Nichtopioid- and opioid analgesics are most important drug in the treatment of pain. Antidepressants, anticonvulsants and other CNS-active drugs can also be used in chronic or neuropathic pain and are the first choice in some disease states. Infusions of centrally acting drugs, nerve stimulation, injection therapy and nerve blocks may help selected patients. Cognitive-behavioral interventions (eg, changes in relationships at home;. Systematic use of relaxation techniques, hypnosis or biofeedback; tiered training) can help relieve pain and pain-related restrictions and assist patients in coping. Non opioid analgesics acetaminophen and NSAIDs are often effective in mild to moderate pain (see table: non-opioid analgesics). Of these, only ketorolac and diclofenac can be given parenterally (.. Editor’s note .: ketorolac has been approved in Germany only as ketorolac tromethamine for postoperative inflammation prophylaxis in ophthalmology; acetylsalicylic acid [Aspisol] can also be administered intravenously). Not opioids cause physical dependence or tolerance development. Non-opioid analgesics class drugs Usual dosage range * indoles diclofenac 50-100 mg, then 50 mg every 8 h 75 mg every 12 h i.v. or i.m. Etodolac (Editor’s note: not approved in Germany!) 200-400 mg every 6-8 h indomethacin 25-50 mg every 6-8 h sulindac (Editor’s note: not approved in Germany!) 150-200 mg every 12 h tolmetin (Editor’s note: not approved in Germany!) 200-400 mg every 6-8 h Naphthylalkanone nabumetone (Editor’s note: not approved in Germany!) 1000-2000 mg every 24 h oxicams piroxicam 20-40 mg every 24 h para-aminophenol acetaminophen (Editor’s note: in Germany better known under paracetamol) 650-1000 mg every 6-8 h propionic fenoprofen (Editor’s note: not approved in Germany !) 200-600 mg every 6 hours flurbiprofen 50-200 mg every 12 hours Ibuprofen 400 mg every 4 hours to 800 mg every 6 h ketoprofen 25-50 mg every 6-8 h naproxen 250-500 mg every 12 h naproxen sodium 275-550 mg every 12 h oxaprozin (Editor’s note: not approved in Germany !) 600-1200 mg every 24 h salicylates aspirin 650-1000 mg every 4-6 h choline Magnesiumtrisalicylat (Editor’s note: not approved in Germany!) 870 mg every 12 h diflunisal (Editor’s note: not approved in Germany!) 250-500 mg every 8 to 12 h salsalate (Editor’s note: not permitted in Germany) 750-2000 mg every 12 hours fenamates meclofenamate (Editor’s note: not approved in Germany!) 50-100 mg every 6-8 h Mefenamic (Editor’s note: not approved in Germany!) 250 mg every 6 h pyrazoles phenylbutazone 100 mg every 6-8 hours up to 7 days pyrrolo-pyrrolo derivatives ketorolac (Editor’s note: not approved in Germany!) 15-30 mg iv or i.m. every 6 hours or 20 mg, followed by 10 mg every 4-6 h on maximum of 5 days Selective COX-2 inhibitors (COXIBs) celecoxib 100-200 mg every 12 h * Oral application, with the exception of ketorolac and diclofenac, parenterally can be given. Acetaminophen (paracetamol) has no anti-inflammatory or anticoagulant effects and does not cause gastric mucosal irritation. Among the NSAIDS include the non-selective COX-1 and COX-2 inhibitors and selective COX-2 inhibitors (COXIBs); all of which are effective analgesics. Acetylsalicylic acid is cheapest, but it has a prolonged antiplatelet effect. Coxibs have the lowest risk for the formation of ulcers and gastrointestinal side effects. However, if a coxib with low-dose aspirin combined, it can not have a gastrointestinal advantage compared to other NSAIDs. Studies suggest that inhibition of COX-2 that occurs with non-selective COX inhibitors and coxibs, has a prothrombotic effect that can increase the risk of MI, stroke, and “claudication”. These effects seem both drug-related as to be dependent on the dose and duration of application. While there is evidence of a very low risk of some of the selective COX inhibitors (eg., Ibuprofen, naproxen) and coxibs (celecoxib), and also when data is still limited, it is still advisable, the potential prothrombotic effects to be considered as a risk of any NSAID therapy and suggest that all NSAIDs should be used with caution in patients with clinically signifikaner atherosclerosis or multiple cardiovascular risk factors. If an NSAID is expected to be used only in the short term, significant adverse effects are unlikely, regardless of the active ingredient. Some clinicians give in cases where long-term treatment is likely (for example, for months.), First, a coxib, as the risk of gastrointestinal side effects is less; others limit its use in patients with a predisposition to gastrointestinal side effects (eg. as elderly patients, patients taking corticosteroids, patients with a positive history of peptic ulcer or gastrointestinal disorders with other NSAIDs) and patients who have problems with or have prior history of intolerance to non-selective NSAIDs. All NSAIDs should be used with caution in patients with renal insufficiency, because coxibs are not kidney-friendly. If the initial prescribed doses cause an insufficient analgesia, a higher dose is given up to the normally regarded as safe maximum dose. In case of insufficient analgesia, the drug should be discontinued. If the pain is not strong, another NSAID can be tried because the response of drug varies to medication. During long-term NSAID treatment monitoring for occult blood in the stool, to changes in blood count, electrolytes, liver and renal function is advisable. Topical NSAIDs can be attached directly to the painful areas in diseases such as osteoarthritis and minor sprains, strains and contusions. A 1.5% solution of diclofenac has been shown to be effective in the treatment of pain and impaired joint function, which is caused by osteoarthritis of the knee. The dose is 40 drops (1.2 ml), which are applied on each affected knees 4 times daily. Other topical diclofenac formulations which may be useful for local pain relief, comprising a paving (2 times daily applied over the affected area), or a 1% agarose gel (2 g 4 times a day for the upper extremities or 4 g 4 times daily for the lower limbs). Opioid analgesics “opioid” is a generic term for natural or synthetic substances that bind to specific opioid receptors in the CNS, where they act agonistic. Opioids are referred to-one as narcotics term that was originally used for any psychoactive substance that induces sleep. Opioids have both analgesic and sleep-inducing effect, but the two effects are different. Some opioids used for analgesia, have both agonistic and antagonistic activity. The abuse potential in humans with a known history of substance abuse or dependence may be / antagonists less than with pure agonists with mixed agonist; However, mixed agonist / antagonists have for analgesia a ceiling effect and induce a withdrawal syndrome in patients who are already physically dependent on opioids. In general, acute pain is best treated with a short-acting pure agonist and chronic pain should, when treated with opioids, are best treated with longer-acting opioids (see table: Opioid analgesics and equianalgesic doses of opioid analgesia *). Because of the higher doses of many long-acting formulations, these drugs have an increased risk of serious side effects (eg. As death due to respiratory depression) in opioid-naive patients. Opioid analgesics drugs adult dose * dose for children † Comments opioid agonists in combination preparations ‡ for moderate pain Codeine Oral: h 0.5-1 mg / kg 30-60 mg every 4 – hydrocodone (Editor’s note: not approved in Germany!) Oral : 5-10 mg every 4-6 h 0.135 mg kg Similarly, such as codeine opioid agonist for moderate to severe pain Fentanyl Transdermal: 12 or 25 mcg / h every 3 days transmucosally: 100-200 mcg every 2-4 h Intranasal: 100-200 mcg every 2-4 h transmucosally: 5-15 mcg / kg can trigger the release of histamine less and therefore less hypotension than other opioids cause transdermal patch 12 mcg / h useful for opioid naive patients; Other doses can only be achieved in patients who were set to opioids Additional analgesia first necessary because the maximum analgesia h 18-24 after application using short-acting transmucosal formulations for breakthrough pain in adults and for sedation in children Hydromorphone Oral: 2-4 mg every 4-6 h Parenteral: 0.5-1 mg every 4-6 h Sustained release: 8-32 mg every 24 hours – Short half-life rectal: 3 mg every 6-8 h – rectal administration before bedtime Levorphanol Oral: 2 mg every 6-8 h Parenteral: 2 mg every 6-8 h – long half-life of meperidine (Editor’s note: not approved in Germany!) Oral: 50-300 mg every 4 hours Parenteral: 50-150 mg every 4 h from 1.1 to 1.75 mg / kg is not preferred because active metabolite (normeperidine) dysphoria and CNS stimulation causes (eg. accumulated as myoclonus, tremors, convulsions) and after taking the start for days, especially in patients with renal insufficiency methadone Oral: 2.5 to 10 mg every 6-8 h Parenteral: 2.5-5 mg every 6-8 h – Application in the treatment of heroin withdrawal, long-term treatment of opioid dependence and analgesia in chronic pain setting a safe, effective dose for analgesia is determined by the long half-life (usually much longer than the duration of analgesia) complicated Requires increasing the dose or more frequent administration close monitoring via several days or longer, as severe toxicity can occur during the plasma levels until steady state increases Oral morphine immediate release: 10-30 mg every 4 h Oral controlled release 15 mg every 12 h Oral sustained-release 30 mg every 24 hours Parenteral: 5-10 mg every 4 h 0.05-0.2 mg / kg every 4 h benchmark Triggers frequently than other opioids histamine release, causing itching oxycodone ‡ Oral: 5-10 mg every 4 h Oral controlled release: 10-20 mg every 12 hours – in combination preparations, the acetaminophen or aspirin containing oxymorphone (Editor’s note: not approved in Germany!) Oral: 5 mg every 4 h Oral controlled release: 5-10 mg every 12 h i.m. or s.c .: 1-1.5 mg every 4 h i.v .: 0.5 mg every 4 h rectal: 5 mg every 4-6 h – May cause less histamine release than other opioids Opioideagonisten / -antagonisten§ buprenorphine i.v. or 0.3 mg every 6 h Sublingual: 2 mg every 12 h transdermal patch: applied 5-20 mcg / h, 1 time / week (in the European Union, doses may be 20 mcg / h exceed) application only patients> 13 years old (equivalent of the adult dose) psychotomimetic effects (eg. as delirium) less pronounced than in other agonists / antagonists, other effects but similar respiratory depression, which may naloxone may not be completely reversible sublingual administration of buprenorphine occasionally chronic for treatment Pain; Butorphanol can be used in the agonist therapy of opioid dependence (Editor’s note: not approved in Germany!) Iv: 1 (0,5-2) mg every 3-4 h in: 2 (1-4) 3-4 mg , 1 mg (1 puff), repeated after 1 h if needed Not recommended Nasal 2-doses sequence repeated every 3-4 h if necessary nalbuphine Parenteral: all h Nasal 10 mg every 3-6 hours not recommended psychotomimetic effects less pronounced than pentazocine, but prominent than morphine Pentazocine Oral: 50-100 mg every 3-4 h Parenteral: 30 mg every 3-4 h (360 mg / day does not exceed) Not recommended Restricted benefits through: ceiling effect for analgesia in higher doses, potential opioid withdrawal in patients with physical dependence on opioid agonists, risk psychotomimetic effects, particularly in patients with acute pain without development of tolerance and physical dependence without Available in tablets combined with naloxone, aspirin or acetaminophen can cause confusion and anxiety, v. a. in elderly patients * Initial dosages for opioid naive patients. Patients with opioid tolerance or severe pain need higher doses. † Not all drugs are suitable for analgesia in children. ‡ These opioid agonist can be combined in a single tablet with acetaminophen, aspirin or ibuprofen. §Opioidagonisten / antagonists are not usually used to treat chronic pain and are rarely drugs of choice for elderly patients. Opioid analgesics are useful in the treatment of acute and chronic pain. They are sometimes used in patients with severe acute pain or pain and a terminal illness such as cancer too little, resulting in unnecessary pain and suffering. Among the reasons for the shortage include underestimation of the effective dose overestimate the risk of side effects I. General. should opioids in the treatment of acute, severe pain not be denied; However, the simultaneous treatment of the disease that causes pain is usually limited, the duration of severe pain and limits the need for opioids on some days or less. In addition, opioids should not be refused generally in the treatment of cancer pain; In such cases, adverse effects can be prevented or treated, and the dependence is of lesser importance. In patients with chronic pain that is not caused by cancer, therapy should first be tried without opioids (Chronic pain: treatment). Opioids should be used if the benefit of pain reduction outweighs the risk of side effects and drug abuse. If an opioid-free therapy has been unsuccessful, opioid therapy should be considered. In such cases, consent can help to clarify the objectives, expectations and risks of treatment and facilitate information and advice about the abuse. Patients (months> 3) receiving chronic opioid therapy should regularly for pain control, control of side effects, and signs will be evaluated by abuse. If patients have persistent pain despite increasing opioid doses, you should not stick to the terms of the treatment, or if the physical or mental functions deteriorate, the opioid therapy should be reduced or stopped. Physical dependence (development of withdrawal symptoms when the drug is discontinued) should be adopted in all patients treated with opioids more than a few days. Thus, opioids should be used as short as possible and dependent patients, the dose should be reduced in order to control withdrawal symptoms when opioids are no longer necessary. Patients with pain due to acute, transient disturbance (e.g., B-fraction, verbs busbars, surgical procedures) should be changed as quickly as possible to an opioid-free drug. Dependence is different from addiction, although there is no universally accepted definition that includes generally compulsive use and overwhelming involvement with the drug, including addiction, loss of control over the use and use despite harm. Equianalgesic doses of opioid analgesics * drug i.v. (Mg) Oral (mg) butorphanol 2 – codeine, hydromorphone 130 200 1.5 7.5 2 4 levorphanol meperidine 75,300 Methadone, morphine 10 20 10 30 10 nalbuphine – oxycodone oxymorphone 15 † 20 15 1 pentazocine 60180 * equivalent doses are based on single-dose studies, and are influenced by clinical experience. Cross-tolerance between drugs is not complete, so that when in replacement of a drug, the equianalgesic dose should be reduced by 50% by another; Methadone should be reduced by 75-90%. † Parentales Oxycodone is available in Europe but not in the US. Almost every administration route of administration is possible. Oral or transdermal administration will be preferred in the long-term use; both are effective and lead to stable blood levels. Sustained release oral and transdermal formulations allow less frequent dosing, which is important for nighttime pain relief. I.v. application offers the fastest onset of action, and therefore the easiest titration, however, the analgesic duration of action is short. Strong and rapid fluctuations in blood level (Boluseffekt) may lead to breakthrough pain at maximum levels in early dosing interval to toxicity or later at trough levels. Continuous i.v. infusion, sometimes with itself controlled by the patient additional doses, eliminates this effect, however, requires an expensive pump; This route of administration is used in post-operative pain most often. I.m. application offers a longer analgesia than the iv administration, but it is painful, and the absorption can be very different; it is not recommended. The continuous s.c. infusion long time can be used, especially in cancer pain. Transmucosal (sublingual) formulation of fentanyl are now available. Lozenges are used for sedation in children and for the treatment of breakthrough pain in cancer patients. Intraspinal opioids (. Eg morphine 5-10 ug epidural or 0.5-1 mg intrathecally in acute pain) may cause pain relief such as morphine is extended when administering a hydrophilic drug; they are typically used postoperatively. Implanted infusion systems (pain pumps) allow neuraxial long-term infusion. These systems can also be combined with other drugs (for example, local anesthetics, clonidine, ziconotide.) .Dosierung and titration The initial dose is changed according to the reaction of the patient; it is gradually increased until the analgesia is satisfactory or adverse effects limit the treatment. Sedation and respiratory rate are monitored on parenteral administration of opioids or administration of opioid naive patients. Particularly for opioid-naive patients, opioid therapy should start with a short-acting drug, because many of the longer-acting opioids are stronger. Because of the variable pharmacokinetics of methadone, the drug at a lower dose should be started and the dose should be no more than 1 time / week be increased. Elderly patients are more sensitive to opioids and are predisposed to adverse effects; opioid naive elderly patients typically require lower doses than younger patients. Newborns, especially premature babies, is also very sensitive to opioids because adequate metabolic pathways are not yet mature. For moderate, temporary pain if necessary an opioid can be given. For heavy or prolonged pain regular doses should be given, without waiting for recurring severe pain; Additional doses are given as necessary in the treatment of cancer. The doses for patients with chronic pain that is not caused by cancer are typically decided from case to case. In the patient-controlled pain (. Editor’s note .: PCA) is a bolus dose administered (in a post-operative setting morphine typically 1 mg every 6 min for a infusomats) when the patient pushes a button; a base infusion (eg. as morphine 0.5-1 mg / h) can, but need not be given. The doctor checked the number and interval of the bolus. Patients with prior opioid exposure or chronic pain need higher bolus and infusion doses basis; the infusion dose is adjusted depending on the response. Bei Patienten mit Demenz kann eine patientenkontrollierte Analgesie nicht angewandt werden, Gleiches gilt für kleine Kinder; bei Jugendlichen ist dies jedoch oft machbar. Während einer Langzeitbehandlung kann die effektive Opioiddosis über einen längeren Zeitraum konstant bleiben. Einige Patienten brauchen intermittierende Dosissteigerungen, typischerweise bei körperlichen Veränderungen, die eine Zunahme der Schmerzen nahelegen (z. B. progressive Neoplasien). Die Angst vor Toleranzentwicklung sollte den angemessenen frühen und offensiven Einsatz eines Opioids nicht behindern. Wenn eine zuvor adäquate Dosis nicht mehr ausreicht, muss die Dosis in der Regel um 30–100% erhöht werden, um die Schmerzen zu kontrollieren. Nichtopioidanalgetika (z. B. Paracetamol, NSAR) werden oft begleitend gegeben. Produkte, die beide Arzneimittel enthalten, sind praktisch, jedoch kann das Nichtopioid die Auftitration des Opioids limitieren.Unerwünschte Nebenw

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