Analgesics | The Massachusetts General Hospital Handbook of Neurology

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

> Table of Contents > Drugs > Analgesics

Analgesics

A. See also

Pain, p. 86, for choice of meds.

B. Acetaminophen

650 mg PO/PR q4h prn. Avoid in liver dz.

C. Anticonvulsants

Q.v. p. 161. Valproate or carbamazepine may be stronger than Neurontin, lamotrigine, topiramate.

D. Na channel blockers

Includes local anesthetics and ACDs.

Carbamazepine, valproate, gabapentin: See Anticonvulsants, p. 161.

P.156

Lidocaine: See also ICU Drips, p. 172. When subcutaneous, epinephrine prolongs its action.
Mexiletine: Check EKG first. Start mexiletine slowly to avoid GI side effects: 150 mg PO qd, then increase slowly to 300 mg tid; check level.

E. Nonsteroidal anti-inflammatory drugs (NSAIDS)

For most types of pain; particularly bone pain, inflammation.

Dosing: Ketorolac (Toradol) is the only NSAID that can be given IM; it is quick and effective, although expensive. When it is given PO, it has no more effect than ibuprofen. Ibuprofen PO may work more quickly PO than naproxen, although the latter requires less frequent dosing.
Side effects: In one overall toxicity index, from safest to worst is salsalate > ibuprofen > naproxen > sulindac > piroxicam > fenoprofen > ketoprofen > meclofenamate > tolmectin > indomethacin.
- Heart: COX-2 NSAIDS increase MI risk 30%-100%; nonselective NSAIDS about 10%.
- CNS: Rebound after NSAID is stopped. Tinnitus with high doses. Rare aseptic meningitis.
  - On the other hand: NSAIDS may lower the risk of Alzheimer's and Parkinson's.
- GI: Nausea, bleeding. Consider checking stool guaiacs; GI prophylaxis, NSAIDS with reportedly fewer GI side effects (e.g., Trilisate), or giving in conjunction with misoprostol.
- Antiplatelet: Salsalate (Disalcid) may impair platelets the least.
- Renal: Fluid retention, decreased GFR. Can cause acute renal failure in high-catecholamine states. Long-term use can cause interstitial nephritis.

F. Norepinephrine reuptake inhibitors

Analgesic effect is duloxetine >> venlafaxine > bupropion. Note: SSRIs have no analgesic effect. Duloxetine seems particularly useful for somatization; see Table 28, p. 105.

G. Opiates

Underutilized for acute (e.g., post-op) pain. In chronic pain, do not confuse physical dependency (withdrawal sx when stopped suddenly) with addiction (escalating dose requirements without other evidence of dz progression).

Dosing:
- Longest acting opiates: MS Contin, methadone, levorphanol, fentanyl patch. These are less likely to produce euphoria and dependence than short-acting opiates.
- IV drip management: When dose is increased, bolus with the difference, or it may take 12-24 h to reach new steady-state level.
Combination therapy: Adding acetaminophen or an NSAID can decrease the need for opiates, even if they were not effective as single agents.
Overdose:
- H&P: Dry mouth, dizziness, constipation, low BP. CNS and respiratory depression with small pupils.
- Rx: For respiratory depression, naloxone 2 mg IV; if only altered mental status, can try 0.4-0.8 mg. If pt responds, give additional doses, preferably as continuous drip. Beware of severe withdrawal sx in addicted pts.

P.157

Withdrawal: From abrupt cessation of heavy prolonged use.
- H&P: Muscle aches, lacrimation or rhinorrhea, pupillary dilation, sweating, diarrhea, yawning, fever, insomnia.
- Rx: Clonidine 0.15 mg PO bid, methadone 40 mg PO bid.
Side effects: Confusion, hypoventilation, constipation, addiction. Differences in side effects may be folk neurology hard to prove in controlled trials.
- Analgesic rebound: Can cause headache when opiate is discontinued, leading to a vicious cycle of dependence.
- Sedation: Try modafinil or methylphenidate. Sedation dissipates with chronic use.
- Constipation: Does not improve with chronic use. Put everyone on 2 senna tabs tid, metoclopramide 10 mg tid (only in pts at low risk for movement disorders), colace 100 mg tid. Lactulose or polyethylene glycol (Miralax) is a good bail-out. Oral Narcan can treat opiate-induced ileus: give 2-3 amp PO (or as enema) q4h until bowel movement.
- Seizures and myoclonus when doses high.

H. TCAs

See Antidepressants, p. 164. For neuropathic pain. Third-line for pain because of their many SEs.

Table 41. Rough comparison of opioid side effects.

Opioid	Comparative Side Effect Profiles (rough)
Morphine, MS Contin (slow release)	Smooth muscle relaxation (cardiac, vascular, GI); respiratory and psychiatric depression; more nausea and itching than hydromorphone
Meperidine (Demerol)	Fast acting, blocks shivering, metabolite buildup lowers seizure threshold, risk of hypotension and cardiac arrest; Vistaril does not help the nausea; MAOI interaction
Hydromorphone (Dilaudid), Fentanyl	Very addictive; respiratory depression, increased ICPs, hypotension, myoclonus Patch available; used for sedation in ICU; causes spasm of sphincter of Oddi, urinary retention, constipation, high ICPs, bradyarrhythmias
Oxycodone, Oxycontin (slow release)	Pure agonist opioid; causes constipation, depression, can be ground and abused; similar side effect profile to morphine
Methadone	Mu-receptor agonist; delayed onset, no high but still dependence potential; used in heroin detox under supervision, useful for severe chronic pain
Codeine	Very weak for pain relief, mostly used for antitussive properties but some dependence and abuse

P.158

Table 42. Equivalent narcotic doses, in mg.

Narcotic	IM/IV	PO	Action
Butorphanol	2		3-4 h
Codeine	120	200	4-6 h
Fentanyl	0.1		1-2 h
Hydrocodone	1.5	7.5	4-5 h
Hydromorphone	1.5	7.5	4-5 h
Levorphanol	2	4	6-8 h
Meperidine	75	300	2-4 h
Methadone	10	20	4-6 h
Morphine	10	60	3-7 h
Nalbuphine	10		3-6 h
Oxycodone	15	30	4-6 h
Oxymorphone	1	6	3-6 h
Pentazocine	30	150	2-3 h
Propoxyphene		130	4-6 h