Antipruritic

Antipruritics, abirritants,[1] or anti-itch drugs, are medications that inhibit the itching (Latin: pruritus) often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like those from mosquitoes, fleas, and mites, and contact dermatitis and urticaria caused by plants such as poison ivy (urushiol-induced contact dermatitis) or stinging nettle. It can also be caused by chronic kidney disease and related conditions.[2]

Abirritants consist of a large group of drugs belonging to different classes with varying mechanisms to treat itch. They may work either directly or indirectly to relieve itch, and evidence on their effectiveness varies from one class to another.[3] Some alternative medicines are also used to treat itch.[4][5] Side effects of abirritants also vary depending on the class of the drug. Even before the emergence of modern evidence-based medicine, abirritants have already been used in many civilizations, but practices and choice of drugs may differ by culture.[6]

Types

A number of drug classes are available as abirritants for itching relief, but there is no one single specific abirritant to treat all forms of itch.[7] Treatments may vary depending on the cause. Commonly prescribed abirritants can be broadly divided into topical and systemic drugs, and may include a combination of one or more drugs, described as below.

Topical
Corticosteroid creams can be applied directly on the skin to treat itch.

Topical formulations are preferred for treating localized itch caused by skin damage, inflammation or dryness.[8] Topical antipruritics in the form of creams and sprays are often available over the counter. The active ingredients usually belong to these classes:

Medication Mechanism of Action Examples
Corticosteroids Suppresses itch originating from immune response and inflammation[10]
Antihistamines Antihistamines have anti-inflammatory properties that can relieve itching by suppressing the underlying inflammation[11]
Anesthetics Prevents the propagation of nerve signals that would otherwise cause an itching sensation[12]
Phosphodiesterase-4 inhibitors Suppresses inflammation to relieve itch[12]
Capsaicin Desensitizes nerves that cause itch[8]

Systemic drugs
Antihistamines are commonly used to treat itching associated with allergies.

Generalized itch, or itching across the whole body, can be a symptom of a dermatological disorder or an underlying systemic problem.[13] Some systemic diseases can that cause generalized itch include diabetes, hypothyroidism, kidney diseases and liver diseases.[14][13] It is usually treated with systemic agents instead of topical agents.[15] Corticosteroids and antihistamines mentioned above can also be used to treat generalized itch.[16] Common systemic abirritants are listed below:

Gabapentin is an anticonvulsant which can also be used to treat itch.
Medication Mechanism of Action Examples
Corticosteroids Suppresses itch originating from immune response and inflammation[10]
Antihistamines Antihistamines have anti-inflammatory properties that can relieve itching by suppressing the underlying inflammation[11][17]
μ-opioid receptor antagonists Blocks the μ-opioid receptor, the stimulation of which causes itch in clinical settings such as itch due to liver diseases[18]
Antidepressants Reduces itch by mediating serotonin and histamine levels in the body.[19] Two main classes of antidepressants are utilized to relieve itch:
Immunosuppressants Suppresses the immune system to reduce inflammation and hence reduce itch[20]
Anticonvulsants Mechanism of action is unclear, but is thought to prevent itching by desensitizing calcium channels in nerves[21]
Thalidomide Thalidomide suppresses itching through a number of ways:
  • Acts as a central depressant;
  • Reduces inflammation;
  • Modulates immune response; and
  • Modulates nerve signal transmission[22]
Butorphanol Butorphanol activates the κ-opioid receptor and blocks the μ-opioid receptor, inhibiting generalized pruritus due to an imbalance between the μ- and κ-opioid systems

Oral antipruritics are usually prescription drugs. Those more recently described include:

Substances proposed to act antipruritically, but not used medically
  • Burow's solution, an astringent aqueous solution of aluminium triacetate, is shown to soothe and to relieve itching.[24]
  • Olive oil
  • Jewelweed has been shown to be devoid of any anti-itch activity in several controlled studies.[25][26][27][28]
  • Calamine lotion, containing zinc oxide and iron(III) oxide, is a traditional remedy for mild itching, such as that typically associated with chicken pox – although the U.S. Food and Drug Administration has asserted that it has little if any scientific evidence.[29][30] Nevertheless, they subsequently recommended applying topical OTC skin protectants, such as calamine, to relieve the itch caused by poisonous plants such as poison ivy, poison oak, and poison sumac.[31]
  • Paste of sodium bicarbonate (baking soda) and water, applied topically[32]
  • Ammonium hydroxide (household ammonia), applied topically[32]
  • Papain-based topical creams.

Alternative treatments

A number of herbs have been used to treat itching such as cannabis, pigweed (portulaca oleracaea), Ashoka (sarco asoca), and fig (fificus carica).[5]

Other unconventional forms of treatment with potential efficacy for treating systemic itch include topical cannabinoids[33] and H4 antihistamines.[34]

Effectiveness

Despite the availability of many forms of treatment, there is only a limited number of case series or small-scale studies examining the efficacy of abirritants.[19] There is a lack of evidence on treatment for chronic pruritus of unknown origin.[35][36] There is also little to no evidence on the efficacy and safety of using abirritants during pregnancy.[37]

Treating itch associated with disease

Some abirritants work by indirectly treating itch through treating the causative medical conditions, which means that the itching associated with the condition will often subside when it is properly treated. This includes antihistamines and corticosteroids, which are effective in treating inflammatory disorders of the skin, in particular atopic dermatitis.[38] Successful treatment of atopic dermatitis with either corticosteroids or antihistamines would resolve the associated itching.[39]

Treating itch directly

Some abirritants treat pruritus directly without necessarily treating the causative medical condition. Abirritants that directly treat itching and are established to be effective are reported here in the table below:

Medication Effectiveness
Gabapentin Gabapentin was found to be effective in decreasing the severity of uremic pruritus compared to placebo.[40]
Butorphanol Continuous intravenous butorphanol reduced the incidence of morphine-induced pruritus significantly.[41]
Thalidomide Thalidomide is effective in treating chronic refractory pruritus among patients who had failed conventional therapy (corticosteroids or antihistamines), with a 50% or greater reduction in symptoms and a shorter time to improvement.[22]
μ-opioid receptor antagonists μ-opioid receptor antagonists such as naltrexone and nalmefene demonstrated significant improvement in treating patients with cholestatic pruritus, or itch arising from urticaria and atopic dermatitis.[18]

Traditional Chinese Medicine
Dictamnus is one of the many herbs used to treat itch in Traditional Chinese Medicine.

Traditional Chinese medicine is extensively used in Asia for relief of itch. It is believed that itching is caused by irritations from wind, dampness or blood stasis, and can be relieved by the use of herbs such as chrysanthemum, gardenia fruit or mung bean.[42] Sometimes these herbal remedies are used in combination with acupuncture and moxibustion,[4] but their efficacy is still unclear.[43] Sericin cream and oral omega-3 fatty acid supplements may show benefit in reducing itch.[36]

Adverse effects

Each class of abirritants has its own set of potential adverse effects.

Systemic Corticosteroids
Systemic corticosteroid treatment can cause redistribution of fat tissue, leading to moon face.[44]

Systemic corticosteroid use has been associated with a wide range of potential adverse effects. In a review article, the following common complications were noted for prolonged use: redistribution of fat tissues (moon face), high blood sugar, infections, delayed wound healing, and HPA axis suppression, where the body's natural production of hormones like corticotropin-releasing hormone and adrenocorticotropic hormone is suppressed as a response to the increased level of corticosteroids in the blood.[44]

There is a lack of data on adverse effects associated with corticosteroid use of a shorter period and lower dose.[44]

Topical Corticosteroids

Both local and systemic side effects can result from topical corticosteroid use, especially in prolonged treatment.[39]

Local side effects can occur regularly from prolonged use,[45] which include skin atrophy (thinning), stretch marks, infections, lighter skin color, and sudden decrease in efficacy of the drug.[39][45]

Systemic side effects are far less prevalent than local ones.[45] Prolonged high potency corticosteroids use on thin skin, especially in children, increases the risk of systemic side effects since thin skin allows for greater absorption.[46] One commonly cited systemic side effect from topical use is HPA axis suppression.[46] A meta-analysis of topical corticosteroid use in children concluded that low-potency corticosteroid at recommended dosages and duration do not cause clinically significant HPA suppression.[47]

Antihistamines

Antihistamines target the molecule histamine by blocking the histamine H1 receptor.[48] First-generation antihistamines like diphenhydramine and chlorpheniramine are able to move from the blood into the brain across the blood–brain barrier, where they block the H1 receptor, reducing the neurotransmitter effect of histamine, leading to central nervous system side effects such as drowsiness and confusion.[48] Second generation antihistamines, such as fexofenadine and cetirizine are less able to move from blood circulation into the brain and are therefore associated with fewer side effects in usual doses.[48]

μ-opioid receptor antagonists

μ-opioid receptor antagonists are usually well-tolerated and have no abuse potential since they do not cause physical dependence.[18] Side effects are dose-dependent and generally limited to the first two weeks of treatment.[49][50][51] Opioid withdrawal symptoms are rare and may include severe lightheadedness, depersonalization and anxiety.[18]

Antidepressants

Serotonin reuptake inhibitors, including both serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), are generally well tolerated.[52] Common side effects include:

  • Sexual dysfunction, which is the most common side effect of all serotonin reuptake inhibitors, manifesting as delayed ejaculation, inability to achieve orgasm and decreased libido.[52]
  • Gastrointestinal effects such as nausea and vomiting, which depend on the dose and usually resolve within the first two weeks of treatment.[52]
  • Central nervous system disturbances such as anxiety, insomnia and sedation.[52]
  • Suicide risk: a combined analysis of placebo-controlled trials of various antidepressants including SSRIs in children and adolescents showed a doubled risk of suicide in those taking antidepressants.[53] In response, the United States Food and Drug Administration issued a warning in 2004 regarding the elevated risk of suicidal thoughts and behavior in children and adolescents.[53]

Immunosuppressants

Immunosuppressants may cause immunodeficiency, resulting in an increased susceptibility to infection. Other side effects include bone marrow suppression, increased risk of cardiovascular disease and increased risk of cancer.[54]

Capsaicin

Being the main chemical that causes heat in chili pepper, the main side effect of capsaicin is a burning sensation that usually persists for several days. A topical anaesthetic can be used to reduce the sensation. In addition, the topical anaesthetic can also provide anti-itch effect on its own.[55]

History
Squill was used to treat itch and is commonly listed in ancient pharmacopeia.

Abirritants have an extensive history in treating itch. The history of abirritants dates back to the Byzantine period, when Alexander of Tralleis, a famous physician, recommended crushed rue and alum mixed in honey for topical application to the scalp for itching caused by scabby conditions of the head.[6]

During the 7th century, Paul of Aegina, a famous Greek physician, described a list of drugs for treatment of itch including plants such as the squill, metallic components, and goat droppings which were applied externally. These drugs are common in ancient pharmacopeia.[56]

The Lorscher Azneibuch written in the monastery of Lorsch in the 7th century described many preparations of abirritants for both systemic and topical use, such as an ointment prepared from stinging nettle seeds.[57]

Mercury-coated girdles were used in the 17th century as an expensive treatment to alleviate symptoms of itch caused by scabies, but mercury toxins in the blood often caused other troubling symptoms in patients.[58]

In the 20th century, many new abirritants for external use emerged, including salicylic acids, naphthol, tar, carbolic acid, thymol, and menthol, which were mostly available in the form of ointments. Alcohol and opium were also commonly prescribed.[6]

See also

References
  1. "Antipruritic definition and meaning | Collins English Dictionary". www.collinsdictionary.com. Retrieved 2021-03-25.
  2. "Pruritus and Systemic Disease: Background, Pathophysiology, Etiology". 2020-12-11. {{cite journal}}: Cite journal requires |journal= (help)
  3. Simonsen E, Komenda P, Lerner B, Askin N, Bohm C, Shaw J, et al. (November 2017). "Treatment of Uremic Pruritus: A Systematic Review". American Journal of Kidney Diseases. 70 (5): 638–655. doi:10.1053/j.ajkd.2017.05.018. PMID 28720208.
  4. Shi ZF, Song TB, Xie J, Yan YQ, Du YP (2017). "The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials". Evidence-Based Complementary and Alternative Medicine. 2017: 6026434. doi:10.1155/2017/6026434. PMC 5497608. PMID 28713436.
  5. Tabassum N, Hamdani M (January 2014). "Plants used to treat skin diseases". Pharmacognosy Reviews. 8 (15): 52–60. doi:10.4103/0973-7847.125531. PMC 3931201. PMID 24600196.
  6. Weisshaar E, Grüll V, König A, Schweinfurth D, Diepgen TL, Eckart WU (December 2009). "The symptom of itch in medical history: highlights through the centuries". International Journal of Dermatology. 48 (12): 1385–94. doi:10.1111/j.1365-4632.2009.04117.x. PMID 20415680. S2CID 28909284.
  7. Yosipovitch G (2009). "Pruritus". Dermatological Signs of Internal Disease. Elsevier. pp. 75–79. doi:10.1016/b978-1-4160-6111-3.00015-x. ISBN 978-1-4160-6111-3.
  8. Yosipovitch G (December 2003). "Assessment of itch: more to be learned and improvements to be made". The Journal of Investigative Dermatology. 121 (6): xiv–xv. doi:10.1111/j.1523-1747.2003.12650.x. PMID 14675224.
  9. Hercogová J (2005). "Topical anti-itch therapy". Dermatologic Therapy. 18 (4): 341–3. doi:10.1111/j.1529-8019.2005.00033.x. PMID 16297007.
  10. Norris DA (July 2005). "Mechanisms of action of topical therapies and the rationale for combination therapy". Journal of the American Academy of Dermatology. 53 (1 Suppl 1): S17-25. doi:10.1016/j.jaad.2005.04.027. PMID 15968260.
  11. Buddenkotte J, Maurer M, Steinhoff M (2010). Thurmond RL (ed.). "Histamine and antihistamines in atopic dermatitis". Advances in Experimental Medicine and Biology. Boston, MA: Springer US. 709: 73–80. doi:10.1007/978-1-4419-8056-4_8. ISBN 978-1-4419-8055-7. PMID 21618889.
  12. Rinaldi G (April 2019). "The Itch-Scratch Cycle: A Review of the Mechanisms". Dermatology Practical & Conceptual. 9 (2): 90–97. doi:10.5826/dpc.0902a03. PMC 6502296. PMID 31106010.
  13. Reamy BV, Bunt CW, Fletcher S (2011-07-15). "A Diagnostic Approach to Pruritus". American Family Physician. 84 (2): 195–202. ISSN 0002-838X. PMID 21766769.
  14. Kantor GR, Lookingbill DP (September 1983). "Generalized pruritus and systemic disease". Journal of the American Academy of Dermatology. 9 (3): 375–82. doi:10.1016/S0190-9622(83)70144-1. PMID 6630598.
  15. Freedberg IM, Sanchez MR (2001). Current dermatologic diagnosis & treatment. Current Medicine. ISBN 1-57340-172-2. OCLC 45129566.
  16. Yosipovitch G, Bernhard JD (April 2013). "Clinical practice. Chronic pruritus". The New England Journal of Medicine. 368 (17): 1625–34. doi:10.1056/NEJMcp1208814. PMID 23614588. S2CID 1912215.
  17. Stöppler, Melissa Conrad. "Itch (Itching or Pruritus)". MedicineNet. Retrieved 3 June 2019.
  18. Phan NQ, Bernhard JD, Luger TA, Ständer S (October 2010). "Antipruritic treatment with systemic μ-opioid receptor antagonists: a review". Journal of the American Academy of Dermatology. 63 (4): 680–8. doi:10.1016/j.jaad.2009.08.052. PMID 20462660.
  19. Patel T, Yosipovitch G (July 2010). "Therapy of pruritus". Expert Opinion on Pharmacotherapy. 11 (10): 1673–82. doi:10.1517/14656566.2010.484420. PMC 2885583. PMID 20426711.
  20. Schmitt J, Schmitt N, Meurer M (May 2007). "Cyclosporin in the treatment of patients with atopic eczema - a systematic review and meta-analysis". Journal of the European Academy of Dermatology and Venereology. 21 (5): 606–19. doi:10.1111/j.1468-3083.2006.02023.x. PMID 17447974. S2CID 34610971.
  21. Matsuda KM, Sharma D, Schonfeld AR, Kwatra SG (September 2016). "Gabapentin and pregabalin for the treatment of chronic pruritus". Journal of the American Academy of Dermatology. 75 (3): 619–625.e6. doi:10.1016/j.jaad.2016.02.1237. PMID 27206757.
  22. Sharma D, Kwatra SG (February 2016). "Thalidomide for the treatment of chronic refractory pruritus". Journal of the American Academy of Dermatology. 74 (2): 363–9. doi:10.1016/j.jaad.2015.09.039. PMID 26577510.
  23. Inui, Shigeki (2015). "Nalfurafine hydrochloride to treat pruritus: a review". Clinical, Cosmetic and Investigational Dermatology. 8: 249–55. doi:10.2147/CCID.S55942. ISSN 1178-7015. PMC 4433050. PMID 26005355.
  24. "CFR - Code of Federal Regulations Title 21". www.accessdata.fda.gov. Retrieved 2022-07-28.
  25. Long, D.; Ballentine, N. H.; Marks, J. G. (September 1997). "Treatment of poison ivy/oak allergic contact dermatitis with an extract of jewelweed". Am. J. Contact. Dermat. 8 (3): 150–3. doi:10.1097/01206501-199709000-00005. PMID 9249283.
  26. Gibson, M. R.; Maher, F. T. (May 1950). "Activity of jewelweed and its enzymes in the treatment of Rhus dermatitis". J. Am. Pharm. Assoc. 39 (5): 294–6. doi:10.1002/jps.3030390516. PMID 15421925.
  27. Guin, J. D.; Reynolds, R. (June 1980). "Jewelweed treatment of poison ivy dermatitis". Contact Dermatitis. 6 (4): 287–8. doi:10.1111/j.1600-0536.1980.tb04935.x. PMID 6447037.
  28. Zink, B. J.; Otten, E.J.; Rosenthal, M.; Singal, B (1991). "The Effect Of Jewel Weed In Preventing Poison Ivy Dermatitis". Journal of Wilderness Medicine. 2 (3): 178–182. doi:10.1580/0953-9859-2.3.178. Retrieved 2008-01-16.
  29. "American Topics. An Outdated Notion, That Calamine Lotion". Archived from the original on 19 June 2007. Retrieved 2007-07-19.
  30. Appel, L.M. Ohmart; Sterner, R.F. (1956). "Zinc oxide: A new, pink, refractive microform crystal". AMA Arch Dermatol. 73: 316–324. PMID 13301048.
  31. September 2, 2008 FDA Document Archived July 16, 2010, at the Wayback Machine
  32. Paul Tawrell, Wilderness Camping and Hiking(Falcon Distribution, 2008), 212.
  33. Baswan SM, Klosner AE, Glynn K, Rajgopal A, Malik K, Yim S, Stern N (December 2020). "Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders". Clinical, Cosmetic and Investigational Dermatology. 13: 927–942. doi:10.2147/CCID.S286411. PMC 7736837. PMID 33335413.
  34. "New Histamine H2-Receptor Antagonists Are on the Way". InPharma. 251 (1): 3–4. August 1980. doi:10.1007/bf03317207. ISSN 0156-2703. S2CID 198228678.
  35. Andrade A, Kuah CY, Martin-Lopez JE, Chua S, Shpadaruk V, Sanclemente G, Franco JV, et al. (Cochrane Skin Group) (January 2020). "Interventions for chronic pruritus of unknown origin". The Cochrane Database of Systematic Reviews. 1: CD013128. doi:10.1002/14651858.CD013128.pub2. PMC 6984650. PMID 31981369.
  36. Millington GW, Collins A, Lovell CR, Leslie TA, Yong AS, Morgan JD, et al. (January 2018). "British Association of Dermatologists' guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018". The British Journal of Dermatology. 178 (1): 34–60. doi:10.1111/bjd.16117. PMID 29357600.
  37. Rungsiprakarn P, Laopaiboon M, Sangkomkamhang US, Lumbiganon P, et al. (Cochrane Pregnancy and Childbirth Group) (February 2016). "Pharmacological interventions for generalised itching (not caused by systemic disease or skin lesions) in pregnancy". The Cochrane Database of Systematic Reviews. 2016 (2): CD011351. doi:10.1002/14651858.CD011351.pub2. PMC 8665832. PMID 26891962.
  38. Wahlgren CF (November 1999). "Itch and atopic dermatitis: an overview". The Journal of Dermatology. 26 (11): 770–9. doi:10.1111/j.1346-8138.1999.tb02090.x. PMID 10635621. S2CID 20259978.
  39. Coondoo A, Phiske M, Verma S, Lahiri K (October 2014). "Side-effects of topical steroids: A long overdue revisit". Indian Dermatology Online Journal. 5 (4): 416–25. doi:10.4103/2229-5178.142483. PMC 4228634. PMID 25396122.
  40. Eusebio-Alpapara KM, Castillo RL, Dofitas BL (April 2020). "Gabapentin for uremic pruritus: a systematic review of randomized controlled trials". International Journal of Dermatology. 59 (4): 412–422. doi:10.1111/ijd.14708. PMID 31777066. S2CID 208335862.
  41. Du BX, Song ZM, Wang K, Zhang H, Xu FY, Zou Z, Shi XY (September 2013). "Butorphanol prevents morphine-induced pruritus without increasing pain and other side effects: a systematic review of randomized controlled trials". Canadian Journal of Anaesthesia. 60 (9): 907–17. doi:10.1007/s12630-013-9989-4. PMID 23813290.
  42. "Chinese Herbal Selections for Itchy Conditions". www.shen-nong.com. Retrieved 2021-03-25.
  43. Zhang W, Leonard T, Bath-Hextall F, Chambers CA, Lee C, Humphreys R, Williams HC, et al. (The Cochrane Collaboration) (April 2005). Zhang W (ed.). "Chinese herbal medicine for atopic eczema". The Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd (2): CD002291. doi:10.1002/14651858.cd002291.pub3. PMID 15846635.
  44. Poetker DM, Reh DD (August 2010). "A comprehensive review of the adverse effects of systemic corticosteroids". Otolaryngologic Clinics of North America. 43 (4): 753–68. doi:10.1016/j.otc.2010.04.003. PMID 20599080.
  45. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ (January 2006). "Adverse effects of topical glucocorticosteroids". Journal of the American Academy of Dermatology. 54 (1): 1–15, quiz 16–8. doi:10.1016/j.jaad.2005.01.010. PMID 16384751.
  46. Dhar S, Seth J, Parikh D (September 2014). "Systemic side-effects of topical corticosteroids". Indian Journal of Dermatology. 59 (5): 460–4. doi:10.4103/0019-5154.139874. PMC 4171913. PMID 25284850.
  47. Wood Heickman LK, Davallow Ghajar L, Conaway M, Rogol AD (2018). "Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis". Hormone Research in Paediatrics. 89 (6): 389–396. doi:10.1159/000489125. PMID 29898449.
  48. Simons FE (November 2004). "Advances in H1-antihistamines". The New England Journal of Medicine. 351 (21): 2203–17. doi:10.1056/NEJMra033121. PMID 15548781.
  49. Dixon R, Gentile J, Hsu HB, Hsiao J, Howes J, Garg D, Weidler D (March 1987). "Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist". Journal of Clinical Pharmacology. 27 (3): 233–9. doi:10.1002/j.1552-4604.1987.tb02191.x. PMID 3680580. S2CID 25620439.
  50. Metze D, Reimann S, Beissert S, Luger T (October 1999). "Efficacy and safety of naltrexone, an oral opiate receptor antagonist, in the treatment of pruritus in internal and dermatological diseases". Journal of the American Academy of Dermatology. 41 (4): 533–9. doi:10.1016/S0190-9622(99)80048-6. PMID 10495371.
  51. Bergasa NV, Alling DW, Talbot TL, Swain MG, Yurdaydin C, Turner ML, et al. (August 1995). "Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial". Annals of Internal Medicine. 123 (3): 161–7. doi:10.7326/0003-4819-123-3-199508010-00001. PMID 7598296. S2CID 36396897.
  52. Khawam EA, Laurencic G, Malone DA (April 2006). "Side effects of antidepressants: an overview". Cleveland Clinic Journal of Medicine. 73 (4): 351–3, 356–61. doi:10.3949/ccjm.73.4.351. PMID 16610395.
  53. Center for Drug Evaluation and Research (2018-11-03). "Suicidality in Children and Adolescents Being Treated With Antidepressant Medications". FDA.
  54. Hsu DC, Katelaris CH (2009-06-01). "Long-term management of patients taking immunosuppressive drugs". Australian Prescriber. 32 (3): 68–71. doi:10.18773/austprescr.2009.035. ISSN 0312-8008.
  55. Leslie TA, Greaves MW, Yosipovitch G (2015). "Current topical and systemic therapies for itch". In Cowan A, Yosipovitch G (eds.). Pharmacology of Itch. Handbook of Experimental Pharmacology. Vol. 226. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 337–56. doi:10.1007/978-3-662-44605-8_18. ISBN 978-3-662-44604-1. PMID 25861788.
  56. Er U, Naderi S (April 2013). "Paulus aegineta: review of spine-related chapters in "Epitomoe medicoe libri septem"". Spine. 38 (8): 692–5. doi:10.1097/brs.0b013e3182760fa0. PMID 23026871. S2CID 205518726.
  57. Brevart FB (June 1994). "Das "Lorscher Arzneibuch": Ein medizinisches Kompendium des 8. Jahrhunderts (Codex Bambergensis medicinalis 1): Text, Ubersetzung und Fachglossar. Ulrich Stoll". Isis. 85 (2): 314–315. doi:10.1086/356835. ISSN 0021-1753.
  58. Puza CJ, Suresh V (May 2018). "Scabies and Pruritus-A Historical Review". JAMA Dermatology. 154 (5): 536. doi:10.1001/jamadermatol.2018.0147. PMID 29801071.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.