Choosing An Opiod

A. WHO ladder approach

The selection of the appropriate analgesic therapy is based on the interplay of the intensity of each patient's pain and current analgesic therapy. Pain intensity can be measured reliably in most patients* with the use of written or verbal numerical rating scales. Pain that is rated 5 or higher on a scale of 0 to 10 interferes with the quality of life and is defined as substantial pain. Pain ratings of 1 to 4 correspond to mild pain; of 5 to 6, to moderate pain; and of 7 to 10, as severe pain. The Three-Step Analgesic Ladder of the World Health Organization uses these three categories of pain to guide analgesic drug therapy (see Figure 1).

Patients receiving no analgesic therapy, who have mild-to-moderate pain should be treated with nonopioid analgesic drugs (step 1). If a patient has mild-to-moderate pain despite taking a nonopioid analgesic, the dose of the nonopioid analgesic should be maximized and a step 2 opioid analgesic (a "mild" opioid such as codeine, hydrocodone or oxycodone) should be added. Patients who have moderate-to-severe pain despite therapy with step 2 opioids require an increase in the dose of the opioid or, if that is not feasible, a change to a step 3 opioid (a "major" opioid such as morphine, hydromorphone or fentanyl).

This method can effectively relieve pain in 80 to 90 percent of patients. Many experts recommend a step 2 opioid as initial therapy for patients with moderate pain and may initiate therapy with a step 3 opioid when pain is severe. Patients who have mild-to-moderate pain persisting while taking a step 3 opioid should have the dose of that opioid increased to an effective level (Levy, 1996).

*Some patients use numbers differently. For these exceptions, pain rated as "4" may be severe, or pain rated as "8" may be very responsive to mild opioids. Clinical judgment is required.



B. Nonopioid analgesics

Nonopioid analgesics include acetaminophen, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). All of these agents have a ceiling effect in analgesia (a maximum dose beyond which analgesic effect does not increase), and all have potential for severe adverse effects.

Acetaminophen is a useful analgesic whose mechanism of action is poorly understood. Excessive doses can cause serious, even fatal, hepatic injury.

NSAIDs (including aspirin) may also be useful analgesics. They work by inhibiting cyclooxygenase (COX), the enzyme that converts arachadonic acid to prostaglandins. NSAIDs vary in their COX-2 selectivity. COX-2 is the enzyme produced in acute inflammation, COX-1 is the one related to many of the adverse effects of the NSAIDs: gastric irritation, renal insufficiency, platelet aggregation inhibition.


C. Opioid analgesics

1. General

In 1682 Sydenham said: "Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium," and it is still true over 300 years later.

a. Pharmacokinetics

Most of the opioids (except methadone and meperidine) have similar first order pharmacokinetics. They are conjugated in the liver and excreted (90 ~ 95%) by the kidney. Peak plasma concentrations are achieved rapidly: 60 ~ 90 minutes after oral administration; 30 minutes after subcutaneous or IM injection; 6 minutes after IV administration. With normal renal clearance, all have half-lives of 3 ~ 4 hours.

b. Dosing

If an immediate-release opioid is given orally for continuous (or stable) pain, it should be dosed every 4 hours. All patients on oral opioids should have access to "prn" or "breakthrough" doses in addition to their regularly scheduled doses. A good rule-of-thumb for breakthrough doses is 10% (5 ~ 15%) of the 24 hour total dose, although some patients may need more.

If pain is uncontrolled after 24 hours (or less if pain is severe), increase the regular dose by 25 ~ 50% for mild to moderate pain and 50 ~ 100% for severe pain.

When a stable 24 dose has been achieved with good pain relief, extended- or sustained-release preparations may be used. Simply divide the 24 hour dose by the dosing method (usually q 12 hours) to calculate the dose.

There is NO MAXIMUM DOSE for opioids: there is no ceiling effect for analgesia and doses are limited only by side effects.

c. Opioid allergy

True anaphylactic reactions to opioids are very rare. Urticaria and broncospasm are more commonly direct effects than allergies. Many side effects are often confused with allergic reactions, but they are adverse effects that are generally easily managed. If true allergy is suspected, an opioid from a different class may be tried.


2. Mild opioids


3 Major Opioids

a. Morphine is the most commonly used opioid because:

b. Fentanyl

c. Hydromorphone

d. Methadone

e. Meperidine (Demerol) is a poor choice for chronic pain therapy because:

  • Poor oral absorption (40%)
  • Short duration of action (half-life 3 hours or less)
  • Principal metabolite (normeperidine) is not analgesic but causes neurotoxicity (tremor, dysphoria, seizures). Normeperidine has a longer half-life than meperidine, thus, it accumulates. It is renally excreted, thus particularly problematic with renal compromise (elderly patients, renal disease, etc.)

Click here to read more about "The Use and Misuse of Demerol"


D. Equianalgesia tables

Equianalgesia tables are used when switching from one opioid to another, or when switching routes of administration. This helps to minimize problems related to underdosing or overdosing. Remember, "equianalgesia" simply refers to how much of drug A is needed to provide the same pain relief as x amount of drug B (note that "potency" refers only to the amount of the drug needed to achieve a given effect, not to its overall ability to relieve pain).

Comparative values are approximate and are achieved by consensus from very limited evidence. Therefore, you must clinically titrate. The only one who can really define the equianalgesic dose is the patient.

If changing opioids because of poor pain relief suspected to be due to tolerance, reduce the dose by 50% to convert.

Charts give values that apply to repeated administration in patients with chronic pain, not to occasional acute use.

IV values should mainly be used when converting from IV to other forms of administration - if starting IV use, always use small doses frequently and titrate up. This is particularly true when using IV administration because of poor pain control with oral administration.