Tramadol Morphine

Side-effects Typical side-effects of tramadol are nausea, sweating and dizziness. In rare cases seizures after high i.v. doses are reported, mostly in combination with other proconvulsant componds or in patients with reduced seizure theshold (Gardner et al., 2000). Tramadol shows a reduced level of opioid side-effects, especially respiratory depression and constipation are less frequent and severe than with standard opioids such as morphine. Tramadol has a very limited abuse potential and is not subject to narcotic control (Cossmann et al., 1997). 

Morphine, tramadol, methadone, oxycodone, hydrocodone, and codeine are all available as oral preparations. Morphine, hydromorphone, oxymor-phone, and fentanyl can be administered intravenously. In addition,... 

Alfentanil, codein, dihydromorphine, etor-phine, fentanyl, heroin, hydromorphone, levo-methadone, morphine, oxycodone, pethidine, piritramide, remifentanil, sufentanil, tilidine, tramadol Buprenorphine, pentazocine Naloxone, naltrexone... 

Tramadol is a pain reliever (analgesic). Its action is similar to opioid narcotics such as codeine and morphine, but it does not depress breathing the way the others can, and less often leads to abuse and addiction. 

Seizures Seizures may be aggravated or may occur in individuals with or without a history of convulsive disorders if dosage is substantially increased above recommended levels because of tolerance. Observe patients with known seizure disorders closely for hydromorphone-, meperidine-, morphine-, or tramadol-induced seizure activity. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Opioids Tramadol, pethidine, oxycodone, morphine, meperidine... 

Heroin, the diacetyl derivative of morphine, is the most important illicit drug derived from the opium poppy. Together with heroin and its metabolites, other synthetic (e.g., methadone, tramadol) and semi-synthetic (e.g., buprenorphine) opioids have been quantified in different biological fluid using HPLC. 

Despite an intensive research effort over the past two decades involving many innovative approaches in the global academic community and by the pharmaceutical industry, the latter representing an aggregate investment in excess of 2.5 billion, the only new opioid-based pain medications either in clinical development or on the market are alternative dosage forms of the classical opioids, morphine, loperamide, and fentanyl, or compounds such as tramadol. ... 

Opioid receptor affinity Tramadol (Frink et al., 1996) itself has a weak opioid receptor affinity, the active metabolite O-desmethyl-tramadol has p-selectivity and p-affinity about 10 times lower than that of morphine. 

The success of prolonged-release morphine prompted the development of prolonged-release formulations for other opioids, for example the matrix made of hydrophobic and hydrophilic matrix formers, for example on hydrocodeine (DHC retard with cetostearyl alcohol and hydroxyethyl-cellulose), oxycodone (oxygesic with stearyl alcohol and polyacrylate) and tramadol (tramundin with cetostearyl alcohol and ethylcellulose). By virtue of the oblong shape of hydrocodeine and tramadol tablets the prolonged-release tablets can be divided, whereby compared with whole tablets release from the divided tablets is slightly accelerated. The difference with these forms is that with increasing dose the release slows down. 

In Great Britain tramadol is available as once-daily tablets made up of granules in a purely fatty matrix (Zydol XL), as described above for morphine, which again reduces the release rate compared with the granules. 

Grunenthal s interest in pain research started in 1962, when Kurt Flick designed a simple molecule containing the essential structural elements of morphine to be a potent analgesic. This prediction was clinically confirmed and today this compound -tramadol - is one of the leading centrally acting analgesics. 

Tramadol, pethidine, oxycodone, morphine, meperidine Buspirone, chlorpheniramine, dextromethorphan, linezolid, lithium, selegiline, tryptophan, St. John s wort... 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

Tramadol has about one tenth the pain-relieving ability of morphine.53 There are two enantiomers, and both contribute to pain relief, but via different mechanisms. (+)-Tramadol and the metabolite (+)-0-desmethy 1-tramadol, which is referred to as Ml, are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine re uptake.25 This latter action enhances the inhibitory effects on pain transmission in the spinal cord. Because the actions of the two enantiomers are complementary, they are usually supplied as a racemic mixture. However, because it is a serotonin-reuptake blocker, interaction with other medications can lead to the occurrence of serotonin syndrome.54... 

Opioid analgesics (see Chapter 14) are the primary medications used during PCA.9 Opioids such as morphine, meperidine, tramadol, fentanyl, and fentanyl... 

The prototypical opioid is morphine (A.137) (Figure A.39). Isolated in a crude form, called opium, morphine has been recognized as a potent pain killer for thousands of years. Although effective, morphine has a low oral availability (F = 25%). Two common derivatives of morphine include hydrocodone (Vicodin, A.138) and oxycodone (A.139), both of which have oral availabilities of greater than 75%. Oxycodone is often sold in an oral continuous-release form under the trade name of OxyContin. Not all opioids are semisynthetic derivatives of morphine. Dextropropoxyphene (Darvon, A.140) and tramadol (Tramal, A.141) are fully synthetic opioids. Both compounds preserve the pharmacophore of morphine as described in the morphine rule (see Chapter 11). Dextropropoxyphene and tramadol are depicted in Figure A.39 to highlight possible pharmacologically active conformations that resemble morphine. 

Tramadol hydrochloride (23 Ultram ) [59] was originally touted as being structurally unrelated to morphine. However, upon closer examination the relationship can easily be seen (Fig. 11.13). 

Tramadol, however, is thousands of times less potent than morphine as an analgesic agent [18]. It is marketed in the racemic form, and each enantiomer has distinct pharmacological actions. The (+)-isomer is a weak MOP agonist, while the (-)-isomer inhibits neurotransmitter reuptake (norepinephrine and serotonin). The O-demethylated metabolite has improved opioid receptor affinity but is still much less potent (35-fold) than morphine. The ability for this metabolite to ameliorate the analgesic effects of tramadol has not been well studied and remains questionable. The drug has been used for decades in Europe, but was only recently introduced in the United States. It has a greater safety profile than morphine, and produces no respiratory depression or constipation. It is also claimed to be nonaddictive, but remains unscheduled. 

Tramadol (25, Tramol), another cyclohexane with opioid properties, has trans l-m-methoxyphenyl,2-dimethylaminomethyl substituents and is in clinical use in West Germany. It was extensively described in a supplement of Arneimittel Forschung.(39) In animal tests its potency is closer to that of codeine than morphine and relatively high clinical doses (50-100 mg) are necessary for pain relief. Side elTects are generally minor and the compound... 

This chapter concentrates on some drug choices in acute rather than chronic pain, but the same principles can be used to determine the appropriateness of other types of analgesic. The drugs considered in this section are paracetamol, non-steroidal anti-inflammatories (NSAIDs specifically diclofenac, ibuprofen, indometacin, naproxen, sulindac and tenoxicam) and opioids (codeine, dihydrocodeine, morphine, pethidine and tramadol). Unless otherwise stated, all pharmacokinetic data originate from standard reference sources [1-5] and apply to adults only. 

MAOIs PETHIDINE, MORPHINE, PHENOPERIDINE, DEXTROMETHORPHAN Two types of reaction are reported 1. Risk of serotonin syndrome with dextromethorphan, pethidine or tramadol and MAOIs 2. Depressive - respiratory depression, hypotension, coma Type 1 reactions are attributed to inhibition of reuptake of serotonin -more common with pethidine, phenoperidine, dextromethorphan. Type II reactions are attributed to MAOI inhibition of metabolism of opioids - more common with morphine Avoid co-administration do not give dextromethorphan, pethidine or tramadol for at least 2 weeks after cessation of MAOI... 

TCAs OPIOIDS 1. Risk of t respiratory depression and sedation 2. t levels of morphine 3. Case reports of seizures when tramadol was co-administered with TCAs 4. TCAs may t codeine, fentanyl, pethidine and tramadol levels 1. Additive effect 2. Uncertain likely t bioavailability of morphine 3. Unknown 4. TCAs inhibit CYP2D6-mediated metabolism of these opioids 1. Warn patients of this effect. Titrate doses carefully 2. Warn patients of this effect. Titrate doses carefully 3. Consider an alternative opioid 4. Watch for excessive narcotization... 

IMATINIB ANALGESICS-OPIOIDS May cause t plasma concentrations, with a risk of toxic effects of codeine, dextromethorphan, hydroxycodone, methadone, morphine, oxycodone, pethidine and tramadol Inhibition of CYP2D6-mediated metabolism of these opioids Monitor for clinical efficacy and toxicity. Warn patients to report t drowsiness, malaise or anorexia. Measure amylase and lipase levels if toxicity is suspected. Tramadol causes less respiratory depression than other opiates, but need to monitor BP and blood counts, and advise patients to report wheezing, loss of appetite and fainting attacks. Need to consider 1 dose. Methadone may cause Q-T prolongation the CHM has recommended that patients with heart and liver disease who are on methadone should be carefully monitored for heart conduction abnormalities such as Q-T prolongation on ECG as they may lead to sudden death. Also need to monitor patients on more than 100 mg methadone daily and thus an t in plasma concentrations necessitates close monitoring of cardiac and respiratory function... 

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