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PROJECT TOPIC AND MATERIAL ON Physicochemical Properties Of Pycnanthus Angolensis Seed Oil
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Chemistry and Therapeutic Effects of Analgesics is an effort to bring together various work (publications) on the chemistry of drugs with analgesic properties and their therapeutic effects.
It seeks to bring to the interest of a chemist, the import of application of specialize knowledge such as chemistry to preparing selected analgesics, showing latent potency of chemical knowledge in solving the problem of various types of pain and that with relatively lesser cost than that usually invested by pharmacologist in trying to understand the inroad to pain management.
The effectiveness of analgesics cannot be over-emphasized; hence this work to an extent reveals the broad world of analgesic and showed light on the chemistry of the treatment of pain.
What is an analgesic?
An analgesic, known colloquially as a painkiller, is any natural or synthetic drug that relieves pain (produces analgesia) without causing loss of consciousness, paralysis, or other major impairment of sensory function or nerve impulse conduction. It is different from anesthetics, which produces anesthesia i.e. relives pain by causing loss of consciousness e.g. of such anesthetic is N2O (Concise oxford dictionary, 2012).
The word analgesic derives from Greek an- (“without”) and -algia (“pain”). The term analgesia refers to an absence of the sensation of pain while still being conscious. An analgesic is any member of diverse group of drugs used to relieve pain. The type of analgesic used depends on the severity of pain; whether it is acute (self-limiting in duration, such as childbirth) or chronic (lasting more than three months) and the response to other medications (Uretsky 2002). However the World Health Organization’s “pain ladder,” originally developed for cancer-related pain, is a widely used protocol for determining in a stepwise manner the suitable drug and dosage for treating pain (WHO, 1990).
The choice of analgesia is also determined by the type of pain: for neuropathic pain, traditional analgesia is less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants (Dworkin et al. 2003). Analgesic drugs act in various ways on the peripheral (PNS) and central nervous systems (CNS), either blocking the signal from the PNS or distorting the interpretation by the CNS (Uretsky 2002).
Medical researchers have developed widely diverse compounds for treating pain, including some synthetic opioids that produce an analgesic effect but that are much less likely to induce dependency. It is important to note that some pain is productive, acting as a warning of injury and a guide to diagnosis and treatment; thus it is also important to realize that while analgesics relieve symptoms, they do not affect the underlying cause (Uretsky 2002).
- EVIEW OF MAJOR CLASSIFICATIONS OF ANALGESICS
There are two major classifications of analgesics: Opioids or Narcotic analgesics and Nonopioids analgesics.
What is an opiod?
A sample of raw opium
The term “opioid” originated in the 1950s. It combines “opium” + “-oid” meaning “opiate-like” (“opiates” being morphine and similar drugs derived from opium). The first scientific publication to use it, in 1963, included a footnote stating, “In this paper, the term, ‘opioid’, is used in the sense originally proposed by George H. Acheson (personal communication) to refer to any chemical compound with morphine-like activities”. By the late 1960s, research found that opiate effects are mediated by activation of specific molecular receptors in the nervous system, which were termed “opioid receptors”. The definition of “opioid” was later refined to refer to substances that have morphine-like activities that are mediated by the activation of opioid receptors. One modern pharmacology textbook states: “the term opioid applies to all agonists and antagonists with morphine-like activity, and also the naturally occurring and synthetic opioid peptides”. Another pharmacology reference eliminates the morphine-like requirement: “Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists)”. Some sources define the term opioid to exclude opiates, and others use opiate comprehensively instead of opioid, but opioid used inclusively, is considered modern, preferred and is in wide use (Offermanns and Stefan 2008).
Natural opioids occur in 2 places:
- In the juice of the opium poppy (morphine and codeine)
- As endogenous endorphins.
The terms opiate and narcotic are sometimes encountered as synonyms for opioid. Opiate is properly limited to the natural alkaloids found in the resin of the opium poppy although some include semi-synthetic derivatives. Narcotic, derived from words meaning numbness or sleep, as an American legal term, refers to cocaine and opioids, and their source materials; it is also loosely applied to any illegal or controlled psychoactive drug. In other jurisdictions all controlled drugs are legally classified as narcotics. The term can have pejorative connotations and its use is generally discouraged where that is the case.
Opiods are primarily used for pain relief, including anesthesia they are also used to suppress cough, suppress diarrhea, treat addiction, reverse opioid overdose, and suppress opioid induced constipation. Extremely strong opioids are approved only for veterinary use such as immobilizing large mammals.
Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. These receptors mediate both the psychoactive and the somatic effects of opioids. Opioid drugs include partial agonists and antagonists, which produce moderate or no effect (respectively) but displace other opioids from binding in those receptors.
The Opioid Analgesics
Opioid analgesics, known also as “narcotic analgesics,” are analgesics derived from opium, as well as semi-synthetics and even synthetics that behave pharmacologically like morphine, and are pain relievers that act on the central nervous system (Uretsky 2002; Ross-Flanigan 2002). The archetypal opioid is morphine, a derivative of the opium poppy. The morphine molecule is the chemical basis of many painkillers, some with minimal abuse potential (Uretsky, 2002). In addition to morphine, other narcotic analgesics include codeine, oxycodone, propoxyphene (Darvon), hydrocodone, and diacetylmorphine (heroin, meperidine (Demerol), and pethidine). All exert a similar influence on the cerebral opioid receptor system. Tramadol and buprenorphine are thought to be partial agonists of the opioid receptors.
Opium is a narcotic formed from the latex (i.e., sap) released by lacerating (or “scoring”) the immature seed pods of opium poppies (Papaver somniferum). The opium latex contains up to 16 percent morphine, as well as codeine and non-narcotic alkaloids, such as papaverine and noscapine (Ross-Flanigan, 2002). Heroin (diacetylmorphine or diamorphine) is a semi-synthetic opioid synthesized from morphine. As with other opiates, heroin can act both as a painkiller and a recreational drug.
Codeine is an alkaloid found in opium. While it can be extracted from opium, most codeine is synthesized from morphine through the process of O-methylation. Codeine is by far the most widely used opiate in the world and very likely most commonly used drug overall.
Opioids, while very effective analgesics may have some unpleasant side-effects. Drowsiness, dizziness, and breathing problems are some unwanted side effects, as well as physical and mental dependence (Ross-Flanigan, 2002). Like all narcotics, opioids can become habit-forming. In addition, up to one in three patients starting morphine may experience nausea and vomiting (generally relieved by a short course of antiemetics). Pruritus (itching) may require switching to a different opioid. Constipation occurs in almost all patients on opioids, and laxatives (lactulose, macrogol-containing or co-danthramer) are typically co-prescribed.
Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression, myoclonic jerks and pinpoint pupils), but there is no dose ceiling in patients who tolerate this.
When used appropriately, opioid analgesics are otherwise safe and effective. However, risks such as addiction and the body becoming used to the drug are serious concerns. Due to the body getting used to the drug, often the dose must be increased. If the drug is being used for treating a chronic disease, the doctor may follow the pattern of the no ceiling limit. What must be remembered, however, is that although there is no upper limit there is still a toxic dose even if the body has become used to lower doses. Frequent administration of heroin has a high potential for causing addiction and may quickly lead to tolerance. If a continual, sustained use of heroin for as little as three days is stopped abruptly, withdrawal symptoms can appear. This is much shorter than the withdrawal effects experienced from other common painkillers such as oxycodone and hydrocodone.
1.5 Other Classifications of Opiod
- Naturalopiates: alkaloids contained in the resin of the opium poppy, primarily morphine, codeine, and thebaine, butnot papaverine and noscapine which have a different mechanism of action; The following could be considered natural opiates: The leaves from Mitragyna speciosa (also known as kratom) contain a few naturally-occurring opioids, active via Mu- and Delta receptors. Salvinorin A, found naturally in the Salvia divinorum plant, is a kappa-opioid receptor agonist.
- Esters of morphineopiates: slightly chemically altered but more natural than the semi-synthetics, as most are morphine prodrugs, diacetylmorphine (morphine diacetate; heroin), nicomorphine (morphinedinicotinate),dipropanoylmorphine (morphinedipropionate,desomorphine, acetylpropionylmorphine, dibenzoylmorphine, diacetyldihydromorphine.
- Semi-syntheticopioids: created from either the natural opiates or morphine esters, such as hydromorphone,hydrocodone, oxycodone, oxymorphone, ethylmorphine and buprenorphne;
- Fully syntheticopioids:
- Endogenousopioid peptides, produced naturally in the body, such as endorphins, enkephalins, dynorphins, and endomorphins. Morphine, and some other opioids, which are produced in small amounts in the body are included in this category.
Tramadol and tapentadol, which act as monoamine uptake inhibitors also act as mild and potent agonists (respectively) of the μ-opioid receptor. Both drugs produce analgesia even when naloxone, an opioid antagonist, is administered.
Some minor opium alkaloids and various substances with opioid action are also found elsewhere, including molecules present in kratom, Corydalis, and Salvia divinorum plants and some species of poppy aside from Papaver somniferum. There are also strains which produce copious amounts of the baine, an important raw material for making many semi-synthetic and synthetic opioids. Of all of the more than 120 poppy species, only two produce morphine.
Amongst analgesics there are a small number of agents which act on the central nervous system but not on the opioid receptor system and therefore have none of the other (narcotic) qualities of opioids although they may produce euphoria by relieving pain—a euphoria that, because of the way it is produced, does not form the basis of habituation, physical dependence, or addiction. Foremost amongst these are nefopam, orphenadrine, and perhapsphenyltoloxamine and/or some other antihistamines. Tricyclic antidepressants have pain killing effect as well, but they’re thought to do so by indirectly activating the endogenous opioid system.
Other analgesics work peripherally (i.e., not on the brain or spinal cord). Research is starting to show that morphine and related drugs may indeed have peripheral effects as well, such as morphine gel working on burns. Recent investigations discovered opioid receptors on peripheral sensory neurons. A significant fraction (up to 60%) of opioid analgesia can be mediated by such peripheral opioid receptors, particularly in inflammatory conditions such as arthritis, traumatic or surgical pain. Inflammatory pain is also blunted by endogenous opioid peptides activating peripheral opioid receptors.