What is tamadol?
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Tramadol is a centrally acting synthetic analgesic of the aminocyclohexanol group with opioid-like effects. Its mode of action is not completely understood but it appears to act by modifying transmission of pain impulses via inhibition of noradrenaline and serotonin re-uptake and also by weakly binding to mu-opioid receptors.

How its work
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Tramadol may work as a pain blocker and may have a very mild antidepressant benefit. Alternatives include non-medication modalities, pain interventions and other medications that may work in a similar manner.

Tramadol has become a standard analgesic for the treatment of moderate to moderately-severe or severe pain; it is a stronger alternative to NSAIDS and an alternative to lower-dose morphine. Scheduling of tramadol would restrict its legitimate therapeutic use and worsen the existing under treatment of pain.

Thus given the already minimal levels of abuse, scheduling tramadol will have little or no impact on abuse and will only increase the potential for harming patients. The nature of the increased potential harm comes from
1) continued under treatment of pain;
2) increased use of NSAIDS;
3) increased use of potent opioids.
This would invert the concept of balancing benefit and risk and undermine the precautionary principle.

Tramadol has demonstrated therapeutic usefulness in the treatment of moderate to moderately-severe or severe pain, e.g. in postoperative and post-traumatic pain, cancer pain, and pain associated with chronic benign diseases. Tramadol’s efficacy overlaps with low doses of morphine.

Classical side effects of morphine-like drugs such as constipation, respiratory depression and sedation are reduced with tramadol.

Studies
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Studies of tramadol extended-release tablets suggest that in addition to relief from pain and improved function, additional benefits of fewer interruptions in sleep and improved compliance may occur. Thus, tramadol is an effective and safe drug for the treatment of pain. As such, tramadol is a unique tool for filling the analgesic gap that exists between NSAIDs and potent prototypic opioids.

It has been recognized for more than a century that the neurotransmitters of the nervous system produce their biological effects through interaction at specific drug binding sites or receptors. These receptors, many of which have been isolated and characterized in the past two decades, are typically specialized proteins on the cell surface. The function of these proteins is to recognize the neurotransmitter and to enable the molecule to bind to the receptor to trigger a biological response— muscle contraction, hormone or neurotransmitter secretion, or increased cardiac rate, for example. These interactions are typically quite specific and are often viewed in terms of a “lock and key”model. Despite this specificity it is usually found that a number of chemical variations around a particular structure can also be accommodated at the receptor site.

When these chemical variants can also trigger the biological response they
are termed “agonists.” However, some molecules can bind to the receptor and not trigger the response, but rather block the response: these drugs are termed “antagonists.”Thus, for example, the naturally occurring atropine from the Belladonna plant can block the actions of the neurotransmitter acetylcholine in the parasympathetic system by interacting with the same receptors that acetylcholine uses.

The alkaloids in opium, including morphine, also interact with specific receptors (opiate receptors) within the central and peripheral nervous systems. At these receptors, the alkaloids in opium mimic the effects of the body’s natural opiates.

There are actually three major structural classes of opiates that occur in the body: enkephalins, endorphins, and dynorphins. The existence of these endogenous molecules was initially theorized because morphine and related drugs had been shown to exert their pharmacological and therapeutic effects through interaction at specific receptors.Due to the specific locations of these interactions, scientists postulated that there must exist corresponding endogenous physiologically employed molecules. A similar argument was employed in the search for the endogenous equivalent of the cannabinoids found in marijuana and led to the recognition of the so-called “endocannabinoid” system.

There are three principal classes of opiate receptors, designated m, k, and d, and there exist a number of drugs that are specific for each of these receptor types. However, most of the clinically used opiates are quite selective for the mÙreceptor: the endogenous opiates enkephalin, endorphin and dynorphin are selective for the mÙand d, d and k receptors respectively.When activated by opioids these receptors produce biochemical signals that block neurotransmitter release from nerve terminals, a process that underlies their blockade of pain signaling pathways as well as other effects, such as constipation, diuresis, euphoria, and feeding.

Brief administration of opioids leads to the development of acute tolerance, whereby increased quantities of the opioid are required to produce the same end result, but this process is rapidly reversed once the administration is ceased.

However, more prolonged administration leads to classical or chronic tolerance from which state recovery to full sensitivity make take several days. These phenomena are not unique to opioid drugs, but rather are common to virtually all drug-receptor interactions and appear to be a common property of pharmacological receptors. Tolerance may also be associated with the state of physical dependence. The chronic administration of a drug, in this context an opioid, may result in a resetting of homeostatic mechanisms, and maintenance of this new state requires continued drug administration. Cessation of drug administration can then result in the phenomenon of withdrawal, during which the nervous system is excessively perturbed as it readapts to its original drug-free state. It should be emphasized that tolerance and physical dependence are physiological responses to continued administration of opioids and are not, contrary to some popular opinion, predictors of addiction. For example, patients with severe pain from bone cancer require very large amounts of opioids, yet these patients do not become addicted and will not even show withdrawal if the drug doses are reduced slowly over a period of days. Unfortunately, misinformation about opioids has led to patients with severe pain being undertreated.