A Cancer Pain Tutorial

A Comprehensive Visual Short Course
on Cancer Pain Management

Opioid Analgesics

This is the major class of analgesics used in the management of moderate and severe pain. Opioids are effective, easily titrated and have a favorable benefit to risk ratio. Opioid tolerance and physical dependence do not equate with addiction Tolerance and physical dependence are physiological states which develop as an expected part of opioid pharmacology. Patients can be withdrawn slowly over a 2-3 week period with careful monitoring and a withdrawal syndrome will not occur.

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Clinical
Information
Opioid addiction is a psychological state manifested by drug seeking behaviors and an unnatural craving for the drug. Clinicians should not be reluctant to give high doses of opioids to patients with advanced disease. It is the clinician's ethical duty to benefit the patient by relieving pain even at the risk of side effects. The clinician's fear of shortening the patient's life by using large doses of opioids is usually unfounded. 

 

Opioid Mechanisms of Action

Opioid receptors bind mu, delta, kappa Receptors can be found in peripheral tissue, the spinal cord, and the central nervous system.

 

Full Morphine-like Agonist

Morphine is the most commonly used opioid agent. It is available in immediate released and sustained action preparations. Other agonists are listed here. These are useful for the patient who experiences dose limiting side effects with one opioid Agonists will not reverse or antagonize the effects of other agonists given simultaneously Full agonists share a very important trait; the effectiveness of full agonists is not limited by a "ceiling effect" with increasing doses. The dose limiting factor is the development of toxicities rather than the attainment of a ceiling. The ceiling effect is the pharmacological term to describe the level of drug in the body above which no additional therapeutic effect is seen as the dose is increased; Only additional drug side effects are seen above the "ceiling".

 

Partial Agonist

This class of agents has less effect than full agonist at the opioid receptor These agents are subject to a ceiling effect, making it less effective analgesics. Examples: buprenorphine

 

Mixed Agonist/Antagonist

These agents block or are neutral at one type of opioid receptor while binding a different opioid receptor.

Mixed agonist/antagonists
are contraindicated in patients receiving an opioid agonist because these agents may precipitate a withdrawal syndrome Their analgesic effectiveness is limited by a dose related ceiling effect.

Examples: pentazocine, butorphanol and nalbuphine.

 

 

 

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Opioid Dosage

Appropriate Dosage

The appropriate dose of an opioid is the amount that controls pain with the fewest side effects.

Titration of Dosage

Keeping toxicity considerations in mind (impaired renal function, time delay, etc.) increase or decrease the next dose by 25-50% of the previous dose. Small modifications when titrating the proper dose are generally ineffective and inappropriate. Since opioid dose/response curves describe logarithmic relationships rather than linear ones, small increases in dose are ineffective. It requires large increases in dose to advance along the curve.

Route Conversion

The parental dose is 1/3 the oral dose because of the Ófirst pass through the liverÓ effect. In changing from the oral to the rectal route begin with the oral dose and titrate upward carefully.

Schedule

Proper dosing requires that the analgesic be given on a regular schedule and not on an as needed basis Rescue doses for breakthrough pain (equaling approximately the hourly dose) should be made available.

Tolerance

Tolerance has not been seen to be a major problem in the typical cancer patient. When a patient requires continually escalating doses, the usual reason is advancing disease. Consider the possibility of a strong emotional component of pain when rapidly escalating doses are required without evidence of advancing disease.

Cessation of Opioids

Patients may become pain free as a result of cancer treatment or an anesthesia or neurodestructive procedure, and they may develop respiratory depression or CNS toxicities when the pain stimulus is removed. Gradually decrease the opioid to avoid withdrawal.

Opioid Therapy in Special Populations

The elderly are more sensitive to the side effects of opioids and usually require lower doses. Children by and large respond the same as adults (See table X for appropriate dosing in children). Tolerance to side effects of opioids develop as it does to other analgesic effects. In the balance, tolerance should be considered beneficial to participants because of that.

 

Routes of Administration

Oral

Preferred because it's convenient and cost effective. The most commonly used opioid morphine is available in tablets (immediate release, sustained release) and liquid various concentrations.

Rectal

Useful when patients have nausea and vomiting Inappropriate when patients have diarrhea or anal/rectal lesions.

Transdermal

Fentanyl, a fat soluble agonist, is available in this form. This route is not suitable for rapid dose titration. Most useful when pain is stable and an alternative route is desirable.

Injection/Infusion

Intravenous and subcutaneous routes provide effective opioid delivery. Avoid the intramuscular route. When intravenous access is not feasible, a subcutaneous opioid infusion is practical and effective.

Patient Controlled Analgesia

Patient Controlled Analgesia (PCA) matches drug delivery to the need for analgesia. The opioid may be administered intravenously, subcutaneously, or intraspinally by a portable pump.

Intraspinal

This is an invasive route for patients with intractable pain or intolerable side effects with other routes. The main indication for intraspinal opioids is intractable pain in the lower part of the body particularly bilateral or midline pain. Profound analgesia is possible without motor, sensory, or synthetic blockade. Use of this route requires skill and expertise that is not available in all settings.

Side Effects of Opioid Therapy

Side effects of opioid therapy are common and predictable. Be prepared to use adjuvant agents to counteract the side effects.

Toxicity

Opioids do not damage organs. All the toxicities are reversible. The same can not be said of simpler drugs such as aspirin or acetaminophen. Toxicity of opioid agents is not common. Since there is no ceiling effect of drug dose, very high levels of opioids can be used usually without developing any CNS toxicity. Central nervous system toxicity is the only dose limiting factor in opioid therapy.

  • Delirium
  • Myoclonus
  • Somnolence
  • Seizures

Other Side Effects

Constipation

Constipation is an inevitable side effect Constipation should be treated prophylactically with regularly scheduled dose of a mild laxative or dietary fiber except in elderly patients who may develop bowel obstruction from too much fiber when on opioids.

Nausea and Vomiting

Treat with antiemetics. Monitor the patient for increased sedation. Antiemetics may contribute to sedation when used with opioids.

Respiratory Depression

Patients receiving long term opioid therapy develop a tolerance to respiratory depressant effects. Serious respiratory depression with chronic opioid therapy is unusual. If the opioid dose is not reduced after the block, respiratory depression may be seen after a patient has had a neurolytic block and the stimulus for pain is removed. If a respiratory depression develops that appears dangerous and needs reversing, the reversal is best accomplished by intravenously titrating naloxone slowly to effect rather than by administering a bolus, which could precipitate a pain crisis.

Opioid Drugs Not Recommended

Meperidine

Long term use of mepreidine may lead to seizures because of buildup of the toxic metabolite, (tremor, confusion or seizures), Normeperidine which is more potent than meperidine ,and it has a long half life.

Cannabinoids

Cannabinoids offer no advantage over the synthetic active ingredient (tetrahydrocannabinol [THC]). Side effects are dysphoria, drowsiness, hypertension and bradycardia preclude its use as an analgesic. There may be efficacy as an antiemetic.

Cocaine

No efficacy has been demonstrated with cocaine as an analgesic alone or in combination with opioids.
Note 0:
Usual Adult Dosage means, "Usual dose for adults and children > 50 kg body weight."
Usual Child Dosage means, "Usual dose for adults and children < 50 kg body weight."
Note 1: Relative Potency may be viewed as how the a particular substance, rendered in blue, "stacks up" in potency against a morphine standard, rendered in red.
Note 2: Asingle unadorned letter "h" is the standard metric abbreviation for hour.
 Note 3: Ref: C. Stratton Hill; Guidelines for Treatment of Cancer Pain, Texas Cancer Council PO Box 12097 Austin Texas (512) 463-3190
Note 4: Fentanyl duration may be shorter. Frequent re-evaluation of pain control recommended. Probably best to use for stable pain and in patients not able to take oral medication. Additional narcotics must always be ordered for "breakthrough" pain when using transdermal fentanyl.
 Note 5:Deaths have been reported when transdermal patch was warmed via contace with a hot water bottle and excessive amounts of this extremely potent substance were absorbed transdermally.