Nonopioid+Analgesics

=**Nonopioid Analgesics **=



This web page gives as very basic outline of nonopioid angalgesics, what they are used for, how they work, and their side effects. [|http://www.virtualcancercentre.com/Treatments.asp?sid=43&title=Simple-analgesics-(non-opioid-analgesics])

An opioid is a chemical substance that has a morphine-like action in the body. The main use is for pain relief and can also be used to reduce inflmation. These agents work by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract. The receptors in these two organ systems mediate both the beneficial effects, and the undesirable side effects. There are a number of broad classes of opioids:
 * natural opiates,** alkaloids contained in the resin of the opium poppy including morphine, codeine and thebaine, but not papaverine and noscapine which have a different mechanism of action;
 * semi-synthetic opiates **, created from the natural opioids, such as hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, diacetylmorphine (Heroin), nicomorphine, dipropanoylmorphine, benzylmorphine and ethylmorphine;
 * fully synthetic opioids**, such as fentanyl, pethidine, methadone, tramadol and propoxyphene;
 * endogenous opioid peptides**, produced naturally in the body, such as endorphins, enkephalins, dynorphins, and endomorphins.



Nociceptive pathways. The drawing illustrates [A] incoming nociceptive impulses, [B] ascending nociceptive tracks, and [C] descending inhibitory tracts that act to blunt incoming pain signals. Abbreviations represent the myriad of neurotransmitters that contribute to pain transmission. They reflect potential targets for pharmacologic intervention to control pain.

There are two primary types of analgesics: narcotic (opioid) and non-narcotic (nonopioid) analgesics.

Non-narcotic analgesics are drugs that have principally analgesic, antipyretic, and anti-inflammatory actions. Acetaminophen is the most commonly used over-the-counter non-narcotic analgesic. Other drugs are not technically part of the analgesic family, but are nonetheless considered analgesics in practice. These include nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. Acetaminophen and NSAIDs can effectively relieve mild to moderate headache and pain of musculoskeletal origin. For moderate to severe pain, they can be used in combination with opioid drugs to enhance pain relief.

Opioids are stronger analgesics that are used when pain signals are too severe to be controlled by non-narcotic analgesics. The primary difference between opioids and non-opioids is in the way how they produce their analgesic effects. The opioid drugs reduce pain by working on special pain receptors in the nervous system, primarily located in the brain and spinal cord. The non-opioids, on the other hand, work more directly on injured body tissues. The opioids decrease the brain's awareness of the pain, whereas the non-opioids affect some of the chemical changes that normally take place wherever body tissues are injured or damaged. These chemical changes at the site of the injury typically result in inflammation and increased pain sensitivity.

Non-opioid pain relievers are often preferred for most types of chronic pain, because they do not produce tolerance or physical dependence and are not associated with abuse or addiction. However, they have two serious drawbacks. The first drawback has to do with ceiling effects. Non-opioids have upper limit of pain relief that can be achieved. Once that upper limit or ceiling is reached, taking additional medication will not provide any further pain relief. Opioids, on the other hand, tend not to have a ceiling. That is, the more you take, the more pain relief you will get. It is for this reason that non-opioids are effective only for mild to moderate pain, whereas opioids are useful for more severe pain intensity.

The second major drawback of the non-opioids are their side effects. Although most non-opioids are quite safe when used for temporary acute pain, problems may arise when people take them over a long period of time (for chronic pain). This is especially true when large quantities of non-opioids are taken. Most are aware of the adverse effects of these drugs on the gastrointestinal system. However, excessive use of the non-opioids can also damage your liver or your kidneys. Non-opiods such as NSAID's and over the counter medication also can interfer with the clotting tendancy of platlets. Consequently non-opiods have the potential to increase the risk of bleeding. Use of non-opiods can also sause a side effect of fluid retention which could cause swelling or bloating. For the elderly the side effects are increased due to the contraindication of over the counter drugs to the precription heart and blood pressure drugs that do not have the same effect when NSAID's are taken.

Non-opioid Analgesic contrainidication in pertainance to Aspirin and other Salicylates are: 1. Ulcers: causing internal bleeding, posible hemorrhaging 2. Asthma: causing attack resemblinb an allergic reaction 3. Diabetes: caused by high doses will cause hyperglacemia or hypoglycemia 4. Gout: by having low doses can cause increase plasma urate; high doses lower plasma urate 5. Influenza: causes Reye's syndrome in children 6. Hypocoagulation states: which causes excessive bleeding.

Implications for dentistry:

 Acetaminophen Pharmacologic Effects: In comparing with aspirin, acetaminophen exerts relatively few important effect on specific organs or systems. The potency and efficacy of acetaminophen as an antipyretic are similar to those of aspirin. It has little if any effect on cardiovascular or respiratory system. It does not inhibit platelet aggrgation, cause occult bleeding or gastric irritation, affect uric acid excretion or drug interactions as aspirin. In overdose it affects the liver. Acute renal toxicity amy also occure and with long-term use, analgesic nephropathy is a posibility but it is of low risk.
 * The Major use of aspirin and other NSAIDs in dentistry is to relieve pain associated with pathologic processes or after surgical procedures. In both cases, the antiinflammatory actions of the NSAID may contribute significant to therapeutic effect sought.
 * Aspirin at doses between 650-1000mh is an acceptable drug for mild to moderate dental pain. For more traumatic surgical procedures newer NSAIDs at dosages taht approach their analgesic ceiling are more efficacious and tolerated than Aspirin. In addition, NSAIDs cause fewer side effects than do opioid containing analgesics.
 * The role of COX-2 inhibitor is acute postsurgical dental pain still neds to be defined but is currently n approved and cannot be recommended for acute pain because it is inferior to ibuprofen in postsurgical dental pain models.
 * There are few chronic inflammatory diseases solely limited to oral structures. The TMJ is one and involved systemic inflammatory disease that would be treated by NSAIDs.

Therapeutic uses of Acetaminophen in Dentistry:  Adverse Effects of Acetaminophen:
 * It is used to control dental pain especially after third molar extractions.
 * It also has a positive dose-effect for analgesia up to 1000mg for postsurgical pain and is ideal with the use in combination with an opioid analgesic agent.


 * Acute overdose from acetaminophen because of the extent of use.
 * Hepatotoxicity appears to result from the formation of the highly reactive metabolite which normally reacts rapidly with glutathione and as a result in largely neutralized. Which results in alkylation of liver protens and cellular injury.
 * Adverse drug interactions between acetaminophen and alcohol is comples and often difficult to predict. This can also be linked to
 * hepatotoxicity.



<span style="line-height: 115%; font-family: 'Times New Roman', 'serif'; font-size: 22pt;">**__Antigout Drugs__** <span style="line-height: 115%; font-family: 'Times New Roman', 'serif'; font-size: 16pt;">Gout is an inflammatory disease, which causes an increase of uric acid in the blood and other body fluids. Uricosuric drugs are used to treat gout. 1-increase the renal rate clearance 2-inhibit urate synthesis Type of Drugs -drugs enhance urate retention by blocking renal tubular secretion -side effects-may lead to renal urate stones, gastrointestinal disturbances, and allergic reactions *Allopurinol -drug reduces the biosynthesis of uric acid and lower both the blood and urine concentration -used for chronic gout -toxic effects- in the skin exfoliative, urticarial, and pupuric lesions; in the blood leukopenia, thrombocytopenia, andagranulocytosis *Colchicine (Plant alkaloid) -inhibit the neutrophil’s engulfment of uric acid crystals, preventing the release of destructive lysosomal enzymes into the extracellular environment -used to treat sever gouty arthritis -non an analgesic, but has a pain reduction affect -absorption/fate= absorbed by GI and partially metabolized by the liver, then excreted in the feces 10 days or more after dose. -side effects- nausea, vomiting, diarrhea; long term use may lead to bone marrow depression, myopathy, and alopecia
 * Mechanism of Action
 * Probenecid and Sulfipyrazon

**__ANALGESICS__**
Analgesics are medications used to relieve pain without reducing the consciousness of the patient. They work by reducing the amount of pain felt and this is generally achieved by interfering with the way the pain message is transmitted by the nerves. Analgesics will not treat the cause of the pain but they will provide temporary relief from pain symptoms. There are three main categories of analgesics. The first is the opioid analgesics which are prescription only medicines that are very potent, being chemically related to morphine. The second is the non-opioid analgesics. Non-opioid analgesics work by affecting the prostaglandin system, which is the system within the body responsible for producing pain. This category includes non-steroidal anti-inflammatory drugs, or NSAIDs, such as Aspirin, ketoprofen and ibuprofen. The last category is adjuvant analgesics, which are medicines typically used for purposes other than pain relief. This includes some antidepressants that may also help to relieve pain in specific circumstances. Non-opioid analgesics act peripherally and not centrally like opioids that depress the central nervous system (CNS) and inhibit the brain's ability to feel pain. Non-opioid analgesics target the chemical substances released by the brain in response to injury that facilitate the transmission of the pain stimuli to the brain. The most prevalent of these chemical mediators is prostaglandin. Non-opioid NSAIDs are effective because they serve to block the release of prostaglandin at the peripheral nerve sites. Prostaglandins serve a variety of regulatory functions within the body. One of these functions is to assist the transmission of pain signals to the brain so that you are readily alerted that damage or dysfunction has occurred within the body. Other prostaglandin actions include the regulating body temperature, inflammation, the elasticity of blood vessels and the contraction of smooth muscle tissue. When damage occurs to the body, prostaglandins are formed from the unsaturated fatty acids released by damaged cells. Prostaglandins contain an enzyme called cyclo-oxygenase (COX). Prostaglandin synthetase amplifies the amount of pain experienced by serving as a pain activator. They increase the sensitivity of the nerves to pain impulses. By reducing the synthesis of prostaglandin the amount of pain stimuli sent to the brain is correspondingly reduced. Analgesics like paracetamol and codeine mostly affect the central nervous system (CNS) while NSAIDs like ibuprofen and aspirin are more effective near the actually site of the pain, exerting their analgesic effect in the periphery. Codeine works on the CNS as a weak opiate agonist that inhibits pain signals so that less pain is felt. Codeine achieves this by binding with receptors at various sites in the CNS to alter the chemical process that stimulates pain signals. Paracetamol is a weak prostaglandin inhibitor that blocks prostaglandin biosynthesis in the CNS. NSAIDs like Aspirin, ibuprofen, diclofenac, and ketoprofen block the pain impulse at the source of the pain. They work by hindering the body's ability to biosynthesise prostaglandin by adhering to the cyclo-oxygenase (COX) that controls the amount of prostaglandin produced by the immune system. The special nerve endings that transmit the pain message are sensitised to prostaglandin so, by restricting its presence, the pain message is reduced. This weakens the physiological chemical process that results in the sensation of pain.