A 32-year-old man with a history of alcohol binge drinking and polysubstance use is found down in his hotel room with bottles of alcohol, oxycodone, alprazolam, amphetamine-dextroamphetamine, and tadalafil. When EMS arrives, he appears comatose with pinpoint pupils and oxygen saturation of 80% on room air. He is intubated at the scene and airlifted to the nearest intensive care unit. Body temperature is 95 degrees F (35 degrees C). Creatine phosphokinase is 12,000 U/L. MRI of the brain demonstrates extensive infarcts consistent with acute hypoxic ischemic injury. Which of the following is the likely culprit for his overdose?

Phosphodiesterase-5 (PDE-5) inhibitors

A 28-year-old woman with a past medical history of fibromyalgia presents to her primary care provider for her annual well visit. She reports that her pain has become more severe over the last several weeks and is no longer well-controlled by NSAIDs. She notes that the pain is beginning to interfere with her sleep and that she feels she no longer has energy to take care of her 2-year-old son. Upon questioning, the patient also endorses feeling more down than usual recently, little interest in seeing friends, and difficulty concentrating on her work. She admits to feeling that she would be “better off dead.” The patient feels strongly that the worsening pain is driving these changes in her mood and that she would feel better if her pain was better controlled. Which of the following is the best next step in management?

Ask the patient if she has an idea about how she might hurt herself

Initiate pharmacotherapy with duloxetine and refer for psychotherapy

Ask the patient if she would voluntarily enter a psychiatric hospital

Add acetaminophen and gabapentin to the patient’s pain regimen

Initiate pharmacotherapy with amitriptyline and refer for psychotherapy

A 67-year-old man comes to the clinic for establishment of care. He recently retired and moved to Florida with his wife. His past medical history includes hypertension, diabetes, chronic back pain, and hyperlipidemia. According to the patient, he takes lisinopril, metformin, atorvastatin, acetaminophen, and methadone. His previous doctor prescribed methadone for breakthrough pain as he has been having more severe pain episodes due to the recent move. He is currently out of his methadone and asks for a refill on the prescription. A physical examination is unremarkable except for mild lower extremity edema bilaterally and diffuse lower back pain upon palpation. What is the best initial step in the management of this patient?

Assess the patient's pain medication history

Refer the patient to a pain management clinic

Inform the patient that methadone is not the best option and do not prescribe

Encourage the patient to switch to duloxetine

Prescribe a limited dose of methadone for breakthrough back pain

A 63-year-old man comes to the emergency department because of pain in his left groin for the past hour. The pain began soon after he returned from a walk. He describes it as 8 out of 10 in intensity and vomited once on the way to the hospital. He has had a swelling of the left groin for the past 2 months. He has chronic obstructive pulmonary disease and hypertension. Current medications include amlodipine, albuterol inhaler, and a salmeterol-fluticasone inhaler. He appears uncomfortable. His temperature is 37.4°C (99.3°F), pulse is 101/min, and blood pressure is 126/84 mm Hg. Examination shows a tender bulge on the left side above the inguinal ligament that extends into the left scrotum; lying down or applying external force does not reduce the swelling. Coughing does not make the swelling bulge further. There is no erythema. The abdomen is distended. Bowel sounds are hyperactive. Scattered rhonchi are heard throughout both lung fields. Which of the following is the most appropriate next step in management?

Surgical exploration of the testicle

Pain management modalities for USMLE Step 3: High-Yield Surgery Lessons

💊 Drug class/MOA - The Analgesic Arsenal

NSAIDs/Acetaminophen:
- NSAIDs: Inhibit COX-1/2 enzymes, reducing prostaglandin synthesis.
- Acetaminophen: Weak, reversible COX inhibitor, primarily in the CNS.
Opioids (e.g., Morphine, Fentanyl):
- Agonists at μ-opioid receptors (GPCRs) in CNS and periphery.
Local Anesthetics (e.g., Lidocaine):
- Block voltage-gated Na⁺ channels, preventing nerve impulse propagation.
Adjuvants:
- Gabapentinoids: Block presynaptic voltage-gated Ca²⁺ channels (α2δ subunit).
- Ketamine: Non-competitive NMDA receptor antagonist.

⭐ Gabapentinoids (Gabapentin, Pregabalin) are first-line for neuropathic pain, like diabetic neuropathy or postherpetic neuralgia.

🎯 Clinical Uses - Targeting the Pain

Multimodal approach is standard of care. Use agents with different mechanisms.
Nociceptive Pain (Somatic/Visceral): Responds well to NSAIDs, acetaminophen, and opioids.
Neuropathic Pain: First-line are adjuvants.
- Gabapentinoids (Gabapentin, Pregabalin).
- TCAs (Amitriptyline), SNRIs (Duloxetine).
Regional Anesthesia: Nerve blocks & epidurals provide potent, localized pain control, reducing systemic opioid needs.

⭐ WHO Analgesic Ladder: A stepwise approach for cancer/chronic pain. Start with non-opioids, add weak opioids for moderate pain, then strong opioids for severe pain. Adjuvants can be used at any step.

💊 Adverse Effects - The Side Effect Slate

Drug Class	Key Adverse Effects
Opioids	Respiratory depression, sedation, constipation, miosis, N/V, pruritus
NSAIDs	GI ulcers/bleeding, acute kidney injury (afferent constriction), platelet dysfunction
Acetaminophen	Hepatotoxicity (overdose; toxic metabolite NAPQI)
Local Anesthetics	CNS toxicity (seizures), cardiotoxicity (arrhythmias), methemoglobinemia
Gabapentinoids	Sedation, dizziness, ataxia, peripheral edema

💉 Management - Blocks, Pumps, & More

Regional/Nerve Blocks: Local anesthetic (e.g., bupivacaine) injected near a nerve/plexus (e.g., brachial, femoral) under ultrasound guidance. Provides targeted, opioid-sparing analgesia.
Neuraxial Anesthesia:
- Epidural: Catheter in epidural space for continuous infusion. Slower onset; ideal for labor or prolonged post-op pain.
- Spinal: Single injection into subarachnoid space. Rapid, dense block. ⚠️ Risk: Post-dural puncture headache (PDPH), hypotension.
Patient-Controlled Analgesia (PCA): IV pump for patient-administered opioid boluses with a programmed lockout interval to prevent overdose.

⭐ PCA pumps require vigilant monitoring for respiratory depression, especially in opioid-naïve patients, the elderly, or those with obstructive sleep apnea (OSA).

Epidural Anesthesia Needle Placement in Pregnant Patient

⚠️ Complications - When Relief Goes Wrong

Opioids
- Acute: Respiratory depression (most feared), sedation, miosis, constipation, nausea/vomiting, pruritus, urinary retention.
- Drug Interaction: ⚠️ Serotonin syndrome risk with tramadol/meperidine + SSRIs/MAOIs.
- Chronic: Tolerance, dependence, opioid-induced hyperalgesia, Opioid Use Disorder (OUD).
NSAIDs & Acetaminophen
- NSAIDs: GI bleeding/ulcers, acute kidney injury (afferent constriction), ↑ cardiovascular risk (MI/stroke).
- Acetaminophen: Hepatotoxicity in overdose (toxic metabolite NAPQI).
Regional Anesthesia (Epidural/Spinal)
- Common: Hypotension (sympathectomy), post-dural puncture headache (PDPH).
- Rare but Severe: Epidural hematoma, epidural abscess, nerve damage, Local Anesthetic Systemic Toxicity (LAST).

⭐ Epidural Hematoma: A neurosurgical emergency. Suspect in patients on anticoagulants post-procedure with new motor/sensory deficits or bowel/bladder dysfunction. Requires urgent MRI and decompression.

⚡ Biggest Takeaways

Opioids (morphine) are μ-agonists; key risks are respiratory depression and constipation. Antidote: naloxone.

NSAIDs (ketorolac) inhibit COX, risking GI bleeds and renal injury. Contraindicated in CKD.

Acetaminophen overdose causes hepatotoxicity (treat with N-acetylcysteine); a key part of multimodal analgesia.

Local anesthetics (lidocaine) block Na+ channels. Bupivacaine has significant cardiotoxicity risk.

Regional techniques (epidurals, nerve blocks) are opioid-sparing and offer superior analgesia.

Ketamine (NMDA antagonist) is effective for opioid-tolerant patients and chronic pain syndromes.

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