6.2 Adjuvant Analgesics

6.2 Adjuvant Analgesics

An adjuvant analgesic (co-analgesic) is a drug whose primary label may not be pain, but which reduces a specific pain mechanism. On the CHPN exam, adjuvants are tested as risk/benefit add-ons. The stem that fails candidates is the one where severe nociceptive cancer pain is treated with gabapentin instead of an opioid. Adjuvants do not replace morphine for a 9/10 pancreatic mass. They sit on top of an appropriate opioid when the mechanism calls for them.

Think in mechanisms, not in a shopping list:

• Damaged nerve (burning, shooting, allodynia) → gabapentinoid, SNRI, or cautious TCA, plus topical lidocaine if the area is focal.
• Prostaglandin-rich bone or tissue inflammation → NSAID if safe, or dexamethasone.
• Peritumoral edema (brain metastases, cord compression, liver-capsule stretch) → dexamethasone.
• Upper-motor-neuron spasm → baclofen.
• Opioid-refractory neuropathic or mixed pain after specialist review → ketamine.

Gabapentinoids: neuropathic pain, renal dosing

Gabapentin and pregabalin bind the alpha-2-delta subunit of voltage-gated calcium channels and reduce excitatory neurotransmitter release in damaged nerves. They are first-line oral adjuvants for chemotherapy-induced peripheral neuropathy, malignant plexopathy, post-herpetic neuralgia, and mixed neuropathic cancer pain.

Both are cleared by the kidney. That is the CHPN safety fact. A dying patient with a creatinine of 2.4 mg/dL who is started on gabapentin 300 mg three times daily will become sedated, ataxic, and myoclonic, and the team will blame the opioid. Renally dose from the start. In frail older adults, start low (often 100 mg at bedtime for gabapentin, or 25–50 mg of pregabalin) and titrate to effect every few days, not every few hours.

Pregabalin has more linear oral absorption than gabapentin, so milligram titration is more predictable, but it is still a renal drug. Neither gabapentinoid is an opioid. Neither treats a pathologic femoral fracture as monotherapy.

SNRIs and tricyclics

Duloxetine and venlafaxine are serotonin/norepinephrine reuptake inhibitors with evidence in neuropathic pain, including diabetic neuropathy and, for duloxetine, chemotherapy-induced peripheral neuropathy. They can also treat comorbid depression, which is not a reason to skip the pain indication. Watch for hyponatremia, nausea, and — with venlafaxine — blood-pressure rise and withdrawal if stopped abruptly. Do not combine casually with tramadol (Section 6.1) or other serotonergic agents.

Amitriptyline and nortriptyline are tricyclic antidepressants used at lower-than-antidepressant doses for neuropathic pain. They are anticholinergic. In an older hospice patient that means constipation on top of opioid constipation, urinary retention, dry mouth, blurred vision, tachycardia, and delirium. Amitriptyline is the worst of the two. Nortriptyline (a secondary amine) is somewhat less anticholinergic and is the TCA more often still considered, but it is still used with caution in the elderly, not as a default sleep aid that happens to treat pain. Cardiac conduction disease is another reason to pick an SNRI or gabapentinoid instead.

Dexamethasone: bone, liver capsule, brain metastases, cord compression

Dexamethasone is the high-yield corticosteroid on this exam. It reduces peritumoral edema and inflammatory cytokine signaling. Four hospice pictures should make you reach for it in addition to an opioid, not instead of one:

1. Painful bone metastases, especially with inflammatory night pain, when an NSAID is unsafe or insufficient.
2. Hepatic capsule stretch from bulky liver metastases — sharp right-upper-quadrant pain worse with inspiration or position.
3. Brain metastases with headache, nausea, or focal signs from vasogenic edema.
4. Malignant spinal cord compression — new back pain, leg weakness, bowel/bladder change — where dexamethasone is disease-modifying while radiation or surgery is arranged.

Typical CHPN-level teaching ranges (always follow the agency and the prescriber): about 4–8 mg daily for bone or liver-capsule pain; often 8–16 mg daily (sometimes higher initially) for brain metastases or cord compression. Give once daily in the morning when possible to limit insomnia. Monitor hyperglycemia, oral thrush, agitation or steroid psychosis, and proximal myopathy if use is prolonged. In the last days of life, the benefit-to-burden ratio is still often favorable for cord compression and capsular pain.

NSAIDs as adjuvants, topical lidocaine, ketamine, baclofen

NSAIDs as adjuvants are the same drugs as in 6.1, now named correctly as co-analgesics for bone and inflammatory pain sitting beside an opioid. The GI, renal, and platelet cautions do not disappear because the opioid is on board. Combining an NSAID with dexamethasone raises gastrointestinal bleed risk; that combination is a classic question trap.

Topical lidocaine (5% patch or gel on intact skin) is for focal neuropathic allodynia — a strip of chest-wall pain after thoracotomy or a dermatomal band after herpes zoster. Systemic absorption is low when used as labeled. It will not treat visceral pancreatic pain or diffuse bone pain.

Ketamine is an NMDA-receptor antagonist used for refractory neuropathic or mixed pain after ordinary opioids and adjuvants have failed. It is specialist territory (palliative medicine, pain, or anesthesia). Adverse effects include dysphoria, hallucinations, hypertension, and tachycardia. The floor nurse does not start ketamine from a standing hospice admission kit.

Baclofen is a GABA-B agonist for spasticity from upper-motor-neuron disease (multiple sclerosis, ALS, spinal metastases). It is not a general cancer-pain opioid substitute. Abrupt withdrawal can cause seizures, rebound rigidity, and hallucinations, so a patient who can no longer swallow needs a taper or a route change, not a sudden stop. Baclofen is renally cleared; reduce the dose when GFR falls.

Worked adjuvant example

A 68-year-old with metastatic breast cancer has 8/10 dull chest-wall pain from rib metastases and a burning band of allodynia in the same dermatome after zoster. Creatinine is 1.8 mg/dL (estimated CrCl about 35 mL/min). She already takes morphine ER 15 mg every 12 hours with little relief of the dull pain, and she is not on an SSRI.

Do not stop the opioid. Increase or titrate the morphine for the nociceptive bone pain (6.3) and add mechanism-specific adjuvants: dexamethasone (or an NSAID if platelets and GI risk allow) for bone inflammation, topical lidocaine on the allodynic band, and a renally reduced gabapentin start (not 300 mg three times daily). Duloxetine could be a neuropathic add-on later if the gabapentinoid is not tolerated. Ketamine is not the opening move. Gabapentin alone, with the morphine held, is the wrong architecture.

Adjuvants answer why it hurts that way. Opioids still answer how much it hurts when cancer pain is severe.