A 38-year-old man presents with sudden onset abdominal pain and undergoes an emergent laparoscopic appendectomy. The procedure is performed quickly, without any complications, and the patient is transferred to the post-operative care unit. A little while later, the patient complains of seeing people in his room and hearing voices talking to him. The patient has no prior medical or psychiatric history and does not take any regular medications. What is the mechanism of action of the anesthetic most likely responsible for this patient’s symptoms?

N-methyl-D-aspartate receptor antagonism

Stimulation of μ-opioid receptors

Increased duration of GABA-gated chloride channel opening

Blocking the fast voltage-gated Na+ channels

Increased frequency of GABA-gated chloride channel opening

A 28-year-old man comes to the emergency department for an injury sustained while doing construction. Physical examination shows a long, deep, irregular laceration on the lateral aspect of the left forearm with exposed fascia. Prior to surgical repair of the injury, a brachial plexus block is performed using a local anesthetic. Shortly after the nerve block is performed, he complains of dizziness and then loses consciousness. His radial pulse is faint and a continuous cardiac monitor shows a heart rate of 24/min. Which of the following is the most likely mechanism of action of the anesthetic that was administered?

Inactivation of sodium channels

Activation of acetylcholine receptors

Inactivation of ryanodine receptors

Inactivation of potassium channels

Which of the following statements regarding the patch shown in the figure is correct?

Excessive use can result in methemoglobinemia.

It is an equal mixture of local anesthetics.

5 ml of a 5 percent mixture contains 50 mg of lignocaine.

It contains lignocaine and ropivacaine in a ratio of 50 percent each.

It should be applied for at least 2 hours before minor procedures.

You are a resident on an anesthesiology service and are considering using nitrous oxide to assist in placing a laryngeal mask airway (LMA) in your patient, who is about to undergo a minor surgical procedure. You remember that nitrous oxide has a very high minimal alveolar concentration (MAC) compared to other anesthetics. This means that nitrous oxide has:

decreased lipid solubility and decreased potency

no effect on lipid solubility or potency

decreased lipid solubility and increased potency

increased lipid solubility and increased potency

increased lipid solubility and decreased potency

A 42-year-old man is brought in to the emergency department by his daughter. She reports that her father drank heavily for the last 16 years, but he stopped 4 days ago after he decided to quit drinking on his birthday. She also reports that he has been talking about seeing cats running in his room since this morning, although there were no cats. There is no history of any known medical problems or any other substance use. On physical examination, his temperature is 38.4ºC (101.2ºF), heart rate is 116/min, blood pressure is 160/94 mm Hg, and respiratory rate is 22/min. He is severely agitated and is not oriented to his name, time, or place. On physical examination, profuse perspiration and tremors are present. Which of the following best describes the pathophysiologic mechanism underlying his condition?

Increased activity of NMDA receptors

Increased influx of chloride ions

Increased inhibition of norepinephrine

Increased inhibition of glutamate

Intravenous anesthetics for USMLE Step 3: High-Yield Pharmacology Lessons

IV Anesthetics - The Off-Switches

GABA-A receptor and anesthetic binding sites

Propofol: Potentiates GABA-A. Rapid induction/recovery. Causes hypotension, apnea, hypertriglyceridemia. Milky appearance.
Etomidate: Potentiates GABA-A. Hemodynamically neutral, ideal for cardiac patients. ⚠️ Causes adrenocortical suppression.
Ketamine: NMDA receptor antagonist. Dissociative anesthesia. Causes bronchodilation, ↑HR, ↑BP. Emergence reactions.
Benzodiazepines (Midazolam): Potentiates GABA-A. Used for sedation and amnesia. Minimal cardiorespiratory depression.

⭐ Ketamine provides analgesia and amnesia while maintaining airway reflexes. Its sympathomimetic effects (↑BP, ↑HR) make it invaluable in trauma and hypotensive states.

Barbiturates & Benzos - GABA's Big Boost

Barbiturates (e.g., Thiopental, Methohexital)
- MOA: ↑ Duration of $GABA_A$ chloride channel opening.
- Kinetics: High lipid solubility causes rapid onset and redistribution.
- Effects: Potent cerebral vasoconstrictor (↓ ICP), but severe respiratory and cardiovascular depressant.
- ⚠️ Contraindicated in acute intermittent porphyria.
Benzodiazepines (e.g., Midazolam, Diazepam)
- MOA: ↑ Frequency of $GABA_A$ chloride channel opening.
- Effects: Slower onset; profound anterograde amnesia and anxiolysis.
- 💡 Reversible with Flumazenil.

⭐ Midazolam is favored for procedural sedation due to its potent amnesic effects, often leaving patients with no memory of the event.

GABA-A receptor with anesthetic binding sites

Propofol - Milk of Amnesia

Mechanism: Potentiates the GABA-A receptor, increasing the duration of Cl⁻ channel opening, leading to neuronal hyperpolarization.
Pharmacokinetics:
- Onset: Rapid (< 1 min).
- Duration: Short (~10 min) due to rapid redistribution from the CNS to peripheral tissues.
- Highly lipophilic; appears as a white emulsion. 📌 "Milk of amnesia."
Clinical Use:
- Induction and maintenance of general anesthesia.
- Sedation for procedures and in the ICU.
Adverse Effects:
- Significant hypotension (↓SVR) & respiratory depression.
- ⚠️ Propofol Infusion Syndrome (PRIS): With prolonged, high-dose infusions → metabolic acidosis, rhabdomyolysis, cardiac failure.

⭐ Unique Property: Possesses anti-emetic effects, making it useful for preventing postoperative nausea and vomiting (PONV).

GABA-A receptor and drug binding sites

Etomidate - The Stable Sleeper

MOA: Potentiates GABA-A receptor activity, increasing the duration of Cl⁻ channel opening.
Key Feature: Unique hemodynamic stability-minimal change in BP, HR, or cardiac output. Ideal for elderly, trauma, or cardiac-compromised patients.
Adverse Effects:
- Adrenocortical suppression (inhibits 11β-hydroxylase) → ↓ cortisol.
- Myoclonus during induction.
- High incidence of postoperative nausea/vomiting (PONV).

⭐ Preferred for rapid sequence intubation (RSI) in hypotensive patients due to its cardiovascular stability.

Intravenous Anesthetics: Receptors and Cerebral Effects

Ketamine - The Dissociative Trip

Mechanism: Potent NMDA receptor antagonist; blocks excitatory glutamate.
Clinical Profile: Creates "dissociative anesthesia" (catatonia, amnesia, analgesia with eyes open).
- Cardiovascular: Sympathomimetic → ↑BP, ↑HR, ↑CO. Ideal for shock/trauma.
- Respiratory: Potent bronchodilator; minimal respiratory depression.
Adverse Effects:
- Emergence reactions: Disorientation, hallucinations, vivid dreams. (Co-administer benzodiazepines to mitigate).
- ↑ Intracranial pressure (ICP), ↑ cerebral oxygen consumption.

⭐ Exam Favorite: Unlike other anesthetics, Ketamine is a cardiovascular stimulant, making it a preferred agent for hemodynamically unstable patients.

Ketamine mechanism of action on NMDA receptor and pathways

High‑Yield Points - ⚡ Biggest Takeaways

Propofol offers rapid onset and recovery and is antiemetic, but causes significant hypotension and apnea.

Ketamine is an NMDA receptor antagonist that causes dissociative anesthesia and bronchodilation while increasing heart rate and blood pressure.

Etomidate is hemodynamically neutral, making it ideal for cardiac-unstable patients, but it causes adrenocortical suppression.

Thiopental's short duration of action is due to rapid redistribution from the CNS to peripheral tissues.

Midazolam provides excellent amnesia and anxiolysis; its sedative effects are reversible with flumazenil.

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