A 14-year-old boy is brought to the emergency department because of a 4-hour history of vomiting, lethargy, and confusion. Three days ago, he was treated with an over-the-counter medication for fever and runny nose. He is oriented only to person. His blood pressure is 100/70 mm Hg. Examination shows bilateral optic disc swelling and hepatomegaly. His blood glucose concentration is 65 mg/dL. Toxicology screening for serum acetaminophen is negative. The over-the-counter medication that was most likely used by this patient has which of the following additional effects?

Irreversible inhibition of cyclooxygenase-1

Increased partial thromboplastin time

Decreased uric acid elimination

Decreased expression of glycoprotein IIb/IIIa

Irreversible inhibition of ATP synthase

A 72-year-old woman with metastatic ovarian cancer is brought to the physician by her son because she is in immense pain and cries all the time. On a 10-point scale, she rates the pain as an 8 to 9. One week ago, a decision to shift to palliative care was made after she failed to respond to 2 years of multiple chemotherapy regimens. She is now off chemotherapy drugs and has been in hospice care. Current medications include 2 mg morphine intravenously every 2 hours and 650 mg of acetaminophen every 4 to 6 hours. The son is concerned because he read online that increasing the dose of morphine would endanger her breathing. Which of the following is the most appropriate next step in management?

Counsel patient and continue same opioid dose

Change morphine to a non-opioid analgesic

Initiate palliative radiotherapy

Initiate cognitive behavioral therapy

A 68-year-old man presents to his primary care physician with pain that started after he visited his daughter as she moved into her new apartment. The patient states that the pain is likely related to all the traveling he has done and helping his daughter move and set up furniture. The patient has a past medical history of obesity, type II diabetes, multiple concussions while he served in the army, and GERD. He is currently taking metformin, lisinopril, omeprazole, and a multivitamin. On physical exam, pain is elicited upon palpation of the patient's lower back. Flexion of the patient's leg results in pain that travels down the patient's lower extremity. The patient's cardiac, pulmonary, and abdominal exam are within normal limits. Rectal exam reveals normal rectal tone. The patient denies any difficulty caring for himself, defecating, or urinating. Which of the following is the best next step in management?

NSAIDS and activity as tolerated

Oxycodone and activity as tolerated

29-year-old construction worker is brought to the emergency department after falling 10 ft (3 m) from the scaffolding at a construction site. He reports that he landed on his outstretched arms, which are now in severe pain (10/10 on a numeric scale). He has a history of opioid use disorder and is currently on methadone maintenance treatment. His pulse is 100/min, respirations are 20/min, and blood pressure is 140/90 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 98%. He is diaphoretic and in distress. Physical examination shows a hematoma on the patient's right forearm. X-ray of the right arm shows a nondisplaced fracture of the ulna. A CT of the abdomen and pelvis shows no abnormalities. The patient requests pain medication. In addition to managing the patient's injury, which of the following is the most appropriate next step in management?

Scheduled short-acting opioid administration

Administration of buprenorphine

Psychiatric evaluation for drug-seeking behavior

Increase of outpatient methadone regimen

A 45-year-old homeless man presents to the emergency department with a 1-week history of an intensely pruritic, red rash on his hands, wrists, and finger webs. The itching is worse at night. Physical examination reveals small, erythematous papules and burrows. A topical drug with which of the following mechanisms of action is most likely to be effective in treating this condition?

Increase in keratinocyte turnover

Inhibition of histamine-1 receptors

Decrease in peptidoglycan synthesis

Inhibition of nuclear factor-κB

Acute pain management for USMLE Step 3: High-Yield Management Lessons

Pain Principles - The Analgesic Ladder

WHO Analgesic Ladder for Acute Pain Management

The WHO analgesic ladder provides a stepwise framework for managing pain, starting with the least potent drugs and escalating as needed. The goal is to stay ahead of the pain.

Non-opioids: NSAIDs, Acetaminophen.
Weak Opioids: Tramadol, Codeine.
Strong Opioids: Morphine, Hydromorphone, Fentanyl.
Adjuvants: Antidepressants (e.g., TCAs, SNRIs), Anticonvulsants (e.g., Gabapentin).

⭐ By the Clock Dosing: For persistent pain, analgesics should be given at regular intervals ("by the clock") rather than only when the patient requests them ("prn"). This maintains a therapeutic level and prevents breakthrough pain.

Non-Opioids - Foundation First

Acetaminophen (APAP)
- Mechanism: Primarily central COX inhibition. First-line for mild-moderate pain.
- Dosing: Max daily dose 4g. Be aware of combination products (e.g., Percocet).
- Toxicity: Hepatotoxicity in overdose. Antidote: N-acetylcysteine (NAC).
NSAIDs
- Mechanism: Peripheral & central COX-1/2 inhibition, reducing prostaglandins.
- Types:
  - Non-selective: Ibuprofen, Naproxen.
  - Parenteral: Ketorolac (potent, for moderate-severe pain).
  - COX-2 selective: Celecoxib (less GI risk, ↑ CV risk).
- ⚠️ Cautions: Renal insufficiency, peptic ulcer disease, cardiovascular disease, aspirin-exacerbated respiratory disease (AERD).

⭐ Ketorolac use is limited to a maximum of 5 days (cumulative duration for all routes) due to significant risk of GI bleeding and renal toxicity.

Opioids - The Heavy Hitters

Mechanism: Full agonists at central μ-opioid receptors.
Indications: Moderate to severe acute pain.
Common Agents (IV):
- Morphine: The standard for comparison. Causes histamine release (itching, hypotension). Active metabolite (M6G) accumulates in renal failure.
- Hydromorphone (Dilaudid): 5-7x more potent than morphine. Less histamine release; better choice in hemodynamic instability or renal dysfunction.
- Fentanyl: 100x more potent than morphine. Fastest onset, shortest duration. Ideal for procedural pain and in renal/liver failure.
Side Effects: Sedation, respiratory depression, constipation, nausea, miosis.
Antidote: Naloxone.

⭐ Meperidine (Demerol) is generally avoided. Its metabolite, normeperidine, is neurotoxic, accumulates in renal failure, and lowers the seizure threshold.

Adjuncts & Blocks - Beyond the Pill

Systemic Adjuncts:
- Ketamine: Low-dose infusion for severe or opioid-tolerant pain (NMDA antagonist).
- IV Lidocaine: Systemic sodium channel blockade for visceral/neuropathic pain.
- Gabapentinoids: (Gabapentin/Pregabalin) Useful for neuropathic pain components.
- Corticosteroids: (Dexamethasone) Potent anti-inflammatory, reduces opioid needs.
Regional Anesthesia & Nerve Blocks:
- Mechanism: Local anesthetic delivered near nerves to block nociception. Ultrasound guidance is standard of care.
- Benefits: Superior, site-specific analgesia; significant opioid-sparing effect, reduced side effects.

Lower Extremity Nerve Anatomy

⭐ Local Anesthetic Systemic Toxicity (LAST): A rare but life-threatening complication of regional anesthesia. Presents with CNS (tinnitus, metallic taste, seizures) and cardiovascular (arrhythmias, collapse) symptoms. Treat immediately with 20% lipid emulsion therapy.

High-Yield Points - ⚡ Biggest Takeaways

Pain is the fifth vital sign; always assess with a validated scale.

Use multimodal analgesia (e.g., NSAIDs, acetaminophen, opioids) to maximize efficacy and minimize opioid side effects.

NSAIDs and acetaminophen are first-line for mild-to-moderate pain; check contraindications like renal or liver disease.

Reserve opioids for moderate-to-severe pain; monitor for respiratory depression, sedation, and constipation.

Patient-Controlled Analgesia (PCA) offers excellent control for postoperative pain.

Regional nerve blocks can significantly reduce systemic opioid needs for localized pain.

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