Tramadol Hydrochloride (sold under the brand names Zydol, Zydol SR and Tramake) is an opioid analgesic with agonist activity. Tramadol is indicated for pain management (treatment and prevention of moderate to severe pain). It comes in the form of tramadol hydrochloride tablets/capsules 50 mg, injection 100 mg and sustained-release tablets 100 mg, 150 mg, 200 mg.
Therapeutic Dose for adults and children over 12 years:
- Oral – 50 mg to 100 mg followed not more frequently than 4 hourly. A total daily dose of more than 400 mg.
- IV/IM – For post-operative pain, an initial dose of 100 mg is given. During the next 60 minutes, 50 mg can be given every 10-20 minutes up to a total dose of 250 mg. Maximum 600 mg daily.
Tramadol is not recommended for children under 12 years, and those with severe renal impairment. For those with moderate renal impairment, increase the dosage interval to 12 hours. In the case of severe hepatic impairment, increase the dosage interval to 12 hours. Precautions on the use of tramadol include head injury, epilepsy, raised intracranial pressure, and patients on other respiratory depressant drugs.
Contraindications include known sensitivity to tramadol and patients taking MAOI‘s or within two weeks of stopping.
Physical and psychological dependence is a potential risk, although tramadol is at present, less abused as a single drug than conventional opioids. Cases of drug abuse and drug dependence have occurred.
In single and repeated dose studies (rodents and dogs) doses are 10 times those used in man produce signs of hepatotoxicity. Symptoms of toxicity are typical of opioids and include restlessness, ataxia, vomiting, tremor, dyspnea and convulsions.
Epidemiology of Tramadol Poisoning
Tramadol is a centrally acting analgesic which acts at opiate receptors, and toxic effects are usually extensions of its pharmacological activity.
No specific figures are available for tramadol. However in 1992 (the latest year for which figures are currently available), 226 deaths (190 males, 36 females) were attributed to opiates and related narcotics. These figures represent 11.4% of deaths from poisoning by drugs, medicaments and biological substances. 144 deaths (130 males, 14 females) were due to accidental poisoning, 32 (20 males, 12 females) to suicide and self-inflicted injury, (females) to homicide and injury purposely inflicted by other persons, and 49 to injury undetermined whether accidentally or purposely inflicted. Tramadol has a lower respiratory depressant effect than other opioids and may have lower abuse potential.
Adverse effects include nausea, vomiting, dry mouth, tiredness. There could also be signs of fatigue, drowsiness, somnolence, dizziness, headache, confusion, hallucinations and infrequently respiratory depression. Rarely convulsions, dependence and dysphoria. Tramadol interacts with other CNS depressant drugs, Carbamazepine lithium, SSRIs and tricyclic antidepressants.
The fatal dose for Tramadol is not known. Two children aged 5 weeks and 6 months presented with coma, miosis and respiratory depression after rectal administration of 100 mg but recovered after treatment with naloxone.
There could also be progressive depression of the central nervous system leading to deep coma, cyanosis and marked reduction of the respiratory rate before a respiratory arrest occurs. Symptoms include in point pupils, nausea and vomiting in less severe cases. Hypotension, tachycardia, hallucinations and rhabdomyolysis have been reported.
Overdose effects of tramadol are usually extensions of its pharmacological activity and include miosis, vomiting, seizures, coma, and cardiovascular collapse. The effects are similar to other opioids, but effects on respiratory depression and smooth muscle are usually less pronounced with tramadol. Cardiovascular collapse can occur. Severe overdoses can result in respiratory depression and pulmonary edema. Cerebral depression and seizures can result from tramadol overdose. Gastrointestinal effects are common. Nausea, vomiting, constipation, abdominal pain, flatulence and xerostomia can occur, as well as urinary retention or frequency. Erythema, pruritus and diaphoresis occur infrequently
For decontamination: Give a dose of activated charcoal if the presentation is within 1-2 hours of ingestion. Gastric aspiration or lavage may be indicated if the presentation is soon after ingestion in a patient known to have taken large quantities. Gastric aspiration may be appropriate if the patient is comatose provided the airway is protected.
A 41-year-old man was found dead in a hotel room. He was previously diagnosed with depression. Multiple containers of medication were found at the scene. Autopsy findings included fully developed rigor mortis and pulmonary edema with hemorrhage. Toxicological analysis of different body fluids was performed and the following results obtained in the blood (mg/L): moclobemide (59.76), clomipramine (I.69), tramadol (10.89), diazepam (2.08), nordiazepam (0.82) and caffeine (9.64). A fatal serotonin syndrome presumably developed as a result of moclobemide-clomipramine interaction. Tramadol could have a synergistic effect on the syndrome. The forensic pathologists ruled that the cause of death was multiple drug intoxication resulting in serotonin syndrome and that the manner of death was suicide.
In another case, a 36-year old HIV positive man believed to have taken up to 110 x 50 mg tramadol tablets was found unresponsive. On arrival at the hospital, he was given 2 mg of intravenous naloxone and immediately became awake and was able to answer questions. Within 30 minutes, the patient became increasingly drowsy with shallow respirations. He again responded to 2 mg of intravenous naloxone. In the next 10 minutes, he became responsive to pain only. At this point, after he again responded to 2 mg naloxone, a continuous infusion of naloxone was initiated at 6 mg/hour. This was titrated up to 12 mg/hour because of increasing lethargy. The patient was also given 1g/kg of activated charcoal orally. Four hours after his arrival at the hospital, a slow wean from the naloxone drip was initiated; this was completed approximately 16 hours later without any further depression of respiratory or mental status. The patient was discharged from the hospital 1 day later.
Antidotes to Tramadol Poisoning
Give naloxone, preferably intravenously, if respiratory depression or coma are present (1.2 mg for an adult and 0.01 mg/kg body weight for children). Repeat dose if there is no response within 2 minutes. Failure of a definite opioid overdose to respond suggests that another CNS depressant drug or brain damage is present. The plasma half-life of naloxone is shorter than that of most opioids and therefore repeated doses may be necessary. If a large dose has been taken and relapse occurs set up an infusion (5 x 400 mcg ampoules naloxone = 2 mg in 500ml 5% dextrose) at a rate = 2/3 of the dose needed to wake the patient up per hour. Tramadol is minimally eliminated from the serum by hemodialysis or hemofiltration.
The Opioid Crisis
The analgesic effect of opioids declines and tolerance builds up over time. Higher doses would then be required to achieve pain relief, and opioid dependence or addiction would result. Aside from problematic use, the danger of opioids includes their potential for causing an overdose.
The United States is beset with an opioid epidemic that, so far, has claimed more than 300,000 lives. Two treatments for opioid addiction, methadone and buprenorphine, work on the same opioid receptors as heroin and other opioids. But these treatments are strictly regulated, discouraging millions of Americans with opioid addiction from using them. Also, these drugs can cause physical dependence or drug dependence, and a person continues to rely on drugs to prevent withdrawal symptoms.
Close to a million people used heroin around 2016 in the United States, and about 11.5 million people used narcotic pain relievers that were not prescribed to them. They used narcotic pain relievers such as heroin, methadone, codeine, and morphine, among others. Over time, the person requires more drug for the same desired effect, and the person develops drug tolerance. The period it takes to become drug dependent varies with each person. When the person stops taking the drugs, the body needs time to recover, and this leads to withdrawal symptoms. Opioid withdrawal can occur whenever prolonged use is stopped or reduced.
The opioid crisis has garnered considerable interest in the United States. More and more deaths related to opioid overdose were seen. Opioids killed at least 40,000 people in 2016. From July 2016 through September 2017, opioid overdoses also increased by 30 percent. To resolve the issue, U. S. President Trump in October 2017, declared the opioid crisis a public health emergency.
Cannabis and Opioid Abuse
With the passage of the US Farm Bill in 2018, which made industrial hemp legal, CBD products have become more accessible and widespread over the last year. Also included in the Farm Bill were the provisions for Hemp Farming Act of 2018, which was proposed to remove hemp (defined as cannabis with less than 0.3% THC) from the list of Schedule I substances, making hemp a typical agricultural product.
Tetrahydrocannabinol or THC is one of the primary active ingredients found in the cannabis plant, otherwise known as marijuana. At low doses, THC acts as a mild sedative, but at high doses, it has hallucinogenic effects. CBD products are now sold online, or one may find them at a dispensary in states where cannabis is legalized.
Like marijuana, CBD comes from the cannabis plant, but it does not produce a high. One report studied CBD use for chronic pain. Their research concluded that there is a considerable indication that cannabis is an effective treatment for chronic pain in adults. These conclusions were supported by a separate study in the Journal of Experimental Medicine. This study shows that using CBD can decrease pain and inflammation. The researchers also found that the people who used CBD would probably not develop a tolerance to the effects of CBD, so they would a continuous increase in their dose is not necessary. They concluded that the cannabinoid CBD could be a useful pain reliever for people suffering from chronic pain.
Also, the results of a study published in the American Journal of Psychiatry revealed that CBD could decrease the levels of stress and cravings experienced by people recuperating from heroin dependence. Pharmacologist and neuroscientist Yasmin Hurd, the first author of the study, is also the director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai. Dr Hurd also stated that an effective non-opioid medication would substantially help reduce the rising death toll, massive health care budgets, and treatment restrictions imposed by strict government regulations amid this obstinate widespread occurrence of opioid use.
The study showed that CBD might minimize signals in the body that activate anxiety and cravings in people who abused opioid in the past. CBD may also lower the heart rates of patients, as well as, and levels of stress hormones. Hurd further explained that the results are evidence that CBD should be regarded as potentially useful alternative remedy patients who are recovering from opioid abuse.
The study done by Hurd and her team looked at the possibility of using cannabidiol or CBD to decrease cravings and anxiety for the treatment of opioid use disorder so that the possibility of relapse and overdose would also be reduced.
The U. S. Food and Drug Administration (FDA) is cognizant that some states have either enacted laws that abolish state limitations on the medical use of cannabis and its byproducts or are considering doing so. It is imperative to organize medical research into the safety and efficacy of cannabis products through sufficient and controlled clinical trials. FDA is open to talks with states who want to give their support for research on medical cannabis and its byproducts so that FDA can provide information on Federal and scientific standards.
More Research Needed
Cannabidiol can reduce heart rate and the levels of stress hormones in the body. This characteristic gives CBD the ability to help patients deal with cravings and anxiety triggered by the sights and sounds in the environment. CBD continues to attract attention as researchers report that it might also help treat opioid addiction. Although many people use cannabidiol for pain relief, it is wise to consider other factors, such as its side effects, before taking it.
Additional cannabis research is needed to be confident of its safety on public health. The states that have accepted medical marijuana as a treatment for opioid addiction have done so with various limitations. For instance, some regulations only allow medical practitioners to prescribe medical marijuana if traditional treatments are unsuccessful, or if cannabis is utilized in conjunction with other traditional treatment options or drug use.