Tramadol and Morphine are Narcotic Analgesics with Strong Analgesic Effect
Pain is a typical pathological process devoid of nosological characteristics. It is the most common symptom which causes sufferings to millions of people. According to the World Health Organization, pain syndromes are one of the main reasons of the appeals to the doctors in the system of primary health care. Despite the efforts undertaken around the world in order to better recognize and treat pain adequately, the data still shows the lack of therapy. Untreated pain or its improper treatment still remains a significant public health problem in many countries. Currently, for the treatment of pain, opioid analgesics are widely used. Such drugs as morphine and tramadol classified into the group of opioid analgesics are widely used in treatment of chronic and acute pain. The aim of the paper is to study the similarities and differences between morphine and tramadol.
Morphine is the main representative of the group of narcotic analgesics. It has a strong analgesic effect. Lowering the excitability of pain centers, it also has an anti-shock action. In large doses, morphine causes a hypnotic effect, which is more pronounced in sleep disturbances associated with pain. Morphine has an inhibiting effect on conditioned reflexes. It increases the effect of narcotic and sleeping pills. Morphine reduces the excitability of the cough center and causes excitation of the vagus nerve center manifested by bradycardia. It also causes miosis as a result of the activation of neurons of the oculomotor nerve. These effects are removed by atropine or other anticholinergics (Cannon, 2007).
Under the influence of morphine, the tone of smooth muscles of internal organs grows. There is an increase in the tone of sphincters of the gastrointestinal tract and the muscle tone of the antral part of the stomach. Peristalsis is weakened. There is also a muscle spasm of the biliary tract and sphincter of Oddi. Morphine increases the tone of the urethral sphincter. Under the influence of morphine, the secretory activity of the gastrointestinal tract is inhibited. In connection with the stimulation of the antidiuretic hormone release, urination may reduce (Neal, 2012).
A characteristic feature of the action of morphine is the inhibition of respiratory center. Small doses cause increasing the depth of the respiratory movements. Large doses of morphine cause further reducing of the depth of breathing with the reduction of pulmonary ventilation. Toxic doses cause the appearance of periodic breathing such as Cheyne-Stokes respiration and subsequent stop of breathing.
After the oral intake, morphine is distributed in organs and tissues. When taking orally, morphine is not very effective due to low bioavailability – 24%. The morphine effect begins in 20-30 minutes after oral intake. The half-life of morphine is short and lasts from 2 to 7 hours. The volume of distribution of morphine is relatively large. It indicates the intensive absorption by tissues including skeletal muscles (Cannon, 2007).
The main pathway for the metabolism of morphine is its glucuronidation occurring in liver and other organs. The major metabolites of morphine are morphine-3-glucuronide and morphine-6-glucuronide. Morphine-6-glucuronide has pronounced to have analgesic properties. To some extent, it determines the analgesic effect of the drug. Basic metabolism of morphine occurs in liver. Liver failure has almost no effect on the processes of glucuronidation. Morphine is well tolerated by patients until the development of the state of precoma. Processes of excretion are not violated even in patients with renal failure. However, an active metabolite (morphine-6-glucuronide) may be cumulated with a decrease in renal excretory function. It causes the extension of action, sedation, and respiratory depression. There are several side effects of this analgesic: “The side effects of morphine that are most problematic include constipation, respiratory depression, sedation, and with some routes of administration, pruritus” (Stolerman, 2010, p. 80).
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Morphine is prescribed as a painkiller in injuries and various diseases accompanied by severe pain such as cancer and heart attack. It is also applied in the perioperative period, as well as in severe shortness of breath associated with heart failure. Morphine is usually not used for labor analgesia as it passes through the placenta and may cause respiratory depression in the newborn (Bruera & Portenoy, 2009).
Contraindications to the use of morphine include increased sensitivity to opioids, respiratory depression, CNS depression, convulsions, increased intracranial pressure, head injury, alcohol intoxication, asthma, cardiac arrhythmias, surgery on the biliary tract, and intake of monoamine oxidase inhibitors.
Tramadol is a narcotic analgesic. It is a synthetic analog of opiates. According to Sinatra, Jahr, and Watkins-Pitchford, “Tramadol is a synthetic analgesic that has an amino-cyclohexanol structure similar to codeine” (2010, p. 137). In terms of chemical structure, tramadol is a derivative of phenanthrene. It is considered partial μ- agonist of opiate receptors. The experiment has revealed that naloxone inhibits analgesia by tramadol only partially. Serotonin receptor antagonists also reduce analgesia. The influence of the drug on the α2-adrenergic receptors which interact with opioids is possible as well. Apparently, due to the low affinity for μ-receptors, tramadol is considered the analgesic of the medium-strength action. It amounts about one-third of the analgesic potential of morphine. When taken orally, bioavailability of tramadol is about 70%. The analgesic effect develops within 15-30 minutes after intake of the drug and lasts for 3-5 hours. The half-life of tramadol is 6.3 hours. The effect of 1 mg/kg of tramadol is comparable to that of morphine at a dose of 1 mg/kg (Fishman, Ballantyne, & Rathmel, 2010).
Indications for the use of tramadol include pain syndrome of strong and average intensity of various etiologies, as well as chronic pain. Tramadol is also prescribed for the conduction of painful diagnostic or therapeutic interventions. It is used to relieve pain in myocardial infarction. Side effects of tramadol include heaviness in head, raised diaphoresis, mental confusion, nausea, dizziness, dry mouth, fatigue, vomiting, and drowsiness. Tramadol is contraindicated in case of hypersensitivity to the active substance: tramadol hydrochloride or other components of the drug. It is also forbidden to use the drug in case of acute alcohol poisoning, with painkillers, sleeping pills, and psychotropic drugs.
The active ingredient of tramadol is connected with opiate receptors in the back parts of the spinal cord, the central regions of the intermediate mid-brain and causes a blockage of pain impulses. In parietal and frontal gyrus, tramadol reduces the excitability of pain center and removes the negative emotional coloring of pain.
It is forbidden to prescribe tramadol concurrently with monoamine oxidase inhibitors. Tramadol can be used after 14 days from the date of discontinuation of intake of MAO inhibitors. When using tramadol, there have not been noted respiratory depression effects. However, these phenomena are not excluded in case of drug overdose or simultaneous treatment with the drugs acting on the central nervous system.
Both tramadol and morphine are narcotic analgesics. It means that by increasing the dose, they can cause dependence in a person. However, morphine is a natural analgesic and tramadol is an analgesic of a synthetic origin. According to McCuistion, Kee, and Hayes, “Morphine, a prototype opioid, is obtained from the sap of seed pods of the opium poppy plant” (2014, p. 358). Tramadol is an analgesic of central acting. “It is not derived from natural sources, nor is it chemically related to opiates” (Apo-Tramadol SR Tablets). It is a nonselective pure agonist of opioid of mu-, delta-, and kappa receptors in the central nervous system with the highest affinity for mu-receptors. Structurally, tramadol contains nitrogen not in the piperidine cycle as in morphine, but in the form of a dimethylamino group (acyclic nitrogen) in the second position of the cyclohexane ring.
Morphine depresses respiration proportionally to the dose intake. In therapeutic doses, it causes decrease of the minute volume of pulmonary ventilation, mainly due to the decrease in the frequency of breathing without causing a noticeable effect on tidal volume. When exposed to toxic doses of morphine, the volume of pulmonary ventilation is reduced drastically. In contrast to morphine, tramadol at recommended doses practically does not inhibit breathing. However, these phenomena are not excluded in the drug overdose or while treatment of agents acting on the central nervous system. Unlike morphine, tramadol has no effect on the gastrointestinal motility (Freynhagen & Bennett, 2009).
Morphine has a strong analgesic action. The force of this effect is 7.5 times less compared with morphine. According to Aronson, “Drug use in the 24 hours averaged 800 mg for tramadol and 40 mg for morphine” (2009, p. 156). After the oral intake of tramadol or morphine, they are almost completely absorbed from the gastrointestinal tract. Metabolites of morphine and tramadol are output mainly with urine. Tramadol and morphine are excreted by kidneys. Both analgesics are used in severe acute and chronic pains, postoperative periods, traumas, cancer patients, etc. Both drugs are forbidden to take with MAO inhibitors and have numerous side effects. In his book, Meyler’s Side Effects of Analgesics and Anti-inflammatory Drugs, Aronson states, “In a comparison of the analgesic effects of intermittent boluses of tramadol or morphine after abdominal surgery in 523 patients, tramadol caused more adverse effects (43 versus 34%), although the difference was not statistically significant” (2009, p. 156).
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In conclusion, analgesics are medications that selectively attenuate or eliminate pain. At therapeutic doses, analgesics oppress only pain sensitivity and do not disturb the consciousness. Traditionally, there are narcotic and non-narcotic analgesics. Both morphine and tramadol are narcotic analgesics. Nevertheless, the main difference between them lies in the fact that tramadol is a drug of the synthetic origin and morphine is natural. This fact characterizes the differences in the drugs properties and side effects.