Adverse effects Opioid

1 adverse effects

1.1 reinforcement disorders

1.1.1 tolerance
1.1.2 physical dependence
1.1.3 addiction


1.2 nausea , vomiting
1.3 drowsiness
1.4 itching
1.5 constipation

1.5.1 treatment


1.6 respiratory depression
1.7 opioid-induced hyperalgesia
1.8 other adverse effects

1.8.1 hormone imbalance
1.8.2 disruption of work
1.8.3 increased accident-proneness
1.8.4 rare side effects

adverse effects

studies have shown opioids safe when used correctly , in ways understood.

carefully titrating dose of opioids can provide effective pain relief while minimizing adverse effects. morphine , diamorphine have been shown have wider therapeutic range or safety margin other opioids. because effective quantity varies , cannot predicted, dose titration starts @ low amounts, increasing until desired or adverse effect occurs.

opioid analgesics not cause specific organ toxicity, unlike many other drugs, such aspirin , paracetamol. not associated upper gastrointestinal bleeding , kidney toxicity.

in older adults, opioid use associated increased adverse effects such sedation, nausea, vomiting, constipation, urinary retention, , falls . result, older adults taking opioids @ greater risk injury.

research suggests when methadone used long-term can build unpredictably in body , lead potentially deadly slowed breathing. used medically, approaching toxicity goes unrecognized because pain medication effect ends long before drug s elimination half-life. according uscdc, methadone involved in 31% of opioid related deaths in between 1999-2010 , 40% sole drug involved, far higher other opioids. regular physician monitoring reduces likelihood of problems.

according cohort study, rate of opioid related death 0.017% per year amongst patients prescribed opioids non-cancer pain 1997 2005 in washington state. increasing dose , age found correlate increased risk of overdose. while cohort study higher level of evidence case-control, case-control study done in canada correlates had opioid related death rate of 0.024% per year amongst patients prescribed opioids non-cancer pain on 10-year period.

reinforcement disorders

tolerance

tolerance process characterized neuroadaptations result in reduced drug effects. while receptor upregulation may play important role other mechanisms known. tolerance more pronounced effects others; tolerance occurs effects on mood, itching, urinary retention, , respiratory depression, occurs more analgesia , other physical side effects. however, tolerance not develop constipation or miosis (the constriction of pupil of eye less or equal 2 millimeters). idea has been challenged, however, authors arguing tolerance develop miosis.

tolerance opioids attenuated number of substances, including:

calcium channel blockers
intrathecal magnesium , zinc
nmda antagonists, such dextromethorphan, ketamine, , memantine.
cholecystokinin antagonists, such proglumide
newer agents such phosphodiesterase inhibitor ibudilast have been researched application.

tolerance physiologic process body adjusts medication present, requiring higher doses of same medication on time achieve same effect. common occurrence in individuals taking high doses of opioids extended periods, not predict relationship misuse or addiction.

physical dependence

physical dependence physiological adaptation of body presence of substance, in case opioid medication. defined development of withdrawal symptoms when substance discontinued, when dose reduced abruptly or, in case of opioids, when antagonist (e.g., naloxone) or agonist-antagonist (e.g., pentazocine) administered. physical dependence normal , expected aspect of medications , not imply patient addicted.

the withdrawal symptoms opiates may include severe dysphoria, craving opiate dose, irritability, sweating, nausea, rhinorrea, tremor, vomiting , myalgia. reducing intake of opioids on days , weeks can reduce or eliminate withdrawal symptoms. speed , severity of withdrawal depends on half-life of opioid; heroin , morphine withdrawal occur more , more severe methadone withdrawal. acute withdrawal phase followed protracted phase of depression , insomnia can last months. symptoms of opioid withdrawal can treated other medications, such clonidine. physical dependence not predict drug misuse or true addiction, , closely related same mechanism tolerance. while there anecdotal claims of benefit ibogaine, data support use in substance dependence poor.

addiction

drug addiction complex set of behaviors typically associated misuse of drugs, developing on time , higher drug dosages. addiction includes psychological compulsion, extent sufferer persists in actions leading dangerous or unhealthy outcomes. opioid addiction includes insufflation or injection, rather taking opioids orally prescribed medical reasons.

in european nations such austria, bulgaria, , slovakia, slow release oral morphine formulations used in opiate substitution therapy (ost) patients not tolerate side effects of buprenorphine or methadone. in other european countries including uk, legally used ost although on varying scale of acceptance.

tamper-release formulations of time-controlled preparations of medications intended curb abuse , addiction rates while trying still provide legitimate pain relief , ease of use pain patients. questions remain, however, efficacy , safety of these types of preparations. further tamper resistant medications under consideration trials market approval fda.

the amount of evidence available permits making weak conclusion, suggests physician managing opioid use in patients no history of substance dependence or substance abuse can give long-term pain relief little risk of developing addiction, abuse, or other serious side effects.

problems opioids include following:

all of opioids can cause side effects. common adverse reactions in patients taking opioids pain relief include nausea , vomiting, drowsiness, itching, dry mouth, dizziness, , constipation.

nausea , vomiting

tolerance nausea occurs within 7–10 days, during antiemetics (e.g. low dose haloperidol once @ night) effective. due severe side effects such tardive dyskinesia, haloperidol used. related drug, prochlorperazine more used, although has similar risks. stronger antiemetics such ondansetron or tropisetron used when nausea severe or continuous , disturbing, despite greater cost. less expensive alternative dopamine antagonists such domperidone , metoclopramide. domperidone not cross blood–brain barrier , produce adverse central antidopaminergic effects, blocks opioid emetic action in chemoreceptor trigger zone. (the drug not available in u.s.) antihistamines anticholinergic properties (e.g. orphenadrine or diphenhydramine) may effective. first-generation antihistamine hydroxyzine commonly used, added advantages of not causing movement disorders, , possessing analgesic-sparing properties. Δ-tetrahydrocannabinol relieves nausea , vomiting; produces analgesia may allow lower doses of opioids reduced nausea , vomiting.

5-ht3 antagonists (e.g. ondansetron)
dopamine antagonists (e.g. domperidone)
anti-cholinergic antihistamines (e.g. diphenhydramine)
Δ-tetrahydrocannabinol (e.g. dronabinol)

vomiting due gastric stasis (large volume vomiting, brief nausea relieved vomiting, oesophageal reflux, epigastric fullness, satiation), besides direct action on chemoreceptor trigger zone of area postrema, vomiting centre of brain. vomiting can prevented prokinetic agents (e.g. domperidone or metoclopramide). if vomiting has started, these drugs need administered non-oral route (e.g. subcutaneous metoclopramide, rectally domperidone).

prokinetic agents (e.g. domperidone)
anti-cholinergic agents (e.g. orphenadrine)

drowsiness

tolerance drowsiness develops on 5–7 days, if troublesome, switching alternative opioid helps. opioids such fentanyl, morphine , diamorphine (heroin) tend particularly sedating, while others such oxycodone, tilidine , meperidine (pethidine) tend produce comparatively less sedation, individual patients responses can vary markedly , degree of trial , error may needed find suitable drug particular patient. otherwise, treatment cns stimulants effective.

stimulants (e.g. caffeine, modafinil, amphetamine, methylphenidate)

itching

itching tends not severe problem when opioids used pain relief, antihistamines useful counteracting itching when occurs. non-sedating antihistamines such fexofenadine preferred avoid increasing opioid induced drowsiness. however, sedating antihistamines such orphenadrine can produce synergistic pain relieving effect permitting smaller doses of opioids used. consequently, several opioid/antihistamine combination products have been marketed, such meprozine (meperidine/promethazine) , diconal (dipipanone/cyclizine), , these may reduce opioid induced nausea.

antihistamines (e.g. fexofenadine)

constipation

opioid-induced constipation (oic) develops in 90 95% of people taking opioids long-term. since tolerance problem not develop readily, people on long-term opioids need take laxative or enemas.

treatment

treatment of oic successional , dependent on severity. first mode of treatment non-pharmacological, , includes lifestyle modifications increasing dietary fiber, fluid intake (around 1.5 l (51 us fl oz) per day), , physical activity. if non-pharmacological measures ineffective, laxatives, including stool softeners (e.g., docusate), bulk-forming laxatives (e.g., fiber supplements), stimulant laxatives (e.g., bisacodyl, senna), and/or enemas, may used. common laxative regimen oic combination of docusate , bisacodyl. osmotic laxatives, including lactulose, polyethylene glycol, , milk of magnesia (magnesium hydroxide), mineral oil (a lubricant laxative), commonly used oic.

if laxatives insufficiently effective (which case), opioid formulations or regimens include peripherally-selective opioid antagonist, such methylnaltrexone bromide, naloxegol, alvimopan, or naloxone (as in oxycodone/naloxone), may tried. 2008 cochrane review found evidence tentative alvimopan, naloxone, or methylnaltrexone bromide.

respiratory depression

respiratory depression serious adverse reaction associated opioid use, seen use of single, intravenous dose in opioid-naïve patient. in patients taking opioids regularly pain relief, tolerance respiratory depression occurs rapidly, not clinical problem. several drugs have been developed can partially block respiratory depression, although respiratory stimulant approved purpose doxapram, has limited efficacy in application. newer drugs such bimu-8 , cx-546 may more effective.

respiratory stimulants: carotid chemoreceptor agonists (e.g. doxapram), 5-ht4 agonists (e.g. bimu8), δ-opioid agonists (e.g. bw373u86) , ampakines (e.g. cx717) can reduce respiratory depression caused opioids without affecting analgesia, of these drugs moderately effective or have side effects preclude use in humans. 5-ht1a agonists such 8-oh-dpat , repinotan counteract opioid-induced respiratory depression, @ same time reduce analgesia, limits usefulness application.
opioid antagonists (e.g. naloxone, nalmefene, diprenorphine)

opioid-induced hyperalgesia

opioid-induced hyperalgesia – individuals using opioids relieve pain paradoxically experience more pain result of medication – has been observed in people. phenomenon, although uncommon, seen in people receiving palliative care, when dose increased rapidly. if encountered, rotation between several different opioid pain medications may decrease development of increased pain. opioid induced hyperalgesia more commonly occurs chronic use or brief high doses research suggests may occur low doses.

side effects such hyperalgesia , allodynia, accompanied worsening of neuropathic pain, may consequences of long-term treatment opioid analgesics, when increasing tolerance has resulted in loss of efficacy , consequent progressive dose escalation on time. appears largely result of actions of opioid drugs @ targets other 3 classic opioid receptors, including nociceptin receptor, sigma receptor , toll-like receptor 4, , can counteracted in animal models antagonists @ these targets such j-113,397, bd-1047 or (+)-naloxone respectively. no drugs approved counteracting opioid-induced hyperalgesia in humans , in severe cases solution may discontinue use of opioid analgesics , replace them non-opioid analgesic drugs. however, since individual sensitivity development of side effect highly dose dependent , may vary depending opioid analgesic used, many patients can avoid side effect through dose reduction of opioid drug (usually accompanied addition of supplemental non-opioid analgesic), rotating between different opioid drugs, or switching milder opioid mixed mode of action counteracts neuropathic pain, particularly tramadol or tapentadol.

nmda antagonists such ketamine
snris such milnacipran
anticonvulsants such gabapentin or pregabalin

other adverse effects
hormone imbalance

clinical studies have consistently associated medical , recreational opioid use hypogonadism , hormone imbalance in different sexes. effect dose-dependent. studies suggest majority (perhaps as 90%) of chronic opioid users suffer hormone imbalances. opioids can interfere menstruation in women limiting production of luteinizing hormone (lh). opioid-induced endocrinopathy causes strong association of opioid use osteoporosis , bone fracture. may increase pain , thereby interfere intended clinical effect of opioid treatment. opioid-induced endocrinopathy caused agonism of opioid receptors in hypothalamus , pituitary gland. 1 study found depressed testosterone levels of heroin addicts returned normal within 1 month of abstinence, suggesting effect not permanent. of 2013, effect of low-dose or acute opiate use on endocrine system unclear.

disruption of work

use of opioids may risk factor failing return work.

persons performing safety-sensitive task should not use opioids. health care providers should not recommend workers drive or use heavy equipment including cranes or forklifts treat chronic or acute pain opioids. workplaces manage workers perform safety-sensitive operations should assign workers less sensitive duties long workers treated physician opioids.

people take opioids long term have increased likelihood of being unemployed. taking opioids may further disrupt patient s life , adverse effects of opioids can become significant barrier patients having active life, gaining employment, , sustaining career.

in addition, lack of employment may predictor of aberrant use of prescription opioids.

increased accident-proneness

opioid use may increase accident-proneness. opioids may increase risk of traffic accidents , accidental falls.

rare side effects

infrequent adverse reactions in patients taking opioids pain relief include: dose-related respiratory depression (especially more potent opioids), confusion, hallucinations, delirium, urticaria, hypothermia, bradycardia/tachycardia, orthostatic hypotension, dizziness, headache, urinary retention, ureteric or biliary spasm, muscle rigidity, myoclonus (with high doses), , flushing (due histamine release, except fentanyl , remifentanil).

both therapeutic , chronic use of opioids can compromise function of immune system. opioids decrease proliferation of macrophage progenitor cells , lymphocytes, , affect cell differentiation (roy & loh, 1996). opioids may inhibit leukocyte migration. relevance of in context of pain relief not known.