Tolerance narcotic analgesics

Tolerance Some patients develop tolerance to the narcotic analgesic. This may occur after days or months of continuous therapy. The dose generally needs to be increased to obtain adequate analgesia. 

Non-narcotic analgesics, unlike the NSAIDs, have little or no anti-inflammatory activity. They have a therapeutic advantage over narcotic analgesics in that they do not cause physical dependence or tolerance. 

Ketorolac is, hke several other NSAIDs, promoted as a non-narcotic analgesic. This is merely a marketing ploy, which does not reflect any special characteristics, except that it is one of many NSAIDs that can be given parent-erally. A pyrrolizine carboxylic acid derivative, it is strnc-turally and pharmacologically related to tolmetin, zomepirac, and indometacin. The trometamol salt of ketorolac enhances its solubility and allows parenteral administration single intramuscular injections are better tolerated than morphine. 

Rimazolium is a non-narcotic analgesic that strongly potentiates the analgesic and antagonizes the respiratory depressant effect of morphine alkaloids in animals and prevents the development of tolerance to morphine in animals and humans (1). Although rimazohum is not a new drug, experience with it is very hmited. 

Tolerance, Dependence, and Addiction Liability. Patients treated with long-term opioid therapy often develop tolerance and usually become physically dependent on narcotic analgesics as well. Tolerance results when exposure to a drug results in its decreased effectiveness with time and larger doses are required to achieve the same response (26). Physical dependence is also an adaptive state that is characterized by a specific constellation of withdrawal symptoms that occur upon abrupt cessation or significant reduction in the dose of the opioid or administration of an opioid antagonist (26). Addiction, however, is distinct from physical dependence, and "the term addiction should never be used when physical dependence is meant" (22). The... 

The initiation or dose escalation of narcotic analgesics may cause drowsiness and impair cognitive function. Tolerance usually develops fairly quickly to these side effects, but other medications that induce somnolence will produce an additive effect when taken concomitantly. If sedation remains problematic, in order to achieve adequate analgesia a psychostimulant such as caffeine, dexamphetamine, or methylphenidate may be added to counteract the side effect (22). 

Many patients and healthcare providers are concerned that a patient will become addicted to narcotic analgesics or develop a tolerance for these dmgs. Both can occur. However, proper pain management can alleviate these potential problems. 

Asthmatic attacks due to non-narcotic analgesics, mostly occur in patients with so-called intrinsic or idiosyncratic asthma (often associated with nasal polyposis, sinusitis and eosinophilia of the blood) (McFadden and Austen 1977). About 10% of patients with this kind of asthma show severe reactions to aspirin, methyl-salicylate, pyrazolone derivatives, indomethacin, ibuprofen, diclofenac and sometimes even phenacetin and paracetamol. (Sodium salicylate is often tolerated.) The special reactivity may appear only in later life and concerns a number of chemically unrelated drugs. In some of these patients analgesic therapy with a morphine derivative such as pentazocine (Fortalgesic) or hyoscine butylbromide (Buscopan) may be necessary. However, in other patients, those with aspirin urticaria rather than asthma, the reaction may also rely on a drug-specific allergic mechanism (de Weck 1971). 

Since morphine releases histamine from central stores [292] and chronic administration of histamine alters brain catecholamine levels [300], it has also been proposed that opiate-induced changes in central concentrations or tissue levels of other biogenic amines may be initiated by decreases in brain histamine [295], Whilst a role for brain histamine has yet to be determined in the antinociceptive effects of the narcotic analgesics, this amine may interact with one or more other amines to subserve the antinociceptive, tolerance and physical dependence effects of morphine-like agents. 

Tolerance develops to the narcotic and analgesic actions of morphine, so that increasingly larger doses are needed to render patients pain free. Tolerance develops to many effects of morphine such as analgesia, euphoria, narcosis, respiratory depression, hypotension, and antidiuresis. Morphine-induced bradycardia may be experienced. However, no tolerance develops to morphine-induced miosis or constipation. If the administration of morphine is discontinued, the tolerance is lost and the preaddiction analgesic doses of morphine become effective once more. 

Obviously, the risk of causing dependence is an important consideration in the therapeutic use of these drugs. Despite that risk, under no circumstances should adequate pain relief ever be withheld simply because an opioid exhibits potential for abuse or because legislative controls complicate the process of prescribing narcotics. Furthermore, certain principles can be observed by the clinician to minimize problems presented by tolerance and dependence when using opioid analgesics ... 

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