5.1 Pain Management & Palliative Care

Pain Management: Nociceptive and Neuropathic Pain

Pain management requires a strategic, stepwise approach, classifying pain broadly into nociceptive and neuropathic categories to guide pharmacotherapy.

Nociceptive Pain and Opioid Therapy

Nociceptive pain, arising from tissue damage (somatic or visceral), typically responds well to non-opioid analgesics (NSAIDs, acetaminophen) and opioids. When escalating to opioid therapy, clinicians must understand Morphine Milligram Equivalent (MME) calculations to safely rotate or initiate opioids. High MME thresholds (e.g., > 50 MME/day) warrant closer monitoring and co-prescription of naloxone due to increased overdose risk.

MME Conversion Process

To convert a patient from one opioid to another, follow these steps:

1. Calculate the total daily dose (TDD) of the current opioid.
2. Convert the TDD of the current opioid to the oral Morphine Milligram Equivalent (MME) using a standard conversion table.
3. Convert the oral MME to the TDD of the new opioid.
4. Reduce the calculated dose of the new opioid by 25% to 50% to account for incomplete cross-tolerance. (If the patient is experiencing uncontrolled pain, a smaller reduction, e.g., 0-25%, may be appropriate).
5. Divide the new TDD into appropriate intervals.

Common MME Conversion Factors (Oral):

• Morphine: 1
• Oxycodone: 1.5
• Hydrocodone: 1
• Hydromorphone: 4
• Codeine: 0.15

Example calculation: A patient taking oxycodone 20 mg PO Q6H (TDD = 80 mg) needs to switch to oral morphine. 80 mg oxycodone x 1.5 = 120 oral MME. A 25% dose reduction yields 90 mg of oral morphine daily. Divided Q8H, this would be morphine 30 mg PO Q8H.

Neuropathic Pain

Neuropathic pain (e.g., diabetic peripheral neuropathy, post-herpetic neuralgia) arises from somatosensory nervous system lesions or diseases. It often presents as burning, tingling, or shooting pain and responds poorly to traditional NSAIDs or opioids.

First-Line Pharmacologic Options:

• Calcium Channel Alpha-2-Delta Ligands (Gabapentin, Pregabalin):
  • Gabapentin: Must be titrated slowly due to sedation and dizziness. Nonlinear pharmacokinetics (decreased bioavailability at higher doses). Requires renal dose adjustment (CrCl < 60 mL/min).
  • Pregabalin: Linear pharmacokinetics, faster onset, generally better tolerated. Also requires renal adjustment (CrCl < 60 mL/min).
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):
  • Duloxetine: FDA-approved for diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain. Avoid in severe hepatic impairment or CrCl < 30 mL/min.
  • Venlafaxine: Off-label use. Norepinephrine reuptake inhibition primarily occurs at higher doses (≥ 150 mg/day). Can cause dose-dependent hypertension.
• Tricyclic Antidepressants (TCAs):
  • Amitriptyline, Nortriptyline: Effective but limited by anticholinergic (dry mouth, constipation, urinary retention), antihistaminergic (sedation, weight gain), and alpha-blocking (orthostatic hypotension) side effects. Nortriptyline (secondary amine) is generally better tolerated than amitriptyline (tertiary amine). Use with extreme caution in older adults (Beers Criteria).

Opioid-Induced Constipation (OIC)

Unlike opioid-induced nausea or sedation, patients do not develop tolerance to opioid-induced constipation. Prevention is critical. The cornerstone of prophylaxis and initial treatment is a bowel regimen combining a stimulant laxative (e.g., senna, bisacodyl) with or without an osmotic laxative (e.g., PEG 3350). Docusate alone is insufficient.

If traditional laxatives fail, Peripherally Acting Mu-Opioid Receptor Antagonists (PAMORAs) are indicated. They block mu-receptors in the gut without crossing the blood-brain barrier, thereby relieving constipation without reversing central analgesia or precipitating systemic withdrawal.

PAMORAs include:

• Methylnaltrexone (Relistor): Given SC or PO. Renally adjusted (CrCl < 30 mL/min). Contraindicated in known or suspected GI obstruction.
• Naloxegol (Movantik): Given PO. Substrate of CYP3A4 (avoid strong CYP3A4 inhibitors like clarithromycin or ketoconazole, or adjust dose). Renally adjusted (CrCl < 60 mL/min).
• Naldemedine (Symproic): Given PO. Also a CYP3A4 substrate.

Palliative Care Principles

Palliative care aims to improve the quality of life for patients with life-threatening illnesses by managing distressing symptoms. It is applicable early in the course of illness, in conjunction with other therapies.

Common End-of-Life Symptoms and Management:

• Dyspnea: The sensation of breathlessness. Low-dose systemic opioids (e.g., oral or parenteral morphine) are the drug of choice. They alter the perception of breathlessness and reduce the ventilatory drive in response to hypoxia/hypercapnia. Benzodiazepines (e.g., lorazepam) may be added if dyspnea is accompanied by severe anxiety.
• Terminal Secretions ("Death Rattle"): Noisy breathing caused by the accumulation of salivary and bronchial secretions in the oropharynx when the patient is too weak to expectorate. Pharmacologic management involves anticholinergic agents to dry secretions. Options include:
  • Glycopyrrolate: Quaternary amine; does not cross the blood-brain barrier, so it causes fewer central CNS side effects (delirium, sedation) compared to others.
  • Scopolamine: Transdermal patch. Crosses the BBB; can cause sedation and delirium.
  • Atropine: Ophthalmic drops administered sublingually. Crosses the BBB.
• Delirium/Agitation: Treat underlying reversible causes (e.g., pain, urinary retention, constipation). If pharmacotherapy is needed for hyperactive delirium, typical antipsychotics like haloperidol are commonly used. Atypical antipsychotics (e.g., olanzapine, quetiapine) are alternatives.