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A Bridge Towards Knowledge
Dania El - Tannir
Dania El - Tannir
Posted On 11/15/2015
1. Opioids and Pethidine
Opioids are drugs that have been used for thousands of years to treat pain.An opioid is a psychoactive chemical that binds to the opioid receptors which are found in specific pain-related areas such as the midbrain region, thalamus, spinal cord and primary sensitive neurons in addition to the gastrointestinal tract (Shäfer M,2010).Three different opioid receptors are known, μ, δ and κ; however, the most clinically relevant is the μ receptor.
Three different classifications of opioids, traditional, according to origin and functionional classification.
The traditional classification, based on the analgesic effect, distinguishes strong, intermediate and weak opioids. Strong opioids refer to the opioids which are pure agonists, whereas the intermediate opioids are partial agonists.
The classification according to the origin differentiates 4 main types of opioids.
Endogenous opioids are opioid peptides and are produced naturally in the body. They are also known as endorphins, enkephalins, dynorphins, and endomorphins (McCubbin JA,1993). They function in modulating different physiological mechanisms such as stress, analgesia, alcohol consumption, gastrointestinal, renal and hepatic functions, learning, memory, cardiovascular responses and other important behaviors (Vaccarino AL. et al.,1998)
Natural opium alkaloids are referred to as “opiates”. They are naturally occurring in the opium plant, Papaver Somniferum other species and exert their effects through the binding to the opioid receptors (Németh-Zámbori É,et al.,2011).
Natural alkaloids belonging to the Phenanthrene class and include morphine, codeine, thebaine and narcotine while the alkaloids belonging to the benzylisoquinoline class 3
include papaverine and noscapine which have a different mechanism of action (Németh-Zámbori É., et al., 2011) (Brunton LL, et al.,2006). Morphine accounts for the highest concentration, among all other opiates, in various varieties of poppy capsule (Stranskam I, et al.,2013)
Esters of morphine are semi-synthetic products derived from morphine or other opiates and are considered as pro-drugs of morphine. The acetylation of morphine yields to diacetylmorphine also known as Heroin (Odell LR, et al., 2006).
Synthetic opioids are structurally distinct chemical products obtained in order to bind to the opioid receptors, and are also sub-classified according to the chemical structure into phenylpyperidines (pethidine, fentanyl), diphenylpropalamines (methadone), morphinans (levorphanol) and benzomorphans (pentazocine).
The classification according to the functiondescribes the pharmacological action of opioids. This includes the agonists (such as morphine), partial agonists (such as buprenorphine), agonist-antagonists (such as pentazocine) and antagonists (such as naloxone).
Pethidine is a strong synthetic opioid which belongs to phenylpiperidine group and is an agonist opioid (Shaumann O, 1940).
It is a potent narcotic and is used as a postoperative analgesic, a premedication for anesthesia or an analgesic during labor. It can be administered orally or parenterally, via the intramuscular, intravenous or epidural routes (Keskin HL, Keskin EA, Avsar AF, Tabuk M, Caglar GS, 2003).
Pethidine exerts its analgesic effect through interaction with μ receptor. It also binds to the κ receptor, but this binding if on no clinical significance. Due to structural similarity to atropine, Pethidine also demonstrates anticholinergic side-effects. The 4
stimulant effect of Pethidine is related to inhibition of dopaminergic and norepinephrine transporters. In addition, and since Pethidine interacts with serotonergic neurons, it is believed that it is associated withthe serotonin syndrome. Pethidine has a rapid onset of action and has a great potential to cause physical dependence and can lead to addiction.
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