wikitox:2.1.1.3_opioids
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— | wikitox:2.1.1.3_opioids [2018/09/01 09:00] (current) – created - external edit 127.0.0.1 | ||
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+ | Link to [[: | ||
+ | Link to [[: | ||
+ | |||
+ | ---- | ||
+ | |||
+ | ====== Opioids ====== | ||
+ | |||
+ | ===== DRUGS INCLUDED IN THIS CATEGORY ===== | ||
+ | |||
+ | * Morphine | ||
+ | * Codeine | ||
+ | * Heroin | ||
+ | * Pethidine (meperidine) | ||
+ | * Diphenoxylate | ||
+ | * Fentanyl | ||
+ | * Methadone | ||
+ | * Oxycodone | ||
+ | * Pentazocine | ||
+ | * (Dextro)propoxyphene | ||
+ | * Buprenorphine | ||
+ | |||
+ | ===== OVERVIEW ===== | ||
+ | |||
+ | Opioids present with a syndrome which includes miosis, coma, respiratory depression and vomiting. A rapid response to naloxone is usual if hypoxic brain damage or other events have not been superimposed. The treatment is primarily supportive, although naloxone may also be used in certain circumstances. In recreational overdoses (i.e. dependent patients), a [[: | ||
+ | |||
+ | ===== MECHANISM OF TOXICITY EFFECTS ===== | ||
+ | |||
+ | Opioids are opioid receptor agonists. Stimulation of these receptors in the central nervous systems leads to analgesia, vomiting and profound sedation in a dose dependent manner. These effects are potentiated by other sedative drugs (e.g. [[: | ||
+ | |||
+ | ===== KINETICS IN OVERDOSE ===== | ||
+ | |||
+ | The opioids are a diverse group of substances. The most important kinetic difference between them is their half-life in overdose which varies from hours to days. | ||
+ | |||
+ | ==== Absorption ==== | ||
+ | |||
+ | Opioids are generally rapidly absorbed, with peak concentrations within two hours of oral ingestion, one hour of IM administration and minutes of IV injection. First pass metabolism is noted with some of these drugs (codeine, morphine, propoxyphene) however these drugs also have active metabolites. Oral controlled release formulations of morphine and oxycodone and topical preparations of fentanyl are also available and are frequently used in palliative care. Absorption from these preparations will continue for up to 12 hours. | ||
+ | |||
+ | Buprenorphine is used as opiate replacement therapy and administered sublingually. | ||
+ | |||
+ | ==== Distribution ==== | ||
+ | |||
+ | These drugs have volumes of distribution of 1-5 L/kg and cross well into the central nervous system. | ||
+ | |||
+ | ==== Metabolism - Elimination ==== | ||
+ | |||
+ | These drugs are primarily hepatically metabolised. The half-life of most of these drugs is between 1 and 5 hours. However methadone (about 20 to 60 hours), buprenorphine (about 35 hours S/L; 1-7 hours IV) and propoxyphene (12 to 24 hours) are exceptions. | ||
+ | |||
+ | ===== CLINICAL EFFECTS ===== | ||
+ | |||
+ | ==== Central nervous system ==== | ||
+ | |||
+ | CNS depression is the major clinical manifestation. Increasing doses lead to increasing degrees of sedation with initial analgesia and sedation, followed by loss of response to verbal stimuli, loss of response to tactile stimuli, loss of control over normal respiration and failure of temperature and blood pressure regulation. | ||
+ | |||
+ | ==== Cardiac ==== | ||
+ | |||
+ | Dextropropoxyphene may lead to cardiac effects and ECG changes. The ECG changes seen in propoxyphene overdose are similar to those seen in [[: | ||
+ | |||
+ | Methadone can the prolongs QT interval and cause torsades de pointes. | ||
+ | |||
+ | ==== Pulmonary ==== | ||
+ | |||
+ | Aspiration and [[: | ||
+ | |||
+ | === Intravenous Abuse === | ||
+ | |||
+ | Complications of intravenous use of opioids include systemic fungal infection, abscess formation, cellulitis, osteomyelitis, | ||
+ | |||
+ | ==== Other ==== | ||
+ | |||
+ | Pentazocine and pethidine may contribute to the development of a [[: | ||
+ | |||
+ | ===== INVESTIGATIONS ===== | ||
+ | |||
+ | ==== Imaging ==== | ||
+ | |||
+ | A chest X-ray should be obtained in severe opioid overdose as aspiration and [[: | ||
+ | |||
+ | ==== ECG ==== | ||
+ | |||
+ | An ECG should be done in overdoses involving propoxyphene and methadone. | ||
+ | |||
+ | ==== Blood concentrations ==== | ||
+ | |||
+ | Drug concentrations are not helpful in the management of overdose. | ||
+ | |||
+ | ==== Urine drug screen ==== | ||
+ | |||
+ | Patients with recreational overdoses should have a urine drug screen for drugs of abuse to identify other substances that may have been taken or abused but is not helpful in the management of an acute overdose. | ||
+ | |||
+ | ==== Other investigations ==== | ||
+ | |||
+ | Patients with suicidal ingestions who present with an opioid syndrome should have paracetamol, | ||
+ | |||
+ | ===== DIFFERENTIAL DIAGNOSIS ===== | ||
+ | |||
+ | The differential diagnosis for a patient presenting with a typical opioid syndrome is any other sedating drug. The presence of [[: | ||
+ | |||
+ | ===== DIFFERENCES IN TOXICITY ===== | ||
+ | |||
+ | Prolonged toxicity is seen following exposure to agents: | ||
+ | |||
+ | * with long half lifes eg methadone, buphenorphine and propoxyphene | ||
+ | * controlled release preparations | ||
+ | * Transdermal patches | ||
+ | * Propoxyphene may cause direct cardiac effects. | ||
+ | |||
+ | Drugs such as codeine, which are prodrugs, have much less toxicity in overdose as they need to be converted to more active metabolites. Drugs administered by the intravenous route in recreational overdoses may involve various adulterants which occasionally will be of clinical importance. | ||
+ | |||
+ | Adulterants found in street drugs include such diverse substances as | ||
+ | |||
+ | * Ketamine | ||
+ | * [[: | ||
+ | * Talc | ||
+ | * Glucose powder | ||
+ | * Strychnine | ||
+ | * Caffeine | ||
+ | * Other illicit drugs, e.g. amphetamines, | ||
+ | |||
+ | Unexplained symptoms in patients with recreational overdose should prompt a search for these substances and should include an ECG to detect cardiotoxic drugs. | ||
+ | |||
+ | ===== TREATMENT ===== | ||
+ | |||
+ | ==== Supportive ==== | ||
+ | |||
+ | Management of opioid toxicity is centered on the maintenance of respiration and cardiopulmonary function, as well as appropriate use of an opioid antagonist. | ||
+ | |||
+ | Patients should be closely observed for the development of respiratory depression. If necessary, naloxone can be given to counteract the sedating effect of opioids. Intubation and ventilation will occasionally be required for patients who have developed respiratory complications of their overdose. | ||
+ | |||
+ | ==== GI Decontamination ==== | ||
+ | |||
+ | \\ Gastric decontamination is effective, particularly in those ingesting sustained released forms. After eliminating the existence of potential contraindications such as ileus, activated charcoal can be administered up to 4 hours post-ingestion of a standard release formulation or up to 12 hours after a sustained release formulation. \\ Consider [[: | ||
+ | |||
+ | Enhanced elimination techniques to increase the rate of removal of opioids are not recommended. | ||
+ | |||
+ | ==== Antidotes ==== | ||
+ | |||
+ | === Naloxone === | ||
+ | |||
+ | **// | ||
+ | |||
+ | Naloxone is an opiate receptor antagonist with a short half life. The duration of action of a single dose is usually less than 1-2 hours. As this is shorter than the duration of action of most opioids, repeat doses are often required to maintain consciousness. \\ Indications include diminished respirations (less than or equal to 12 per minute), with pinpoint pupils, reduced level of consciousness or evidence of opiate use. \\ Naloxone may be administered via the intravenous, | ||
+ | |||
+ | **// | ||
+ | |||
+ | Naloxone is given 0.1- 0.4 mg IV or IM repeated every 2-3 minutes up to a total dose of 2 mg. Larger doses of up to 12 mgs may be needed for buphrenorpine. \\ Failure to respond to 2 mg means further doses are unlikely to be helpful. Use the minimum dose necessary to raise the patient' | ||
+ | |||
+ | **// | ||
+ | |||
+ | Patients should be observed carefully for relapse for at least 2-3 hours. If a patient does redevelop marked sedation after their first naloxone dose, an infusion of naloxone may be required (commencing with a dose that is half to two thirds of the dose required initially to wake them given per hour). \\ Titrate infusion rate to response. \\ pCO_2 estimation is the most accurate way to assess respiratory depression due to opioids and should be regularly measured in patients on infusions. \\ Controlled release morphine and oxycodone, methadone and propoxyphene overdoses may require a continuous infusion for as long as several days. | ||
+ | |||
+ | **//Adverse effects// | ||
+ | |||
+ | Over-administration of an opioid antagonist may precipitate a withdrawal syndrome in the opioid dependent with onset of agitation, hypertension, | ||
+ | |||
+ | ==== Treatment of specific complications ==== | ||
+ | |||
+ | === Propoxyphene induced arrhythmias === | ||
+ | |||
+ | Patients ingesting propoxyphene with abnormal ECGs (increased PR, QRS & QT durations) should be monitored until the ECG returns to normal. Treatment of tachy- and bradyarrhythmias should be similar to that used in [[: | ||
+ | |||
+ | ==== Other ==== | ||
+ | |||
+ | Pentazocine and pethidine may contribute to the development of a [[: | ||
+ | |||
+ | ===== INVESTIGATIONS ===== | ||
+ | |||
+ | ==== Imaging ==== | ||
+ | |||
+ | A chest X-ray should be obtained in severe opioid overdose as aspiration and [[: | ||
+ | |||
+ | ==== ECG ==== | ||
+ | |||
+ | An ECG should be done in overdoses involving propoxyphene and methadone. | ||
+ | |||
+ | ==== Blood concentrations ==== | ||
+ | |||
+ | Drug concentrations are not helpful in the management of overdose. | ||
+ | |||
+ | ==== Urine drug screen ==== | ||
+ | |||
+ | Patients with recreational overdoses should have a urine drug screen for drugs of abuse to identify other substances that may have been taken or abused but is not helpful in the management of an acute overdose. | ||
+ | |||
+ | ==== Other investigations ==== | ||
+ | |||
+ | Patients with suicidal ingestions who present with an opioid syndrome should have paracetamol, | ||
+ | |||
+ | ===== DIFFERENTIAL DIAGNOSIS ===== | ||
+ | |||
+ | The differential diagnosis for a patient presenting with a typical opioid syndrome is any other sedating drug. The presence of [[: | ||
+ | |||
+ | ===== DIFFERENCES IN TOXICITY ===== | ||
+ | |||
+ | Prolonged toxicity is seen following exposure to agents: | ||
+ | |||
+ | * with long half lifes eg methadone, buphenorphine and propoxyphene | ||
+ | * controlled release preparations | ||
+ | * Transdermal patches | ||
+ | * Propoxyphene may cause direct cardiac effects. | ||
+ | |||
+ | Drugs such as codeine, which are prodrugs, have much less toxicity in overdose as they need to be converted to more active metabolites. Drugs administered by the intravenous route in recreational overdoses may involve various adulterants which occasionally will be of clinical importance. | ||
+ | |||
+ | Adulterants found in street drugs include such diverse substances as | ||
+ | |||
+ | * Ketamine | ||
+ | * [[: | ||
+ | * Talc | ||
+ | * Glucose powder | ||
+ | * Strychnine | ||
+ | * Caffeine | ||
+ | * Other illicit drugs, e.g. amphetamines, | ||
+ | |||
+ | Unexplained symptoms in patients with recreational overdose should prompt a search for these substances and should include an ECG to detect cardiotoxic drugs. | ||
+ | |||
+ | ===== TREATMENT ===== | ||
+ | |||
+ | ==== Supportive ==== | ||
+ | |||
+ | Management of opioid toxicity is centered on the maintenance of respiration and cardiopulmonary function, as well as appropriate use of an opioid antagonist. | ||
+ | |||
+ | Patients should be closely observed for the development of respiratory depression. If necessary, naloxone can be given to counteract the sedating effect of opioids. Intubation and ventilation will occasionally be required for patients who have developed respiratory complications of their overdose. | ||
+ | |||
+ | ==== GI Decontamination ==== | ||
+ | |||
+ | \\ Gastric decontamination is effective, particularly in those ingesting sustained released forms. After eliminating the existence of potential contraindications such as ileus, activated charcoal can be administered up to 4 hours post-ingestion of a standard release formulation or up to 12 hours after a sustained release formulation. \\ Consider [[: | ||
+ | |||
+ | Enhanced elimination techniques to increase the rate of removal of opioids are not recommended. | ||
+ | |||
+ | ==== Antidotes ==== | ||
+ | |||
+ | === Naloxone === | ||
+ | |||
+ | **// | ||
+ | |||
+ | Naloxone is an opiate receptor antagonist with a short half life. The duration of action of a single dose is usually less than 1-2 hours. As this is shorter than the duration of action of most opioids, repeat doses are often required to maintain consciousness. \\ Indications include diminished respirations (less than or equal to 12 per minute), with pinpoint pupils, reduced level of consciousness or evidence of opiate use. \\ Naloxone may be administered via the intravenous, | ||
+ | |||
+ | **// | ||
+ | |||
+ | Naloxone is given 0.1- 0.4 mg IV or IM repeated every 2-3 minutes up to a total dose of 2 mg. Larger doses of up to 12 mgs may be needed for buphrenorpine. \\ Failure to respond to 2 mg means further doses are unlikely to be helpful. Use the minimum dose necessary to raise the patient' | ||
+ | |||
+ | **// | ||
+ | |||
+ | Patients should be observed carefully for relapse for at least 2-3 hours. If a patient does redevelop marked sedation after their first naloxone dose, an infusion of naloxone may be required (commencing with a dose that is half to two thirds of the dose required initially to wake them given per hour). \\ Titrate infusion rate to response. \\ pCO_2 estimation is the most accurate way to assess respiratory depression due to opioids and should be regularly measured in patients on infusions. \\ Controlled release morphine and oxycodone, methadone and propoxyphene overdoses may require a continuous infusion for as long as several days. | ||
+ | |||
+ | **//Adverse effects// | ||
+ | |||
+ | Over-administration of an opioid antagonist may precipitate a withdrawal syndrome in the opioid dependent with onset of agitation, hypertension, | ||
+ | |||
+ | ==== Treatment of specific complications ==== | ||
+ | |||
+ | === Propoxyphene induced arrhythmias === | ||
+ | |||
+ | Patients ingesting propoxyphene with abnormal ECGs (increased PR, QRS & QT durations) should be monitored until the ECG returns to normal. Treatment of tachy- and bradyarrhythmias should be similar to that used in [[: | ||
+ | |||
+ | ===== LATE COMPLICATIONS - FOLLOW UP ===== | ||
+ | |||
+ | Patients with recreational overdoses should be referred to drug and alcohol services. If the patient is not sedated and has not received naloxone within the previous three hours, the patient may be discharged. Patients with propoxyphene overdoses should have ECG monitoring until their ECG returns to normal. Long term sequelae are only likely if there has been a period of hypoxia with subsequent hypoxic brain injury. | ||
+ | |||
+ | See {{: | ||
+ | |||
+ | ===== REFERENCES ===== | ||
+ | |||
+ | Meredith TJ, Jacobsen D, Haines JA, Berger J-C (eds). Naloxone, flumazenil and dantrolene as antidotes. IPCS/CEC evaluation of antidotes series Vol 1. //Cambridge University Press// | ||
+ | |||
+ | Chamberlain JM, Klein BL.A comprehensive review of naloxone for the emergency physician. //Am J Emerg Med// 1994; | ||
+ | |||
+ | Hoffman RS, Goldfrank LR.The poisoned patient with altered consciousness. Controversies in the use of a 'coma cocktail' | ||
+ | |||
+ | Kelly AM, Kerr D, Dietze P, et al. Randomised trial of intranasal versus intramuscular naloxone in pre hospital treatment of suspected opioid overdose. //Med J Aust// | ||
+ | |||
+ | Sporer KA. Buprenorphine: | ||
+ | |||
+ | ===== FURTHER RESOURCES ===== | ||
+ | |||
+ | Opioid treatment line (for the PUBLIC to be referred to) Phone 1800 642 428 | ||
+ | |||
wikitox/2.1.1.3_opioids.txt · Last modified: 2018/09/01 09:00 by 127.0.0.1