Opioids are euphoric substances that result in high doses to sedation and respiratory depression. Respiratory depression may with special antidotes (e.g., naloxone) or by intubation and ventilation to be treated. Withdrawal initially manifests as anxiety and craving for the substance, followed by increased respiratory rate, sweating, yawning, tearing, runny nose, mydriasis and stomach cramps, later piloerection, tremors, muscle twitching, heart palpitations, high blood pressure, fever, chills, loss of appetite, nausea, vomiting and diarrhea. The diagnosis is made clinically and confirmed by a urine test. The withdrawal can be treated by substitution with a long-lasting opioid (z. B. methadone) or with buprenorphine (a mixed opioid agonist-antagonist).
Opioid is a term for a series of natural materials (originally derived from the opium poppy) and their semi-synthetic and synthetic analogs that bind to specific opioid receptors. Opioids are potent analgesic with a limited medical importance for the treatment of cough and diarrhea. They are often abused because they are widely available and have euphoric properties; see also opioid analgesics and opioid-dependent disease and rehabilitation.
Opioids are euphoric substances that result in high doses to sedation and respiratory depression. Respiratory depression may with special antidotes (e.g., naloxone) or by intubation and ventilation to be treated. Withdrawal initially manifests as anxiety and craving for the substance, followed by increased respiratory rate, sweating, yawning, tearing, runny nose, mydriasis and stomach cramps, later piloerection, tremors, muscle twitching, heart palpitations, high blood pressure, fever, chills, loss of appetite, nausea, vomiting and diarrhea. The diagnosis is made clinically and confirmed by a urine test. The withdrawal can be treated by substitution with a long-lasting opioid (z. B. methadone) or with buprenorphine (a mixed opioid agonist-antagonist). “Opioid” (originally derived from the opium poppy) for a number of natural products and their semi-synthetic and synthetic analogs that bind to specific opioid receptors a term. Opioids are potent analgesic with a limited medical importance for the treatment of cough and diarrhea. They are often abused because they are widely available and have euphoric properties; see also opioid analgesics and opioid-dependent disease and rehabilitation. Pathophysiology There are three three opioid receptors: delta, kappa and mu. They are found throughout the CNS, but especially in areas that are associated with pain perception. The receptors are located also in some sensory nerves, on mast cells and some cells in the gastrointestinal tract. Opioid receptors are stimulated by endogenous endorphins, which cause usually analgesia and a sense of well-being. Opioids are therapeutically used primarily as a painkiller. Opioids differ in their receptor activity, and some (eg. B. buprenorphine) have a combined agonist and antagonist activity. Substances with pure antagonist activity (eg. As naloxone, naltrexone) are also available. Exogenous opioids may be incorporated in a variety of ways: orally, intravenous, subcutaneous, rectal, inhaled through the nasal mucosa or smoke. The maximum effect occurs approximately 10 min after i.v. Injection, a, within 10-15 min after nasal insufflation, and 90-120 min after oral ingestion, although the time may vary depending on the specific substance to the peak of the effect and the duration of action. Chronic effects Tolerance develops quickly, and more and higher doses are needed. The tolerance to the various effects of opioids often develops irregular. So heroin addicts can be largely tolerant of the euphoric and respiratory suppressive effects, but still continue to have constricted pupils and constipation. Low withdrawal symptoms from opioids can occur after only a few days of use. The severity of symptoms increases with the level of the opioid dose and duration of dependence. The long-term effect of opioids itself is minimal; even decades of use of methadone seems rather physiologically well tolerated, although some long-term opioid users experiencing chronic constipation, excessive sweating, peripheral edema, fatigue, and decreased libido. However, and extenders (eg. B. prescription stimulants) have many long-term users who inject opioids harmful side effects caused by impurities (for example, talc z.), As well as heart, lung and liver damage caused by infections such as HIV and hepatitis B or C that are characterized by the sharing of needles and not sterile injection techniques spread (substance use by injection) .Schwangerschaft the use of opioids during pregnancy may lead to fetal opioid dependence. Symptoms and signs Acute effects Acute Opioidintoxikation is seen by euphoria and drowsiness. Mast cells effects (eg. As redness, itching) are common, especially with morphine. Gastrointestinal side effects are nausea, vomiting, decreased bowel sounds and Verstopfung.Toxizität or overdose The most important toxic effect is a reduced respiratory rate and depth of breathing, which can develop to apnea. Other complications (eg. As a pulmonary edema within minutes to a few hours after an opioid overdose develops usually), and death resulted primarily from hypoxia. The pupils are miotisch. Delirium, hypotension, bradycardia, decreased body temperature, and urinary retention may also occur. Normeperidine, a metabolite of meperidine, accumulates with repeated use (also in therapeutic use); It stimulates the central nervous system and can cause seizures. Serotonin syndrome occurs occasionally when fentanyl, meperidine, tramadol oxycodone or concurrently with other drugs that serotonergic effects have (z. B. SSRIs, MAOIs) were taken. This syndrome consists of one or more of the following findings: hypertension tremor and hyperreflexia Spontaneous clonus Inducible clonus plus restlessness or sweating Ocular clonus plus restlessness or sweating body temperature> 38 ° plus ocular or inducible clonus withdrawal The opioid withdrawal syndrome generally involves… symptoms of increased CNS activity. Start and duration of withdrawal symptoms depend on the specific substance and its half-life. Symptoms may h after the last dose of heroin occur with a peak within 48 to 72 hours until they subside after about a week after the 4th On fear and a strong desire for the substance increased respiratory rate follows at rest (> 16 breaths / min), mostly by yawning, sweating, tear or runny nose, mydriasis and abdominal cramps accompanied. Later piloerection can (goosebumps), tremor, muscle twitching, heart palpitations, high blood pressure, fever and chills, loss of appetite, nausea, vomiting and diarrhea develop. The opioid withdrawal does not lead to fever, seizures or loss of consciousness. Although it may be uncomfortable in certain circumstances, an opioid withdrawal is not fatal. The withdrawal syndrome among users of methadone (which has a long half-life has) develops slowly and appears less severe than heroin withdrawal, although some users describe it as worse. Even after the withdrawal symptoms have subsided, lethargy, malaise, anxiety and insomnia may persist up to several months. The craving for the drug can persist for years. Diagnosis Clinically determined Diagnosis of opium use is usually made clinically and partly by additional urine drug testing; Laboratory tests are carried out as necessary to identify substance-related complications. Substance levels are determined not routinely. Therapy Supportive therapy With opioid withdrawal Sometimes drug therapy (. For example, with an opioid agonist, opioid agonist-antagonist, opioid antagonist, or clonidine) toxicity or overdose, the keeping free the respiratory tract and the support of the breathing activity is extremely important. Naloxone 0.4 mg i.v. Possibly. Endotracheal intubation patients with spontaneous respiration can with an opioid antagonist such. As naloxone, are treated. Dosage: 0.4 mg i.v. (For children <20 kg, 0.1 mg / kg); Naloxone has no agonist activity and a very short half-life (see Table: Symptoms and treatment of specific toxins). Naloxone helps most patients quickly to unconsciousness and respiratory failure due to an opioid. When a iv Access can not be established immediately, is a i.m., s.c. or intranasal administration are also effective. A 2nd or 3rd dose can be given when there is no response within 2 min. Almost all patients respond to three 0.4 mg doses (nasal spray is a Einzeldosisinhalator with 4 mg). If they do not, the patient's condition is not based on a probable overdose of an opioid, although higher doses of naloxone may be required at a massive opioid overdose. Because some patients can become agitated, delirious and aggressive when their consciousness returns, and because naloxone triggers an acute withdrawal, gentle fixtures should be applied before naloxone is given. In order to improve the withdrawal of long-term users, some experts recommend the titration of naloxone in very small doses (0.1 mg) if the clinical situation does not require immediate withdrawal. Apnea patients may initially iv naloxone 2 mg be treated if this can be given without delay; note that the dose is higher than in patients who are somnolent. In some parts of the US and some countries naloxone is available without a prescription, so apneic patients from friends or family can be saved. If naloxone is administered and readily available, intubation is rarely required. Patients should be observed for several hours after they have achieved the spontaneous breathing again. Since the effect duration of naloxone is shorter than the other of enigen opioids, can occur within a few hours after the overdose of methadone or slow-release oxycodone or morphine tablets again a respiratory depression. Thus, the observation period should depend on the half-life of the opioid involved. Normally, patients who have taken longer acting opioids should be admitted for observation; Patients who have taken short-acting opioids may be released after several hours. When a new respiratory depression occurs, naloxone should be administered repeatedly at an appropriate dose. The optimal dosage is not clear. Many doctors use repeated bolus doses of the same dose that was initially effective. Others use a continuous naloxone infusion; They usually start with about two-thirds of the originally effective dose per hour. In theory, the continuous infusion should allow the dose is titrated to maintain the respiratory rate without triggering a relapse; However, in practice this can be difficult, and the patient's life depends on the security of i. v. Line-respiratory depression will recur quickly when the infusion is stopped (eg., By the patient who pulls out the i. .v access). Both therapies require close monitoring, usually in an ICU. Patients should monitored until no pharmacological activity of naloxone is more present and have eased the opioid-related symptoms. The serum half-life of naloxone is in about 1 hour so that an observation period of 2-3 h is observed after administration of naloxone. The half-life of i.v. Heroin is relatively short and recurrent respiratory depression following administration of naloxone is rare. Acute pulmonary edema are treated with supplemental oxygen and often by invasive or non-invasive methods of respiratory support (eg positive airway pressure [BiPAP], endotracheal intubation.) .Entzug and detoxification Treatment may have several strategies: No treatment (cold turkey) substitution methadone or buprenorphine, clonidine to relieve the symptoms long-term support and possibly naltrexone The opioid withdrawal syndrome is self-limiting; Although it is very unpleasant, but not life threatening. Lighter metabolic and physical withdrawal symptoms can last for six months. The withdrawal is usually monitored in outpatient facilities, except that a hospital stay for the simultaneous treatment of physical or mental disorders or the patient is required. Options for the withdrawal treatment of cold withdrawal, that the abrupt discontinuation of the drug, or the gift of another opioid (substitution) which is tapered off after a controlled scheme. Clonidine may cause a relief of symptoms during withdrawal. The US Substance Abuse and Mental Health Services Administration (SAMHSA) provides information on drug-supportive care. The methadone substitution at more dependent patients the preferred method of opioid withdrawal, because it has a longer half-life and a less strong sedative and euphoric effects at appropriate doses. Any doctor can initiate a methadone treatment during hospitalization or for 3 days out-patient treatment, further treatment is then continued in an approved methadone program. Methadone is administered orally in the minimum dose that prevents serious, but not necessarily all withdrawal symptoms. The most common dose is once daily at 15-30 mg; Doses ? 25 mg may lead to dangerous sedation in patients who have not yet developed tolerance. Symptom tables were not used to estimate the appropriate dose. Higher doses should be used when the patient is demonstrably physical withdrawal symptoms. After the appropriate dose has been established, it should be gradually reduced by 10-20% every day when the decision is made to continue the drug at a constant dose (methadone treatment). Patients are often anxious during Ausschleichens the drug and require more of the substance. A methadone withdrawal for dependent patients who had been in a methadone program can be particularly difficult because the dose of methadone in this program may be daily 100 mg once; in these patients the dose should be reduced gradually over several weeks to 60 mg once daily initially, before a complete detoxification can be addressed. It is known that methadone can be brought to QTc prolongation and severe arrhythmias including torsades de pointes, in conjunction (long QT syndrome and torsade de pointes tachycardia). So this substance should be very carefully applied and the patient be evaluated thoroughly in the initial phase and during dose titration and monitored. Also, the combined opioid agonist-antagonist buprenorphine sublingual given, has been successfully used in withdrawal. He is in a combination with naloxone as an i.v. Preparation available to prevent further abuse. The first dose is given when the first signs of withdrawal symptoms noticeable. The dose should be titrated as quickly as possible to control severe symptoms effectively. Normally, a sublingual dose of 8-16 mg is used daily. Buprenorphine is then reduced continuously over several weeks. The SAMHSA Web site provides additional information about buprenorphine and the necessary training for the qualification of "waivers" to prescribe the drug. Protocols for the use of buprenorphine for detoxification or maintenance treatment are available for download from the US Department of Health and Human Services. Clonidine, a centrally acting adrenergic drug can suppress autonomic symptoms and signs of opioid withdrawal. Starting from dosages in an amount of 0.1 mg p.o. every 4-6 h, can vary depending on compatibility up to 0.2 mg p.o. every 4-6 hours to be increased. Clonidine may cause hypotension and drowsiness, and a withdrawal can trigger restlessness, insomnia, irritability, tachycardia and headaches. Fast and ultra-fast protocols were evaluated for use in the withdrawal and detoxification. In fast protocols combinations of naloxone, nalmefene and naltrexone are used to induce a withdrawal, and clonidine and various adjuvant drugs are used to suppress the withdrawal symptoms. Some quick protocols used a buprenorphine, to suppress withdrawal symptoms from opioids. Ultrafast protocols use large boluses of naloxone and diuretics to improve the excretion of opiates, while patients are under general anesthesia; these ultrafast protocols are not recommended because they have a high risk of complications and no significant additional benefit. Doctors need to understand that detoxification is not a treatment per se. It is only the first step and needs to be accompanied by a continuous treatment program that various types of counseling and may include the use of non-opioid antagonists (eg. As naltrexone). For more information US Substance Abuse and Mental Health Services Administration (SAMHSA)