Morphine analgesic action

According to Eddy, as quoted by Small, the analgesic action of neopine, n omorphine, 6-acetylneomorphine or 3 6-diacetylneomorphine (p. 218) is definitely less than that of morphine and its corresponding analogues. The first two are about half as toxic as codeine and morphine respectively, and the second pair are more toxic than their morphine analogues. None of the four shows the Straub reaction and the convulsant action is less marked. 

Hamann SR, Martin WR. (1994). Hyperalgesic and analgesic actions of morphine, U50-488, naltrexone, and (-)-lobeline in the rat brainstem. Pharmacol Biochem Behav. 47(1) 197-201. Hamann W, di Vadi PP. (1999). Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. Lancet 353(9152) 560. 

The analgesic action of fentanyl surpasses that of morphine by approximately 100-fold. It has a suppressive action on the respiratory center and slows heart rate. Fentanyl is used in... 

Oxymorphone is 10 times as potent as morphine, with actions similar to those of hydromorphone. Oxymorphone, however, has httle antitussive activity, and as such is a useful analgesic in patients with pulmonary disease who need to retain the ability to cough. 

Delta and kappa receptors can also contribute to analgesia, particularly at spinal level. Although morphine also acts on kappa and delta sites but it is not clear that up to what level they contribute in its analgesic action. 

Analgesic action Salicylates relieve pain by both central and peripheral action. The site of action of central analgesia seems to be the hypothalamus. It does not have cortical action on the reaction component of the pain but raises the threshold to pain perception. Unlike morphine, they do not produce sedation and there is no drug tolerance or dependence and are not effective against visceral pain. 

Buprenorphine is a semi-synthetic derivative of thebaine, one of the opium alkaloids. It is approximately 30 times as potent as morphine. A dose of 0.3 mg intramuscularly has a duration of analgesic action of 6-18 h. Buprenorphine is also effective sublingually. The average bio-availability by this route is about 55%, but absorption is slow and the time to achieve peak plasma concentrations is variable, with a range of 90-360 min. The onset of action is rather slow (5-15 min) after both intramuscular and intravenous administration, possibly due to slow receptor association. Buprenorphine binds to and dissociates from the p receptor very slowly, which may account for its low potential for physical abuse. It also means that buprenorphine-induced respiratory depression is difficult to reverse with naloxone, even with very high doses. Doxapram may in these circumstances be useful. Drowsiness and dizziness are the most common side effects, although they rarely... 

If disturbances of gastrointestinal function prevent the use of oral sustained-release morphine, the fentanyl transdermal system (fentanyl patch) can be used over long periods. Furthermore, buccal transmucosal fentanyl can be used for short episodes of breakthrough pain (see Alternative Routes of Administration). Administration of strong opioids by nasal insufflation has been shown to be efficacious, and nasal preparations are now available in some countries. Approval of such formulations in the USA is growing. In addition, stimulant drugs such as the amphetamines have been shown to enhance the analgesic actions of the opioids and thus may be very useful adjuncts in the patient with chronic pain. 

Dextromethorphan is the dextrorotatory stereoisomer of a methylated derivative of levorphanol. It is purported to be free of addictive properties and produces less constipation than codeine. The usual antitussive dose is 15-30 mg three or four times daily. It is available in many over-the-counter products. Dextromethorphan has also been found to enhance the analgesic action of morphine and presumably other -receptor agonists. However, abuse of its purified (powdered) form has been reported to lead to serious adverse events including death. 

Analgesic efficacy and clinical use Codeine (Honig and Murray, 1984) has a morphine-like action profile with analgesic and antitussive properties. As compared to morphine the analgesic potency is 5—1 Ofold lower. The compound is used for the treatment of mild to moderate pain and for cough inhibition (Eccles,1996). 

Bustamante, D., Miranda, H.F., Pelissier, T., Paeile, C. Analgesic action of clonixin, nifedipine and morphine using the formalin test, Gen. Pharmacol. 1989, 20, 319-322. 

The demonstration of the existence of strictly defined SARs. which is perhaps Ihe most important criterion of drug action at a specific receptor site, has made possible the most important pharmacologic discoveries. For example, the analgesic actions of morphine and related agents, which are indicative of specific receptors, led to die discovery of endogenous opiate peptides, i.e., the leucine and methionine enkephalins and endorphins. 

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. 

Many attempts have been made to modify the morphine molecule or break it down to some constituent that might retain its analgesic action without its tendency to develop tolerance and addiction. However, only very closely related derivatives of morphine have been found to maintain its analgesic action and still retain to a considerable degree the undesirable potentiality to develop tolerance and addiction. 

Methadone, in general, exerts a pharmacological action similar to that of morphine. Its action on smooth muscle resembles that of meperidine. analgesic potency, but /-methodone is twice as effective. When used in comparable analgesic doses, methadone is as toxic as morphine and exerts the same effects on the pulse rate and respiration as does morphine. Methadone exerts no sedative effect and, hence, is of no value as a preanesthetic agent. 

---