Wd Count: 1472
Introduction
Dextropropoxyphene is a drug used as a painkiller. The mild opioid can alleviate long-term or short-term pains. Dextropropoxyphene is an opioid that is a morphine-related drug. It acts on the neural system in the spine and the brain and hence relieves pain. The drug has been available for use by blending it with other drugs or on its own. In the recent past, use of the drug has been rejected by several countries, among them Australia, because of safety reasons. In Australia, the drug has been recently in March 2012 following discoveries that Dextropropoxyphene can cause changes in the electrical activity of the heart. This has been due to health and even death related cases from drug overdose. This has been more common for pharmaceutical products with dextropropoxyphene and paracetamol as their main constituents. However, drugs containing only paracetamol did not show the adverse effects on the users. Some of products containing Dextropropoxyphene that have been banned include Capadex, Paradex, Di-Gesic and Doloxene.
According to European Medicines Agency (1), drugs containing dextropropoxyphene are weak analgesics with little efficiency. The research showed that these drugs were no more effective than alternative painkillers. These drugs have more adverse effects than paracetamol used at the prescribed and required dose. The drug has a thin therapeutic index. This means that a thin line exists between the useful and the harmful amount to a patient. Consequently, chances of overdose on the drug are high with a high probability of fatality. In case of overdose, deaths have occurred within an hour of ingestion (Medsafe, 2). There have been many incidents of fatality due to accidental overdose. In most of these incidents, the victims took medicine prescribed for another person. Withdrawal from the use of dextropropoxyphene has taken place to promote the health of people in many countries. In Australia, withdrawal of the drug from the market from occurred in March 2012.
Pharmacology and Toxicology of Dextropropoxyphene
Dextropropoxyphene has a similar molecular structure to methadone (morphine). Its analgesic properties arise from the dextro-isomer, dextropropoxyphene. It is a µ-opiod receptor agonist with an affinity similar to that of codeine. According to Twycross (3), the drug undergoes dose dependent first-pass metabolism. Norpropoxyphene, which is the main metabolite, does not cross the thin membrane separating the brain and blood as much as dextropropoxyphene. It has a plasma half-life of about four hours and has weaker analgesic effect as compared to morphine (Bryant, 4). Conversion of dextropropoxyphene to an active metabolite, which is norpropoxyphene, makes dextropropoxyphene to be less toxic and still effective (Saeb-Parsy, 5). Dextropropoxyphene is the most toxic of the narcotic analgesics tested, with high values of D. magna (Whitacre, 6). A high mortality rate has been associated with the drug in the UK. The drug has substantial dysphoric effects and can lead to cardiotoxicity. The drug has no pros over other painkillers such as aspirin and codeine. According to Twycross (3), when regularly taken, the drug’s potency can rise to reach that of codeine and dihydrocodeine.
Drug Interactions
The drug hinders hepatic metabolism of benzodiazepines, β-blockers, warfarin, and carbamazepine. It has a higher risk of toxicity when administered with ritonavir. They are particularly dangerous in combination with alcohol or CNS depressants. The drug increases the effect of cyclobenzaprine hydrochloride, dapoxetine, dibenzepin, and diazepam (MIMS, 7). It does not have an effect on the metabolism of lorazepam and has no clinical effect on diazepam. Tobacco reduces the level of dextropropoxyphene in blood and alleviates pain. Sedatives and antidepressants increase the drug’s sedative action. Sunlight has no impact on the sensitivity of the drug (Upfal, 8).
Mechanism of action
Dextropropoxyphene is a mild opiod analgesic. It acts by binding itself to mu- and kappa-receptors to block sensitivity of pain in the cerebral cortex. This hinders the flow of sensation to the high centers. Absorption of the drug occurs in the gastrointestinal tract. Absorption of the napsilate form is slower than that of the HCl form. It is after one to two hours that the concentration of the drug in the blood reaches maximum levels. After absorption, concentration of the drug occurs in the liver, brain, and lungs and the drug binds itself to proteins.
The average half-life of the drug is approximately 12 hours. This may be longer in older patients. The medicine undergoes considerable first- pass metabolism. The main metabolite is norpropoxyphene that penetrates the brain to a smaller extent with a weaker opioid effect. Excitatory effects include tremulousness and seizures. The first-pass metabolism of the drug is dependent on the dosage meaning that the availability of the drug increases with an increase in oral doses. This is a pharmacokinetic platform for believing that single doses are less effective than repeated doses (Hanks, Cherny and Fallon, 9). Dextropropoxyphene has a long elimination life (Schanzer, 10). Excretion is through urine as metabolites or in breast milk. Demethylation of the drug occurs in the liver, yielding nordextropropoxyphene whose excretion is through the kidneys (ADIS Press, 11).
Indications, dosage, and contraindications
Administration of dextropropoxyphene is oral, and the drug can alleviate mild to moderate pain. Adults should take 65mg with a dosage of 3 times daily. Renal or hepatic impairment necessitates a reduction in the dosage. Taking of the drug can be with or without food without any major effects in each case. However, according to Upfal (8), ingestion of the drug on an empty stomach results in quick pain relief. Food slows down absorption of the drug. The patient may fall into a coma in case of over dosage. Other effects include respiratory depression, seizures, circulatory collapse, diabetes insipidus, or ECG abnormalities. Management is via a thorough institution of supportive and symptomatic therapy. Drugs such as IV naxolene can undo the intoxication. There are circumstances under which an individual should not take the drug. A pharmacist should not administer dextropropoxyphene in case of pregnancy, porphyria, hypersensitivity, or chronic respiratory diseases. Use of dextropropoxyphene in pregnant women can cause respiratory depression to the newborn baby. Use of the drug in children is limited as the safety and effect of the drug on children is unknown (Aspen, 12). Individuals with suicidal tendencies and renal diseases should not take the medicine. The same applies for lactating mothers. Ingestion of the drug concurrently with alcohol has a CNS additive effect on the drug. Intake of the drug above the prescribed dosage over long periods leads to dependency on the drug (Nelms and Sucher, 13). The probability of addiction to the drug is lower than that to codeine.
Impacts of Dextropropoxyphene
Dextropropoxyphene leads to hallucinations, hypoglycemia, hepatic reaction, and even affects the heart’s electric pulses. In cases of overdose on the drug, all these effects pronounce themselves even more (NPS, 14). The drug causes vomiting, skin rashes, dizziness and weakness, constipation and abdominal pain. It also affects the cardiovascular system due to norpropoxyphene that has a stabilizing effect on the membrane. Co-proxamol, a mixture of paracetamol and dextropropoxyphene, usually leads to hypersensitivity pneumonitis. The medicine leads to fibrous myopathy, thus affecting the musculoskeletal system. In the long term, the user of dextropropoxyphene may develop dependence. However, the drug can be been used to enable patients and addicts to be able to withdraw from morphine. Young patients, below 35 years, mostly develop severe respiratory failure while the drug causes carcinogenic shock in the older folk. Hemolytic anemia, perineal ulceration, and hepatoxicity can occur as a consequence due to the use of the drug. The drug can interact with other drugs resulting in drastic effects. When taken with alcohol it can result in cardiorespiratory arrest. It can also hinder the metabolism of alprazolam and the oxidative metabolism of carbamazepine. Heavy smoking, however, can increase the elimination of dextropropoxyphene (Aronson, 15).
Therapeutic roles and dangers of using dextropropoxyphene
Dextropropoxyphene, which is a congener of methadone, relieves acute and chronic pain (Mckay and Walters, 16). This is especially helpful to victims of accidents who still suffer aches and pains from the different incidents that caused the pain. It has similar effects to morphine, but it causes less constipating and lasts longer, when compared to morphine (Udaykumar, 17). Dextropropoxyphene has considerably good oral efficacy. Use of the drug has increased efficacy with acetaminophen and NSAIDS hence making the analgesic suitable for dental pain that may be particularly acute (King Saud University, 18). On the other hand, the drug has acute adverse effects that lead to hypotension, seizures, decreased libido, and cholestasis. In some cases, it may cause convulsions that could be fatal (Drug Information Systems, 19). Extensive research done in many countries has looked into the therapeutic role of the drug vis-à-vis the dangers arising from its use (Helms and Quan, 20). Since the risks outweigh the advantages, most countries have found it only logical to outdo marketing and use of the drug completely. It is advisable for patients that were dependent on Dextropropoxyphene to use paracetamol. In addition, if the paracetamol is not effective, patients are advised to use ibuprofen. This should be used for short durations and in low dosages.
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