Relevant drug abuse history is mostly provided by the care givers, family members, friends or EMS providers. Possession of pill bottles, drug supplies or eyewitness accounts also aids in diagnosis. Administration of a trial dose of naloxone by EMS is often helpful in confirming the diagnosis. Important aspects that have to be taken into consideration for ascertaining drug abuse include ingestion time, quantity and identification of  co-ingestants.

Physical examination

• Manifestation of clinical triads -central nervous system (CNS) depression, respiratory depression, and pupillary miosis along with subnormal level of consciousness suggests possible opiate toxicity
• Respiratory depression is the distinct symptom to look out for in a case of suspected drug toxicity. Respiratory function impairment like bradypnea and hypopnea are commonly observed with opiate abuse. Rates as low as 4-6 breaths per minute are often observed in case of moderate-to-severe intoxication. Body`s hypoxic drive to breathe is negated under the sedation of CNS in case of severe overdose.
• Drowsiness, conjunctival injection, euphoria, ventricular arrhythmias, acute mental status changes and seizures are the frequent symptoms observed. Nightmares, anxiety, agitation, dysphoria, depression, paranoia, and hallucinations are the less common symptoms observed in cases of  high dose toxicity
• Presence of needle tracks in case of intravenous drug abuse
• CNS hypoxia induced hypertension and pupillary dilation in severe cases
• Presentation of mydriasis or midpoint pupils may indicate morphine, meperidine, pentazocine, diphenoxylate /atropine (Lomotil), and propoxyphene intoxication
• Orthostatic hypotension may be presented in case of opioid mediated mild peripheral vasodilation. Reevaluation to diagnose the use of co-ingestants is highly recommened in case of persistent or severe hypotension
• • Pruritus, flushed skin, and urticaria due to histamine release indicate opioid abuse
• Generalized seizures due to initial CNS excitation is commonly observed in infants and children. Meperidine or propoxyphene ingestions by adults may lead to seizure activity
• Pink frothy sputum, muscular rigidity, dyspnea, hypoxia and bronchospasms indicate opioid induced acute lung injury
• Temporary Hearing loss is associated with heroin and alcohol abuse
• Tendencies for nausea and emesis in initial stages of drug induced toxicity. Opioid prolong gastro intestinal transit times invariability leading to delayed and prolonged absorption.

• Weakness

  Readers will gain knowledge of the wide variety of treatments used to treat opiate addiction, including their strengths and weaknesses, and the promising pharmacological targets identified by preclinical research. [ncbi.nlm.nih.gov]

  Opiate Withdrawal and the Opiate Addiction Process Withdrawal from opiates can be uncomfortable, and can cause symptoms such as agitation, insomnia, anxiety, weakness, depression, abdominal cramping, nausea, and diarrhea. [irishealingretreat.com]

  Tramadol acts as a weak opioid agonist, meaning that it activates the opioid receptors in the brain, but on a much less intense level than other opioids. [therecoveryvillage.com]

  […] happiness or sadness; seizure (convulsions); problems with urination; or low cortisol levels--nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness. [drugs.com]

  Weakness. Headache. Dry mouth. Heartburn/Indigestion. Fever. Trouble concentrating. Sleep problems. Mood swings. Depression. If you regularly experience any of the above physical symptoms, you may be addicted to Tramadol. [drugabuse.com]

• Falling

  In particular, we submit that patients whose disorders fall under the bipolar spectrum - and its hyperthymic and cyclothymic temperamental substrates are at increased risk for substance use, possibly moving towards addiction through exposure to intrinsically [ncbi.nlm.nih.gov]

  With such rampant accessibility, and a perceived blessing from medical professionals, it’s no wonder so many people fall prey to the power of sleeping pills. [addictioncenter.com]

  That’s why so many addicts relapse and fall back into their old, destructive habits – the fight never truly ends. [inspiremalibu.com]

  This feature makes naltrexone a good choice to prevent relapse (falling back into problem drug use). Methadone to treat addiction is dispensed only at specially licensed treatment centers. [pastop.org]

  That will lead to his ultimate goal: fewer addicts buried just because they happened to fall to such a powerful drug. Copyright 2016 by KSAT - All rights reserved. [ksat.com]

• Asymptomatic

  Patients are usually asymptomatic and are often diagnosed coincidentally after a chest radiograph. When they do occur, symptoms are nonspecific and can include abdominal pain, chest pain and dyspnea. [go.gale.com]

• Bradypnea

  Respiratory function impairment like bradypnea and hypopnea are commonly observed with opiate abuse. Rates as low as 4-6 breaths per minute are often observed in case of moderate-to-severe intoxication. [symptoma.com]

• Nausea

  […] maintained) and include: lacrimation, rhinorrhoea and sneezing yawning hot and cold flushes, sweating and piloerection craving anxiety, restlessness and irritability disturbed sleep gastrointestinal tract symptoms (for example anorexia, abdominal pain, nausea [sahealth.sa.gov.au]

  However, it may cause other side effects, such as constipation, respiratory depression, dizziness, nausea and sedation. Naltrexone can help with withdrawal symptoms, but it does come with side effects such as anxiety, nausea and muscle pain. [therecoveryvillage.com]

  Opiate Withdrawal and the Opiate Addiction Process Withdrawal from opiates can be uncomfortable, and can cause symptoms such as agitation, insomnia, anxiety, weakness, depression, abdominal cramping, nausea, and diarrhea. [irishealingretreat.com]

  When this happens, naloxone can induce withdrawal symptoms including nausea, headache, sweating, restlessness, vomiting, and trembling. [verywellmind.com]

  Nausea and vomiting. Constipation. Loss of appetite. Sweating. Weakness. Headache. Dry mouth. Heartburn/Indigestion. Fever. Trouble concentrating. Sleep problems. Mood swings. Depression. [drugabuse.com]

• Diarrhea

  Constipation – diarrhea Depression – euphoria Drowsiness – insomnia During the first few weeks after stopping opiates, the body’s endorphins begin stabilizing. This helps to counterbalance the withdrawal effects. [recoveryconnection.com]

  Opiate Withdrawal and the Opiate Addiction Process Withdrawal from opiates can be uncomfortable, and can cause symptoms such as agitation, insomnia, anxiety, weakness, depression, abdominal cramping, nausea, and diarrhea. [irishealingretreat.com]

  Diarrhea and vomiting can cause severe dehydration, and it’s important to continuously drink water and try to eat in order to keep up your strength. [orlandorecovery.com]

  Diarrhea is another very uncomfortable and potentially dangerous withdrawal symptom. Loss of fluids and electrolytes from diarrhea can cause the heart to beat in an abnormal manner, which can lead to circulatory problems and even heart attack. [healthline.com]

• Abdominal Cramps

  Opiate Withdrawal and the Opiate Addiction Process Withdrawal from opiates can be uncomfortable, and can cause symptoms such as agitation, insomnia, anxiety, weakness, depression, abdominal cramping, nausea, and diarrhea. [irishealingretreat.com]

  Symptoms in this stage include: Diarrhea Goosebumps Chills Abdominal cramps Nausea Vomiting Stage Three Once you reach stage three, it’s easy to think you’re in the clear and over your withdrawal period. [orlandorecovery.com]

  The reaction frequently includes sweating, shaking, headache, drug craving, nausea, vomiting, abdominal cramping, diarrhea, inability to sleep, confusion, agitation, depression, anxiety, and other behavioral changes. [drugs.com]

  Abdominal cramps Diarrhea Extreme sweating Excessive sleeping Fever Nausea Pain Seizures Vomiting How Long Does Opiate Withdrawal Last? The length of withdrawal symptoms depends on the individual and other health factors. [recoveryconnection.com]

• Abdominal Pain

  Patients may present with 1: sudden onset of abdominal pain right lower quadrant pain and tenderness absence of fever and gastrointestinal symptoms encountered in healthy patients, such as marathoners, because of low omental blood flow Primary omental [radiopaedia.org]

  When they do occur, symptoms are nonspecific and can include abdominal pain, chest pain and dyspnea. [go.gale.com]

  pain, nausea, vomiting and diarrhoea) muscle, bone and joint aches and pains, headache, muscle cramps tremor. [sahealth.sa.gov.au]

  Some side effects of Tramadol may include: Abdominal pain Constipation Coughing Diarrhea Dizziness Dry mouth Fever Headache Heartburn Irritability Joint pain Lightheadedness Loss of appetite Nervousness Runny nose Shivering Sore throat Trouble concentrating [therecoveryvillage.com]

  You will have a number of symptoms that may include nausea and vomiting, abdominal pain, and anxiety. This reaction is called withdrawal. [familydoctor.org]

• Hypertension

  The anti-hypertensive (blood pressure lowering) drug clonidine is sometimes added to shorten the withdrawal time and relieve physical symptoms. [health.harvard.edu]

  Patients' choices (eg, regarding diet, exercise) contribute to the onset or severity of several chronic diseases, including hypertension, CHD, and diabetes. 4 Furthermore, while the initial choice to use opioids may have been voluntary, once opioid addiction [helpmegetoffdrugs.com]

  The FDA publishes the following as potential overdose signs of Flexural: Drowsiness Rapid heart rate (tachycardia) High blood pressure (hypertension) Tremors Slurred speech Agitation Confusion Dizziness Nausea Vomiting Hallucinations Loss of muscle control [americanaddictioncenters.org]

• Hypotension

  Some side effects include kidney dysfunction, heart disorders and hypotension. Clonidine may be taken every six hours. Methadone, like buprenorphine, can be used on a daily basis for maintenance as well as for withdrawal symptoms. [therecoveryvillage.com]

  Vomiting Hallucinations Loss of muscle control (ataxia) Coma Less common and more serious symptoms of a Flexeril overdose, according to the drug’s prescription information published by the FDA, include: Chest pain Seizures Extremely low blood pressure (hypotension [americanaddictioncenters.org]

  Reevaluation to diagnose the use of co-ingestants is highly recommened in case of persistent or severe hypotension • Pruritus, flushed skin, and urticaria due to histamine release indicate opioid abuse Generalized seizures due to initial CNS excitation [symptoma.com]

  The most common side effects from treatment with Lucemyra include hypotension (low blood pressure), bradycardia (slow heart rate), somnolence (sleepiness), sedation and dizziness. Lucemyra was also associated with a few cases of syncope (fainting). [fda.gov]

• Tachycardia

  The FDA publishes the following as potential overdose signs of Flexural: Drowsiness Rapid heart rate (tachycardia) High blood pressure (hypertension) Tremors Slurred speech Agitation Confusion Dizziness Nausea Vomiting Hallucinations Loss of muscle control [americanaddictioncenters.org]

• Miosis

  Opioids use Mu and kappa receptors of CNS and PNS to intercede their physiological effects such as analgesia, respiratory depression and miosis (pupillary constriction). [symptoma.com]

  […] and decreased anxiety) Respiratory depression (can cause death in overdose) Decreased gastrointestinal motility (can cause constipation) Cough suppression Suppression of corticotropin-releasing factor and adrenocorticotropin hormone Pinpoint pupils (miosis [emedicine.medscape.com]

• Agitation

  Opiate Withdrawal and the Opiate Addiction Process Withdrawal from opiates can be uncomfortable, and can cause symptoms such as agitation, insomnia, anxiety, weakness, depression, abdominal cramping, nausea, and diarrhea. [irishealingretreat.com]

  The reaction frequently includes sweating, shaking, headache, drug craving, nausea, vomiting, abdominal cramping, diarrhea, inability to sleep, confusion, agitation, depression, anxiety, and other behavioral changes. [drugs.com]

  Withdrawal symptoms include: Nausea Muscle cramping Depression Agitation Anxiety Opiate cravings The National Institute on Drug Abuse (NIDA) publishes that between 26.4 million and 36 million people around the globe abuse opiate drugs, which includes [americanaddictioncenters.org]

  Librium is sometimes used to diminish significant agitation. Chloral hydrate or trazadone might be used to help you sleep. If you go through withdrawal without medical supervision, you won’t have access to these valuable resources. [healthline.com]

• Headache

  When this happens, naloxone can induce withdrawal symptoms including nausea, headache, sweating, restlessness, vomiting, and trembling. [verywellmind.com]

  Restlessness, anxiety, and headache are only few symptoms of opiate withdrawal. What are the others? How can you addres ... A practical guide on how to help a loved one who is dealing with painkiller addiction here. ... [addictionblog.org]

  Common side effects include respiratory depression, headache and constipation. Clonidine can help suppress the fight-or-flight response triggered by the body producing excess norepinephrine, but it doesn’t help manage cravings and malaise. [therecoveryvillage.com]

  The reaction frequently includes sweating, shaking, headache, drug craving, nausea, vomiting, abdominal cramping, diarrhea, inability to sleep, confusion, agitation, depression, anxiety, and other behavioral changes. [drugs.com]

• Tremor

  Dangerous side effects of Ativan abuse can include: Respiratory depression Excessive sedation Seizures Tremors Memory impairment Loss of consciousness Extended use of Ativan can also cause changes in brain functioning. [addictioncenter.com]

  If dependence has developed, you may notice the following withdrawal symptoms if you stop using the drug: 1 Sweating Panic Nervousness Nausea and vomiting Uncontrollable shaking/tremor Muscle spasm Runny nose Sneezing Cold chills Diarrhea Cough Difficulty [drugabuse.com]

  The withdrawal symptoms — agitation; anxiety; tremors; muscle aches; hot and cold flashes; sometimes nausea, vomiting, and diarrhea — are not life-threatening, but are extremely uncomfortable. [health.harvard.edu]

  […] sweating and piloerection craving anxiety, restlessness and irritability disturbed sleep gastrointestinal tract symptoms (for example anorexia, abdominal pain, nausea, vomiting and diarrhoea) muscle, bone and joint aches and pains, headache, muscle cramps tremor [sahealth.sa.gov.au]

• Hyperactivity

  BACKGROUND: Polymorphisms in genes such as DAT1, 5HTTLPR, D4DR4, and MAO-A have been linked to attention deficit hyperactivity disorder (ADHD) and susceptibility for opiate addiction. [ncbi.nlm.nih.gov]

  […] illnesses are those that are often diagnosed in individuals who are grappling with an addiction to opiates, such as heroin or prescription painkillers: Bipolar disorder Depressive disorders Post-traumatic stress disorder Anxiety disorders Attention-deficit/hyperactivity [galaxrecovery.com]

  Those symptoms may include: Mood Symptoms: Lack of motivation Depressed mood Hyperactivity Physical Symptoms: Weight loss Cramping Diarrhea Itchy skin Joint and muscle pain Nausea and vomiting Headaches Psychological Symptoms: Loss of concentration or [lakeviewbehavioralhealth.com]

  […] have been cited as co-occurring alongside substance use disorders, including opioid addiction, include: Panic and anxiety disorder Depression Abuse of and addiction to other drugs Bipolar disorder Oppositional defiant disorder (ODD) Attention deficit hyperactivity [sierratucson.com]

  Those symptoms include: Mood Symptoms Lack of motivation Depressed mood Hyperactivity Physical Symptoms Weight loss Cramping Diarrhea Itchy skin Joint and muscle pain Nausea and vomiting Headaches Psychological Symptoms Loss of concentration or interest [riverwoodsbehavioral.com]

• Stupor

  = কেপালকানি | kepaalkaaniAn addictive substance, such as opium, that reduces pain, alters mood and behavior, and usually induces sleep or stupor. [khandbahale.com]

  It can also cause clammy skin, breathing problems, stupor (or coma), a dangerous drop in circulation, and cardiac arrest (heart attack). If you stop taking opioids you may get sick. This depends upon how much and how long you have been using. [brattlebororetreat.org]

  “This acted like a charm, as he came to in a minute from the stupor he was in and rested very easily.” Physicians like Schuppert used morphine as a new-fangled wonder drug. [smithsonianmag.com]

  For severe overdose, patients may experience respiratory depression, stupor, and coma. A severe overdose may be fatal. [emedicine.medscape.com]

Abuse and dependence

Urine drug testing (UDT) is a routine test conducted to check for the presence of drugs in suspected cases. The UDT result can be obtained in 1-4 days. Sweat and hair samples are also used for the test in some cases. Blood alcohol levels are also checked.

Withdrawal

Complete blood count test and analysis of electrolytic imbalances are routinely performed. Urine drug screen is not recommended 

Intoxication

Half-life, bio transformation and excretory path of the drug are vitals factors in accurate drug abuse detection. Comprehensive UDT is performed in suspected drug abuse cases. Thin-layer chromatography (TLC) though inexpensive is not recommended owning to its failure to detect commonly abused drugs including fentanyl. Though more sensitive than TLC, enzyme immunoassay and radioimmunoassay are also less specific as the molecules with similar functional groups cross-react with antibodies.  Gas-liquid chromatography (GLC) and gas chromatography-mass spectrometry (GC-MS) are  very sensitive and specific in diagnosis but have major drawbacks. Running tests for diagnosis are  time consuming, labor intensive, and expensive.

A minimum of 300 ng/mL concentration is required  for confirming presence of heroin, methadone, morphine, and codeine. 

Addiction

IV drug abuse are always associated with additional risks of contracting blood borne infections and in such case the following tests are recommended to rule out the possibility of such infections.

• Liver function test (LFT)
• Rapid plasma reagent (RPR)
• Hepatitis testing
• HIV testing
• Blood cultures (in appropriate clinical setting)
• Imaging studies(lung x-ray) to rule out pulmonary fibrosis. Injecting drugs contaminated with microcrystalline talc often results in such pathological conditions

Assessment of physical dependence

Manifestation of withdrawal symptoms lasting for 30-60 minutes after an intramuscular injection or IV of naloxone of (0.2-0.8 mg) proves physical dependence. This procedure is highly recommended especially before starting of  opiate antagonist maintenance therapy after detoxification as the development of withdrawal symptoms persuade patients to discontinue the treatment.

As per federal governments regulations, the drug testing results are submitted directly to medical review offices to avoid misdiagnosis.

Medical interventions are necessary to treat acute cases of opioid intoxication, overdose, and withdrawal. Treatment strategies followed in chronic opioid abuse include opioid agonist therapy (OAT), psychotherapy, and pain management in patients undergoing maintenance therapy.

Opioid intoxication
General supportive measures upon admission for opioid intoxication is as follows

• Assessment of patient`s airway to ensure it is clear
• Provision of support ventilation when required
• Assessment and support of cardiac function
• Provision of IV fluids
• Frequent monitoring of the vital signs and cardiopulmonary status
• Administration of Naloxone IV to reverses the respiratory depression and sedation by heroin intoxication

Opioid overdose

Naloxone is the drug of choice for first-line treatment of opioid overdose. At home naloxone treatment is initiated in many countries and is met with success. Implementation of such programs should be throughly supervised to prevent further complication due to lack of immediate medical care and ineffective management of associated side effects.

Community-based programs offered naloxone and other opioid overdose prevention services to over 53,000 caregivers and patients who abuse drugs in 1996.  FDA has approved the use of naloxone (Evzio) autoinjector which delivers 0.4 mg dosage (as IM or SC in the anterolateral aspect of the thigh) to treat opioid overdose at home. The device is equipped with an audio and video instructions and it also instruct users to undergo emergency medical care directly after use [6] [7] [8].

Opioid maintenance therapy

Improvement and management of withdrawal symptoms is central in case of opioid maintenance therapy. This is achieved by using legally procured opioid agonists in place of heroin or other opioids. This strategy will help in successful management for many risk factors associated with drug-abusing lifestyle.

Methadone maintenance therapy (MMT)

The need for multiple daily heroin doses can be effectively replaced with MMT. Methadone is a synthetic opioid agonist which requires only a single dose a day to remain effective. It is mainly used to counterbalance the drug-abusing lifestyle of the victims and help in reducing criminal behaviors and needle sharing practice thereby decreasing the risk of contracting HIV and other blood borne diseases. MMT has been a standerd treatment option for opioid maintenance therapy for more than 30 years.

Methadone is a highly regulated Schedule II medication, which is available only at specialized methadone maintenance clinics. It can house only 15-20% of US heroin addicts and often create controversy in populace fearful of addicts in different recovery phases. In addition to that effectiveness of methadone clinics is under question owing to several reasons including inability of patients to present themselves in clinics and due to the fear of stigmatization associated with it.

Buprenorphine maintenance therapy (BMT)

Recent introduction of BMT has resulted in commendable improvements in the medical management of opioid-dependent patients. Buprenorphine (mu-opioid partial agonist), like methadone has similar mode of action and is effective in containing the withdrawal symptoms. Advantages of BMT over MMT is that it has a wider margin of safety in case of accidental overdose. This is termed as "ceiling effect" as buprenorphine becomes ineffective at higher doses. Owning to its safe nature it is available by prescription as a Schedule III medication. One major concern regarding the use of buprenorphin is the possible oral or intravenous drug abuse. Combination of buprenorphine with naloxone in a 4:1 ratio (Suboxone, Zubsolv) or a 6-7:1 ratio (Bunavail) is used to circumvent this issue. Naloxone is not effective when administered orally and when consumed intravenously it will lead to withdrawal symptoms thereby discouraging the patients from misusing it.

Limitation of BMT

Only certified physicians who meet the criteria outlined in the Drug Abuse Treatment Act of 2000 are allowed to follow BMT. An 8-hour certificate course on this subject will permit clinicians to include buprenorphine in their treatment. The upper limit of patients under buprenorphine is 30 per physician but this limit will soon be increased [9]. The efficacy of BMT over existing treatment was proved in a recent study by Ling et al on patients using buprenorphine implants to overcome opioid dependence. The study proved that the physiological and psychological difficulties associated with maintenance therapy is much less as evidenced by less opioid use asseed through UDT.

l-alpha-acetylmethadol (LAAM) therapy

LAAM therapy for opioid-dependence maintenance treatment which was used initially is discontinued now owning to risks associated with it like prolonged QT interval, incidence of cardiac arrhythmia and death. LAAM was given a black box label by the FDA and is recently banned in the European Union.

Prevention of opioid dependence relapse

Relapse after long periods of abstinence has been reported in individuals experiencing stress. These issues can be evaded by prescribing beta-adrenoceptor antagonist propranolol (beta blockers) as early as after 1 month and as late as 2 years after abstinence. The efficacy of this approach has been proved in a randomized, placebo-controlled trial. Similarly efficacy of injectable, sustained-release form of naltrexone (Depotrex) in preventing stress induced relapsee has also been proved. Catechol-O -methyltransferase (COMT) inhibitors can also provide similar effects. Patients with prominent deficits in apt decision-making can be benefited and prevented from relapsing following this treatment.

Opiate withdrawal

Opiate withdrawal is less lethal when compared to barbiturates and benzodiazepines withdrawal in terms of resultant morbidity or mortality.  Finalizing the course of detoxification (safe withdrawal form opioids) program, including the decision to perform it as outpatient or inpatient therapy depends several criteria like presence of co morbid medical and psychological problems, social support and involvement of multiple drugs.

Common drugs used in detoxification include

1. Methadone, buprenorphine – This treatment is based on the principle of cross-tolerance in which one opioid is replaced with another followed by gradual withdrawal of both
2. Alpha-2 agonists (e.g.clonidine and lofexidine) – This treatment helps in managing unpleasant withdrawal symptoms associated with abstinence.

Clinical trials have proved that buprenorphine and methadone treatment is superior to alpha-2 agonists in detoxification. Buprenorphine has a shorter duration of withdrawal symptoms when compared to others.

Psychotherapies and support groups

Standard drug counseling should always be practiced along with detoxification program for achieving complete withdrawal and to prevent relapse. Psychotherapies focusing on cognitive behavioral, supportive, or analytical aspects of patient under methadone programs has found to have positive influence. The efficacy of psychosocial intervention in opioid detoxification was assessed by Cochrane by carefully evaluating 1592 patients undergoing treatment under 11 different studies. Addition of psycho social interventions (behavioral, counseling, and family therapies) regardless of the specific psycho social approach to the pharmacological treatment where found out to significantly reduce dropouts cases and relapses.

Pain management

Patients with chronic pain (noncancer) who are prescribed with higher doses of opioids owning to their previous drug abuse history are at higher risk of developing addiction. Alternate treatment of pain is thus of paramount importance in such OAT patients.

Recommendations

• Discuss with patients in a nonjudgmental manner to reassure them that they will receive adequate pain management despite of undergoing OAT
• Aggressive pain treatment with conventional opioid analgesics at higher doses to overcome cross-tolerance
• Communicate with physicians to verify the methadone and buprenorphine doses, and give updates of any benzodiazepines or opioids administered that may be detected on UDT
• Use of continuous scheduled dosing orders rather than as-needed orders
• Continuation of methadone maintenance dose and addition of short-acting opioid analgesics in patients receiving MMT
• A close monitoring of consciousness and respiration is required in BMT with opioids. Competition between buprenorphine and opioid analgesics for mu receptors complicate the conditions owning to increased availability of naloxone as buprenorphine's rate of dissociation from mu receptors is extremely flexible.

The physicians ability to choose the most effective treatment increases with clinical experience. Several options are available and the decision to choose one should be made after considering all the associated risk factors. Some of the commonly followed approach include continuation of BMT and titration of a brief-lived opioid analgesic for a positive effect and dividing buprenorphine doses to 6-8 hours break to take advantage of its short-acting analgesic properties. Giving an opioid analgesia treatment when required and stopping BMT and when there is more need for opioid analgesia restarting BMT will be highly recommeded. For inpatient treatment MMT should be adopted along with administration of short-acting opioid as pain medication. Naloxone should be used in case of emergency. Upon discharge continue treatment with BMT.

Improvement in social functions ,reduction of drug abuse and performance at work and school are the factors considered while measuring the success in prognosis. The type of agent used along with external factors (medical care, work status, legal situations, family and psychological problems) will also influence the outcome of prognosis. Relapse rate after opioid treatment varies from 25-97% as evidenced by several studies. Professionals have a much higher success rate when it comes to positive prognosis when compared to patients with poor educational level and income. Cigarette smokers tend to have a higher elapsing rate than nonsmokers.

Research in this field have indicated the role of certain factors contributing to specific substance abuse and in development of related problems. However there is a lack of direct evidence to pinpoint an specific reason for development of any specific drug abuse disorder.

Etiological factors  relevant in substance abuse include:

• Genetic factors: Individual with a familial history (especially first degree relative) of opioid addiction are more prone to addiction than those who have none.
• Indirect genetic influences: Genetically acquired attributes like temperamental nature (e.g. impulsive and novelty seeking nature) is associated with increased risk for developing addiction. Social skills and preferences in peer selection, which are  inborn is also considered to be strong factor. Close associations with peers who indulge in drug abuse will inevitability lead to substance abuse. Heredity and environment thus plays an important role in substance abuse etiology [5].
• Coping factors: Failure to learn functional coping mechanisms in early years of life may lead to inability to manage negative mood states . This may in turn result in opioid dependence for relief and elation to counteract the negativity. The resulting surge of exultation experienced with drug abuse can quickly culminate in addiction.
• Pleasure experienced in the brain: The brains`s pleasure and reward center producing specific chemicals helps us in experiencing pleasure, joy, and elation. Opioids targets this centre to provide a instant surge of pleasure that cannot to experienced spontaneously. 

United States

Prescribtion of opioids  along with  other analgesics like nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen or muscle relaxants is very common in chronic pain management.

Automation of Reports and Consolidated Orders System (ARCOS) from 2004 to 2011 revealed that there is 100% increase in medical use of opioids  and  20% decrease in codeine use.  Percentage increase in prescription of other opioids is as follows

• Buprenorphine: 2318%
• Fentanyl: 35%
• Hydromorphone: 140%
• Oxycodone: 117%
• Hydrocodone: 73%
• Morphine: 64%
• Methadone: 37%

Drug Abuse Warning Network`s (DAWN) retrospective data analysis in drug abuse revealed a 384% increase in  buprenorphine abuse from 2006 to 2011. Percentage increase of other opioid abuse between 2004 and 2011 is as follows

• Hydromorphone: 438%
• Oxycodone: 263%
• Morphine: 146%
• Hydrocodone: 107%
• Fentanyl: 104%
• Methadone: 82%
• Codeine: 39%

DAWN`s data also points out that nonmedical drug abuse related to opioid analgesics resulted in 420,040 of the approximately 1.4 million ED visits in 2011.

Key finding in Dart and co worker`s data analysis on Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System from 2002-2013 is listed below. Hydrocodone, hydromorphone, fentanyl, morphine, oxycodone, and tramadol where the prescription opioids selected for the study.

• Prescriptions of opioids were at the maximum during the fourth quarter of 2012
• Abuse of opioids was maximum in mid-2010 in all the groups under study except for college students
• Incidence of  non medical opioid abuse  increased from 0.14 per 100,000 population in 2008 to 0.35 per 100,000 in 2013
• Heroin usage was found to be taxing during 2002-2013. Heroin-related death rate which was stable during  2002 to 2010 climbed swiftly in subsequent years

The Centers for Disease Control and Prevention (CDC) in 2012 reported that opioid analgesics were responsible for 72% (16,007 of 22,114) of the pharmaceutical overdose deaths and heroin overdose was responsible for another 5925 deaths.

The major findings from the report of US poison control centers in 2013 on drug abuse is as follows

• 20,135 exposures to pure opioids resulted in  778 cases of major toxicity and 84 deaths
• 17,290 exposures to opioid combinations with acetaminophen, aspirin, or ibuprofen lead to 308 cases of major toxicity and 52 deaths

The report of Centers for Disease Control and Prevention (CDC) in 2012 on drug abuse pointed out that 

• Opioid analgesics are responsible for 72% (16,007 of 22,114) of the deaths relating to pharmaceutical overdose
• Heroin drug abuse is responsible for 5925 deaths
• 31.4% of opioid-related deaths in the United States from 1999-2010  was methadone contributed
• 39.8% of all single-drug opioid-related deaths involved methadone abuse
• Methadone`s contribution towards death associated with drug overuse is significantly greater than any other opioid-related deaths among multi and single-drug deaths

Propoxyphene, a frequently prescribed narcotic often paired with acetaminophen is found to have a high risk of serious cardiac toxicity. However reports of propoxyphene exposure still continues despite its withdrawal from US market on November 19, 2010 .

Local prescribing tendencies is the deciding factor in etiology of drug overdose cases admitted in ED. Most experienced clinician may find polypharmacy overdoses involving opioids challenging but ability to diagnose the difficult cases through pharmacologic reversal of the opioid component is helpful in management of such cases.

Neurotransmission in the central nervous system (CNS) and peripheral nervous system (PNS) are altered in the presence of opioid. Three main types of opioid receptors along with many less defined receptors with considerably minor effects are activated upon opioid administration.

Opioids use Mu and kappa receptors of CNS and PNS to intercede their physiological effects such as analgesia, respiratory depression and miosis (pupillary constriction). Mu receptors are also involved in evoking euphoria and Kappa receptor activation has a sedative effect. Sigma receptors, which mediate dysphoria, hallucinations, and psychosis; and Delta receptors, which mediates euphoria, analgesia, and seizures are the other two influential opiate receptors.

The effects of the above stated opiate receptors can be antagonized using opiate antagonists like naloxone, nalmefene, naltrexone.

Opioids group of drugs are generally classified into two groups

1. agonist, partial agonist or agonist-antagonist agents based on this nature of action
2. natural, semisynthetic, or synthetic based on its origin

Mode of action of opioids is as follows: The perception of pain is decreased upon opioid administration. It should be noted that it has no effect in modulation the stimulus associated with the pain. Opiods are easily absorbed by the mucosal structures of gastrointestinal and respiratory tract rendering an instant effect. Opioid agonists act by lowering the sensitivity to external stimuli and by inducing euphoria.

Subcutaneous ("skin popping") and intravenous ("mainlining") injection are the common methods adopted by street users to administer heroin and morphine . Raw opium is usually consumed or smoked and the powder is sometimes sniffed ("snorted"). Time to attain the maximum effect of opioids is as follows : intravenous route (10 minutes), inhalation of butorphanol, heroin (after 10-15 minutes), intramuscular route (30-45 minutes), oral route (90 minutes) and for dermal application of fentanyl ( 2-4 hours). In case of oral administration, absorption usually take place in the small intestine. Delayed absorption is often reported in case of toxic doses mainly attributed to the delay in intestinal transit time induced by the drugs.

Majority of opioids are metabolized into inactive compounds in liver and is subsequently eliminated from the body through urine. Lipid soluble drugs (e.g. fentanyl, buprenorphine) are stored in adipose tissues of the body. Patients with liver diseases (e.g., cirrhosis) experience a prolonged episode of drug effects owning to the impaired hepatic metabolism. Drug accumulation and toxicity are the common complication reported in such patients. Similarly impaired renal function can also lead to toxic accumulation of drug or its active metabolites (e.g., normeperidine).

Practicing clinicians should seriously consider all the risk factors associated with prescribing opioid medications to prevent a possible abuse or dependence. Information from family, friends and previous health care providers should also be weighed upon before reaching conclusions. Screening of risk factors in patients should be a routine procedure before commencing a long term opioid based therapy. The factors to be screened includes  

• History of substance  abuse (personnel or familial) -  It is considered as the strongest fore teller of drug abuse
• History of legal problems
• Mental disorder
• Younger age (<45) 
• Use of tobacco
• Childhood sexual abuse

Screening tools are available to assist physicians in identifying patients requiring  intense monitoring under long-term opioids treatment for chronic pain management [10]. Scientifically validated tools includes

• Revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R)
• The Opioid Risk Tool
• Diagnosis, Intractability, Risk, Efficacy (DIRE) instrument

Identification of patents with high  level risk factors is thus made easy and will help physicians to decide against giving an opiod based treatment at least until the risk factors are addressed properly.

As the accuracy of these screening tools is not 100%, results obtained should not be used to deny treatment, but rather be used to identify patients requiring constant monitoring under  long-term opioid treament. 

Addiction is a chronic condition with relapsing and remitting nature. It is associated with chronic morbidity and high risk of mortality. Most of the patients presented before medical practitioners have a history of illegal drug addiction. 

Opioid addiction (dependence syndrome) is a condition characterized by compulsive drug abuse despite the knowledge of harmful consequences. Continuation of opioid abuse even after sustaining overdoses or associated infections are classic examples. Drug-related impairments (e.g. sedation, overdose) and accidents are common among patients exercising excessive or unsanctioned use prescribed opioid.

Opioid substitution therapy employing drugs like methadone helps in successful management of addiction. This therapy has substantial evidence base to prove its efficacy in improving physical and societal health outcomes. Significant reduction in crimes related to drugs, transmission of blood borne infections and mortality are often observed in patients undergoing substitution therapy. Opioid substitution therapy aids in De-addiction and minimizing health related risks associated with the drug abuse. World Health Organization, recognizing its effectiveness, has included methadone in its Essential Medicines List for treating opioid addiction [1] [2] [3] [4].

Opioids commonly known as opiates are a group of drugs mainly used to treat pain. It includes drugs like morphine and codeine which are obtained from the opium poppy plant. Synthetic or partially synthetic chemicals like  Vicodin, Percodan, oxycodone and heroin also belong of this group.

Opioids can be administered orally, can be inhaled, injected or smoked. Prescription medication opioid are used as suppositories in some instances. Using prescription pain medications like oxycodone, codeine, and morphine for recreational purpose is regarded as abuse. It should also be noted that using opiods like heroin is illegal and may invite unnecessary legal problems. Consumption of opioids leads our brain to produce intense temporary gratification. Abuse of opioids  can rapidly lead to addiction with subsequent life threatening health problems including brain damage especially in case of long term abuse. Addiction will often urge the user do whatever things to procure drugs despite of serious consequences. Addition can affect the patient at two levels 

Physical - the body of daily user craves for the drug

Mental - the abuser actively craves for pleasure induced by drugs

Effects of opioid abuse is dependent on the type of opioid and  on the way it is consumed. Even a very little use of opioid can lead to addiction. In long run, opioid abuse may hamper brain`s ability to produce the natural pain killers and dopamine (“feel-good” chemical). 

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