Non-opioid analgesics.  These pain relievers include aspirin, acetaminophen (Tylenol), non-steroidal anti-inflammatory drugs (NSAIDs), and COX-2 specific inhibitors.  As mild analgesics, they are considered the first rung on the World Health Organization (W.H.O) pain-fighting ladder.  NSAIDs "turn off" non specific prostaglandins, substances produced by the body that contribute to inflammation and pain and the protective lining of the gastro-intestinal tract and platelet function.  Both are most commonly used to treat cancer patients with mild, chronic pain.  They also can be part of the treatment for patients with more severe pain if there's an inflammatory component to their disease and in specific types of pain, such as bone pain.

Comments:  NSAIDs can cause gastrointestinal disturbances, including stomach-lining bleeding and blood platelet problems, and can be toxic to the kidney and liver.  While COX-2 specific inhibitors may offer GI protection and platelet function, FDA advisory committee recommends use with caution in patients with coronary artery disease, high blood pressure and kidney disease.  NSAIDs also can interact with other drugs – even over-the-counter preparations.  Antacids, for instance, can decrease the absorption of NSAIDs, reducing their pain-reliving effect.  Prescription medicines also can have adverse effects when mixed with NSAIDs.  NSAIDs can augment the action of diuretics, lithium, oral hypoglycemic agents and phenytoin (Dilantin).  They also have a "ceiling effect" – meaning there is a dose beyond which an additional amount of drug does not result in additional pain relief.  Some commonly prescribed medications such as Percocet and Vicodin are combinations of opioids and acetaminophen. (Caution: Excess use of such medications can cause health problems related to acetaminophen overdose.)

Adjuvant analgesics.  These agents were originally developed for conditions other than pain, but also are now commonly used for the treatment of pain. Adjuvants can be used alone or with opioid derivatives.  Some examples of adjuvant medications are: Membrane Stabilizing Drugs

Pregabalin (Lyrica), which the FDA approved in December 2004, is related to gabapentin and is also effective in treating neuropathic pain, specifically diabetic peripheral neuropathy and postherpetic neuralgia. It is as effective as gabapentin but at lower doses, which may indicate fewer side effects for patients.

Tricyclic antidepressants (desipramine and nortriptylene, amitriptyline) , atypical antidepressants ( venlafaxine, mirtazapine, duloxetine, escitalopram),  and anticonvulsant (anti-seizure) medications.  These medications have proven effectiveness in treating patients with "neuropathic" pain, or pain caused by an abnormality anywhere in a nerve pathway that disrupts nerve signals.  In cancer, nerve damage and secondary neuropathic pain may be caused by tumor invasion or compression of nerve structures or by certain cancer treatments, such as surgery, radiotherapy or chemotherapy.

Comment: Antidepressants may cause dry mouth, sleepiness, constipation, a drop in blood pressure, or blurred vision.   Older anticonvulsants, such as carbamazepine (Tegretol), clonazepam (Klonopin), Phenytoin (Dilantin), when used without monitoring, may lead to liver problems and a decreased number of red and white blood cells.  Gabapentin (Neurontin), which has proven effectiveness in treating neuropathic pain, is a newer, safer anti-convulsant that generally is well tolerated.   Other anti-convulsants that have been used to treat neuropathic pain include topiramate (Topomax) and lamotrigine (Lamictal).

Anxiety-relieving drugs in the benzodiazepines class may be used to treat muscle spasms that often accompany severe pain.  These include alprazolam (Xanax), clonazepam (Klonopin) and Lorazepam (Ativan)

Comment: Benzodiazepines may cause drowsiness, urinary incontinence and physical dependency.

Muscle Relaxants (Tizanedine), metaxalone, cyclobenzaprine, baclofen.  This group of medication with proven effectiveness developed specifically for treatment of spasm.

Local Anesthetics (lidocaine, bupivacaine, mexiletine)  used for neuropathic and nociceptive pain.  Their mechanism of action is through blockade of sodium channels.

Comment: Disadvantage of local anesthetics include instability of most preparations for oral use (except mexiletine) limiting routes of administration and treatment options, potential for nuerotoxicity and cardiac toxicity and hypersensitivity.

Neuroleptics, such as olanzepine (Zyprexa), often are useful for the side effect of nausea, and in certain instances may help reduce the agitation and suffering associated with pain.
Antihistamines can help relieve itching related to some cancer treatments.

Comment:  Antihistamines may cause drowsiness.

Steroids are more frequently used in Europe than the United States to improve patients' moods, decrease swelling, lessen nausea and improve appetite.

Comment:  Steroids, such as Prednisone, can cause increased appetite, fluid buildup, stomach irritation and bone problems such as osteoporosis.

Opiates or Opioids.  Opioid analgesics are chemically related to morphine, which is extracted from opium poppies or synthesized in a laboratory. They are the mainstays of cancer pain treatment. However, until recently, doctors hesitated to prescribe them due to fear of causing addiction. (Addiction is very uncommon among cancer patients, according to the American Cancer Society.)  Experts sometimes disagree on when to use opiates.  Some agree with the WHO ladder which suggests using mild opiates for moderate pain and then converting to strong opiates if pain persists or worsens.  Others believe it makes more sense to start with a strong – and effective – opiate.

• Long-acting opiates have significant advantages for treating cancer pain.  Taken effectively, patients do not experience the peaks and troughs common to many pain relief treatments.  Frequently, longer-acting opiates are delivered by a skin patch containing fentanyl or by long-acting tablet forms of morphine (MSContin, Kadian, Avinza or Roxanol SR), oxycodone (Oxycontin), Methadone and hydromorphone extended release (Palladone)
• Shorter-acting opiates are effective for "break through" pain and can be used along with the longer-acting drugs.

Opiates may be taken by mouth, delivered by a skin patch or rectal suppository, given by injections into the subcutaneous tissues, intravenously or infused into the patient's epidural or intrathecal space.  Local anesthetics may be given topically or in combination with opioids given intrathecally (into the fluid around the spinal cord) to relieve severe pain and reduce side effects from systemic opioids.

Comments: Opiates can cause drowsiness, nausea, constipation and vomiting, however, these side effects can be minimized with other medications or therapies, and frequently, except for constipation, become less of a problem with regular long-term use of opioids, usually given in one of the long-acting preparations.  Long-term use of opioids also can cause drug tolerance—meaning you may need increasingly larger doses of medication to control pain.