Buying Heroin Can Tho

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Buying Heroin Can Tho

This section explains how using drugs and alcohol can affect your mental health. It also explains how you can get help to stop using drugs and alcohol. This information is for people affected by mental illness in England who are 18 or over. See this 46 second video for why this is important. People use drugs and drink alcohol for lots of different reasons. Whatever your reason, using drugs or alcohol may have a long-term negative effect on you. The possible long-term effects include the following. If you use alcohol or drugs for a long time it can cause serious issues for your mental well-being. Drugs can make you more unwell and more likely to try and harm yourself or take your own life. There is also some evidence that using some drugs may cause mental illness for the first time. For example, research has shown that cannabis can increase your chances of developing psychosis or a psychotic disorder. Psychosis is a medical term. If you have psychosis you will process the world around you differently to other people. This can include how you experience, believe or view things. You might see or hear things that others do not. Or believe things other people do not. Some people describe it as a 'break from reality'. There are different terms use to describe psychosis. You can find more information about 'Psychosis' by clicking here. In this section we have listed some of the different types of substances that could have an impact on your mental health. Please be aware that this list is not a list of all substances. Taking any substances can be dangerous. They can also have bad interactions with any medications or other substances you might use. They are a specialist charity that provides information on drugs. You can find their website here: www. Cannabis is one of the most commonly used drugs in England. According to one study, 1 in 13 people aged had used it in the last year. Young people aged are more likely to use cannabis. The same study shows that just under 1 in 5 young people had used cannabis between and Some people take cannabis because it makes them feel relaxed or happy, but It can also make you feel anxious or feel paranoid. Some people may experience things that aren't real. This is a sign of drug-induced psychosis. Some studies have shown that the risk of psychosis may be higher if you:. If you have been using cannabis and you feel that it is affecting your health, make an appointment to see your GP as soon as you can. Your doctor should not judge you and should not tell other people you use drugs. Some people with a mental illness have problems using alcohol. Alcohol is legal, which means it is easier to get. It can make the feelings of some mental health issues feel worse. The long-term effects of alcohol also depend on how much you drink, and how regularly you drink it. If you drink too much on a regular basis then you could cause yourself serious physical and mental harm. Drinking can make you do something you would not normally do. This can include self-harm and suicide. Very high levels of alcohol can cause psychosis. These are drugs that contain one or more chemical substance. They produce effects that are similar to cocaine, cannabis and ecstasy. This is a common term that people use. It is used because some NPS were legal before However, the name is now wrong, because since they have been made illegal. Some new psychoactive drugs can cause confusion and a feeling of panic. You can also have hallucinations. Hallucinations can affect the way you behave. Your behaviour can become erratic and can put your own safety at serious risk. Some NPS can be very dangerous. They can kill you or hurt you very badly. There is a higher risk of this if taken with alcohol or other psychoactive drugs. In the short-term, these drugs can make you feel wide awake and alert. This can make it difficult for you to relax or get to sleep. They might cause you to have a drug-induced psychosis. In the long-term, amphetamines might make you anxious and depressed. They can also be addictive. Benzodiazepines are a type of tranquilisers. They are used to treat anxiety. They are also used as a muscle relaxant. Sometimes a doctor will tell you to take benzodiazepines to help you with anxiety. But people also buy them illegally because of their relaxing effects. They can be addictive, and so doctors only give them for a short time. In the short-term, these drugs can make you feel calmer. Depending on the type you take, they could make you feel confused or overly sleepy. Taking benzodiazepines with other drugs or alcohol can be dangerous. It can affect your breathing. It can also increase the risk of overdose and death. In the long-term, some people become addicted. This can have a big effect on their day-to-day life. In the short-term, cocaine can make you feel awake, talkative and confident. After this wears off, you can feel tired and depressed after taking it. In the long-term, cocaine use can affect how you feel. It can affect your relationships with friends and family. Cocaine is also addictive and over time you are more likely to have ongoing problems with depression, paranoia or anxiety. Cocaine can cause fits, heart attacks and strokes. If you mix it with some other drugs you are more likely to overdose or die. In the short-term, ecstasy may make you feel energetic, very happy, chatty and confident. It can also sometimes make you feel anxious, confused or trigger drug-induced psychosis. In the long-term, ecstasy use can lead to memory problems. You may also develop depression and anxiety. In the short-term, heroin can make you feel relaxed and happy. It takes away pain and can make you feel sleepy. But there is a higher risk that you could take too much or overdose with heroin than some other drugs. Heroin can be taken in lots of different ways, including by injection. However, there is a high risk of getting an infection if you inject heroin, particularly if you share needles with someone else. Heroin is very addictive. It can have serious long-term effects. You may feel that heroin becomes more important than other things in your life. This might make it harder to keep a job and affect your relationships. In the short-term, LSD may make you experience things that aren't real. Sometimes the experience will be enjoyable, and sometimes it will be frightening. This is known as a bad trip. If you have a history of mental health problems taking LSD can make it worse. If you panic during a trip on LSD it can be scary. Your local NHS trust may have a policy that says how they will help people with dual diagnosis. Check on their website to see if you can find out more about what to expect locally. If you are not already getting help with your mental health from your local mental health team, a good first step is to make an appointment to see your GP. Your GP may offer you medication and therapy to treat your mental illness. They may refer you to a drug and alcohol service to help you with your drug use. If your needs are too complicated for your GP to deal with alone, you might need more specialist support. They should offer this support and work with drug and alcohol services to give you all the help you need. The Department of Health and Social Care says that people with dual diagnosis are a key group of people who should get help from mental health services. You should not be stopped from getting help if you have drug or alcohol problems and severe mental illness. They say that people who have a severe mental illness and drug or alcohol problem should get help under the Care Programme Approach CPA. Under the CPA you will have a care co-ordinator to plan your care. They will help to write a care plan. This should account for all the different needs you might have such as:. NICE also say that you should be able to give your views on the care plan to make sure that it meets your needs. And the care plan should be shared with your carers or family if you agree. You can read the NICE guidance online here: www. There may be a team in your area which helps people with dual diagnosis. It is sometimes called the dual diagnosis team. However, not all areas of the country have them, and it may have a different name. If there isn't one in your area, you could try contacting your local community mental health team CMHT for help. As well as NHS services, you could try contacting local charities. Many charities have support services or support groups for people struggling with substance misuse. You can find some national charities listed in the Useful Contacts section below. Some people with dual diagnosis have told us that it has been difficult to get the help they need. For example, you may have been told that mental health services cannot help you because of your drink or drugs problem. But the Department of Health and Social Care is very clear that mental health services should try to help you if you have dual diagnosis. The National Institute for Health and Care Excellence NICE also say that you should not be turned away from mental health services because you have a drug or alcohol problem. You can ask for a copy of their policy for eligibility criteria. You may then be able to use this to show you are eligible for their support. If you are not happy with the services you get, talk to the person in charge of your care. This might be your GP or your 'care coordinator'. They might be able to change things for you. An 'advocate' may be able to help you to get your point of view across. You might need to make a complaint to the NHS if you do not get the help you need. Supporting someone struggling with dual diagnosis can be difficult. It might help to speak to the person you are helping, to see what support they want. For example, some people might just want someone to talk with. Other people might want more practical help, such as with booking appointments or helping them speak to professionals. We Are With You and Adfam are two charities that offer support and advice to relatives, friends and carers of those struggling with substance misuse. You can find their contact details in the Useful Contacts section below. You might also feel that you need support for yourself. You may be able to get practical support to help you with your caring responsibilities. But this can only happen if the person who you care for wants you to be involved. Speak to the mental health team if you have ideas about what services should be available or how things could work better. Drinkline This is the national alcohol helpline. They provide information and selfhelp materials for callers worried about their own drinking, and to support the family and friends of people who are drinking. They are confidential, you do not have to give your name and they can provide advice on where to get help. Telephone : Open weekdays 9am — 8pm, weekends 11am — 4pm. Webchat Drinkchat : www. Adfam This is a national charity for families and friends of drug users. It offers confidential support and information. Frank Frank provides information and advice on drugs to anyone concerned about drugs and solvent misuse, including people misusing drugs, their families, friends and carers. Open 24 hours a day, every day Text : Email : Online form here: www. Website : www. Alcohol Change UK Alcohol concern is the national organisation for alcohol misuse. It does not provide services, but they do produce information on alcohol. We Are With You This is a drug and alcohol treatment agency. Their services deal primarily with drug and alcohol problems including support for families. Al-Anon Family Groups This is a service for families and friends of alcoholics. Al-Anon family groups provide understanding, strength and hope to anyone whose life is, or has been, affected by someone else's drinking. They are recovering addicts who meet regularly to help each other stay clean. They have groups around the country. Helpline : 10am — midnight Website : www. Alcoholics Anonymous AA AA provides an opportunity for people to get together to solve their problem with alcohol and help others to recover. Cocaine Anonymous CA CA is a fellowship of men and women who use the 12 step, self-help programme to stop cocaine and all other mind-altering substances. Telephone : Open 10am — 10pm every day. DrugWise DrugWise provides information and publications on a wide range of drug related topics. PostScript A charity committed to supporting individuals to reduce the harms caused by prescribed drugs that are associated with dependence and withdrawal. They do this through a wrap-around service of one to one therapy, group therapy and a telephone support service. Release They offer advice and information on drug problems. They have expertise in legal matters surrounding drugs. Email : ask release. Turning Point This is an organisation that works with people affected by drug and alcohol misuse, mental health problems and learning disabilities. Advice and information About mental illness Learn more about conditions Drugs, alcohol and mental health. Drugs, alcohol and mental health This section explains how using drugs and alcohol can affect your mental health. Download Drugs, alcohol and mental health factsheet. Share: Contact us:. Overview There are many reasons why you might use drugs and alcohol. Some people use them to try and deal with their symptoms of their mental illness. This is called 'self-medication'. Drugs and alcohol can make the symptoms of your mental illness worse. Some drugs may make it more likely for you to get a mental illness, and they may make it harder to treat. Mental health, and drug and alcohol services should work together to give you the support you need. If you have any problems getting help, you could make a complaint. Need more advice? If you need more advice or information you can contact our Advice and Information Service. Contact us Contact us. About How can drugs and alcohol affect my mental health? Needing to take more to get the same effect. High blood pressure and strokes. Problems with your liver and pancreas. Development of certain cancers e. Difficulty obtaining or maintaining an erection. Problems with orgasms. Difficulties becoming pregnant. Feeling like you must use the drug or alcohol. This is known as being dependent. Having sudden mood changes. Having a negative outlook on life. Loss of motivation. Problems with relationships. Being secretive. Having episodes of drug-induced psychosis. What is psychosis? Drugs and effects Which substances can affect my mental health? Alcohol Also known as: bevvies, booze Some people with a mental illness have problems using alcohol. The short-term effects of an NPS depend on what you take. These drugs can also affect your judgement, which could put you at risk. When you stop taking the drug, you may feel depressed and you might find it hard to sleep. Getting help How can I get help? This should account for all the different needs you might have such as: social care, housing, and physical health. Worried about your mental health? Care Programme Approach by clicking here. Problems What can I do if I have problems trying to get help? You can find more information about: Advocacy by clicking here. Complaints by clicking here. Carer's, friends and relatives What if I am a carer, friend or relative? NICE also says that if you are caring for someone with a dual diagnosis you can: be involved in their care planning, and work with services to help those services improve. You can find more information about: Supporting someone with a mental illness by clicking here. Confidentiality — for carers, friends and relatives by clicking here. Useful contacts Drinkline This is the national alcohol helpline.

Vietnam’s Pharmaceuticals Industry: A Comprehensive Guide for 2022

Buying Heroin Can Tho

Official websites use. Share sensitive information only on official, secure websites. Address correspondence to Dr. Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area. The World Health Organization reports that drug interactions are a leading cause of morbidity and mortality. Furthermore, there has been a dramatic increase in deaths related to methadone use, both for the treatment of pain and illicit use, in the United States in recent years. Drug interactions have been implicated in many of these deaths. Interactions between cocaine, alcohol, and other substances will also be summarized. Drug interactions can occur through several mechanisms. One or more mechanisms may be involved in the expression of a clinically significant drug interaction. The primary mechanisms of drug interactions include effects of drugs on hepatic metabolism of pharmaceuticals including effects on cytochrome P CYP enzymes or effects on glucuronidation, medication effects on the function of the drug transporter, P-glycoprotein, and effects on absorption of drugs. For example, some drugs when taken in combination exhibit synergism that can increase drug effects resulting in toxicity. The opioid medications, methadone and buprenorphine are extensively metabolized by human liver. Specifically CYP3A4 plays a significant role in the metabolism of methadone, and buprenorphine. Perhaps the best studied mechanism for drug interactions is seen with medications that inhibit the function of hepatic metabolic enzymes. Laboratory assays are well-developed and provide insights on the inhibitory effect of a specific compound on major liver CYP enzymes, particularly CYP3A4. With buprenorphine, a CYP3A4 substrate, systemic exposure increase is noted following concomitant administration with ketoconazole, a strong CYP3A4 inhibitor. Drug interactions with other CYP3A4 inhibitors, listed in the Table 1 , below may cause an increase in systemic levels or pharmacodynamic effects of buprenorphine. Although assays that can reliably show induction of CYP enzymes exist, these assays are unable to predict drug interactions when the compounds inhibit some CYP enzymes while inducing other CYP enzymes. In such situations, we often learn of inducing properties of a drug through clinical observations. For example, HIV antiretroviral ARV medications such as ritonavir, nelfinavir, and nevirapine, are known to inhibit CYP3A4; however, they are shown to reduce the plasma levels of methadone, possibly due to induction of other CYP enzymes involved in its metabolic clearance. Glucuronidation can also be a late step in the metabolism of drugs which undergo a series of metabolic steps with intermediates produced as a result of metabolism by CYP enzymes. Glucuronidation renders a metabolite water soluble so that it can then be excreted. An example of a clinically significant drug interaction mediated by inhibition of glucuronidation is that of the effect of methadone on zidovudine elimination. Methadone can inhibit zidovudine glucuronidation resulting in increased concentrations that, in some cases, may produce zidovudine toxicity. Some drug interactions occur as a result of the production of a pharmacologically active metabolite as in the case of simultaneous cocaine and alcohol consumption which results in the formation of cocaethylene, a cocaine-like compound that can contribute to toxicities associated with the abuse of these substances. This has been observed when methadone-maintained patients were administered the ARV medication, stavudine, resulting in sub-therapeutic stavudine concentrations. Pharmacodynamic interactions can result when two or more drugs with the capability of producing similar pharmacological effects in an individual are ingested in the same time frame resulting in significant adverse effects. For example, when buprenorphine and benzodiazepines e. It can be difficult to determine what mechanism s are responsible for adverse drug interactions. Controlled studies in humans that include simultaneous administration of medications and measurement of plasma drug concentrations are important to understanding the pharmacokinetic and pharmacodynamic drug interactions important in the treatment of common medical and mental disorders. In the following sections, important drug interactions that have been described will be briefly reviewed. The majority of injection drug users are addicted to heroin or opium. There are several medical treatments available for opioid dependent patients. These include medical withdrawal from opioids and maintenance treatment with methadone or buprenorphine. Medical withdrawal from opioids has been shown to have a high relapse rate. US FDA-approved therapies for opioid maintenance therapy include methadone, l-acetyl-methadol not currently manufactured in the U. This population represents a significant risk for personal harm and harm to others should they relapse to opioid use and continue high risk injection drug use and sexual practices. For that reason, much research has been devoted to determining the presence of clinically significant drug interactions between opioids and ARV medications. Some methadone-maintained patients with HIV disease who were started on AZT therapy for HIV infection were noted to develop symptoms that appeared to be consistent with opioid withdrawal including muscle and joint pain, dysphoria, insomnia, and depression. The results of this study led to another question: did interactions between methadone and AZT characterize interactions between AZT and other opioid therapies? To test this question, another study was conducted in which the interaction of AZT with either buprenorphine, LAAM, or naltrexone was examined. In fact, what was observed were non-clinically significant decreases in AZT concentrations in patients treated with buprenorphine or LAAM; the opposite of that observed with methadone. These findings indicated that the observation for methadone was not representative of what would occur in the context of other opioids in combination with ARV therapies. To date, a number of frequently utilized ARV therapies have been examined in combination with methadone and other opioid therapies. These drug interactions are summarized in Table 2. Selected important drug interactions are summarized below. Interactions between methadone and several HIV therapies demonstrate the potential for adverse drug effects that can occur when absorption of a drug is altered. Methadone is a full mu opioid receptor agonist. A general effect of such drugs is to slow gastrointestinal mobility. Methadone has been associated with significant decreases in HIV medications that are sensitive to the acidic environment of the stomach. Didanosine DDI or Videx in tablet formulation and stavudine d4T are two non-nucleoside reverse transcriptase inhibitors NRTIs that may produce sub-therapeutic plasma concentrations of methadone when administered to methadone-maintained individuals. This formulation has been shown to be associated with therapeutic plasma concentrations in both methadone-maintained 23 and buprenorphine-maintained individuals. Adverse events related to inhibition of the clearance of opioid medications have the potential to produce opioid toxicity including altered cognition and decreased respiration. Delavirdine is a non-nucleoside reverse transcriptase inhibitor that inhibits the function of CYP 3A4. Of equal concern are the drug interactions that result in diminished concentrations of opioid therapies. For example, co-administration of a medication that induces methadone metabolism could result in a reduction of plasma methadone concentrations in a methadone-maintained patient leading to the potential development of opiate withdrawal symptoms. The onset of opiate withdrawal may be associated with abuse of opioids or other illicit substances and resumption of high risk behaviors related to drug abuse with risk for HIV transmission. This may be one reason that withdrawal does not occur even with induction of buprenorphine metabolism. Further, buprenorphine is a partial mu opioid agonist with a high affinity for and slow dissociation from the mu opioid receptor which may protect buprenorphine-maintained individuals from opiate withdrawal. The use of ARV medications in those who also require opioid therapy for treatment of opioid addiction can be challenging with methadone. However, to date, none of the adverse drug interactions that have been observed between methadone and ARVs have been observed in buprenorphine-maintained individuals. These findings may be useful to clinicians who must treat both HIV disease and opioid dependence in the same patient. What are the practical implications of drug interactions between opioid therapies and HIV medications? The necessary tapering of methadone to achieve buprenorphine induction could potentially destabilize the patient. Rather, clinicians with such patients should be aware of major drug interactions that may occur between ARV and methadone and adjust medication doses accordingly. Tuberculosis can also occur independently and is seen more frequently in individuals addicted to heroin. Medications used to treat tuberculosis can have significant interactions with methadone. The best known of these interactions is that of the effect of rifampin, a first-line agent used in combination with isoniazid for the treatment of tuberculosis infection, to induce methadone metabolism. Some patients receiving buprenorphine also develop opiate withdrawal symptoms when treated with rifampin, however at this time, the final data is still pending. This same finding is likely to be true for buprenorphine-treated patients, although this has not yet been examined. While rifabutin can also induce CYP 3A4, it appears not to produce the withdrawal symptoms rifampin does. This increasingly common infection also occurs in methadone-treated patients who will similarly require substitution of rifampin with rifabutin in this clinical circumstance. Isoniazid is a CYP 3A4 inhibitor, 41 but has not been associated with adverse events in opioid-maintained patients to date, perhaps because any effect to inhibit opioid metabolism is opposed by the concomitantly administered rifampin in patients with tuberculosis and receiving chronic opioid therapy. These medications have a high rate of adverse symptoms and side effects associated with their use including depression, anxiety, malaise, myalgia, fatigue, and anemia ribavirin. To date, two studies have been reported in the literature and both have shown no significant drug interactions between methadone and interferon. There are four antibiotic treatments, specifically antifungal and antibacterial therapies that cause potentially clinically significant drug interactions with methadone as a result of inhibition of CYP 3A4 which can increase methadone concentrations. Both the antifungal medications fluconazole 47 and voriconizole 48 are inhibitors of this enzyme and might increase methadone plasma concentrations when administered concomitantly. Similarly, ciprofloxacin inhibits CYP 3A4 and there has been a case report of life-threatening opioid toxicity when this medication was given to a methadone-maintained individual. Because buprenorphine is a substrate of CYP 3A4, its plasma concentrations would likely be increased in the presence of any of these antibiotics as well. However, the ceiling effect for opioid agonist effects of buprenorphine could diminish any potential opioid toxicity. While exhaustive work examining drug interactions between opioids and medications commonly used to treat mental illness has not been undertaken, there are some findings that can be summarized in this review. Affective disorders, particularly major depression are common in opioid dependent patients. The serotonin reuptake inhibitors exert a variety of effects on the cytochrome P enzyme system. Both fluoxetine and fluvoxamine have been examined in vitro for evidence of potential for drug interactions with methadone and buprenorphine. Both fluoxetine and fluvoxamine with fluvoxamine being more potent than fluoxetine inhibit CYP 3A4 and 2D6. In vitro studies showed both antidepressants to be associated with decreased metabolism of methadone and buprenorphine. Further, discontinuation of fluvoxamine was associated with the onset of opiate withdrawal. Discontinuation of the concomitant medication will result in resumption of normal methadone metabolism which could decrease methadone plasma concentrations to the point that the patient experiences opiate withdrawal. This subsequent opiate withdrawal may lead to non-adherence to the treatment regimen and increased use of illicit substances, underscoring the importance of clinician awareness of the potential for such interactions. Other serotonin reuptake inhibitors including sertraline 56 and citalopram 57 have not been associated with adverse drug interactions with methadone or buprenorphine. However, both sertraline and citalopram have been associated with inhibition of CYP 2D6. Since methadone metabolism is contributed to by CYP 2D6, it is possible that methadone concentrations could increase in a patient receiving one of these antidepressants in combination with methadone. Although no clinical reports of serotonin syndrome have been reported in conjunction with methadone treatment and treatment with serotonin reuptake inhibitors, it is a consideration should those receiving concomitant therapies develop symptoms of neuromuscular hyperactivity including tremor, clonus, myoclonus, and hyperreflexia. Other symptoms of serotonin syndrome include rigidity, autonomic hyperactivity diaphoresis, fever, tachycardia and tachypnea as well as altered mental status characterized by agitation, excitement and confusion. Other antidepressant medications have not been reported to have significant interactions with methadone or buprenorphine. Mirtazepine has no reported interactions with these opioids. Duloxetine, an antidepressant medication also approved for treatment of neuropathic pain particularly in patients with diabetes, a common co-morbid medical condition in patients with opioid dependence, is a substrate of CYP 2D6. Methadone has been reported to not only be a substrate of this enzyme, but also has some ability to inhibit its function. As such, methadone could potentially lead to increased duloxetine exposure; 59 however a formal drug interaction study has not been conducted. However, the use of amitriptylene as either an antidepressant or for the treatment of pain syndromes warrants clinician awareness of the potential for drug interactions between amitriptylene and methadone. John's wort is an over-the-counter herbal remedy purported to have antidepressant properties. Its use is widespread and represents a potential for adverse drug interactions. This medication is known to induce both CYP 3A4 and P-glycoprotein which can result in increased metabolism and elimination of methadone and buprenorphine. John's wort and other medications underscore the need to query patients about the use of over-the-counter remedies, herbal, and nutriceutical use when other medications are prescribed for concomitant medical conditions. There are few reports of antipsychotic medications having adverse drug interactions with opioids. Some of the older neuroleptic medications would not be expected to have clinically significant pharmacokinetic drug interactions with opioids because their major metabolic pathways are not shared by methadone or buprenorphine. Pharmacodynamic interactions might occur, however, as a result of increased sedation or cognitive dysfunction that could be experienced when these medications are given concomitantly. There is a report of increased plasma methadone concentrations in those treated with quetiapine. This interaction results from quetiapine's ability to inhibit CYP 2D6 as well as to inhibit P-glycoprotein. No clinically significant pharmacokinetic drug interactions have been reported for methadone or buprenorphine when administered concomitantly with risperidone, clozapine, aripiprazole, olanzepine, or ziprasodone. The use and abuse of anxiolytic medications, benzodiazepines and sedative-hypnotics by those with opioid addiction and being treated with buprenorphine or methadone is common. The anxiolytics share common pharmacological properties of sedation and when abused, altered cognition. In combination with methadone or buprenorphine, these drugs have potential for significant harm. Opioids such as methadone and, to a lesser extent, buprenorphine as a result of its partial agonist effect, can decrease respiration through agonist action at mu receptors in the medullary respiratory center. Benzodiazepines and alcohol act synergistically in that these drugs facilitate inhibition at gamma-aminobutyric acid GABA receptors and alcohol decreases the excitatory effect of glutamate at N-methyl-D-aspartic acid NMDA receptors. Fatalities have been reported when methadone and alprazolam were co-ingested. Buprenorphine has also been associated with deaths when ingested by the intravenous route in combination with benzodiazepines. The impairment associated with combined methadone or buprenorphine use with benzodiazepines as well as the morbidity and mortality that has been linked to co-ingestion of these drugs indicates that caution should be used in prescribing benzodiazepines to those receiving methadone or buprenorphine treatment of opioid dependence. Further, clinicians should monitor for evidence of benzodiazepine abuse substance-related disorders resulting from benzodiazepine abuse should be treated in these patients. Anticonvulsant medications are commonly prescribed to patients treated with methadone or buprenorphine to treat either seizure disorders or mental illnesses including bipolar disorder and schizoaffective disorder. Several anticonvulsants have clinically significant drug interactions with methadone. Carbamazepine, phenytoin, and phenobarbital are all inducers of CYP 3A4 and have been associated with opiate withdrawal when administered to methadone-maintained patients. Whether such drug interactions occur in buprenorphine-treated patients has not been evaluated, but induction of buprenorphine metabolism is likely to occur since it is a substrate of CYP 3A4. Newer anticonvulsant medications do not have the same broad spectrum effects on CYP enzymes or drug interactions with opioids. Oxcarbazepine, lamotrigene, and topiramate have not been reported to have adverse drug interactions with methadone or buprenorphine. These anticonvulsants are likely to be better choices for clinical use in opioid-maintained patients. Psychostimulant medications frequently prescribed for attention deficit hyperactivity disorder, night shift work or narcolepsy include amphetamines, methylphenidate, pemoline, or modafinil. Psychostimulant medications have not been reported to produce adverse drug interactions in methadone or buprenorphine-treated patients. Antihistamine drugs are commonly prescribed for a variety of medical symptoms. CYP 2D6 contributes to the metabolism of some of the antihistamine medications promethazine, diphenhydramine and chlorpheniramine. In addition, some antihistamines such as promethazine and diphenhydramine may inhibit CYP 2D6. While clinical reports of adverse events related to pharmacokinetic and pharmacodynamic interactions are not in the literature, these medications have the characteristics that might result in adverse interactions. This could result from direct pharmacokinetic interactions as well as a synergistic effect of use of the opioids in combination with an antihistamine. Opioid addicted patients often develop co-occurring medical illnesses. Some of the more common medical illnesses seen in opioid-dependent patients are those associated with the cardiovascular and pulmonary systems. A few commonly prescribed medications include digoxin, quinidine, verapamil, cholesterol-lowering statin drugs, heparin, and theophylline. Adverse interactions between these medications and either methadone or buprenorphine are not found in the clinical literature. Aspirin, a very frequently utilized medication for pain and for its anticoagulant properties is metabolized by a serum esterase which is inhibited by methadone. Recently, it has been found that cocaine can significantly diminish buprenorphine concentrations. Methamphetamine has not been associated with adverse drug interactions in combination with either methadone or buprenorphine. Stimulants used to treat attention deficit hyperactivity disorder ADHD include methylphenidate, amphetamine, and pemoline. To date, no clinically important drug interactions have been reported between methadone or buprenorphine and these medications. It is worth noting, however, that stimulants have been used with opioid medications to obtain a desired euphoria that results from the opposing actions of the opioids sedation with stimulant effects of drugs e. A pharmacodynamic interaction has been reported to occur between alcohol and methadone. Severe adverse events including deaths have occurred in patients who co-ingest these substances, 84 although a direct effect on pharmacokinetics of methadone has not been found, but alcohol appears to be eliminated more rapidly in those receiving methadone. Interestingly, no drug interaction of clinical significance has been detected between methadone and disulfiram 85 These findings highlight the need to treat co-occurring alcohol disorders in opioid addicted patients receiving opioid agonist therapy. There are several important consequences of drug interactions that occur between opioids used in the treatment of opioid dependence and other drugs. Drugs that induce the metabolism of opioids or drugs that induce P-glycoprotein resulting in opioid efflux can produce opiate withdrawal symptoms if plasma concentrations become sub-therapeutic. Should this occur, patients may not adhere to the medication to which they attribute the opiate withdrawal symptoms. Non-adherence can have significant consequences in worsening of disease. For HIV disease, non-adherence can result in viral mutations with the development of resistance to currently available antiretroviral medications increasing the likelihood of disease progression in patients and the likelihood of viral transmission to those with whom they are in intimate contact. In addition, the development of opiate withdrawal can contribute to relapse to illicit drug use in order to relieve the adverse symptoms. Illicit drug use and intoxication is associated with an increased risk of overdose and unsafe practices such as injection drug use. These practices can place the patient at risk for the complications of injection drug use such as abscesses, cellulitis, endocarditis, and osteomyelitis. Another concern when drug interactions occur that increase opioid concentrations is that of opioid toxicity. Cognitive dysfunction and decreased respiration can be life threatening. However, if the medication that is causing induction of metabolism is discontinued, methadone concentrations will rise, possibly to toxic levels, unless the methadone dose is tapered to that on which the patient was stable before starting the medication. Further, patient selection for either methadone or buprenorphine treatment based on identification of cardiac risk factors, family history, medical history of cardiac disease or history of arrhythmia, or the finding of a prolonged QT interval prior to starting opioid therapy can be helpful in diminishing the likelihood of this complication. Another important aspect of understanding drug interactions between opioids and other medications is that of optimally matching treatments to patients. It can be difficult for patients to adhere to prescribed medication regimens. The occurrence of adverse symptoms when medications are given together contributes to non-adherence. Because patients may not want to divulge their lack of adherence to a regimen associated with adverse effects, there can be consequences related to worsening of the conditions which the medications were meant to improve. Anticipation of adverse events when medications known to have interactions are to be given can improve adherence. Patients should be counseled about the possible interactions including the time to expected adverse effects should they occur and the treating clinician should be prepared to make adjustments to the medication regimen should a drug interaction occur. Drugs that induce the metabolism of a drug require new enzyme production so that the onset of opiate withdrawal generally occurs after about 7 days. Inhibitors can delay metabolism with onset of drug administration so that increases in opioid exposure can occur soon after initiating the medications. The same is true for pharmacodynamic interactions that occur at the time of the drug use. While knowledge of drug interactions may be helpful in selecting medications; the fact that a drug interaction may occur should not exclude the use of a medication; nor can opioid doses be adjusted in anticipation of a drug interaction. Not all patients will develop drug interactions. The occurrence is related to doses of medications e. Finally, the existence of these interactions between methadone and buprenorphine and myriad other medications they may be receiving, underscores how critical it is for clinicians who are caring for patients receiving opioid agonist treatment to routinely query their patients regarding medications they are receiving for treatment of other medical conditions. In addition, given the potential interactions between methadone and buprenorphine and substances of abuse, in order to optimize treatment outcomes, they must discuss with patients the use or mis-use of other substances that may interact with their methadone or buprenorphine. Providing guidance to clinicians with data on these real or potential drug interactions will allow them to better manage their patients' overall medical care by increasing their general awareness of interactions between opioids and HIV antiretrovirals and other medications thereby improving outcomes avoiding suboptimal levels of medications and also minimizing the likelihood of adverse events avoiding toxicity and overdose. There remains much to be learned about drug interactions between opioids used in the treatment of opioid dependence and other drugs. Most medications in combination with opioids have not been directly studied in humans. In vitro studies indicating the likelihood of drug interactions are not always predictive of what will occur in people. The ongoing study of frequently prescribed medications with opioids will help to enhance clinical outcomes and to increase safety with medication treatments in this high risk and challenging population. Declaration of Interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper. As a library, NLM provides access to scientific literature. Am J Addict. Published in final edited form as: Am J Addict. Find articles by Lynn Sullivan. Find articles by Srikanth Nallani. PMC Copyright notice. The publisher's version of this article is available at Am J Addict. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. No clinically significant interaction Significant decrease in didanosine concentrations. Significant decrease in stavudine concentrations. Increased methadone and LAAM concentrations; no cognitive impairment Increased buprenorphine concentrations; no cognitive impairment. Not associated with increased levels of methadone Significant increases in buprenorphine and report of cognitive dysfunction Opiate withdrawal may occur Opiate withdrawal may occur 29 - No clinically significant interaction 34 - Data suggest that the PK interaction is not clinically relevant; however, patients should be monitored for opiate withdrawal symptoms Methadone levels are decreased. No clinically significant interaction 45 , Increased methadone plasma concentrations May cause increased methadone plasma levels and discontinuation has been associated with onset of opioid withdrawal No associated adverse drug interaction Potentially lead to increased duloxetine exposure Could be associated with increases in plasma methadone concentrations Increased metabolism and elimination of methadone Increased metabolism and elimination of buprenorphine Associated with increased desipramine levels Associated with delirium Increased plasma methadone concentrations Associated with increased sedation and impaired performance on psychological tests 65 , Fatalities have been associated Associated with opiate withdrawal May have synergistic depressant effect Cardiac and Pulmonary Disease Medications. Decrease in trough methadone concentrations Increased metabolism and diminished plasma concentrations 76 - Severe adverse events including death 84 , Alcohol appears to be eliminated more frequently

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