting sympathomimetics to a lesser extent than indirect acting ones.

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Meperidine and MAO Inhibitors

When meperidine is combined with MAO inhibitors, it can lead to serotonin syndrome, characterized by symptoms like excitation, hyperpyrexia, HTN, diaphoresis, rigidity, seizures, coma, and death.

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High Extraction Ratio (ER)

Drugs with a high extraction ratio (ER ≥ 0.7) have their metabolism primarily limited by blood flow to the liver. This means that changes in blood flow can significantly impact their clearance.

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Low Extraction Ratio (ER)

Drugs with a low extraction ratio (ER ≤ 0.3) have their metabolism primarily limited by the activity of hepatic enzymes. Changes in enzyme activity, such as induction or inhibition, will have a greater effect on their clearance.

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Lidocaine's ER

Lidocaine has a high extraction ratio (ER). This means its metabolism is primarily limited by blood flow to the liver.

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Propranolol's ER

Propranolol has a high extraction ratio (ER). Its metabolism is limited by blood flow to the liver.

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Diazepam's ER

Diazepam has a low extraction ratio (ER). This means its metabolism is primarily limited by the activity of hepatic enzymes.

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Mepivacaine's ER

Mepivacaine has a low extraction ratio (ER). Its metabolism is limited by the activity of hepatic enzymes.

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Alfentanil's ER

Alfentanil has a low extraction ratio (ER). Its metabolism is primarily limited by the activity of hepatic enzymes.

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Additive Drug Interactions

Additive interactions occur when two drugs with similar mechanisms of action are combined, resulting in an effect that is the sum of their individual effects.

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Antagonistic Drug Interactions

Antagonistic interactions occur when two drugs with opposing mechanisms of action are combined, resulting in a diminished effect.

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Synergistic Drug Interactions

Synergistic interactions occur when two drugs are combined, and their effects are greater than the sum of their individual effects.

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Ketamine Isomers

Ketamine exists as two mirror-image forms, S (+) and R (-), with differing properties. The S (+) isomer is more potent and has quicker effects, while the R (-) isomer is less potent and has slower effects.

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Racemic Ketamine

The commercially available form of ketamine is a mixture of both S (+) and R (-) isomers in equal proportions. This mixture combines the effects of both isomers.

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Ketamine Distribution

Ketamine readily enters the body's tissues due to its high lipid solubility, leading to a large volume of distribution. This means it distributes widely throughout the body.

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Ketamine Redistribution

After initial rapid distribution to the brain, ketamine levels in the bloodstream decrease as it moves into other tissues. This process is called redistribution.

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Ketamine and Cerebral Blood Flow

Ketamine causes vasodilation, widening blood vessels in the brain, leading to an increase in cerebral blood flow. This enhances drug delivery to the brain.

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Ketamine Effects on Cytokines

Ketamine inhibits the production and activity of cytokines, molecules involved in inflammation and immune responses. This contributes to its analgesic properties.

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Ketamine and Neutrophil Production

Ketamine specifically suppresses the production of cytokines by neutrophils, a type of white blood cell responsible for fighting infections.

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Propofol Hyperkalemia

High potassium levels in the blood, a potential complication of prolonged propofol infusion, especially in children and those with mitochondrial disorders.

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Propofol Hyperlipidemia

High levels of lipids (fats) in the blood, a potential side effect of propofol, especially during prolonged infusions.

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Propofol Side Effects

Several potential side effects associated with propofol, including hyperkalemia, hyperlipidemia, metabolic acidosis, and muscle breakdown.

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Propofol in Children

Propofol use in children is associated with a higher risk of hyperkalemia and hyperlipidemia.

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Propofol Prevention

Strategies to prevent complications from propofol use, including minimizing infusion duration, adequate carbohydrate intake, and avoidance of lipid overload.

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Propofol Treatment

Managing propofol-related complications involves stopping the infusion, providing alternative sedation, maintaining hemodynamic stability, and supporting nutrition and renal function.

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Ketamine's Actions

Ketamine interacts with various receptors in the brain, affecting neurotransmitters, pain pathways, and muscle function.

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Ketamine and Glutamate

Ketamine reduces glutamate release, a neurotransmitter involved in pain perception.

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Ketamine and GABA

Ketamine enhances the effects of GABA, a calming neurotransmitter.

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Ketamine and Opioid Receptors

Ketamine interacts with opioid receptors, contributing to its analgesic effects.

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Study Notes

Anesthesia Review - Drug Interactions and Mechanisms

  • Sodium bicarbonate: Reduces bupivacaine solubility, causing precipitation. Inactivates catecholamines.

  • Neostigmine: Increases ester local anesthetic effects (procaine, cocaine, tetracaine).

  • Etomidate: Inhibits cytochrome P450 17α hydroxylase and 11β hydroxylase, reducing cortisol and aldosterone synthesis.

  • MAO inhibitors: Increase indirect sympathomimetics (ephedrine, amphetamine) effects. Potentially cause hypertensive crises with tyramine-containing foods (aged cheese, wine). Increase direct sympathomimetics (epinephrine, norepinephrine) effects to a lesser extent. When given with meperidine, it can cause serotonin syndrome (excitation, hyperpyrexia, HTN, diaphoresis, rigidity, seizures, coma, death).

Hepatic Biotransformation

  • High extraction ratio (ER ≥ 0.7): Rate-limiting is blood flow to liver (metabolism at max). Lidocaine, Propranolol. Reduced hepatic blood flow (reduced cardiac output) and vasopressors (isoproterenol, noradrenaline) increase lidocaine concentration.

  • Low extraction ratio (ER ≤ 0.3): Rate-limiting is enzyme activity, enzyme induction can increase metabolism. Diazepam, mepivacaine, alfentanil.

  • Competitive inhibition: Midazolam and fentanyl compete with CYP3A4. Propofol inhibits CYP3A4 and reduces midazolam clearance by 37%.

Elimination

  • Ion trapping: Phenobarbital (weak acid) excretion increases in acidic urine.

  • Ion secretion: Probenecid inhibits penicillin secretion. Quinidine reduces digoxin volume of distribution and clearance.

Pharmacodynamic Interactions

  • Additive interactions: Combining drugs with similar mechanisms (rocuronium + vecuronium; 2 volatile anesthetics + nitrous oxide).

  • Antagonistic interactions: SCH + non-depolarizing muscle relaxant (NDMR); Neostigmine + NDMR; Flumazenil + benzodiazepines; Naloxone + opioid; Butorphanol + midazolam (increased sedation, less amnesia).

  • Synergistic interactions: Small doses of two drugs producing a larger effect (opioid potentiation by NSAIDs; NDMR potentiation by volatile anesthetics; aminosteroid + benzylisoquinoline NDMR).

  • Hyperkalemia; Hyperlipidemia/hypertriglyceridemia associated risks: acute refractory bradycardia, sinus arrest, asystole, cardiomyopathy, cardiac failure, hypotension, fatty liver, hepatomegaly, skeletal myopathy, rhabdomyolysis, acute renal failure.

Propofol

  • Increased incidence: More common in children, prolonged infusion (>48 hours), or sedation in patients with TBI, sepsis, or respiratory issues.

  • Risk factors: Pediatric age, Cumulative dose (>75 µg/kg/min; >4 mg/kg/hr), duration of infusion (>48 hrs), severe inciting illness (CNS origin/TBI, sepsis), catecholamines/corticosteroid supplementation, inadequate carbohydrate intake, subclinical mitochondrial disease.

  • Early markers: Unexplained metabolic acidosis, elevated serum lactate, elevated creatinine kinase, elevated myoglobin levels, hyperlipidemia, ECG changes (ST elevation in V1-V3).

  • Prevention: Avoid high doses, minimize infusion duration, avoid infusion in children or individuals with mitochondrial disease, adequate carbohydrate intake, avoid lipid overload, high index of suspicion-serum triglyceride 2 days post-continuous infusion.

  • Treatment: Mainly supportive: stop propofol infusion, start alternative sedation, maintain hemodynamic stability (IV crystalloids/colloids, vasopressors/inotropes, transvenous pacing), provide nutritional support (avoid additional lipids, add dextrose to IV fluids, 4-8 mg/kg/hour glucose). Renal support (dialysis, continuous renal replacement therapy), maintain oxygenation.

Ketamine

  • Introduction: Phencyclidine derivative for induction, two optical isomers (S(+) and R(-)), widely used.

  • Chemistry: Phencyclidine derivative, racemic mixture.

  • Pharmacodynamics: Positive modulation of GABA receptors (lower GABA needed); allosteric agonism (high doses); disinhibitory effects (extrapyramidal pathways, myoclonus); central nervous system (decreased CMRO2, cerebral blood flow, intracranial pressure, increased cerebral perfusion pressure); cardiovascular (minimal, hemodynamic stability); respiratory (minimal, does not usually cause apnea, hyperventilation). endocrine (transient cortisol/aldosterone inhibition). Analgesia more potent with S+ isomer; potency differences in isomers.

  • Pharmacokinetics: Rapid onset (high lipid solubility, vasodilatation, increased drug delivery), redistribution, onset 30-60 seconds. Less protein bound; large volume of distribution; rapid hepatic biotransformation; recovery - differences in isomers; salivation/EEG suppression; apoptosis effects - differences in isomers. Inhaled agents affect.

Etomidate

  • Introduction: Phencyclidine derivative, induction of anesthesia, short-term sedation, hemodynamically unstable patients, neurosurgical procedures, trauma.

  • Mechanism of Action: Positive modulation of GABA receptors (lower GABA needed), allosteric agonism, disinhibitory effects (extrapyramidal pathways); central nervous system (decreased CMRO2, cerebral blood flow, intracranial pressure); cardiovascular system (minimal, hemodynamic stability). respiratory, endocrine. adrenal suppression up to 72 hours.

  • Clinical uses: Induction (especially if poor cardiovascular reserve); neurosurgery; trauma (questionable intravascular volume status). Short term sedation for hemodynamically unstable patients.

Midazolam

  • Introduction: Common short-acting benzodiazepine.

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This quiz explores the critical drug interactions and mechanisms in anesthesia. This includes the effects of various anesthetics and their interactions with other medications. Ideal for students and professionals looking to deepen their understanding of pharmacology in anesthesia.

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