Pain can be defined as the unfavorable feeling, usually as a sing of the medical issue such as tissue injury (nociceptive), pain due to cancer, inflammation, or after surgery (postoperative) 1.2. Pain can be classified as chronic or acute, acute pain is that which does not remain for log period time usually between days to weeks, however chronic pain according to the International Association for the Study of Pain (IASP) is pain remain more than three months 1.threre are various groups of drugs that are used to treat or mange pain each class of these groups act by different techniques and each have their advantages and disadvantages these groups include opioids, local anesthetics , agonist of alpha 2 receptor, nonsteroidal anti-inflammatory drugs (NSAIDs)”,anticonvulsants, acetaminophen and antidepressants drugs3 . management of pain need the realization of the type of pain and effectiveness, mechanism, unwanted effects of different agents used in the treatment 1″,2.
Non-opioid analgesic considered the initial phase or line in pain treatment including nonsteroidal anti-inflammatory drugs and acetaminophen which are effective in relieving modest to moderate pain and they are easy to get as they are over the counter drugs(OTC)1″,2.
nonsteroidal anti-inflammatory drugs (NSAIDs) act by suppressing the action of cyclooxygenase enzymes which stimulate the formation of prostaglandins (PGs), that cause dilation, increase permeability of blood vessels and sensitivity to damages1″,4 .it also lower secretion of acid and platelet accumulation1. cyclooxygenases also stimulate thromboxanes (TX)which stimulate the aggregation of platelets and constriction of blood vessels1. The two isoforms of the enzymes facilitate different actions, cyclooxygenase 1 (COX-1) is found produce in various tissues normally to form products that help in activation of platelets , and protection of the gastric lining “,however cyclooxygenase 2 (COX-2) is involved in mediating inflammation (including pain)1”,4.nonsteroidal anti-inflammatory drugs are of two types, first is non selective cyclooxygenase inhibitors which affect both COX-1 and COX-2 such as ibuprofen , naproxen and aspirin1 . they are effective in relieving pain but they have side effects and that primary because of COX-1 suppression which mediate important functions the main problem is ulcer because of increase acid section and reduce the protective effect that is way it is recommend to have proton-pump inhibitor along with it especially in long use to decrease acid also are associated with emesis “,drowsiness “,renal complications and nusea1″,2″,5 , the second class of NSAIDs is selective COX-2 inhibitor such as for example etoricoxib and celecoxib they have been introduce first at the beginnings of 1990, this group have the advantage of no gastrointestinal and renal complications that related with non-selective COX inhibitors1. However , they over the extensive and long use studies release that they are associated with increase the chance of cardiovascular problems which end with lot of them pull back from the market this is due to suppression of COX-2 which is responsible for production of PG-12 that suppress the platelet aggregation and at the same time the COX-1 which is not inhabited lead to production TXA-2 that stimulate the aggregation of platelets that will result in thrombosis formation this is also associated with non-selective COX inhibitors but less than selective ones as the suppression of cox-1 is present even though it varies in time of inhibition 1”,2.eventually , the long term large doses of NSAIDs of any class lead to thrombotic cardiovascular complication and coronary heart disease CHD except naproxen which have long suppression effect on COX-1 ( less TXA2)1.
Opioid-analgesic are used for the moderate to sever pain when the NSAIDs and acetaminophen fails to relief the pain such as in cancer patients and surgery, as opioids are the strongest medications in case of reducing pain 1″,2″,6.
Opioids mediate the same effect of the endorphins natural pain decreasing chemicals1.they reduce the neural activities through the G-protein-coupled opioid receptors which will lead to increase potassium resulting in hyperpolarization and reduce calcium leading to decease the release of the neurotransmitter1.there types of opioids receptions Mu, Delta and kappa mu receptors mediate the supraspinal analgesia and the known complications of opioids including euphoria “,decrease the gastrointestinal movement “,sedation, and depression od respiration the kappa receptor leads to spinal analgesia and almost same unwanted effects of mu receptor “,Delta receptor cause psychomimetic impacts and does not cause euphoria 1”,7. all opioid medications act on the Mu receptor “,however have some binding to other opioid receptor and also, various opioids interact with distinct subtypes of the Mu receptor6″,7 .so, this explain why they have different effects on pain and different side effects6”,7.
We can consider opioids as weak and potent, weak opioid including codeine and dihydrocodeine which have less effect on pain but also less sever adverse effects and the more potent such as morphine and dihydromorphine which are the choice in case of pain associated with cancer and other sever conditions1″,6″,7 , more lipid soluble opioid (buprenorphine , fentanyl) that can be give through the skin and are associated with less unpleasant effects than morphine and appear to be effective in pain such as neuropathic pain “,osteoarthritis , and back pain1.
Opioid undergoes biotransformation in the liver , most opioid undergoes first phase metabolism give products that are with stronger effect than the drug it self “,such as codeine and some have not phase 1 metabolism such as morphine and hydromorphone this make them better for people with failure of the liver or to avoid the chance of interaction with other medications6″,7 .some opioid are inactivated under the first phase of metabolism including methadone which is better than others in case of renal complication as the products are not active and not eliminate by the urine such some other opioid after the second phase metabolism give active and most are cause neural toxicity such as morphine-3-glucuronide6”,7 .
Even though, opioid are an amazing pain reducing medication they are associated with serious unwanted effect which makes them used only in some serious situation these include nausea, constipation “,sedation , addiction, affect the awareness and cognition “,and respiratory depression which may lead to death 6”,7.another problem that associated with the use of opioid analgesics is the requirement of dose increasing over use to get the same effect due to the development of tolerances 1.people are affected in different ways due to genetic polymorphisms7.