Ondansetron for Opiate Withdrawal | Symptoms of Opiate Withdrawal

What Is Ondansetron?

Ondansetron is a generic drug available under the brand name Zofran. Ondansetron is available in the form of a disintegrating tablet, solution, fil, and an IV variation. The tablet is most commonly administered to patients to prevent nausea and vomiting.

For the most part, ondansetron is used for nausea and vomiting relating to medical treatments including chemotherapy, radiation and surgery. It’s classified as an antiemetic. Antiemetics are a class of drugs that reduce nausea and vomiting. Ondansetron is believed to work by blocking the effects of serotonin. Ondansetron competes for the 5-HT3 (serotonin) binding sites on nerve cells in the gastrointestinal tract or the central nervous system.

There are side effects of ondansetron including drowsiness, headache, and diarrhea. This medication may also cause constipation and dizziness. One of the most serious side effects of ondansetron is serotonin syndrome, which is a medical emergency. Serotonin syndrome is exceedingly rare and only occurs in combination with multiple other medications that increase serotonin levels. People who take methadone and ondansetron are at an increased risk of experiencing this condition.

People are advised against combining ondansetron with other medications affecting serotonin levels for this reason. There is some evidence ondansetron for opiate withdrawal could be useful, but why is that?

Opioids and opiates can include naturally derived substances like morphine, as well as hydrocodone and oxycodone. Heroin is also an opioid. These drugs are not only psychologically addictive but also lead to physical dependence. When someone is physically dependent on opioids or opiates and they stop taking the drugs, they can experience withdrawal symptoms. The body has adapted to the presence of drugs after a point, which can be as short as a few weeks. When the substance is taken away, the body has to readjust.

Opiate withdrawal symptoms vary from mild to severe. The severity and length of symptoms depend on factors like how long someone used opioids and how heavily. The symptoms are the result of the body trying to go back to a normal state of functionality. Along with drug cravings, other symptoms can include fatigue, insomnia, anxiety, depression, diarrhea, nausea, and vomiting.

Withdrawal symptoms continue as the body goes through the process of cleansing itself from opiates. Withdrawal from some substances, including alcohol, can be deadly. Opiate withdrawal generally isn’t life-threatening, but it is uncomfortable and complications are possible.

While most of the physical symptoms of opiate withdrawal end within a week, some can linger for weeks or months. Psychological symptoms tend to last longer, especially for people who have misused opiates for a long time. For example, a person may experience anxiety and depression even months after abstaining from opioids.

The benefit of a medically supervised detox program is the ability to better manage withdrawal symptoms. These symptoms can include mental and physical side effects of opiate withdrawal. Some medications ease a person through detox and prevent complications, as well as raise the chance of achieving long-term success in recovery.

While opiate withdrawal isn’t life-threatening in most cases, nausea and vomiting can lead to complications. Aspiration is possible, which occurs when vomiting and then inhaling stomach contents causes lung infection. Vomiting and diarrhea can also cause dehydration. Ondansetron for opiate withdrawal can be useful in reducing nausea and vomiting.

While ondansetron for opiate withdrawal can be helpful, it’s not a cure-all for addiction. Ondansetron is a medication that can mitigate some of the physical symptoms of opiate dependence. Opioid addiction is separate from dependence. Treating opioid withdrawal symptoms is only one part of a larger, more comprehensive treatment approach.

Another important consideration when discussing ondansetron for opiate withdrawal is attempting to self-medicate. The best course of action for opiate withdrawal is professional treatment. Attempting to self-medicate through detox can be dangerous or deadly.

If you’re struggling with opioid dependence or addiction, please call The Recovery Village. We offer a variety of detox and opioid addiction treatment programs that are specialized and can improve your chances of eliminating substance use disorder from your life.

Editor – Camille Renzoni

Cami Renzoni is a creative writer and editor for The Recovery Village. As an advocate for behavioral health, Cami is certified in mental health first aid and encourages people who face substance use disorders to ask for the help they deserve. Read more

Medically Reviewed By – Dr. Conor Sheehy, PharmD, BCPS, CACP

Dr. Sheehy completed his BS in Molecular Biology at the University of Idaho and went on to complete his Doctor of Pharmacy (PharmD) at the University of Washington in Seattle. Read more

Medical Disclaimer

The Recovery Village aims to improve the quality of life for people struggling with substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare providers.

Ondansetron – StatPearls – NCBI Bookshelf

Continuing Education Activity

Ondansetron is one of the medications most commonly used for the empiric treatment of nausea and vomiting. Ondansetron has excellent utility as an antiemetic drug, and it is effective against nausea and vomiting of various etiologies. Common uses of ondansetron include the prevention of chemotherapy-induced and radiation-induced nausea and vomiting, the prevention of postoperative nausea and vomiting, and off-label use for the prevention of nausea and vomiting associated with pregnancy. However, it is not effective for motion sickness-induced nausea. This activity will cover the mechanism of action, pharmacology, adverse event profiles, eligible patient populations, contraindications, and monitoring. It also highlights the interprofessional team’s role in managing patients needing ondansetron therapy.

Objectives:

• Identify the antiemetic mechanism of action of ondansetron.

• Outline the approved and off-label indications for using ondansetron.

• Summarize the adverse event profile of ondansetron.

• Review the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients who can benefit from therapy with ondansetron.

Access free multiple choice questions on this topic.

Indications

Nausea and vomiting are common complaints seen by emergency department physicians and primary care clinicians daily.[1] Ondansetron is on the World Health Organization’s (WHO) List of Essential Medicines, a list of medications considered effective and safe in meeting the essential needs of a health care system. Other antiemetics that appear on this list with ondansetron include dexamethasone and metoclopramide. In 2006 (the last year of its patent), the brand-name version of ondansetron was the 20th highest-selling brand-name drug in the United States, and its popularity continues today. Ondansetron has widespread utility as an antiemetic drug and is effective against nausea and vomiting of various etiologies.

The FDA-approved indications include the prevention of chemotherapy-induced nausea and vomiting(CINV), radiation-induced nausea and vomiting, and the prevention of postoperative nausea and vomiting (PONV).[2] It is considered first-line therapy for the treatment of chemotherapy-induced and radiation-induced nausea and vomiting.[3][4]

Off-label use for the prevention of nausea and vomiting associated with pregnancy. Ondansetron has minimal efficacy against nausea and vomiting caused by motion sickness, mediated by different control centers and pathophysiologic mechanisms. There are limited data available from pediatric populations. Ondansetron is used in pediatric populations for the acute treatment of cyclic vomiting syndrome; however, there is little information available on the efficacy of this disease. [5] Ondansetron is used off-label for severe refractory diarrhea associated with neuroendocrine tumors (carcinoid syndrome).[6]

Mechanism of Action

Ondansetron is a selective 5-HT3 serotonin-receptor antagonist used for its antiemetic properties. It is one of the four FDA-approved 5-HT3 serotonin-receptor antagonists used to combat nausea and vomiting, including granisetron, dolasetron, and the second-generation drug, palonosetron.[7]

Ondansetron acts both centrally and peripherally to prevent and treat nausea and vomiting. Central effects are mediated by the antagonism of 5HT-3 serotonin receptors in the area postrema. The area postrema, located on the fourth ventricle floor, contains the “chemoreceptor trigger zone.” This zone senses neurotransmitters like serotonin, toxins, and other signals and plays a role in mediating the sensation of nausea and subsequent vomiting. Ondansetron also has effects peripherally by acting on the vagus nerve. It works on the 5-HT3 receptors that can be found at the vagus nerve terminals. The vagus nerve can sense nausea and vomiting triggers within the GI tract, such as stomach irritants. It forms synapses within the nucleus tractus solitarius of the brainstem, another region important in vomiting. The peripheral actions of ondansetron are thought to be the predominant mechanism for its antiemetic effects.[8][9]

Pharmacokinetics

Absorption: Ondansetron undergoes rapid absorption from the GI tract, and the peak plasma concentration (Tmax) is approximately 1.5 hours after an 8 mg single oral dose. The absolute bioavailability of ondansetron after oral administration is approximately 60%(50%-70%). The lower bioavailability is attributed to first-pass metabolism. The systemic bioavailability of ondansetron increases nonlinearly with increasing doses from 8 mg, 16 mg, 32 mg, and 64 mg because of saturation of the first-pass metabolism. The bioavailability of ondansetron is significantly higher in patients with cancer (85% to 87%) than in healthy individuals (50%-70%), possibly due to alterations in metabolism.

Distribution: Ondansetron and its metabolites are extensively distributed in tissues. The apparent volume of distribution(Vd) at a steady state is approximately 1.8 L/kg. Ondansetron crosses the blood-brain barrier to a lower extent, with the CSF concentration only about 10%-15% of the plasma concentration in human volunteers. Adenosine binding cassette subfamily 1(ABCB1) is a drug efflux transporter known to transport ondansetron across the blood-brain barrier, thus limiting its accumulation in the CNS. In a patient with decreased activity of ABCB1, the concentration of ondansetron in the brain increases and improves efficacy.[10]

Metabolism: The liver is the primary site of metabolism. The primary mechanism of metabolism is oxidation. 8-hydroxy ondansetron represents the major metabolite (40%), followed by 7-hydroxy ondansetron (< 20%) and 6-hydroxy ondansetron (<5%). Minor metabolism also occurs via N-demethylation to yield N-demethyl ondansetron. The active metabolite of ondansetron is  8-hydroxy ondansetron which is rapidly metabolized to glucuronide and sulfate conjugates in the liver, resulting in low blood concentrations and, thus, a very small contribution to ondansetron’s antiemetic activity. Cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4, are involved in the metabolism of ondansetron. In humans, CYP1A1/2 plays the most crucial role, while CYP2D6 plays a minor role in the metabolism of ondansetron. The role of CYP3A4 is important at higher concentrations of ondansetron.[11]

Excretion: Hepatic metabolism accounts for nearly 95% of ondansetron clearance, and less than 5% is excreted unchanged in the urine. The clearance and elimination half-life of ondansetron vary according to age. The elimination half-life after an 8 mg oral or intravenous dose is approximately 3-4 h in adults, but on average, it is 5.5 hours in the elderly. Clearance ranges from 0.381 L/h/kg to 0.262 L/h/kg, depending on age. In adults, clearance is 0.351 5L/h/kg. The clearance per body weight is higher in younger children. However, the clearance is decreased in infants due to the underdeveloped cytochrome P450 enzyme system.[12]

Administration

Routes of administration include oral, intramuscular (IM), and intravenous (IV). Oral formulations are available in dissolving tablet and soluble film forms. Ondansetron tablets should be administered 1 to 2 hours before radiotherapy, 30 minutes before chemotherapy, and an hour before anesthesia induction. Oral and IV formulations have been shown to have similar efficacy for treating emetogenic chemotherapy.

Dosing varies depending on the route of administration and the etiology. However, 16 mg per dose IV is the maximum recommended single dose due to the risk for QTc prolongation and arrhythmias. Standard dosing to prevent postoperative nausea and vomiting includes 8 mg every 12 hours orally or 4 mg given intravenously. No dosage adjustments are necessary for IV or oral administration in patients with renal impairment. The same holds for patients with mild to moderate hepatic impairment, but the maximum daily dosing is reduced to 8 mg IV or 8 mg orally in patients with severe hepatic impairment. Pediatric dosing is weight-based at 0.15 mg/kg per dose, with a maximum of 16 mg per dose.

Use in Specific Patient Populations

Patients with Hepatic Impairment: No dose adjustments of ondansetron are necessary for mild to moderate hepatic impairment. In patients with severe hepatic impairment, clearance of ondansetron is reduced; the volume of distribution and the plasma half-life is increased. Consequently, ondansetron should be used with caution, and the maximum recommended daily intravenous dose isis reduced to 8 mg.[11]

Patients with Renal Impairment: No dosage adjustments are necessary for IV or oral administration in patients with renal impairment.[11]

Pregnancy Considerations: Ondansetron is a former FDA  “Pregnancy Category B” drug. It should only be used when other medications have been trialed and failed to treat pregnancy-associated nausea, vomiting, and hyperemesis gravidarum.[8] According to ACOG(The American College of Obstetricians and Gynecologists) guidelines, pyridoxine alone or combined with doxylamine is the preferred pharmacological therapy for nausea and vomiting. However, in refractory cases with persistent symptoms, ondansetron, 4 mg orally every 8 hours, may be considered(if there is no dehydration).[13] A possible association between ondansetron use in the first trimester and cleft palate has been reported. Electrolyte and electrocardiogram monitoring are suggested in patients treated with ondansetron having risk factors for arrhythmia, such as a family history of prolonged QT interval, heart failure, and electrolyte disturbances.[14] Recommendations for pregnant women with gynecological cancer suggest that 5HT-3 antagonists (including ondansetron ) can be used as supportive medication.[15]

Breastfeeding Considerations: In a pharmacokinetic study, the relative infant exposure to ondansetron is less.[16] Ondansetron is commonly used for nausea during and after a cesarean section, usually in doses of 4 to 8 mg intravenously. Using ondansetron during cesarean section does not affect the onset of breastfeeding. No adverse drug reactions have been reported in infants. Additionally, ondansetron is indicated for use in infants as young as one month. No specific precautions are required.[17]

Adverse Effects

The most commonly reported side effects (occurring in more than 10% of adults) include headaches, fatigue, dry mouth, malaise, and constipation. Some less common effects range from central nervous system (CNS) manifestations, such as drowsiness and sedation, to local injection site reactions and pruritus.[18][19] A transient increase in liver function tests has been reported as well. The pattern of liver enzyme elevation is normally hepatocellular, with rare cases of clinically apparent acute liver injury or jaundice.[20]

Although typically clinically insignificant, EKG interval changes such as QTc elongation can be seen. These changes typically occur within 1 to 2 hours after administration, returning to baseline within 24 hours. As with any medication that causes QTc elongation, there is a concern for Torsade de Pointes and other arrhythmias. [21] IV administration has a higher risk for arrhythmias; consequently, the FDA does not recommend a single dose greater than 16 mg IV.[22] Isolated cases of sinus bradycardia and asystole have also been reported.[23] Cases of intestinal obstruction due to impaired gut motility have been reported.[24] Stevens-Johnson syndrome has been reported in patients with multiple comorbidities.[25]

Drug-Drug Interactions

Concurrent administration of pimozide with ondansetron should be avoided due to the risk of QTc prolongation.[26] Amiodarone may also prolong the QTc interval; hence administration with ondansetron requires monitoring.[27] There is a risk of serotonin syndrome when taking ondansetron in conjunction with other serotonergic medications.[28][26]

Contraindications

Ondansetron is contraindicated in patients with hypersensitivity to the drug or any components of it.[29] Severe hypersensitivity reactions, including anaphylaxis, have been reported.[30][31] Ondansetron is also contraindicated in patients currently taking apomorphine. Concomitant use of ondansetron and apomorphine can lead to profound hypotension and loss of consciousness, with ondansetron enhancing the hypotensive effects of apomorphine.[32] Patients with phenylketonuria (PKU) should be cautious, as the dissolving tablet formulation can contain phenylalanine, leading to irreversible neurological damage in PKU patients.[33]

Monitoring

Due to the potential for dose-dependent QTc interval elongation, the FDA recommends EKG monitoring along with potassium and magnesium in susceptible populations, such as the elderly or other at-risk groups. These at-risk groups include patients with electrolyte abnormalities such as hypokalemia, hypomagnesemia, heart failure, bradyarrhythmias, or patients on other medications that may prolong the QTc interval.[22][34] 

Pregnant patients should be monitored for adverse fetal outcomes associated with ondansetron therapy.[35][36][37] Current evidence does not suggest routine EKG and electrolyte monitoring for ondansetron without known risk factors.  Monitoring should be done in high-risk patients receiving ondansetron intravenously.[23][35]

Toxicity

There is no known antidote to ondansetron, and supportive measures are used for overdose. A case report describes an ondansetron overdose in an infant presenting with seizures, QTc prolongation, hepatotoxicity, and serotonin syndrome. The patient required endotracheal intubation, supportive care, and lorazepam for seizures.[38]

Enhancing Healthcare Team Outcomes

Ondansetron is a widely prescribed medication for nausea and vomiting from various causes. The drug is relatively safe, but prescribers, including nurse practitioners, primary care providers, internists, surgeons, and emergency department physicians, need to monitor the drug in specific populations. Due to the potential for dose-dependent QTc interval prolongation, clinicians should monitor EKG, potassium, and magnesium levels in a susceptible population. It includes the elderly or patients with electrolyte abnormalities such as hypokalemia, hypomagnesemia, heart failure, bradyarrhythmias, or patients on other medications that may prolong the QTc interval. Current evidence does not demonstrate a need to pre-screen this population before administering ondansetron for patients without any of the above risk factors.

An interprofessional team approach is critical for diagnosing and managing symptoms, treating patients with nausea and vomiting, and managing the adverse effects of the treatments. Clinicians (MDs, DOs, NPs, PAs) usually prescribe ondansetron for labeled indications. Oncologist consultation is necessary for CINV. Pharmacists should ensure proper dose, perform medication reconciliation and consult prescribers about any concerns. Nursing staff should monitor patients administering medicine and inform clinicians of any side effects observed. Emergency department physicians should rapidly stabilize the patient in case of arrhythmia. Severe cases may require consultation with an intensivist and MICU/IMC level of care. Medical toxicologist consultation may become necessary in the overdose. If the overdose is intentional, psychiatric consultation is essential. An interprofessional team approach would maximize the efficacy and minimize potential adverse drug reactions for the patients requiring ondansetron, resulting in better patient outcomes. [Level 5] A prospective study involving 789 patients demonstrated that an interprofessional team approach among clinicians, residents, clinical pharmacists, and oncologists reduced potential medication errors, eventually enhancing patient safety. [Level 3]

Review Questions

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References

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Disclosure: Alexandria Griddine declares no relevant financial relationships with ineligible companies.

Disclosure: Jeffrey Bush declares no relevant financial relationships with ineligible companies.

Postoperative care after facelift

Facelift surgery is one of the most effective rejuvenation procedures. The success of facial plastic surgery depends on both the surgeon and the patient. The surgeon cannot achieve satisfactory results with facial plastic surgery if patients do not follow the postoperative treatment properly.

Immediately after the facelift

The patient must be monitored for the first 24 hours after the facelift. The bandage is removed only after 24 hours. The patient’s head should be elevated during sleep for at least the first week after surgery. You should be careful sleeping on your side. Analgesics, sleeping pills after plastic surgery of the face, as a rule, are not required, but should be at hand. Physical activity should be limited on the day of facial plastic surgery and up to a week after it. Ice packs for facial plastic surgery may be recommended for selected patients.

Bleeding after facial plastic surgery

Light bleeding from the surgical site during and after facial plastic surgery is not unusual. Elevating the head and applying an ice pack with light pressure to the face and neck will usually reduce bleeding after facelift surgery. An increase in blood pressure during facial plastic surgery in patients with bending down, sneezing, coughing, straining in the toilet and other similar actions are the main causes of bleeding. Thus, the patient after facial plastic surgery should completely refrain from activities that can lead to an increase in blood pressure for 10 days in order to avoid complications in the form of bleeding or seroma.

Swelling after a facelift

Swelling after a facelift is a natural consequence of any surgery or injury. The size of the edema depends on the density of the tissues and the severity of the injury. Swelling around the eyes, cheeks, face, neck and chest is not uncommon. Edema begins immediately after facial plastic surgery and reaches its maximum on day 2-3. From the 3rd day after facial plastic surgery, edema tends to decrease. Swelling or swelling after a facelift causes a feeling of tightness and tension in the skin. It can interfere with smiling, cause chewing difficulties and discomfort in the surgical area. By the 5th-7th day, edema is significantly reduced, however, remaining to a small extent for 3-4 weeks. By this time, the swelling goes away, and the compaction of the injury zone remains for a long time.

Pain after facial plastic surgery

If necessary, analgesics such as acetaminophen, analgin, ketarol and ketanov can be taken in the first days after facial plastic surgery. It is not recommended to take aspirin and drugs of this group. They increase the risk of bleeding and bruising. Drugs are indicated for severe pain. Patients should not consume alcoholic beverages. They can provoke bleeding, slow down recovery processes and affect the effect of other drugs taken by the patient. Pain is not a frequent companion of facial surgeries. And discomfort from an injury or bandage usually goes away after the first 2-3 days. Persistent pain after facial plastic surgery should require attention, because. may be a sign of complications such as bleeding, bruising and inflammation.

Diet after face plastic surgery

After the face plastic surgery, you should start with drinking water, then you can switch to juices and light food. Dehydration is unacceptable. Fluid intake after facial plastic surgery should be regular and sufficient. Drinking normalizes the digestive tract and prevents nausea and vomiting. A high calorie and protein content in the diet is very important in the days following the facial plastic surgery.

Postoperative wound care

Patients should start showering with soap and water the day after the facelift. Regularity can reach 2-3 times a day. Postoperative sutures after facial plastic surgery should not be wiped, it is enough to blot moisture from them. The seams must be wiped with an alcohol solution or other antiseptic solution. To soften the crusts in the area of ​​the seams after the plastic surgery of the face, you can use a solution of hydrogen peroxide or just water. Some surgeons recommend applying antibacterial ointment to the stitches. Stitches should be dry, clean, pale and painless.

Hypopigmentation after facial plastic surgery

In some cases, after facial plastic surgery, some areas of the skin lose color and look white. This is normal and goes away on its own. Applying moist heat to the area can speed up the removal of the discoloration. In young patients, bruising is rare after facial plastic surgery, more often manifesting itself in the form of a slight yellowness.

In older patients, bruising after facial plastic surgery can be quite significant and appear as dark spots on the skin. Significant bruising usually resolves in 2-3 weeks. Massage, contrast showers, heparin ointments can slightly speed up the process of disappearance of bruises after facial plastic surgery.

Antibiotics after facial plastic surgery

The use of antibiotics to prevent infections in facial surgery is justified only in relation to implantation and long-term operations. There are no other justifications for prescribing systemic antibiotics after facial plastic surgery.

Nausea and vomiting after facial plastic surgery

In case of nausea and/or vomiting after facial plastic surgery, the patient does not eat until the complaints disappear. After facial plastic surgery, drugs to stimulate the function of the gastrointestinal tract and antiemetics, such as Zofran \ Latran, can be used.

Nosova Olga Olegovna

Head of the Beauty Space Clinic, plastic surgeon, full member of the European Academy of Facial Plastic Surgery (EAFPS), member of the European Society of Rhinologists (ERS), member of the Society of Plastic Reconstructive and Aesthetic Surgeons OPREH (SPRAS). Author of 12 scientific papers in the field of plastic and aesthetic surgery.

Guidelines for the use of opiates in chronic non-cancer pain | Drozdov V.N.

Chronic pain is a widespread problem faced by physicians in many specialties. According to the International Association for the Study of Pain (IASP), chronic non-cancer pain should be considered pain that bothers the patient for more than 3 months [1]. The prevalence of chronic pain, according to various authors, ranges from 7 to 55% [2]. In a number of patients with severe acute pain or chronic pain (lasting more than 6 months), the use of non-opioid analgesics does not achieve a sufficient analgesic effect, which leads to inadequate pain relief.

Opinions about the possibility of using opioids for the treatment of pain have changed in the last 3 decades. Previously, the possibility of chronic use of opiates only in the treatment of pain caused by cancer was considered, but recently opiates have also been used in the treatment of chronic pain caused by non-cancer pain.
Recently, a number of randomized clinical trials have been performed to evaluate the effectiveness of narcotic analgesics in the treatment of non-cancer pain.
The World Health Organization has included opiates in a 3-step scheme for choosing analgesic therapy (Fig. 1), when physiotherapy, massages and therapy with other analgesic drugs (paracetamol, NSAIDs, tricyclic antidepressants, anticonvulsants) cannot provide sufficient control over pain and quality of life of the patient.
One of the reasons for the refusal of both the doctor and the patient to take opiates is the fear of developing drug dependence when taking them [3]. Of course, this risk exists, but it is not as significant as it seemed before. In a study conducted in 100 patients taking opiates for 14 months for chronic pain syndrome of non-oncological origin, the average daily dose increased by only 2.8% [4]. Of the 153 spinal patients in orthopedic clinics, 11 (7.2%) patients required an increase in the dose of opiates within 3 years of taking the drugs, and only in 3 (2%) patients, an increase in the dose of opiates was not due to an increase in pain syndrome, and when they were canceled, the “syndrome cancellation” [5]. In another study, 10 patients switched opiates (morphine) to other analgesic drugs within 60 hours, 3 out of 10 patients noted the withdrawal of opiates from the treatment regimen due to increased pain, but none of them noted psychological dependence on morphine [6] . Data from these and other studies suggest that less than 2.8% of patients with non-cancer pain develop opiate dependence. Despite this, it is the risk of developing drug dependence that remains the main reason for not using opiates in patients with non-cancer pain.
The risk of developing drug dependence is not affected by the period of action of the drugs; it is equally possible with the use of both short-acting opiates and dosage forms with long-term maintenance of the therapeutic concentration of opiates in the blood [7,8]. The pharmacological form of the drugs had no effect on the risk of drug dependence. Cases of drug abuse have been described both among patients who received injections, and took tablet forms, and used transdermal forms of opiates [9,10].
The most effective are measures aimed at a preliminary assessment of the individual risk of developing psychophysiological dependence on drugs; training of doctors; rational dose management of narcotic drugs; control over the intake of drugs by patients; simultaneous use of other painkillers; effective treatment of a disease that causes pain [11–20].
One of the important factors preventing the development of drug dependence is the correct selection of patients. Several questionnaires have been developed to assess the risk of developing drug addiction: SOAPP (Screener and Opioid Assessment for Patients), SISAP, etc. The simplest is the SISAP questionnaire [21] (Table 1).
It is also necessary to give the patient clear instructions on the regimen of taking the drug: 1 – the patient should not go to another doctor (including the ambulance service) to prescribe painkillers without notifying his doctor, 2 – the patient should not change the dose and the mode of taking drugs without the doctor’s permission, even if pain relief is ineffective, 3 – the patient should come to the doctor’s office with used packages and unused drug. There is also the practice of signing by the patient and the doctor of an agreement on compliance with the regimen of taking drugs.
When prescribing narcotic drugs to evaluate the effectiveness of the treatment of pain, it is necessary to carefully document the pain syndrome. The most rational and simple way to do this is to use the visual analogue scale (VAS) or the verbal assessment scale (VAS). The ineffectiveness of the therapy or the development of undesirable complications are the most common causes of violations by patients of dosages and drug regimens. This may be due to both a worsening of the course of the disease and a violation of the metabolism of drugs. One of the reasons for the decrease in the effectiveness of opiates is a change in the activity of liver cytochromes P450 (CYP3A4, CYP2D6, CYP3A4, CYP2D6). The activity of these enzymatic systems can fluctuate both in the population and change under the influence of other drugs taken, including due to competition for the enzyme [22–25] with the same metabolic pathways of opiates and other drugs (Table 2).
When choosing an opiate, it is necessary to take into account the features of its pharmacokinetics (Table 3). For patients with chronic pain of non-oncological origin, drugs with a long-term analgesic effect are indicated. It is better to prescribe drugs with a longer half-life or slow-release substances, since increasing the dosage of the drug does not lead to an increase in the duration of analgesia. It must be remembered that there is individual sensitivity of α-receptors to various opiates, so changing the drug may be no less effective than increasing the dose.
With prolonged use of opiates, it is necessary to constantly monitor the development of adverse events. The most common of them are constipation, nausea, vomiting, itching, drowsiness, lethargy, respiratory depression. Adverse events such as nausea, vomiting, constipation can be corrected with symptomatic therapy. With the development of drowsiness, respiratory depression, a dose reduction or replacement of the opiate is required.
One of the effective methods of treating chronic pain with the help of opiates is complex therapy. It includes the appointment of patients with chronic pain, in addition to opiates, other analgesics: paracetamol, NSAIDs, antidepressants, antispasmodics. Complex therapy allows not only to reduce opiate doses by 25–50% [26–28], but also to increase the effectiveness of pain syndrome treatment, as well as reduce the number and severity of adverse reactions [29–31].
Compliance with the basic rules for the use of opiates, especially in the form of modern dosage forms as part of complex therapy, will significantly reduce pain with a minimal risk of drug addiction and/or adverse reactions. The number of non-cancer patients requiring such therapy is increasing. These are patients with osteoarthritis, chronic back pain, patients with adhesive disease, Crohn’s disease, chronic pancreatitis, etc. Currently, long-acting opiates are most often prescribed for osteoarthritis. Osteoarthritis (OA) as a disease does not lead to life-threatening complications, but its leading clinical symptom, chronic pain syndrome, can lead to patient disability.
The appearance in clinical practice of transdermal forms containing the opioid fentanyl (Durogesic) has opened up new perspectives in analgesic therapy. Durogesic, acting within 72 hours after application, allows you to achieve a stable analgesic effect, improve the activity and mobility of patients, as well as their general condition and mood (Fig. 1). Durogesic is well tolerated by patients, with its use developing a significantly smaller number of adverse events than with the use of other opiates, such as morphine (Table 4). Mostly, patients develop such adverse reactions as nausea, vomiting, constipation, which are easily stopped by symptomatic therapy [32-35]. Serious adverse events, such as respiratory depression, were noted in less than 2% of patients and only at high doses, mainly in cancer patients [36].
In Russia, there is no experience yet in the use of Durogesic in the treatment of OA, but the results of treatment of pain syndrome with Durogesic are widely discussed in foreign literature. Thus, R. Langford (Great Britain) presented data from a randomized, double-blind, placebo-controlled study of the efficacy of Durogesic [37]. The clinical study included 416 patients with OA. 202 patients received Durogesic 25 mcg/h, 197 patients placebo, treatment was carried out for 42 days. The results of OA treatment were assessed using the WOMAC scale (Fig. 2).
In patients treated with Durogesic, significantly compared with patients treated with placebo, both the total coefficient and the indicators of pain, joint mobility and physical activity decreased. Only 4 out of 202 patients receiving Durogesic needed an increase in the dose of Durogesic to relieve pain. Only one patient developed adverse events (dyspnea, itching and rash) that required discontinuation of the drug. Adverse reactions such as nausea and constipation were stopped without discontinuation of the drug.
The first results of the use of Durogesic 25 mcg / h allow us to state:
• Durogesic can be one of the methods of analgesia in patients with OA, especially when NSAIDs are ineffective or when life-threatening complications of their use develop.
• Durogezik not only reduces pain, but also increases the mobility of the joints and physical activity of the patient.
• Durogezik has a beneficial effect on the psychological state of the patient and thus significantly improves the quality of life.
• When using it, there are no life-threatening complications for the patient. Developing adverse events are easily stopped and disappear on their own after discontinuation of the drug.
The use of Durogesic opens up new possibilities in pain relief in patients with severe forms of osteoarthritis, especially at the stage of preparation for its surgical treatment. Successful analgesic therapy will allow these patients to maintain physical activity until the time of surgery, significantly reduce pain, facilitate psychological preparation for surgery, and thereby improve the results of surgical treatment.

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