Buprenorfin , sold under the brand name Subutex, among them, is an opioid used to treat opioid addiction, acute pain, and chronic pain. Can be used under the tongue, by injection, as a skin patch, or as an implant. For opioid addiction usually only begins when withdrawal symptoms have begun and for the first two days of treatment under the direct supervision of a health care provider. For long-term treatment of addiction, buprenorphine/naloxone combination formulations are recommended to prevent abuse by injection. Maximum pain killers are generally within one hour with effects of up to 24 hours.
Side effects may include respiratory depression (decreased breathing), drowsiness, adrenal insufficiency, QT prolongation, low blood pressure, allergic reactions, and opioid addiction. Among those with a history of seizures, there is a further risk of seizures. Withdrawal opioid after quitting is generally mild. It is unclear whether use during pregnancy is safe and used when breastfeeding is not recommended. Buprenorphine affects different types of opioid receptors in different ways. Depending on the type of receptor it may be agonist, partial agonist, or antagonist.
Buprenorfin was approved for medical use in the United States in 1981. In 2012, 9.3 million of these drug prescriptions were written in the United States. Buprenorphine can also be used recreationally with injections or in the nose to produce height. Sometimes used recreation, not heroin. In the United States it is a Schedule III controlled substance. For tablets, wholesale costs in the United States are between 0.86 and 1.32 USD per daily dose per 2017.
Video Buprenorphine
Medical use
opioid addiction
Its primary use is for initial treatment for opioid addicts. It should only start after withdrawal symptoms have begun. For long-term treatment of addiction, a combination of buprenorphine/naloxone formulations is usually recommended. Monthly injections have been approved in the United States and should be available by 2018.
Buprenorfin versus methadone
Both buprenorphine and methadone are drugs used for detoxification, short-term and long-term opioid replacement therapy. The effectiveness of buprenorphine and methadone looks similar, with similar side effects. Buprenorphine may have slight respiratory depression in cases of abuse.
Chronic pain
Transdermal patches are available for the treatment of chronic pain. This patch is not indicated for use in acute pain, pain that is expected to last only for a short time, or pain after surgery, is also not recommended for opioid addiction.
Maps Buprenorphine
Adverse effects
Common adverse drug reactions associated with the use of buprenorphine are similar to other opioids and include: nausea and vomiting, drowsiness, dizziness, headache, memory loss, cognitive and neurological inhibition, sweating, itching, dry mouth, shrinking of the pupil. eye (miosis), orthostatic hypotension, men's ejaculatory difficulties, decreased libido, and urinary retention. Constipation and CNS effects are seen less frequently than morphine.
Respiratory effects
The most severe side effects associated with buprenorphine are respiratory depression (insufficient breath). It occurs more often in those who also consume benzodiazepines, alcohol, or have an underlying lung disease. The usual inverting agents for opioids, such as naloxone, may be only partially effective and additional efforts to support breathing may be necessary. Respiratory depression may be less than other opioids, especially with chronic use. However, in acute pain management settings, buprenorphine appears to cause similar rates of respiratory depression as other opioids such as morphine
Buprenorphine dependency
Treatment Buprenorphine carries the risk of causing psychological or physical dependence. Buprenorphine has a slow onset and a long half-life of 24 to 60 hours. Once a person has stabilized the drug, there are three options: continuous use, switch to buprenorphine/naloxone, or medically supervised withdrawal.
Pain Management
People taking high-dose buprenorphine therapy may not be affected by large doses of opioids such as oxycodone, morphine, or hydromorphone.
It is also difficult to achieve acute opioid analgesia in people taking buprenorphine for opioid replacement therapy.
Pharmacology
Pharmacodynamics
Opioid receptor modulator
Buprenorphine has been reported to have the following pharmacological activity:
- ? - Opioid receptor (MOR): A very strong partial agonist. Binds to high affinity, but only partially activates the receptor. This behavior is responsible for the ability of buprenorfin to block most of it? agonist and phenomenon of withdrawal effect when used in opioid-dependent individuals.
- ? - Opioid receptor (KOR): Partial agonist or functional antagonist. Possible therapeutic applications as animal models show antidepressant, anxiolytic, stress-relieving, and anti-addictive properties with? antagonist.
- ? - Opioid receptor (DOR): Antagonist. Possibility of drug prize attenuation.
- Nociceptin receptor (NOP, ORL-1): Weak affinity. A very weak partial agonist. May be involved in a lack of respiratory depression with buprenorphine in overdose.
In simplified terms, buprenorphine can essentially be considered a non-selective opioid-antagonist receptor modulator, a mixture of agonists, acting as a weak partial agonist MOR, a KOR antagonist, a DOR antagonist, and relatively low. -difference, a very weak partial agonist from ORL-1.
Although buprenorphine is a partial agonist of MOR, human studies have found that it acts like a full agonist with respect to analgesia in opioid intolerant individuals. In contrast, buprenorphine behaves like a partial agonist MOR with respect to respiratory depression.
Buprenorphine is also known to bind with high affinity and hostile to alleged opioids.
The full analgesic efficacy of buprenorphine requires both 11- and exon 1-associated examples of opioid-receptor-sausage variants.
Buprenorphine active metabolism is not considered clinically important in the effects of the central nervous system.
More actions
Unlike opioids and other opioid antagonists, buprenorphine only binds weakly and has little if any activity on sigma receptors.
Buprenorphine also blocks the voltage-gated sodium channel through local anesthetic binding sites, and this underlies strong local anesthetic properties.
Similarly for various other opioids, buprenorphine has also been found to act as a toll-4 receptor agonist, albeit with a very low affinity.
Pharmacokinetics
Buprenorphine is metabolized by the liver, via CYP3A4 (also CYP2C8 apparently involved) isozyme cytochrome P450 enzyme system, becoming norbuprenorphine (by N -dealkylation). Glucuronidation of buprenorphine is mainly done by UGT1A1 and UGT2B7, and norbuprenorphine by UGT1A1 and UGT1A3. Glucuronide is then removed primarily through excretion into the bile. The elimination half-life of buprenorphine is 20 to 73 hours (average 37 hours). Because of especially liver elimination, there is no risk of accumulation in people with renal impairment.
One of the main active metabolites of buprenorphine is norbuprenorphine, which, in contrast to buprenorphine itself, is a full agonist of MOR, DOR, and ORL-1, and partial agonists in KOR. However, relative to buprenorphine, norbuprenorphine has a very small antinociceptive potential (1/50 of buprenorphine), but significantly suppresses respiration (10-fold more than buprenorphine). This can be explained by the very poor brain penetration of norbuprenorphine because of the high affinity of the compound for P-glycoprotein. In contrast to norbuprenorphine, buprenorphine and its glucuronide metabolites are neglected by P-glycoprotein.
Glucuronide buprenorphine and norbuprenorphine are also biologically active, and are the main active metabolites of buprenorphine. Buprenorphine-3-glucuronide has an affinity for MOR, DOR (K i = 270 nM) and ORL-1 (K i = 36 Ã,ÂμM), and no affinity for KOR. It has a small antinociceptive effect and has no effect on respiration. Norbuprenorphine-3-glucuronide has no affinity for MOR or DOR, but it does not bind KOR (K i = 300 nM) and ORL-1 (K i = 18 Ã,ÂμM ). It has a sedative effect but has no effect on respiration.
Chemistry
Buprenorphine is a semi-synthetic analogue of thebaine and quite soluble in water, such as hydrochloride salt. It is degraded in the presence of light.
Detection in body fluids
Buprenorphine and norbuprenorphine can be quantized in blood or urine to monitor use or abuse, confirm the diagnosis of poisoning, or assist in medical investigations. There is significant overlap of drug concentration in body fluids in the spectrum of possible physiological reactions ranging from asymptomatic to coma. Therefore, it is important to have knowledge of drug delivery routes and the level of tolerance to individual opioids when results are interpreted.
History
In 1969, researchers at Reckitt & amp; Colman (now Reckitt Benckiser) has spent 10 years trying to synthesize opioid compounds "with structures that are substantially more complex than morphine that can sustain desired action while removing undesirable side effects". Physical dependence and withdrawal from buprenorphine alone remain an important issue because buprenorphine is a long-acting opioid. Reckitt found success when researchers synthesized RX6029 which has shown success in reducing dependence on experimental animals. RX6029 was named buprenorphine and started human trials in 1971. In 1978, buprenorphine was first launched in England as an injection to treat severe pain, with a sublingual formulation released in 1982.
Society and culture
Rule
In the United States, buprenorphine (Subutex) and buprenorphine with naloxone (Suboxone) were approved for opioid addiction by the US Food and Drug Administration in October 2002. The FDA rescheduled buprenorphine from Schedule V drug to drug Schedule III shortly before Subutex and Suboxone approval. ACSCN for buprenorphine is 9064, and being a Schedule III substance it has no annual production quotas imposed by DEA. The salt used is hydrochloride, which has a free base conversion ratio of 0.928.
In the years prior to Suboxone's approval, Reckitt Benckiser has lobbied Congress to help draft the Drug Treatment Treatment Act 2000 (DATA 2000), which authorizes the Secretary of Health and Human Services to grant a waiver to physicians with certain training to prescribe and administer drugs narcotics Schedule III, IV, or V for the treatment of addiction or detoxification. Prior to the enactment of this law, such treatment is not permitted in an outpatient setting except for clinics designed specifically for drug addiction.
The waiver, which can be given after the completion of an eight-hour course, is required for opioid-based outpatient treatment with Subutex and Suboxone. Initially, the number of patients approved by an approved doctor may be limited to ten. This was eventually modified to allow approved doctors to treat up to one hundred patients with buprenorphine for opioid addiction in an outpatient setting. This limit was recently enhanced by the Obama administration, increasing the number of patients that doctors can prescribe to 275. However, due to this patient's limit and the required eight-hour training course, many patients who can constantly find it very difficult to get a prescription, though effectiveness of the drug.
In the European Union, Subutex and Suboxone, the preparation of sublingual tablets of high doses of buprenorphine, was approved for the treatment of opioid addiction in September 2006. In the Netherlands, buprenorphine is a List II drug of the Opium Law, although specific rules and guidelines apply to prescription and dispensation.
Brand name
Buprenorphine is available under the trade names Cizdol, Suboxone, Subutex (commonly used for opioid addiction), Temgesic (sublingual tablets for moderate to severe pain), Buprenex (solution for frequent injection for acute pain in primary care settings), Norspan and Butrans (transdermal preparation is used for chronic pain).
Buprenorphine has been introduced in most European countries as a transdermal formulation (marketed as Transtec) for the treatment of chronic pain that does not respond to non-opioids.
Veterinary
It has the medical use of animals for the treatment of pain in dogs and cats.
Research
Depression
A clinical trial conducted at Harvard Medical School in the mid-1990s showed that the majority of people with unipolar non-psychotic depression who are refractory to conventional antidepressants and electroconvulsive therapy can be successfully treated with buprenorphine. Clinical depression is not currently an approved indication for the use of any opioids.
Buprenorphine/samidorphan (ALKS-5461), a combination product of buprenorphine and samidorphan (the Î ± -opioid receptor antagonist), is currently undergoing Phase III clinical trials in the United States for augmentation of antidepressant therapy for drug-resistant depression.
Cocaine dependency
In combination with samidorphan or naltrexone (? -opioid receptor antagonists), buprenorphine is being investigated for the treatment of cocaine dependence, and the effectiveness recently demonstrated for this indication in large-scale clinical trials (n = 302) (at high doses of buprenorphine 16 mg but not a low dose of 4 mg).
Neonatal nipples
Buprenorphine has been used in the treatment of neonatal abstinent syndrome, a condition in which newborns exposed to opioids during pregnancy show signs of withdrawal. Current use is limited to infants enrolled in clinical trials conducted under a new drug application approved by the FDA (IND). The ethanol formulations used in the neonate are stable at room temperature for at least 30 days.
Obsessive-compulsive disorder
In one study, buprenorphine was found to be effective in a subset of individuals with obsessive-compulsive disorder of treatment obstruction.
References
External links
- US. Federal federal buprenorphine program for opioid addiction
- Australian national buprenorfin policy
- Bitter pills: Wired Magazine article on Suboxone
- Subu Must Die - How do country addicts go cold turkey: An article New Republic about Subutex misuse in Georgia state
Source of the article : Wikipedia
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