- 1 Pharmacology
- 2 Available opioid analgesics
- 3 Effectiveness
- 4 Administration
- 5 Adverse effects
- 6 References
Opioid analgesics, also called narcotics, are drugs usually used for treating pain. Opioid analgesics are defined as "all of the natural and semisynthetic alkaloid derivatives from opium, their pharmacologically similar synthetic surrogates, as well as all other compounds whose opioid-like actions are blocked by the nonselective opioid receptor antagonist naloxone.
There a several opioid receptors. All are G-protein-coupled cell surface receptors. Clinically useful analgesic families vary in their receptor effects; they range from pure agonists of all receptor types, to selective agonists, to agonist-antagonists.
Reduced metabolizers of codeine, tramadol, oxycodone, hydrocodone may have reduced effect due to decreased conversion to morphine.
Available opioid analgesics
Current opioid analgesics are below 
A number of oral forms are combined with acetaminophen to reduce the possibility of diversion to injected abuse, although acetaminophen also has a distinct and potentially synergistic analgesic effect. Acetaminophen has been found to be more toxic, with or without opioids, than had been generally believed, and the FDA has recommended restrictions on its uses. The American Pain Foundation is concerned that these recommendations consider the matter carefully, lest there be undertreatment with appropriate opioids.  Combination with aspirin and other non-narcotic agents was common before the widespread use of acetaminophen
|Specific drug||Potency relative to oral morphine||Chemical class||Receptor action||Metabolism||Comments|
|Naturally occurring opium alkaloids|
|Morphine||1||morphine||mu, kappa (weak)|
|Codeine||0.15||codeine||mu (partial agonist)||Good oral absorption|
|Diacetylmorphine (heroin)||1||morphine||mu, kappa (weak)||Faster blood-brain transfer than morphine but both produce the same primary active metabolite (morphine prodrug)|
|Oxycodone||1.5||thebaine/codeine||mu (partial)||Oxycodone may increase mortality relative to codeine and hydrocodone and may cause more drug toxicity in geriatrics than codeine or hydrocodone.|
|Hydromorphone (Dilaudid)||4||thebaine||mu||Mostly hepatic||Oral bioavailability is approximately 24%|
|Buprenorphine||thebaine||mu, antagonist of delta and kappa|
|Fully synthetic opioids|
|Meperidine||0.1||Meperidine||mu||Good oral absorption; toxic metabolite accumulates on prolonged use|
|Fentanyl||2.4||Meperidine||mu||Transdermal and transmucosal absorption|
|Methadone||3||methadone||mu||Good oral absorption. Bioavailability of methadone ranges between 36 to 100%. Different half-lives for analgesia and for blocking withdrawal|
|Tramadol||0.1||tramadol||mu||Also inhibits monoamine oxidase; can raise norepinephrine and serotonin, and cause serotonin syndrome|
|Propoxyphene||0.23||propoxyphene||mu||L-isomer is antitussive; analgesic D-isomer was removed from the U.S. market as too risky for its limited effectiveness.|
Opioids are commonly prescribed for pain, and their usage may be increasing. In emergency rooms, non-Hispanic white patients are more likely to receive narcotics than patients of other ethnicities.
Opioids are effective for short term use (1-16 weeks).
Chronic benign pain
The role of long term treatment of chronic non-cancer pain is not clear.
- A systematic review by the Cochrane Collaboration found "weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive."
- A systematic review by the Agency for Healthcare Research and Quality found that "evidence on long-term opioid therapy for chronic pain is very limited but suggests an increased risk of serious harms that appears to be dose-dependent".
One systematic review found that trials of short term opioids did not improve functional status compared to placebo in chronic pain. However, a second systematic review, found that opioids improved functional status compared to placebo, but not compared to other drugs.
Most trials are funded by industry.
Tables of morphine equivalent daily dose and IV to PO conversion are available to help dosing, but must be used with caution. Some opioids, such as methadone, do not lend themselves to simple conversion due to greatly differing half-lives. While an antagonist or partial antagonist may have equianalgesic dosing in an opioid-naive patient, switching from, for example, long-term morphine to buprenorphine can cause withdrawal.
Routes of administration
Most opioids can be administered parenterally. Recent developments have provided alternate formulation that improve oral effectiveness of drugs historically injected, such as morphine.
Novel routes are being found effective, such as transdermal skin patches that provide a constant low-rate dose, and transmucosal and intranasal routes for quick action.
Fear of addiction had long interfered with the extended use of opioids even in terminal patients. Current practice, however, includes the indefinite use of opioids in nonterminal patients with pain that can only be controlled by opioids. The World Health Organization, for example, has a "pain pyramid" for rheumatic disease, which begins with acetaminophen or equivalents, and moves to increasingly powerful opioids. Long-term opioid therapy is prescribed both for analgesia, and also the treatment of opioid dependence.
Mortality may be increased upon both starting and topic opioid maintenance.
Advice for using administering chronic narcotics and for treating acute pain among patients on chronic methadone is available. Special technique may also be needed for patients receiving buprenorphine for chronic pain.
There are challenges in prescribing opioids with specialized actions, such as partial agonists and mixed agonist/antagonists. These may interfere with the effectiveness of breakthrough medications for additional acute pain. Such drugs also may be ineffective or produce withdrawal in patients receiving other long-term opioids.
Monitoring chronic use
Appropriate use may be improved with prescription-drug monitoring programs in which prescribers can track all opioid prescriptions for a patient. In the United States, the U.S. Department of Justice's Drug Enforcement Administration coordinates the State Prescription Drug Monitoring Programs. Prescription-drug monitoring programs have been studied for the Ohio Automated Rx Reporting System (OARRS). Two additional systems under development are bu the United States Department of Health and Human Services and one by the Department of Justice.
- Immunoassay. Immunoassay is available rapidly and at the point of care, but does not reliably detect semisynthetic and synthetic opioids.
- Chromatography - either gas chromatography-mass spectrometry (GC-MS) or high-pressure liquid chromatography (HPLC) detects all opioids.
Oxycodone and codeine may increase mortality relative to codeine and hydrocodone and may cause more drug toxicity in geriatrics than codeine or hydrocodone. In contrast to hydrocodone, oxycodone and codeine and metabolized by cytochrome P-450 CYP2D6 which may lead to variable pharmacokinetics due to single-nucleotide polymorphisms and drug interactions.
Constipation may be reduced by methylnaltrexone, a mu-opioid receptor antagonist. In a randomized controlled trial of patients with advanced illness, 48% of patients receiving methylnaltrexone had a bowel movement compared to 15% of patients received placebo (number needed to treat = 3.0. Click here to adjust these results for patients at higher or lower risk.) Although mu-receptors provide analgesia, methylnaltrexone is a charged quaternary amine so that it does not well cross the blood-brain barrier. Methylnaltrexone can also help patients taking chronic opiates for non-malingnant pain.
Dietary agents and inert physical agents may help. A high-fiber diet is desirable, possibly with fiber supplements such as psyllium and metacellulose. The stool softener docusate is often prescribed. Stronger laxatives are not desirable.
In addition, lack of employment may be a predictor of aberrant use of prescription opioids.
Opioid agonist therapy includes buprenorphine and methadone. Although buprenorphine–naloxone may be less effective than methadone, it has more predictable dosing, and can be prescribed by qualifying office-based physicians.
Mortality and Overdose
Death from overdose on opioids may be more common than traffic accidents in the United States. The rate of overdose is increasing faster among women and men according to the Centers for Disease Controll.
Chronic use of the equivalent of more than 20 mg/day of morphine may lead to unintentional or intentional overdose.
In veterinary medicine, there is a maximum effective analgesic dose of buprenorphine, although the frequency of administration may usefully be increased.
With chronic use for treatment of pain, dependency may lead to substance abuse and "aberrant medication-taking behaviors" may occur. From 2000-2005, the abuse of prescribed opiods, especially oxycodone extended release (OxyContin) and hydrocodone, has increased. From Contracts may reduce abuse, but comparative studies provide conflicting results. Most agreements stated, "patients agreed not to abuse illicit drugs or alcohol, obtain opioids from more than 1 provider or pharmacy, or request a refill before the previous prescription should have been completed."
Pruritis from histamine release may occur. Anecdotally, one of the reason for using antihistamines as adjuvants, such as hydroxyzine and promethazine, are to alleviate some of these side effects, as well as nausea. The less sedating hydroxyzine also may potentiate analgesia and have a better antipruritic effect although promethazine may be stronger against nausea.
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- need to dig up the Cornell handbook
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