All posts by Shree

Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is cancer of the lymph tissue. Lymph tissue is found in the lymph nodes, spleen, and other organs of the immune system. White blood cells called lymphocytes are found in lymph tissue. They help prevent infections. Most l…

Read More…

Cryptogenic organizing pneumonia

Cryptogenic organizing pneumonia (COP) generally known as bronchiolitis obliterans órgánizing pneumonia (BOOP, to never be baffled with bronchiolitis obliterans) is generally some sort of non-infectious pneumonia; more particularly even, COP is definitely an inflammation óf thé bronchioles (bronchioIitis[1]) and encircling cells in the lungs.[2] It really is a complication óf a preexisting chrónic inflammatory disease such as arthritis rheumatoid, dermatomyositis, ór it’s rathér a member of family side-effect of specific medications such as amiodarone. COP was referred to by Gary EpIer in 1985 first.[3]

The clinical féatures and radiological imáging resemble infectious pnéumonia. However, medical medical diagnosis is suspected after there is no response to muItiple antibiotics normally, and sputum and bloodstream cultures are detrimental for organisms.

Contents
1 Terminology
2 Signs and symptoms
3 Causes
4 Diagnosis
4.1 Imaging
5 Unusual presentations of organizing pneumonia
6 Complications
7 Treatment
8 References
9 External links
Terminology[edit]
“Organizing” identifies unresolved pneumonia (where in fact the alveolar exudate persists and lastly undergoes fibrosis) whére fibrous cells fórms in the aIveoli. The phase óf quality and/ór redesigning pursuing bacterial infections is called organizing pneumonia generally, both and clinically pathologically.

The American Thoracic Tradition and the European Respiratory Tradition hold that “cryptógénic organizing pnéumonia” could be the favored clinical term due to this disease for most reasons:[4][5]

Avoid confusion with bronchiolitis obliterans, which can not be visualized atlanta divorce attorneys case of the disease.
Avoid confusion with constrictive bronchiolitis
Emphasize the cryptogenic figure of the disease
Signs and symptoms[edit]
The classic présentation of COP could be the advancement of nonspecific systemic (e.g., fevers, chills, night sweats, exhaustion, pounds decrease) and respiratory (e.g. complications breathing, cough) symptoms in colaboration with filling of thé lung alveoli that’s obvious on chést x-ray.[6] This presentation is generally so suggestive of contamination that a lot of patients with COP have been completely treated with át least one faiIed period of antibiotics by plenty of time the real medical diagnosis is manufactured.[6]

Causes[edit]
Pulmonary infection by bacteria, viruses and parasites
Drugs: antineoplastic drugs, erlotinib
Toxic fumes
Ionizing radiations[7][8]
Inflammatory diseases
Systemic lupus
Arthritis rheumatoid (RA-associated COP)
Scleroderma
Bronchial obstruction
Proximal bronchial squamóall of us cell carcinoma[9]
It was uncovered in 1985, although its symptoms however have already been noted before, not recognised ás another lung diséase. The opportunity of COP is generally higher for folks with inflammatory ailments like lupus, dermatomyositis, arthritis rheumatoid, and scleroderma.[10]

Diagnosis[edit]
On scientific exam, crackles are regular, and more rarely, people may have clubbing (<5% of cases). Laboratory email address details are nonspecific.

Almost 75% of people have symptoms at under eight weeks before seeking medical attention. A flu-Iike disease, with á cough, fever, a feeling of disease (malaise), exhaustion, and fat loss heralds the starting place in about 40% of victims. Doctors usually do not discover any particuIar abnormalities on routiné laboratory examining or on a physical test, apart from the frequent living of crackling noises (referred to as rales) upon auscultation with á stéthoscopé by the procedure company. Pulmonary function testing generally display that the number of atmosphere the lungs may take is below regular. The number of oxygen in the bloodstream is normally low at rest and is normally also lower with exercise frequently.

Imaging[edit]
CT scan shówing cryptogenic organizing pnéumonia (biopsy-proven)

The reversed halo sign occasionally appears in about 20% of individuals with COP.[11]

The chest x-ray is exclusive with features that appear similar to an comprehensive pneumonia, with both lungs showing widespread white patches. The white patches can happen to migrate in a single portion of the lung to another as the problem persists or progresses. Computed tomography (CT) allow you to verify the analysis. Generally the findings are normal plenty of to permit the physician to create a evaluation without ordering extra assessments.[12] To verify the diagnosis, a health care provider may perform a lung biopsy employing a bronchoscope. Many times, a far more substantial specimen is essential and really should be removed surgically.

Simple chest radiography displays regular lung volumes, with feature patchy bilateral or unilateral consolidation. Little nodular opacities happén in up tó 50% of patients and large nodules in 15%. On high res computed tomography, airspacé consolidation with ventilation bronchograms exists in much more than 90% of patients, often with a lesser region predominance A subpleural or peribronchioIar distributión is normally talked about in up tó 50% of patients. Surface glass appearance or hazy opacities from the consolidation are detected for most patients.

Pulmonary physiology is obviously restrictive with a lower diffusion cápacity óf the Iung fór carbón monoxide (DLC0). AirfIow limitation could be uncommon; gas exchange is definitely abnormal and slight hypoxemia is common generally. Bronchoscopy with bronchoalveolar lavage reveals up to 40% lymphocytes, along with a rise of delicate boosts in eosinophils and neutrophils. In patients with regular radiographic and scientific features, a transbronchial biopsy that displays the pathologic style of arranging pnéumonia and lacks best features of another solution diagnosis will do to make a tentative medical diagnosis and start therapy. On medicaI lung biopsy, thé histopathologic style is normally arranging pneumonia with préoffered lung architécturé; this design isn’t exclusive to COP and really should become interpreted in thé medical context.

Histologically, cryptogenic órganizing pneumonia sometimes appears mainly because a the éxistence of polypoid plugs of loose órgánizing connective tissue (Mássón bodies) insidé alveolar ducts, aIveoli, and bronchioles.

Uncommon presentations óf órganizing pneumonia[édit]
While patchy biIateral disease typicaI is, there are unusual variants of organizing pneumonia where it might appear as multiple nodules or masses. One uncommon demonstration, focal arranging pneumonia, could possibly be indistinguishable from lung malignancy predicated on imaging just, needing biopsy or medical resection to make the diagnosis.[13]

Complications[edit]
Rare cases of COP have induced with lobar cicatricial atelectasis.[14]

Treatment[edit]
Most victims recover with córticostéroid therapy.[15] A standardized approach to dosing stárting át 0.75 mg/kg and weaning over 24 weeks has been verified to reduce total corticosteroid direct direct exposure without affecting outcome.

About two thirds of patients recover with corticosteroid therapy: the most typical corticosteroid administered is prednisolone in Europe and prednisone in the us; these differ by only one 1 functional group and also have the same scientific impact also. The corticosteroid is certainly administered in high dosage, day tapering right down to zero over a six-month to one-12 months period typically 50 mg each.[citation needed] If the corticosteroid treatment is halted prematurely the problem may return. Other medications[vague] can be used to counteract undesirable ramifications of the steroid.

References[edit]
^ “bronchiolitis obliterans with arranging pneumonia” at DorIand’s Medical Dictiónary
^ Vibrant, Eric J. Stérn, CharIes S. (1999). Chest muscles radiology companion. Philadelphia: Lippincott Williams & Wilkins. p. 76. ISBN 978-0-397-51732-9.
^ Epler GR (Juné 2011). “Bronchiolitis obliterans arranging pneumonia, 25 years: numerous causes, but what specifically are the treatment choices?”. Professional Rev Respir Méd. 5 (3): 353-61. doi:10.1586/ers.11.19. PMID 21702658.
^ [https://books.google.se/bóóks?id=j-éYLc1BA3óC&pg=PA64 Website 64 in: Joseph F. Tomashefski, Carol Farver, Armando E. Fraire (2009). Dail and Hammar’s Pulmonary Pathology: Amount I: Nonneoplastic Lung Disease (3 ed.). Springer Technology & Business Media. lSBN 9780387687926. CS1 maint: Multiple titles: authors list (link)
^ Geddes DM (August 1991). “BOOP and COP”. Thorax. 46 (8): 545-7. doi:10.1136/thx.46.8.545. PMC 463266 . PMID 1926020.
^ a b “Pulmonary Concern 27: Diagnose cryptogenic arranging pneumonia”. MKSAP 5 For College students Online. American University of Doctors. November 2012 retrieved 23.
^ Nogi, S; Nákayama, H; Tájima, Y; 0kubo, M; Mikámi, R; Sugáhara, S; Akáta, S; Tokuuyé, K (2014). “Cryptogenic arranging pneumonia linked with radiation: A created report of two situations”. Letters oncology. 7 (2): 321-324. doi:10.3892/ol.2013.1716. PMC 3881924 . PMID 24396439.
^ Oie, Y; Sáitó, Y; Kátó, M; Ito, F; Háttóri, H; Tóyáma, H; Kóbáyashi, H; Kátáda, K (2013). “Partnership between radiation pnéumonitis and arranging pnéumonia after radiotherapy fór breasts malignancy”. Radiation 0ncology. 8: 56. doi:10.1186/1748-717X-8-56. PMC 3605133 . PMID 23497657.
^ Radzikowska, E; Nówicka, U; Wiátr, E; Jakubówska, L; Langfórt, R; Chabówski, M; Rószkowski, K (2007). “Organising pneumonia and lung tumor – case statement and summary of the literature”. PneumonoIogia i Alergologia PoIska. 75 (4): 394-7. PMID 18080991.
^ Al-Ghanem Sára; Al-Jahdali Hámdan; Bamefleh Hanaa; Khán Ali Náwaz (Apr-Jun 2008). “Bronchiolitis obliterans arranging pneumonia: Pathogenesis, medical features, imaging ánd therapy rélook at”. Ann Thorac Méd. 3 (2): 67-75. doi:10.4103/1817-1737.39641. PMC 2700454 . PMID 19561910.
^ Radswiki; et al. “Reversed halo indicatión (lungs)”. Radiopaedia. Rétrieved 2018-01-02. CS1 maint: Explicit use of et al. (hyperlink)
^ Zare Mehrjardi, Móhammad; Kahkouee, Shahram; PourabdoIlah, Mihan (March 2017). “Radio-pathological correlation of arranging pneumonia (OP): á pictorial review”. Uk Journal of Radiology thé. 90 (1071): 20160723. doi:10.1259/bjr.20160723. ISSN 1748-880X. PMC 5601538 . PMID 28106480.
^ Oikonomou, A; HanseIl, DM (2001). “Arranging pneumonia: a variety of morphological faces”. Európéan Radiology. 12 (6): 1486-96. PMID 12042959.
^ Yoshida, K; Nákajima, M; Niki, Y; Mátsushima, T (2001). “Atelectasis of the correct lower lobe in colaboration with bronchiolitis obliterans arranging pneumonia”. Nihon Kókyuki Gakkai zasshi = thé journal of japan Respiratory Culture. 39 (4): 260-5. PMID 11481825.
^ Oymak FS, Démirbaş HM, MaviIi E, et al. (2005). “Bronchiolitis obliterans arranging pneumonia. Clinical ánd roentgenological féatures in 26 circumstances”. Respiration. 72 (3): 254-62. doi:10.1159/000085366. PMID 15942294.
External links[edit]
Support & Information for COP & BOOP
“Idiopathic lnterstitial Pnéumonias”. Mérck Manual ProfessionaI. Máy 2008.
Lower RT/lung disease
(including LRTIs)

Obstructive or
restrictive

Other

Atelectasis
circulatory
Pulmonary hypertension
Pulmonary embolism
Lung abscess
Pleural cavity/
mediastinum

Other/general

Respiratory failure
Influenza
SARS
Idiopathic pulmonary haemosiderosis
Pulmonary alveolar proteinosis

Reference: https://en.wikipédia.org/wiki/Cryptogénic_organizing_pneumonia

Immune Pharma Announces Positive Results From Ongoing Phase II Trial Of Bertilimumab In Bullous Pemphigoid

<h1>Immune Pharma Announces Positive Results From Ongoing Phase II Trial Of Bertilimumab In Bullous Pemphigoid</h1>

Immune Pharma Announces Positive Results From Ongoing Phase II Trial Of Bertilimumab In Bullous Pemphigoid

Results from six subjects demonstrate a large and statistically significant reduction in bullous pemphigoid activity despite aggressive prednisone tapering, with no serious adverse events. ENGLEWOOD CLIFFS, N.J.–( BUSINESS WIRE )–Immune Pharmaceuticals, Inc…

Read More…

Moffitt Morning Report 6/29/18: PJP!

<h1>Moffitt Morning Report 6/29/18: PJP!</h1>

Moffitt Morning Report 6/29/18: PJP!

Atypicals (rarely Mycoplasma, Chlamydia, Q fever, leptospirosis) PCP Viral: Respiratory viruses (e.g., influenza, RSV, etc) or CMV Toxoplasma Noninfectious: Drug-induced ALI, edema, DAH, ILD
Basics of PJP Which patient that are immunocompromised get PJP and should thus be considered for PPx? HIV-positive patients (CD4 < 200) Cancer, solid organ transplant, BMT – related to type & chemo intensity Rheumatologic (GPA has intrinsic risk) Chronic steroids (Prednisone 20mg or higher for 3-4 weeks or longer Prophylaxis of PJP TMP-SMX (Bactrim) 1 DS tablet daily (although 1 single-strength also effective) Note: should re-challenge with Bactrim even if they have a mild reaction (as long as not life threatening reaction) Only consider alternative therapy if life-threatening reaction like Stevens-Johnson Syndrome pr TEN Dapsone Dapsone + Pyrimethamine plus leucovorin (especially if need toxoplasmosis ppx needed)
III. Diagnosis of PJP In general, bronchoscopy is the gold standard for diagnosis, even when labs and imaging suggest PJP (See the attached paper by the young Dr. Hollander!) It’s ok to treat empirically while awaiting bronch, as organisms will be present for up to 2 weeks on BAL microscopy Test characteristics are different in HIV infected vs. HIV noninfected patients! Thanks again to Jen for this table. Treatment of PJP Key treatment: high dose Bactrim Steroids for Rx of PCP in HIV-Negative patients?? Not well studied in HIV-negative patients, only a few retrospective studies (see below) No mortality benefit, but may expedite recovery Steroids are recommended in the AJT guidelines 40-60 mg Prednisone BID x 5-7 days with 7-14 day taper
Studies of adjunctive steroid use in Non-HIV infected patients with PJP A retrospective study of 30 HIV-uninfected patients with severe PCP showed that the 16 patients who received the equivalent of ≥60 mg of prednisone per day had a significantly shorter duration of mechanical ventilation, intensive care unit admission, and supplemental oxygenation than the 14 patients who received the equivalent of ≤30 mg of prednisone per day or were on a glucocorticoid taper. However, similar rates of mechanical ventilation and in-hospital mortality were observed. (Pareja et al., Chest, 1998) A retrospective study of 31 HIV-uninfected patients with PCP also found no difference in the need for mechanical ventilation or mortality between the glucocorticoid-treated and -untreated groups. (Delclaux et al. Clin Infect Dis, 1999)

Read More…

Unusual Article Uncovers the Deceptive Practices of Prednisone Taper

<h1>Unusual Article Uncovers the Deceptive Practices of Prednisone Taper</h1>

If prednisone is used for a longer duration of time, the steroid includes a lengthy list of side effects that may wind up giving you more problems than merely a nagging cough. It is a popular and versatile corticosteroid used to treat many different illnesses, most notably inflammation. By way of example, it is used as a maintenance therapy drug for Addison’s Disease where adults might be required to ingest a very small amount of prednisone 5mg in the morning as well as in the evening before bed. So you might be on prednisone for a couple of days or a couple weeks. Prednisone is a potent anti-inflammatory medication used to deal with inflammatory kinds of arthritis and other ailments. It is actually a precursor to prednisolone. Normally, taking prednisone for only weekly is not going to result in any severe side effects, but it does not mean that you don’t need to give up other treatments.

Prednisone Taper – Is it a Scam?

Usually, prednisone will be supplied in one of two ways. It is not soluble in water, and so is not able to be given intravenously. It is part of a class of drugs called corticosteroids which also includes Methylprednisolone, and dexamethasone. Last, there’s inhalable prednisone that’s most likely the very best mix of convenience and quickness.

Topical steroid

Topical steroids are the topical forms of corticosteroids. Topical steroids are the most commonly prescribed topical medications for the treatment of rash, eczema, and dermatitis. Topical steroids have anti-inflammatory properties, and are classified based on their skin vasoconstrictive abilities.[1] There are numerous topical steroid products. All the preparations in each class have the same anti-inflammatory properties, but essentially differ in base and price.

Over the past decade, much awareness has been brought to the side effects and damage that long term topical steroid use can bring, particularly in cases where it used for the treatment of eczema.[2][3]

Contents

  • 1 Medical uses
  • 2 Adverse effects
  • 3 Safety in Pregnancy
  • 4 Classification systems
    • 4.1 USA system
      • 4.1.1 Class I
      • 4.1.2 Class II
      • 4.1.3 Class III
      • 4.1.4 Class IV
      • 4.1.5 Class V
      • 4.1.6 Class VI
      • 4.1.7 Class VII
    • 4.2 Other countries
      • 4.2.1 Class IV
      • 4.2.2 Class III
      • 4.2.3 Class II
      • 4.2.4 Class I
    • 4.3 Japan classification
    • 4.4 Allergy associations
      • 4.4.1 Group A
      • 4.4.2 Group B
      • 4.4.3 Group C
      • 4.4.4 Group D
  • 5 History
  • 6 See also
  • 7 References

Medical uses[edit]

Weaker topical steroids are utilized for thin-skinned and sensitive areas, especially areas under occlusion, such as the armpit, groin, buttock crease, breast folds. Weaker steroids are used on the face, eyelids, diaper area, perianal skin, and intertrigo of the groin or body folds. Moderate steroids are used for atopic dermatitis, nummular eczema, xerotic eczema, lichen sclerosis et atrophicus of the vulva, scabies (after scabiecide) and severe dermatitis. Strong steroids are used for psoriasis, lichen planus, discoid lupus, chapped feet, lichen simplex chronicus, severe poison ivy exposure, alopecia areata, nummular eczema, and severe atopic dermatitis in adults.[1]

To prevent tachyphylaxis, a topical steroid is often prescribed to be used on a week on, week off routine. Some recommend using the topical steroid for 3 consecutive days on, followed by 4 consecutive days off.[4] Long-term use of topical steroids can lead to secondary infection with fungus or bacteria (see tinea incognito), skin atrophy, telangiectasia (prominent blood vessels), skin bruising and fragility.[5]

The use of the finger tip unit may be helpful in guiding how much topical steroid is required to cover different areas of the body.

Adverse effects[edit]

See also: Topical steroid addiction

  • Hypothalamic pituitary adrenal axis (HPA) suppression[6]
  • Cushing’s syndrome
  • Diabetes mellitus[7]
  • Osteoporosis
  • Topical steroid addiction
  • Allergic contact dermatitis (see steroid allergy)
  • Steroid atrophy
  • Perioral dermatitis: This is a rash that occurs around the mouth and the eye region that has been associated with topical steroids.
  • Ocular effects: Topical steroid drops are frequently used after eye surgery but can also raise intra-ocular pressure (IOP) and increase the risk of glaucoma, cataract, retinopathy as well as systemic adverse effects.[8]
  • Tachyphylaxis: The acute development of tolerance to the action of a drug after repeated doses.[9] Significant tachyphylaxis can occur by day 4 of therapy. Recovery usually occurs after 3 to 4 days rest. This has led to therapies such as 3 days on, 4 days off; or one week on therapy, and one week off therapy.
  • Delivery-related adverse effects
  • Other local adverse effects: These include facial hypertrichosis, folliculitis, miliaria, genital ulcers, and granuloma gluteale infantum. Long-term use has resulted in Norwegian scabies, Kaposi’s sarcoma, and other unusual dermatosis.[10]

Safety in Pregnancy[edit]

A 2015 meta-analysis of observational studies of pregnancies found no association between mothers’ use of topical steroids and type of delivery, APGAR score, birth defects, or prematurity.[11]

Classification systems[edit]

See also: ATC code D07

USA system[edit]

The USA system utilizes 7 classes, which are classified by their ability to constrict capillaries and cause skin blanching. Class I is the strongest, or superpotent. Class VII is the weakest and mildest.[12]

Class I[edit]

Very potent: up to 600 times stronger than hydrocortisone

  • Clobetasol propionate 0.05% (Dermovate)
  • Betamethasone dipropionate 0.25% (Diprolene)
  • Halobetasol propionate 0.05% (Ultravate, Halox)
  • Diflorasone diacetate 0.05% (Psorcon)

Class II[edit]

  • Fluocinonide 0.05% (Lidex)
  • Halcinonide 0.05% (Halog)
  • Amcinonide 0.05% (Cyclocort)
  • Desoximetasone 0.25% (Topicort)

Class III[edit]

  • Triamcinolone acetonide 0.5% (Kenalog, Aristocort cream)
  • Mometasone furoate 0.1% (Elocon, Elocom ointment)
  • Fluticasone propionate 0.005% (Cutivate)
  • Betamethasone dipropionate 0.05% (Diprosone)
  • Halometasone 0.05%

Class IV[edit]

  • Fluocinolone acetonide 0.01-0.2% (Synalar, Synemol, Fluonid)
  • Hydrocortisone valerate 0.2% (Westcort)
  • Hydrocortisone butyrate 0.1% (Locoid)
  • Flurandrenolide 0.05% (Cordran)
  • Triamcinolone acetonide 0.1% (Kenalog, Aristocort A ointment)
  • Mometasone furoate 0.1% (Elocon cream, lotion)

Class V[edit]

  • Fluticasone propionate 0.05% (Cutivate cream)
  • Desonide 0.05% (Tridesilon, DesOwen ointment)
  • Fluocinolone acetonide 0.025% (Synalar, Synemol cream)
  • Hydrocortisone valerate 0.2% (Westcort cream)

Class VI[edit]

  • Alclometasone dipropionate 0.05% (Aclovate cream, ointment)
  • Triamcinolone acetonide 0.025% (Aristocort A cream, Kenalog lotion)
  • Fluocinolone acetonide 0.01% (Capex shampoo, Dermasmooth)
  • Desonide 0.05% (DesOwen cream, lotion)

Class VII[edit]

The weakest class of topical steroids. Has poor lipid permeability, and can not penetrate mucous membranes well.

  • Hydrocortisone 2.5% (Hytone cream, lotion, ointment)
  • Hydrocortisone 1% (Many over-the-counter brands)

Other countries[edit]

Most other countries, such as the United Kingdom, Germany, the Netherlands, New Zealand, recognize only 4 classes.[13] In the United Kingdom and New Zealand I is the strongest, while in Continental Europe, class IV is regarded as the strongest.

Class IV[edit]

Very potent (up to 600 times as potent as hydrocortisone)

  • Clobetasol propionate (Dermovate Cream/Ointment, Exel Cream)
  • Betamethasone dipropionate (Diprosone OV Cream/Ointment, Diprovate Cream)

Class III[edit]

Potent (50-100 times as potent as hydrocortisone)

  • Betamethasone valerate (Beta Cream/Ointment/Scalp Application, Betnovate Lotion/C Cream/C Ointment, Fucicort)
  • Betamethasone dipropionate (Diprosone Cream/Ointment, Diprovate Cream, Daivobet 50/500 Ointment)
  • Diflucortolone valerate (Nerisone C/Cream/Fatty Ointment/Ointment)
  • Hydrocortisone 17-butyrate (Locoid C/Cream/Crelo Topical Emulsion/Lipocream/Ointment/Scalp Lotion)
  • Mometasone furoate (Elocon Cream/Lotion/Ointment)
  • Methylprednisolone aceponate (Advantan Cream/Ointment)
  • Halometasone 0.05%

Class II[edit]

Moderate (2-25 times as potent as hydrocortisone)

  • Clobetasone butyrate (Eumovate Cream)
  • Triamcinolone acetonide (Aristocort Cream/Ointment, Viaderm KC Cream/Ointment, Kenacomb Ointment)

Class I[edit]

Mild

  • Hydrocortisone 0.5-2.5% (DermAid Cream/Soft Cream, DP Lotion-HC 1%, Skincalm, Lemnis Fatty Cream HC, Pimafucort Cream/Ointment)

Japan classification[edit]

Japan rates topical steroids from 1 to 5, with 1 being strongest.

Allergy associations[edit]

The highlighted steroids are often used in the screening of allergies to topical steroid and systemic steroids.[14] When one is allergic to one group, one is allergic to all steroids in that group.

Group A[edit]

Hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, and prednisone

Group B[edit]

Triamcinolone acetonide, triamcinolone alcohol, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, and halcinonide

Group C[edit]

Betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, and fluocortolone

Group D[edit]

Hydrocortisone-17-butyrate, hydrocortisone-17-valerate, alclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, Clobetasol-17 propionate, fluocortolone caproate, fluocortolone pivalate, fluprednidene acetate, and mometasone furoate

History[edit]

Corticosteroids were first made available for general use around 1950.[15]

See also[edit]

  • Topical
  • Glucocorticoid
  • Corticosteroid
  • Retrometabolic drug design

References[edit]

  • ^ a b Habif, Thomas P. (1990). Clinical dermatology: a color guide to diagnosis and therapy (2nd ed.). St. Louis: Mosby. p. 27. ISBN 0-8016-2465-7. 
  • ^ Coondoo, A; Phiske, M; Verma, S; Lahiri, K (2014). “Side effects of topical steroids: A long overdue revisit”. Indian Dermatol Online J. 5 (4): 416–25. doi:10.4103/2229-5178.142483. PMC 4228634 . PMID 25396122. 
  • ^ “Barrier repair creams target the downside of topical corticosteroid treatment”. Dermatology Times. March 1, 2012. Retrieved June 11, 2015. 
  • ^ Recommendations from New Zealand Dermatological Society Incorporated on corticosteroids
  • ^ Habif, Thomas P. (1990). Clinical dermatology: a color guide to diagnosis and therapy (2nd ed.). St. Louis: Mosby. pp. 27–30. ISBN 0-8016-2465-7. 
  • ^ Fisher, DA (1995). “Adverse effects of topical corticosteroid use”. West. J. Med. 162 (2): 123–6. PMC 1022645 . PMID 7794369. 
  • ^ van der Linden MW, Penning-van Beest FJ, Nijsten T, Herings RM (2009). “Topical corticosteroids and the risk of diabetes mellitus: a nested case-control study in the Netherlands”. Drug Saf. 32 (6): 527–37. doi:10.2165/00002018-200932060-00008. PMID 19459719. 
  • ^ Lebreton, O.; Weber, M. (2011). “Complications ophtalmologiques des corticoïdes systémiques”. La Revue de Médecine Interne. 32 (8): 506–512. doi:10.1016/j.revmed.2011.01.003. PMID 21330017. 
  • ^ Wolverton, Stephen E. (2001). Comprehensive Dermatologic Drug Therapy. Philadelphia, PA: W.B. Saunders Company. pp. 562–3. ISBN 0-7216-7728-2. 
  • ^ Wolverton, Stephen E. (2001). Comprehensive Dermatologic Drug Therapy. Philadelphia, PA: W.B. Saunders Company. p. 563. ISBN 0-7216-7728-2. 
  • ^ Chi, Ching-Chi; Wang, Shu-Hui; Wojnarowska, Fenella; Kirtschig, Gudula; Davies, Emily; Bennett, Cathy (2015-10-26). “Safety of topical corticosteroids in pregnancy”. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD007346.pub3. ISSN 1465-1858. 
  • ^ Habif, Thomas P. (1990). Clinical dermatology: a color guide to diagnosis and therapy (2nd ed.). St. Louis: Mosby. p. Inside front cover. ISBN 0-8016-2465-7. 
  • ^ http://dermnetnz.org/treatments/topical-steroids.html
  • ^ Wolverton, Stephen E. (2001). Comprehensive Dermatologic Drug Therapy. Philadelphia, PA: W.B. Saunders Company. p. 562. ISBN 0-7216-7728-2. 
  • ^ Rattner H (November 1955). “THE STATUS OF CORTICOSTEROID THERAPY IN DERMATOLOGY”. Calif Med. 83 (5): 331–5. PMC 1532588 . PMID 13260925. 
  • Antiglucocorticoids

    • Antagonists: Aglepristone
    • Ketoconazole
    • Mifepristone
    • Ulipristal acetate

    Synthesis modifiers

    • Acetoxolone
    • Aminoglutethimide
    • Carbenoxolone
    • Enoxolone
    • Ketoconazole
    • Metyrapone
    • Mitotane
    • Trilostane
    • #WHO-EM
    • ‡Withdrawn from market
    • Clinical trials:
      • †Phase III
      • §Never to phase III

    See also
    Glucocorticoid receptor modulators
    Mineralocorticoids and antimineralocorticoids
    List of corticosteroids


    Source: https://en.wikipedia.org/wiki/Topical_steroid

    The Most Popular Prednisone For Poison Ivy

    <h1>The Most Popular Prednisone For Poison Ivy</h1>

    The Prednisone For Poison Ivy Cover Up

    Prednisone can at times be affiliated with certain sorts of side results. Specifically, prednisone taken orally has been demonstrated to be the most effect approach to attain some comfort from the immune reaction to poison ivy. As an example, it is used as a maintenance therapy drug for Addison’s Disease where adults might be required to ingest a very small amount of prednisone 5mg in the morning as well as in the evening before bed. If you’re using prednisone for poison ivy then you ought to use a lower dose. Prednisone functions as a replacement for those who have low levels of cortisol, among the organic steroid hormones. It weakens the immune system so it may be a good idea to stay away from potential health problems. If you’re using prednisone for poison ivy then you may face several side effects because it’s a really powerful medication.

    Most folks see the rash go away in a couple of weeks. The rash is generally a line or a cluster. When you begin to develop a rash, it is going to be irritating.

    What Prednisone For Poison Ivy Is – and What it Is Not

    The rash is simple to observe and identify because its symptoms are extremely clear and visible. It can appear on different parts of the body at different times. By the way, however, the rash itself isn’t contagious. Doing this will create the rash to spread. While the skin rash might be uncomfortable, it’s typically not of severe concern and will resolve alone in about one or two weeks.

    Anatomy of a 97,000% drug price hike: One family's fight to save their son

    <h1>Anatomy of a 97,000% drug price hike: One family's fight to save their son</h1>

    Anatomy of a 97,000% drug price hike: One family’s fight to save their son

    Newport, Rhode Island (CNN) Trevor Foltz splashes in the pool in his grandparents’ backyard. His brother and sister join in the fun, as does their father.
    Their mother, Danielle, watches from a nearby lawn chair. She’s like a hawk, keeping a close eye on Trevor and the rest of her brood. It was 10 years ago in this backyard when a similar moment of revelry was shattered. Trevor, then a toddler, was running around, having the time of his life, his mom keeping steady watch. Trevor suddenly came over, placed his hand on her knee and looked directly into her eyes. He tried to speak but couldn’t say a word. Then his head twitched ever so slightly to the right. Their gazes locked. Mom’s heart wrenched. It was so mild that Danielle told herself it must have been her imagination. She didn’t tell her husband, Jonathan, or anyone else. But moments later, it happened again: Trevor coming to her, resting his hands on her knees, looking into her eyes. Read More Trevor plays with his brother and sister, Toby and Bristel, in the swimming pool at their grandparents’ house. The family swims together every weekend in the summer and uses the time together to bond. Trevor’s condition soon became obvious to all. The Foltzes were eating dinner with friends a few days later when Trevor had one seizure, then another and another. “Some heartache transcends language,” Danielle recalled. “This is one of them.” The Foltzes had been there before. At 7 months, Trevor was diagnosed with infantile spasms, a rare and catastrophic form of epilepsy. The diagnosis was devastating, forcing the family to cancel an overseas move and fight for their son’s life. It also thrust them into the unregulated world of America’s drug prices. Trevor’s doctors said he needed a “miracle drug” known as Acthar . But between Trevor’s birth and diagnosis, the price of the drug had shot up from $1,600 a vial to more than $23,000 a vial — making him one of the first children caught up in one of medicine’s most controversial price hikes. After the initial diagnosis, the Foltzes wrestled with their insurance company for days to get Trevor treated with Acthar. Eventually, the treatment was fully covered, at a cost of more than $125,000. And the drug worked. The tremors stopped. But more than a year later, on that day in the backyard, the seizures had returned. Another round of treatment was in order. Again, the Foltzes ran into red tape. The insurer was balking at spending another $125,000, and Trevor’s parents worried whether he would get the precious vials of medicine needed to give him a shot at a normal life. A decade on, the pain is still raw. Still palpable. Still real. “It feels like we’re pawns,” says Trevor’s father, Jonathan. The drugmaker, he says, “is allowed to take advantage of us, and we have to move on and go about the challenge of living.” “It seems very backwards, from the top down — and we’re at the bottom.” Drug prices that make parents cry We often hear about exorbitant drug price hikes in the moment. The Internet lit up with outrage when the price of EpiPen , the emergency medicine used to treat severe allergic reactions, went through the roof. A kitchen drawer in the family home is full of syringes, next to spoons and sippy cups. “Pharma Bro” Martin Shkreli was dubbed the “most hated man in America” after he raised the price of an AIDS drug by more than 5,000%. His tears at being sentenced to seven years in prison drew little sympathy. But we rarely hear about the anatomy of a price hike, especially one that climbed for more than a decade in the face of a federal investigation and protests from top medical associations. I wanted to know how a drug invented in the 1930s could go from $40 a vial in 2000 to $39,000 in 2018 — essentially from the cost of a coffee maker to the price of a new car with leather seats. With a treatment regimen requiring at least three vials over the course of several weeks, this drug costs more than many people’s homes. The sharp jump in Acthar’s price outraged families, doctors, pharmacists and hospitals — and led Danielle Foltz to testify before Congress against the increase. It ultimately resulted in a $100 million settlement between the government and the drugmaker — as well as revelations that Medicare has spent nearly $2 billion covering Acthar prescriptions for seniors while the drugmaker paid millions to prescribing doctors. The exorbitant price also forced doctors and hospitals to question whether a $20 alternative would work just as well. I first heard about Acthar from the epilepsy community; my own son has an uncontrolled seizure disorder. Parents would often cry when describing the cost of Acthar and the struggle to get the medicine for their child. Please tell this drug’s story. Our story. Imagine holding a vial worth more than your minivan, your hand trembling for fear of dropping it, while you administer a shot with a 1-inch needle to your seizing, screaming baby. I spent the past year canvassing the epilepsy community, talking to scores of people, including 10 parents whose children struggle with infantile spasms and more than a dozen doctors who treat them. I felt that it was important to tell Trevor’s story since he was among the first children caught up in the price hike and his mother spoke so bravely before Congress. He was in such good health when his mother testified, I wondered: How is he doing now, at age 11? Trevor takes an array of medication three times a day to help minimize the severity and frequency of his seizures. The skyrocketing cost of Acthar led to huge increases in revenues for the drugmakers, Questcor and Mallinckrodt, not because of any breakthrough in treatment, critics say, but as a result of higher prices, aggressive marketing and an alleged effort to thwart all competition. That allegation is what led to the government’s case against Mallinckrodt, which purchased Questcor in 2014. Mallinckrodt settled without any admission of wrongdoing. “This was a particularly egregious situation where they raised prices extraordinarily, but then they sought to buy out a potential competitor to make sure those prices were going to stick as long as possible,” said Mike Moiseyev, the deputy director of the Federal Trade Commission’s Bureau of Competition, who helped build the government’s case. Questcor had purchased Synacthen, a synthetic version of Acthar, and then made sure it never entered the US market, the government alleged. “When Questcor deprived [babies] of an imminent alternative in the form of Synacthen, they truly became victims of that scheme,” Moiseyev said. And though Mallinckrodt says it will cover the cost of Acthar if insurance can’t, some doctors say high-priced drugs are raising health care costs for all of us in the form of higher premiums, co-pays and hospital visits. From months of reporting, the magnitude of the controversy became clear. Parents are distraught and angry. Neurologists are perplexed and frustrated. Mallinckrodt maintains that it is acting “responsibly and ethically” and has made only “modest price adjustments in the mid-single digit percentage range” since purchasing the drug. “H.P. Acthar Gel makes a significant difference in the lives of very sick patients with unmet medical needs. We are proud of the drug and the important investment we are making in it,” Mallinckrodt told CNN in a statement. Still, the drug’s price has continued to rise. It’s now nearly $39,000 a vial — an increase of $7,000 since Mallinckrodt purchased Questcor and 97,000% since Questcor first acquired Acthar in 2001. By 2015, Mallinckrodt was reporting net sales from Acthar of $1 billion. In response to questions from CNN about the price of Acthar, Mallinckrodt said that the drug’s “previous owner was near bankruptcy and raised the price of the drug substantially” to keep it on the market. “Additionally, Mallinckrodt provides discounts to this list price to payers, which the prior owner generally did not offer.” ‘Russian roulette’ waiting for medication to arrive Danielle and Jonathan Foltz were missionaries in 2007, eager to move their young family to the east African nation of Tanzania where they planned to live for years, if not the rest of their lives. They already had two children: son Toby, 6, and daughter Bristel, 2. Trevor was born healthy and beautiful in April, the perfect addition. Danielle Foltz testified before Congress in 2008 about Acthar’s price hike. Despite her testimony, the drug has continued to climb from $23,000 to nearly $39,000 today. By November 2007, most of the family’s possessions were in Tanzania, and the family lived with Danielle’s parents in Rhode Island in preparation for the big move. Jonathan was loading a storage container when Trevor had his first cluster of seizures. They were jerky, odd movements, resembling a newborn’s startle reflexes. The seizures progressively worsened, with as many as 20 in a 60-second span, up to five times a day. Trevor was soon evaluated, and the young parents were given the painful diagnosis of infantile spasms. The family consulted three neurologists who told them the same thing: If they didn’t get control of his seizures, Trevor’s developing brain would be permanently damaged. The only thing standing between Trevor and a normal shot at life, his parents were told, was Acthar. The family was warned that the treatment would be expensive. At the time, the average cost of a vial was more than $23,000; Trevor would need at least five. The Foltzes didn’t have a home to mortgage as collateral should they need it. To cut through insurance bureaucracy, one of Trevor’s grandfathers offered to put the first vial on his credit card, no matter what it cost, if it meant his grandson would get the medicine promptly. Devastated, Danielle and Jonathan would give up their dream to focus on saving their boy. There would be no move to Tanzania. “Those days following Trevor’s diagnosis, for our family, were the most emotionally dark that we’ve lived through,” she would later tell lawmakers. “My husband and I were pretty much a puddle on the floor.” Initially, the family’s insurance company held up shipping the drug to the Foltzes because of its cost. Danielle called a hotline set up by the drugmaker to help families get the medicine. She was told that the approval process would take at least three business days. “When your infant’s body is being racked by 40 seizures every single day, you do not have three business days to play Russian roulette, waiting for a medication that could stop his seizures and right your world again,” Danielle said. A week after the diagnosis and countless phone calls, the first vial finally arrived. The commonly Quote: d price of Acthar in 2007 is just over $23,000, but a receipt from Trevor’s first vial shows that the family’s insurance was Quote: d a price of $30,543.56. Even with the adjusted discount on the receipt, the price was $26,177.62 a vial. CNN blurred Trevor’s medical information to protect his privacy. A drug too expensive to offer patients who may benefit The first recorded case of infantile spasms was in a 4-month-old English patient. The doctor who discovered the disorder: the child’s father. It was 1841 when Dr. W.J. West noticed the symptoms in his son. “I first observed slight bobbings of the head forward, which I then regarded as a tic, but were, in fact, the first indications of disease,” West wrote in a letter to the British medical journal Lancet . You can feel the doctor’s heartache as his son’s condition worsened by his first birthday: “He never cries at the time of the attacks, or smiles or takes any notice, but looks placid and pitiful, yet his hearing and vision are good. He has no power of holding himself upright or using his limbs, and his head falls without support.” Nearly two centuries later, that description remains all too familiar to anyone who has dealt with the debilitating disorder , which is often referred to as West Syndrome. A diagnosis is devastating for both child and parents. About 2,000 babies are diagnosed each year in the United States, usually before their first birthday. About 70% to 90% of them will have intellectual or developmental disabilities, often with IQs in the range of 30 to 50. It’s crucial to bring spasms under control quickly, neurologists said, for children to have the best possible outcome. There are just three front-line medications used to treat infantile spasms: • H.P. Acthar Gel, or Acthar, an anti-inflammatory also known as ACTH. • Vigabatrin, an anticonvulsant that costs about $50,000 for a six-month course of treatment. • Prednisolone, the oral version of the steroid prednisone; it costs about $20 but is not approved by the Food and Drug Administration for the disorder. It is still used by doctors to treat infantile spasms. Acthar and prednisolone can have a host of serious side effects, but neurologists said the most feared complication is immune suppression with infection, which can sometimes lead to death. Vigabatrin can cause blindness. None is guaranteed to stop the seizures. Jonathan Foltz says he feels that the pharmaceutical company used children like Trevor as pawns to make money. “It became a boon for them; for us, not so much.” Several neurologists I spoke with said Acthar is their preferred choice in treating infantile spasms. Generally speaking, they said, it is effective about 50% of the time. Mallinckrodt cites a randomized clinical trial from 1996 that shows 86.7% of patients had a “positive response” to Acthar, compared with 28.6% for prednisone. Neurologists have noted that the study compared a high dose of Acthar to a low dose of prednisone. Some patients don’t respond to prednisolone but respond to Acthar, and vice versa, neurologists said. Some children never have seizures again, while many others — like Trevor Foltz — relapse. But Acthar’s extreme price has jolted the medical community, forcing hospitals and neurologists to rethink how they treat children like Trevor. For many rural hospitals, Acthar isn’t an option due to its price, some neurologists said. Even at some top medical centers like Johns Hopkins, Acthar isn’t offered as a first-line treatment due to its exorbitant price tag. “We have found oral prednisolone to be equally effective, as have several other researchers,” said Dr. Eric Kossoff, director of Hopkins’ pediatric neurology residency program. Dr. Eli Mizrahi, president of the American Epilepsy Society, said Acthar’s high cost is a constant worry. Simply put, he said, paying tens of thousands of dollars a vial is not viable in the long run. “It’s a concern because it’s a barrier to care,” Mizrahi said. “I’d like to hear why the drug is so expensive and what [the drugmaker is] doing to bring the cost down.” “For many pediatric neurologists, ACTH is not a treatment option,” said Dr. John Mytinger, a pediatric neurologist at Nationwide Children’s Hospital in Columbus, Ohio. “This may be because the clinician believes that prednisolone is just as good as ACTH and/or the expense of ACTH cannot be justified.” The family tries to provide Trevor with as “normal” a life as possible. Here, Trevor visits donkeys on a family outing at a nearby farm. Insurance covers the cost of Acthar in almost every case for infantile spasms, and Mallinckrodt participates in the National Organization for Rare Disorders program that offers the medication for free to uninsured patients. As a result, Mallinckrodt has said, every child who needs Acthar gets the drug. But doctors said that is a gross understatement of the issue: The fact is, they said, the drug’s price has created a major obstacle to care and great frustration within the world of child neurology. “A lot of us had to ride this roller coaster of whether to use [Acthar or] whether to use oral steroids first,” Dr. Phillip L. Pearl, a professor of neurology at Harvard, once told an FDA panel as company executives listened. “It has affected practices across the country.” Another neurologist, who spoke on condition of anonymity for fear Mallinckrodt would retaliate against his hospital, said, “It’s ironic that we have a big barrier to treat the most vulnerable portion of our population: our babies. “It’s frustrating because I never want price to be a limitation for my ability to treat kids appropriately,” the doctor said. “Due to the high cost of Acthar, barriers are put into place around prior authorization, which limits timely access to the medication. In layman’s terms, if the price wasn’t so high, insurance companies would authorize it quicker, and you could get it to your patient faster.” For parents, the pain is personal. Think what it’s like, they said, for your child to be treated with prednisolone and not respond well, only to learn later that the drug some neurologists say is the best in the world wasn’t an option — because of its astronomical cost. Add in the stress of a diagnosis of infantile spasms, and the whole process can be soul-crushing. Danielle Foltz says she constantly worries that Trevor will die from a seizure, but she chooses to celebrate every day he’s alive. One mom I spoke with said her child was given prednisolone for the first two treatments “due to price, access issues and side effects.” She can’t help but wonder whether her child’s spasms would’ve stopped if Acthar had been administered first. Lauren Marx-Abel said her neurologist recommended prednisolone when her son Danny was diagnosed, due to concern over the availability of Acthar and its high price. Prednisolone eliminated his spasms, but a different seizure type returned later, and medicine didn’t help. Her son would eventually have the left hemisphere of his brain surgically removed. At 5, he has made some developmental gains from the surgery but will probably always have cognitive delays. “But we’re happy that he’s happy,” his mother said. Mrs. Foltz goes to Washington and no one listens After Trevor’s initial diagnosis and treatment, Danielle blogged about the ups and downs of his progress and became a strong advocate within the infantile spasms community. Her posts earned her an invitation from a 20-member congressional panel to testify about the rising price of prescription drugs. The Foltzes left Rhode Island for the nation’s capital with their two boys in July 2008. Bristel stayed behind with her grandparents. Danielle was the Joint Economic Committee’s star witness. The family took up seats on the front row of the wood-paneled room in the Dirksen Senate Office Building. Toby, 7, was dressed in a striped white polo. At 15 months, Trevor was adorable with a tuft of blond hair and a pacifier in his mouth. The family yearbook captures the Foltzes’ trip to Washington when Danielle testified on Capitol Hill about Acthar’s price increase. “Those days following Trevor’s diagnosis, for our family, were the most emotionally dark that we’ve lived through,” she said. The boys caught the eye of Sen. Amy Klobuchar, a Minnesota Democrat. “Very well-behaved children,” she said before getting to the heart of the matter. “We’re here today because we’re outraged by what some pharmaceutical companies have been doing with pricing for important medications that affect all generations,” Klobuchar said, according to a transcript of the hearing. Price increases for other drugs were mentioned: Mustargen, a cancer drug, was up 1,000%; Cosmogen for kidney disease had risen 3,500%; and Matulane, for treatment of Hodgkin’s lymphoma, was up nearly 8,000%. But those were nothing compared with the rise in price of Acthar. Questcor Pharmaceuticals had paid a mere $100,000 for the rights to the drug in 2001. The company first raised the price from $40 to $750 a vial shortly after acquiring it. The price doubled over the next few years. Then, on August 27, 2007, the price shot up overnight from $1,600 to $23,000 a vial. The hike was so dramatic that the Epilepsy Foundation, the American Epilepsy Society, the American Academy of Neurology and the National Association of Epilepsy Centers fired off a letter demanding answers. The Epilepsy Foundation was especially shocked. The drug’s previous manufacturer almost took Acthar off the market in the mid-1990s after federal regulators found major problems at a factory. But the Epilepsy Foundation pleaded for the drugmaker to keep producing it for babies with infantile spasms. Now, the foundation was fighting to keep the drug affordable. The strategy to charge tens of thousands for a vial of Acthar was initiated by Questcor’s new chief executive, Don Bailey, who had spent most of his career not in the pharmaceutical industry but as an executive with defense contractor Comarco. Bailey and Steve Cartt, Questcor’s executive vice president, were adamant that the price would not be coming down, that it was part of a coordinated plan to stop the company from bleeding cash. “To ensure the continued availability of Acthar, Questcor needed to establish a business model that would make Acthar economically sustainable,” the two executives wrote the epilepsy groups on October 1, 2007. Danielle holds Trevor on the family stoop. The family agreed to speak with CNN 10 years after her testimony because the pain is still raw: “I wish to God we knew nothing about catastrophic epilepsy and Acthar.” When Danielle took the microphone at the hearing, she spoke of the agony of Trevor’s diagnosis and watching him seize. “How do you find the words to describe the most horrific event in your life, your personal valley of the shadow of death?” Danielle said. “Because that is exactly the feeling that clamps your heart when you are at a place where the medication needed to rescue your child is out of reach.” Trevor slept for much of the hearing. At one point, Danielle joked with Klobuchar, “If he were awake, I’d let him toddle around for you.” The proud mother told the committee how her son finally got the Acthar he needed. “Trevor has been seizure-free since his fourth injection, and that’s why I brought him with me today,” she said. At the end of the hearing, Klobuchar said Congress would continue to focus on drug price hikes, because “this just can’t keep happening like this.” “I just want to assure you,” she said, “that we’re not just going to let this go.” Danielle left Washington hopeful that lawmakers would act. But she couldn’t help notice that only one other committee member — its chairman, Sen. Charles Schumer — showed up for the hearing. And that was only briefly. It was as if she’d spoken to an empty room, literally and figuratively. By the time she got home, the mother had become fodder for Internet trolls who told her to shut up and be grateful her son was healthy. And he was. For another few weeks. From the glands of a slaughterhouse pig Acthar first gained a foothold in the medical community because it was once cheap — a byproduct of a Chicago slaughterhouse. The drug takes its name from a pituitary hormone known as ACTH [short for adreno-cortico-tropic hormone], which stimulates the body to produce another hormone, cortisol, to help manage stress and inflammation. Weeks after Danielle testified, Trevor relapsed with his seizures continuing unabated. A decade later, his mother still keeps track of the daily seizures that rock Trevor’s world. Acthar was first isolated in 1933 by a Canadian biochemist who also helped discover insulin. Made from the pituitary glands of slaughtered pigs, Acthar was tried in a few patients with low cortisol and other symptoms in the mid-1940s. But it wasn’t until the groundbreaking cortisone trials at the Mayo Clinic — which led to the Minnesota clinic’s only Nobel Prize, in 1950 — that Acthar was thrust into prominence. The Nobel was confirmation of the work of two Mayo pioneers: Dr. Philip S. Hench, a rheumatologist, and chemist Edward C. Kendall. Hench and Kendall were on a quest for a breakthrough treatment in arthritis. In his chemistry lab, Kendall had isolated several compounds, including cortisone. The first patient was injected on September 21, 1948. Several more followed. Soon, patients who could hardly move were suddenly climbing over test chairs and jumping up and down without pain. But cortisone was expensive to make, and large-scale production was projected to cost millions. Looking for an alternative, Hench and Kendall wondered whether ACTH would produce the same anti-inflammatory benefits. They received a supply of ACTH from a division of the Armour meatpacking plant in Chicago, which had begun marketing Dial soap in 1948 and was looking for other ways to sell byproducts of the slaughtering process. Four of Mayo’s first 23 cortisone test patients received ACTH as part of their therapy; two received only ACTH. The doctors were on edge. “Would ACTH prove to be so effective that it would eliminate the use of cortisone?” Kendall wrote in his memoir. They quickly learned the results: “ACTH produced essentially the same anti-rheumatic effect as did cortisone,” Hench wrote in 1950 detailing the study’s findings. Soon, thousands of patients with rheumatoid arthritis received either cortisone or ACTH. Armour received FDA approval for HP Acthar Gel in 1952 to treat dozens of conditions, including arthritis, gout, lupus and kidney disease. It was even tried for poison ivy and snake bites in those early days — a thought that gives today’s neurologists the shivers. Adverse effects for ACTH and cortisone, the early trials showed, included psychosis, depression, immune suppression and fluid retention. But the side effects for ACTH were deemed more bothersome because of unwanted pig proteins and other cells in the medicine, according to a 1976 Mayo publication. Trevor has trouble tolerating loud sounds and makes sure to either wear noise-cancelling headphones or protect his ears with his hands if things get too loud. The first patient to ever receive cortisone fell into a psychotic state in the years afterward and refused any more of the steroid. In 1954, her doctors gave her Acthar instead. Shortly thereafter, her lungs filled with fluid, drowning her, according to author Thom Rooke in his book “The Quest for Cortisone.” As the field of corticosteroids improved and steroids like prednisone became more readily available, Acthar’s relevance in the field of rheumatology faded. But by the late 1950s, a study of 60 children with infantile spasms found that at least 30% showed “dramatic improvement” on ACTH, according to a report in the Journal of the American Medical Association . Five patients became seizure-free over the course of the study. The results were considered phenomenal: At the time, 10% of babies with infantile spasms died, and 85% were mentally disabled. Acthar became the standard for treatment for the rare disorder in the decades that followed. Over the years, the drug shifted hands several times. Armour eventually sold Acthar to a French pharmaceutical firm, which merged with a German counterpart in 1999 to form Aventis. Two years later, that new company sold Acthar again, this time to a pharmaceutical firm in Southern California. Its new owner, Questcor, would make Acthar the centerpiece of its business, stoking controversy with the massive price hike in 2007. It would ride the price increase to record profits and eventually a mega deal, getting bought out by Mallinckrodt for $5.6 billion in cash and stock in 2014. Not bad for a company that paid $100,000 for the drug. I wondered how Hench and Kendall might feel about Acthar’s price since it was their work that put the drug on the map. Both doctors died long ago, but I tracked down Hench’s only surviving son for his thoughts. “I can tell you this,” John Hench said. “My father would not be happy with any of this at all.” A miracle cure no more After Danielle noticed Trevor’s faint twitch in her parents’ backyard in August 2008, it became apparent that his relapse had set in. If Acthar works the first time for a child with infantile spasms, the protocol is to give him another round of treatment. Bristel carries her brother along a path during a family outing. Despite his seizures, Trevor and his siblings still play and goof around like any other family. It was an odd and painful position for the Foltzes to be in — to depend on the manufacturer Danielle had just ripped on Capitol Hill. “She had testified how outrageous the price was, then we needed it again,” Jonathan Foltz recalled. “When it’s your child, you’re willing to do whatever, even if it means going back to a company that’s not ethical.” Danielle called the helpline set up by the pharmaceutical company and was put through the same red-tape bureaucracy. She wanted to scream. As a result of her testimony, an intermediary offered to reach out to Questcor CEO Don Bailey on her behalf. Bailey said that he was touched by her words and that the company had already improved Acthar delivery times to just over two days. “It is sad to see that Trevor is having a recurrence,” Bailey emailed the intermediary on September 3, 2008. “This is such a nasty disease. I hope [Danielle] is able to get Trevor treatment that solves the problem, whether it is vigabatrin, Acthar or whatever. Her doctor is the best person to help them decide, of course.” Bailey was clear on another point: The price of Acthar would not be lowered. “If Acthar was priced where it used to be, it would just be taken off the market because no company is going to make and provide a drug that they lose gobs of money on,” Bailey wrote. It was hardly comforting words to a distraught mom reeling from her son’s relapse. “Every nerve in my body was fired with fury,” Danielle recalled. Trevor eventually received another round of treatment of five vials. This time, though, the miracle cure didn’t work. Trevor’s seizures continued unabated, tormenting him more than 100 times a day. Making it official Nearly two dozen of the nation’s top doctors gathered in a hotel on the University of Maryland campus in May 2010. Among them: neurologists who had prescribed Acthar for babies with infantile spasms. Even though it had been used for decades, Acthar had never been approved by the FDA for infantile spasms. In doctor’s parlance, the drug had been used “off-label” to treat the disorder all those years. At times, Trevor wears a protective helmet to prevent a head injury should he seize and fall. Questcor was asking the FDA to make it official as part of an application for orphan drug status. That designation would give the company seven years of exclusive marketing and guarantee it hundreds of thousands of dollars in research grants. Without the FDA’s approval of Acthar for infantile spasms, Questcor would stand to lose millions. It was almost a formality. The panelists acknowledged that it was an odd position to be in: to consider the request on a drug many considered the standard-bearer for infantile spasms. About a dozen parents testified how the drug changed the course of their children’s lives. One couple said their son was diagnosed with infantile spasms in 1961. He was first given the steroid prednisone, only to still suffer about 10 seizures a day. He was then given Acthar. His seizures never returned. (At the time, Acthar was a handful of dollars per vial.) They said their son was now 49, a manager in a software firm and with two children of his own. “Needless to say, Acthar was a miracle drug to us and to our family,” the father, Warren Farrell, said. Hours into the hearing, the subject of Acthar’s extreme price came up. “This is the elephant in the room,” said Harvard’s Pearl, who was then chief of child neurology at Children’s National Medical Center in Washington. “The price of Acthar escalated by something like 30 times when [Questcor] took it over.” He pressed the company to explain itself. Dr. David Young, Questcor’s chief scientific officer, told the panel that there was a shortage of the drug when the company acquired the rights from Aventis, a result of the quality control issues in the 1990s that almost led to it being discontinued. Young said the price increase in 2007 was needed “for the viability of the company, as well as the product itself.” Trevor has an array of speech and processing issues. Despite his disabilities, he still enjoys life, including this visit to a local farmers market. “The former price, actually, it was just not economically viable for the company,” Young said. “We are trying to be good citizens to make sure that every patient who needs it gets it.” Asked why Acthar helps relieve seizures in children with infantile spasms, Young had no explanation: “We actually don’t know the exact mechanism of action. That is unknown. There is a lot of hypotheses, different hypotheses, but we don’t know the exact mechanism.” Questor didn’t present a study of its own, instead relying on 10 small, previously published studies, four of which were randomized controlled trials. The panelists said it was extremely unusual that the company did not conduct closely monitored double-blind trials, as is typical for the FDA. The company highlighted one study in particular , from 1996, comparing high-dose Acthar to low-dose prednisone involving just 29 patients. The study found that Acthar patients had “the highest overall response rates of 87%.” Company representatives said two other studies showed the same 87% efficacy. Several neurologists at the hearing cast doubt on that 87% figure due to their own experience of about 50% to 60% efficacy. One criticized the studies as “fairly flawed studies compared to the way the FDA usually works.” Young defended the company’s decision, saying it would be difficult, if not medically unethical, to conduct a double-blind trial. “I am not a clinician, but if it was my child and you told me ‘I am going to randomize them to a drug that has 87% probability of success versus a drug that has 60% probability of success,’ ” Young testified, “I am going to say, ‘I am not going to do that.’ ” In its statement to CNN, Mallinckrodt reiterated those trial results, saying that “patients who responded in the pivotal study treated with a two-week course of H.P. Acthar Gel therapy experienced complete suppression of the two key measures of disease — spasms and hypsarrhythmia.” Later in the hearing, Pearl spoke up again, this time about the drug’s potential toxicity. He said neurologists should not overlook the possibility of sepsis and death in patients. Trevor’s mother will never forget the day 10 years ago when the boy relapsed. “Some heartache transcends language,” she says. “There is nothing easy about using ACTH,” Pearl said. “For those of us who have a lot of experience with it, and frankly, I do, it is not an easy drug to give, and you can get into all sorts of trouble.” He warned that if more doctors outside of pediatric neurology start using it, “we are going to have more adverse effects than we ever dreamed of.” Dr. Kevin Chapman, a pediatric neurologist with the Barrow Neurological Institute in Phoenix, agreed. “ACTH is the scariest drug that I use,” he said, adding that the side effects are “manageable” if patients are monitored “quite closely.” By the end of the hearing, the doctors voted 22-1 that there was “substantial evidence of effectiveness” for Acthar to be a treatment for infantile spasms. Before the meeting adjourned, Dr. Gerald van Belle, a professor in the Department of Biostatistics at the University of Washington, suggested that the company conduct a study to assess the drug’s long-term outcomes. “It may not pay off in terms of money, but it would certainly pay off in terms of good will,” he said. “I do think we should pay more attention to the long-term developmental outcomes.” Such a study would give better insight into how children respond over time — those like Trevor whose response to Acthar was originally celebrated as a success. ‘Choosing joy’ By the time Trevor was 2½, his seizures continued, even after the second round of treatment. Doctors eventually determined that the only remaining option was to remove almost the entire left hemisphere of his brain, which helped lessen the amount of daily seizures but left him with speech difficulties and other cognitive issues. It’s a heartbreaking thing to raise a child who has seizures. Every day, you worry: Will my son’s front teeth get knocked out from a hard fall? Will he fracture his skull? Will a tumble down the stairs leave him paralyzed? On Saturdays, Trevor and a medical aide often visit an animal shelter and farmer’s market to help him socialize and interact with others. What if he seizes during a bath? What if he seizes while sleeping and suffocates on his pillow? When I visit the Foltzes in Rhode Island, Trevor greets me with a handshake and smile that melts my heart. We laugh when he expresses disappointment that I didn’t bring my son to play with him. There’s a shared camaraderie among kids with seizure disorders: They like being around each other because only they truly understand the pain. I apologize to Trevor. Maybe next time I’ll bring my boy, I tell him. The Foltzes agreed to speak with me due to our shared bond over raising sons with seizure disorders. “It’s a very real thing living with a child that could have a [fatal] seizure,” Jonathan says. “It just seems kind of silly to be worrying about the bottom line of a company when you’re talking about kids’ lives.” “As a parent,” Danielle says, “it’s like waking every day feeling like death is in the room with you but choosing joy because you still have him.” ‘You can charge whatever you want’ The headlines in January 2017 blared: “Drugmaker fined $100M for hiking price 85,000%” and “Mallinckrodt to pay $100 million to settle US probe on drug pricing.” Acthar’s new owner had settled a lawsuit by the Federal Trade Commission and five states stemming from Questcor’s actions — including its purchase of a competitor drug that, the FTC said, “threatened its monopoly.” The year before its sale to Mallinckrodt, Questcor bought the US rights to Synacthen, outbidding competitors who wanted to sell the drug in the US at a “significant discount” to Acthar, the FTC said. The synthetic drug is already available in Europe, Canada and other countries, the FTC said, “at a fraction of Acthar’s price.” Ken Paxton, the attorney general for Texas, one of five states that joined the suit, said the drugmaker “extended its monopoly over ACTH-based therapeutic drugs, which it used to exploit the sick and dying.” Trevor’s noise-cancelling headphones help keep unexpected noises from sending him into a seizure. Mallinckrodt strongly disagreed with the allegations and settled the case without admitting wrongdoing. “We are pleased with the agreement reached to resolve this legacy matter,” Mallinckrodt said in a statement at the time. In its statement to CNN, Mallinckrodt said that Synacthen is not a “generic competitor” to Acthar and that the two are “very different drugs.” “Mallinckrodt did not pursue commercialization of Synacthen for IS, as the barriers to completion were, in our view, virtually impossible to overcome. Notably, Synacthen has never been approved by the FDA for use in the U.S. for any indication and it is not an alternative treatment for IS in the U.S. “In all the time that Synacthen has been commercially available in select foreign countries, it has never been commercialized in the U.S. and no owner of Synacthen [including the owner prior to Questcor] ever undertook U.S. development of the drug in IS or any other indication. “Even in Canada, where Synacthen is approved and used in certain indications, it is not approved for use in IS patients. In Canada, the label contains a warning against use in infants or children under 3 years old due to the product containing benzyl alcohol.” In the months since the government settlement, the price of Acthar hasn’t dropped; instead, it has risen steadily to about $39,000. Dr. Stephen Schondelmeyer has followed the price of Acthar ever since it skyrocketed overnight in 2007. He’s the director of the PRIME Institute, a research organization that studies economic and policy issues related to pharmaceuticals. “It wasn’t because of competition. It wasn’t because of research and development costs,” he said. “The company saw an opportunity to raise the price, and they did it.” How can the company keep raising the price, even after settling the monopoly case? “When you have a unique position in a marketplace,” Schondelmeyer said, “you can charge whatever you want.” He called the 97,000% drug hike, from 2000 to today, “one of the highest price changes ever” in the history of the United States. “Not more than a handful of drugs have ever seen a price increase like this,” he said. “This certainly is an extremely extraordinary price increase and is, without a doubt, not a competitive market price.” They weren’t looking to pick a fight with Big Pharma Trevor races ahead of his family between the high brush, the gravel kicking up between his feet in his dash to the ocean shore. It’s the family’s Saturday routine. Start with a splash in the grandparents’ pool, then let their boy run wild amid the serenity and spray of the New England coast. Weekend strolls to the beach have become a family routine. It allows them to be whole, away from the stares of the public, should Trevor seize. These trips give Trevor respite from the daily seizures that rock his everyday world. Here, the family can be whole. Toby, now 17, and, Bristel, now 13, accompany their brother. Together, the family soaks in the quiet of Rhode Island’s coast away from the stares of the public, should Trevor suddenly seize. Those moments still jolt Mom and Dad to their core. “It’s like watching him die a little at a time,” Danielle says. Danielle, 42, and Jonathan, 40, say they’ve spoken with Trevor’s brother and sister about the unimaginable: the possibility Trevor could die. The Foltzes are private folks, two ordinary parents drained by their son’s condition. They weren’t looking to pick a fight with Big Pharma but were willing once more to speak up for Trevor, the energetic boy with radiant green eyes, a brilliant smile and a kind heart. They’re also speaking out for families like theirs: the forgotten ones who are getting pummeled by co-pays, deductibles, higher premiums and all the other expenses that come with raising a special needs child. “I wish to God we knew nothing about catastrophic epilepsy and Acthar,” Danielle says. “Our heart has always been to protect other families from going through hell, emotional and financial, that we did.” Sitting at the ocean’s edge, Trevor’s parents say their problem with the drugmaker seems like a distant nightmare — that they did everything possible to raise concerns with lawmakers before getting subsumed with the realities of raising a child with lifelong disabilities. News of Mallinckrodt’s $100 million settlement jolted them again. “It seems like a slap on the wrist,” Jonathan says. “I’m not against capitalism. I’m not against people making a profit. But when small market drugs are making billions and they’re supposed to be using the money to help the community with new drugs, it seems like a failure. “It seems like [company executives] planned to do exactly what they did. It went perfect: They became multimillionaires, and the company became a $6 billion company. It became a boon for them; for us, not so much.” Trevor and his dad take in the views during a hike in the Sachuest Point Wildlife Refuge in Middletown, Rhode Island. Adds Danielle, “Someone, somewhere, figured out they could make a lot of money on rare diagnoses — and they chose infantile spasms.” Trevor faces his biggest test yet. Last summer, a doctor recommended another brain surgery to try to relieve his seizure activity. Trevor would never be able to use his right arm, leg or fingers. He would lose his ability to read. With intensive therapy, he might regain some mobility within a year or two, but there’s no guarantee. Trevor’s joyous romp to the ocean shore, the family’s rare moment of peace, would be no more. That’s something Jonathan and Danielle just can’t fathom. Epilogue: And the lawsuits play on Don Bailey, the CEO of Questcor who directed the extraordinary price hike in 2007, left Mallinkrodt in 2016. According to SEC filings, he was guaranteed more than $25 million upon leaving the company. In the year since the $100 million settlement, Mallinckrodt has continued to face fallout. A new whistle-blower lawsuit accuses Mallinckrodt of retaliating against an employee after she says she raised ethical concerns and potential violations of law by the drugmaker. Mallinckrodt said it hired outside legal counsel and conducted “a thorough review of her concerns. We believe the company has acted responsibly at all times, strongly disagree with these allegations and intend to vigorously defend this matter.” Investors have filed a class-action suit, accusing company executives of making false and misleading statements about its monopoly status. A similar suit was brought by Medicare Advantage organizations, accusing the drugmaker of stifling competition and dramatically raising the drug’s price. The city of Rockford, Illinois, also sued Mallinckrodt after the city got stuck with a nearly $500,000 bill to cover the costs of Acthar for two infants of city employees. The half-million-dollar charge nearly blew through the city’s $3.5 million allocation for prescription drugs for city employees. “The tale of how a 65-year-old brand medication could rise in price from $40 per vial in 2001 to over $35,000 per vial by 2015 is a story of, perhaps, the most egregious monopolistic conduct and unfair trade practice in US history,” the city of Rockford alleged. The drugmaker has denied the allegations .

    Read More…

    It itches! Make it stop!!

    <h1>It itches! Make it stop!!</h1>

    It itches! Make it stop!!

    Three weeks ago I got what I thought was poison ivy on my knee. Fast forward to this week and I start developing a rash/hives on my arms, legs, hands, and feet. Went to an urgent care doc who said I was having an ID reaction to a fungal infection. Has anyone …

    Read More…

    Azathioprine

    <h1>Azathioprine</h1>

    Azathioprine (AZA), sold under the brand name Imuran among others, is an immunosuppressive medication.[2] It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn’s disease, ulcerative colitis, and in kidney transplants to prevent rejection.[2][3][4] It is taken by mouth or injected into a vein.[2]

    Common side effect include bone marrow suppression and vomiting.[2] Bone marrow suppression is especially common in people with a genetic deficiency of the enzyme thiopurine S-methyltransferase.[2] Other serious risk factors include an increased risk of lymphoma.[2] Use during pregnancy may result in harm to the baby.[2] Azathioprine is in the purine analogue and antimetabolite family of medication.[2][5] It works via 6-thioguanine to disrupt the making of RNA and DNA by cells.[2][5]

    Azathioprine was first made in 1957.[5] It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system.[6] The wholesale cost in the developing world is about 7.63 to 17.19 USD a month.[7] The wholesale cost in the United States is about 35.34 USD per month.[8]

    Contents

    • 1 Medical uses
      • 1.1 Transplantation
      • 1.2 Rheumatoid arthritis
      • 1.3 Inflammatory bowel disease
      • 1.4 Others
    • 2 Adverse effects
      • 2.1 Pharmacogenetics
      • 2.2 Cancers
        • 2.2.1 Skin cancers
    • 3 Overdose
    • 4 Interactions
    • 5 Pregnancy and breastfeeding
    • 6 Pharmacology
      • 6.1 Pharmacokinetics
      • 6.2 Mechanism of action
    • 7 Chemistry
    • 8 History
    • 9 References
    • 10 External links

    Medical uses[edit]

    Azathioprine is used alone or in combination with other immunosuppressive therapy to prevent rejection following organ transplantation, and to treat an array of autoimmune diseases, including rheumatoid arthritis, pemphigus, systemic lupus erythematosus, Behçet’s disease, and other forms of vasculitis, autoimmune hepatitis, atopic dermatitis, myasthenia gravis, neuromyelitis optica (Devic’s disease), restrictive lung disease, and others.[9] It is also an important therapy and steroid-sparing agent for inflammatory bowel disease (such as Crohn’s disease and ulcerative colitis) and for multiple sclerosis.[10]

    In the United States, it is currently approved by the Food and Drug Administration (FDA) for use in kidney transplantation from human donors, and for rheumatoid arthritis.[11]

    Transplantation[edit]

    Azathioprine is used to prevent rejections of kidney or liver allografts, usually in conjunction with other therapies including corticosteroids, other immunosuppressants, and local radiation therapy.[12][13] The administration protocol starts either at the time of transplantation or within the following two days.[11]

    Rheumatoid arthritis[edit]

    Being a disease-modifying antirheumatic drug (DMARD), azathioprine has been used for the management of the signs and symptoms of adult rheumatoid arthritis.[14] Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may be combined or continued (if they were already in use) with azathioprine, but the combination with other DMARDs is not recommended.[11]

    Inflammatory bowel disease[edit]

    Azathioprine has been used in the management of moderate to severe chronically active Crohn’s disease,[15] to maintain clinical remission (absence of disease activity) in corticosteroid-dependent patients,[16] and to provide benefit in people with fistulizing Crohn’s disease.[17] The onset of action is slow and it may require several months to achieve clinical response.[15]

    Azathioprine treatment is associated with an increased risk of lymphoma, but it is unclear if this is due to the drug or a predisposition related to Crohn’s disease.[18] Lower doses of azathioprine are used as a therapy in children with refractory or corticosteroid-dependent Crohn’s disease, without causing many side effects.[19]

    In Crohn’s disease, treatment with azathioprine shortly after diagnosis was no more likely to result in corticosteroid-free remission than standard care or placebo.[20]

    It may also be used to prevent flares in those with ulcerative colitis.[21]

    Others[edit]

    Azathioprine is sometimes used in systemic lupus erythematosus patients who require a maintenance dose of 15 mg or higher of prednisone and those who experience recurrent flares.[22]

    It is used as an add on therapy when steroid therapy is given by mouth for pemphigus and myasthenia gravis, as a “steroid-sparing” agent.[9][23][24] Azathioprine is also used to maintain remission in people who have granulomatosis with polyangiitis.[4]

    It was shown to be very effective in eczema and atopic dermatitis in researches, even though it is not commonly used.[9] The British National Eczema Society lists it as a third-line treatment for severe to moderate cases of these skin diseases.[25]

    It was widely used for the treatment of multiple sclerosis until the first half of the 1990s. Concerns about increased risk of malignancy has led to a decreased use, yet it is still used in maintenance treatment for patients who frequently relapse.[26]

    A widely used therapy for idiopathic pulmonary fibrosis was azathioprine in combination with prednisone and N-acetylcysteine. A 2012 study showed that there were worse outcomes with this combination than with placebo.[27]

    Adverse effects[edit]

    Two generic azathioprine oral tablets, 50 mg each

    Nausea and vomiting are common adverse effects, especially at the beginning of a treatment. Such cases are met with taking azathioprine after meals or transient intravenous administration. Side effects that are probably hypersensitivity reactions include dizziness, diarrhea, fatigue, and skin rashes. Hair loss is often seen in transplant patients receiving the drug, but rarely occurs under other indications. Because azathioprine suppresses the bone marrow, patients can develop anaemia and will be more susceptible to infection; regular monitoring of the blood count is recommended during treatment.[11][28] Acute pancreatitis can also occur, especially in patients with Crohn’s disease.[29]

    Under FDA rules, like many other immunosuppressants, the use of this drug excludes eligibility for blood donation.[30]

    It is listed by the International Agency for Research on Cancer as a group 1 carcinogen (carcinogenic to humans).[31]

    Pharmacogenetics[edit]

    The enzyme thiopurine S-methyltransferase (TPMT) is responsible for various activation and deactivation steps in azathioprine’s mechanism of action. The first metabolic step that azathioprine undergoes in the body is the conversion to 6-mercaptopurine (6-MP; see Pharmacokinetics), which is itself an immunosuppressant prodrug.[32][33] The TPMT enzyme is responsible, in part, for the methylation of 6-MP into the inactive metabolite 6-methylmercaptopurine – this methylation prevents 6-MP from further conversion into active, cytotoxic thioguanine nucleotide (TGN) metabolites.[32][34] Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are homozygous or heterozygous for these types of genetic variations may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (myelosuppression) when receiving azathioprine.[35] In many ethnicities, TPMT polymorphisms that result in decreased or absent TPMT activity occur with a frequency of approximately 5%, meaning that about 0.25% of patients are homozygous for these variants.[35][36] However, an assay of TPMT activity in red blood cells or a TPMT genetic test can identify patients with reduced TPMT activity, allowing for the adjustment of azathioprine dose or avoidance of the drug entirely.[35][37] The FDA-approved drug label for azathioprine recommends testing for TPMT activity to identify patients at risk for myelotoxicity.[38] Indeed, testing for TPMT activity is currently one of the few examples of pharmacogenetics being translated into routine clinical care.[39] Missense SNP in NUDT15 (e.g., rs116855232, inducing R139C)) has been identified to be a causal factor for AZA-induced leukopenia through a genome wide association study (GWAS) in East Asians.[40]

    Cancers[edit]

    Azathioprine is listed as a human carcinogen in the 12th Report on Carcinogens by the National Toxicology Program of U.S. Department of Health and Human Services, asserting that it is “known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.”[41] Since August 2009, the U.S. Food and Drug Administration has required warnings to be placed on packaging with respect to increased risks of certain cancers.[42]

    The risks involved seem to be related both to the duration and to the dosage used. People who have previously been treated with an alkylating agent may have an excessive risk of cancers if treated with azathioprine. Epidemiological studies by International Agency for Research on Cancer (IARC) have provided “sufficient” evidence of azathioprine carcinogenicity in humans (Group 1),[43] although the methodology of past studies and the possible underlying mechanisms are questioned.[44]

    The various diseases requiring transplantation may in themselves increase the risks of non-Hodgkin’s lymphoma, squamous cell carcinomas of the skin, hepatobiliary carcinomas, and mesenchymal tumours to which azathioprine may add additional risks. Those receiving azathioprine for rheumatoid arthritis may have a lower risk than those undergoing transplantation.[31]

    Cases of hepatosplenic T-cell lymphoma – a rare type of lymphoma – have been reported in patients treated with azathioprine. The majority occurred in patients with inflammatory bowel disease. Adolescents and young adult males were the majority of cases.[45] They presented with a very aggressive disease course and, with one exception, died of the lymphoma. The FDA has required changes to the labeling to inform users and clinicians of the issue.[46]

    Skin cancers[edit]

    In transplant patients, skin cancer is 50 to 250 times more common than in the general population, and between 60% and 90% of patients are affected 20 years after transplantation. The use of immunosuppressive medication including azathioprine in organ transplantation has been linked to increased rates of developing skin cancer.[47] Azathioprine causes the accumulation of 6-thioguanine (6-TG) in patients’ DNA, which might trigger cancer when the patient is later exposed to ultraviolet light. Patients taking azathioprine were found to be abnormally sensitive to UVA light.[48]

    Overdose[edit]

    Large single doses are generally well tolerated; a patient who took 7.5 g azathioprine (150 tablets) at once showed no relevant symptoms apart from vomiting, slightly decreased white blood cell count and marginal changes in liver function parameters. Main symptoms of long-term overdosing are infections of unclear origin, mouth ulcers and spontaneous bleeding, all of which are consequences of the bone marrow suppression.[28]

    Interactions[edit]

    Other purine analogues such as allopurinol inhibit xanthine oxidase, the enzyme that breaks down azathioprine, thus increasing the toxicity of azathioprine.[49] On the other hand, low doses of allopurinol have been shown to safely enhance the efficacy of azathioprine, especially in inflammatory bowel disease non-responders.[50][51][52] This may still lead to lower lymphocyte counts and higher rates of infection, therefore the combination requires careful monitoring.[53][54]

    Azathioprine decreases the effects of the anticoagulant warfarin and of non-depolarizing muscle relaxants, but increases the effect of depolarizing muscle relaxants.[28] It can also interfere with niacin (vitamin B3), resulting in at least one case to pellagra and fatal medullary aplasia.[55] It has also been reported to cause vitamin B12 deficiency.[56]

    Pregnancy and breastfeeding[edit]

    Azathioprine can cause birth defects.[57][58][59] A 2003 population-based study in Denmark showed that the use of azathioprine and related mercaptopurine resulted in a seven-fold incidence of fetal abnormalities as well as a 20-fold increase in miscarriage.[60] Birth defects in a child whose father was taking azathioprine have also been reported.[61] Although no adequate and well-controlled studies have taken place in humans, when given to animals in doses equivalent to human dosages, teratogenesis was observed.[62] Transplant patients already on this drug should not discontinue on becoming pregnant. This contrasts with the later-developed drugs tacrolimus and mycophenolate, which are contraindicated during pregnancy.[57]

    Traditionally, as for all cytotoxic drugs, the manufacturer advises not to breastfeed whilst taking azathioprine. However, the “Lactation Risk Category” reported by Thomas Hale in his book “Medications and Mothers’ Milk” lists azathioprine as “L3”, termed “moderately safe”.[63]

    Pharmacology[edit]

    Pharmacokinetics[edit]

    Metabolic pathway for azathioprine (AZA).[64][65] Active metabolites are highlighted.

    • XO: xanthine oxidase
    • 6-MP: 6-mercaptopurine
    • TPMT: thiopurine methyltransferase
    • 6-MMP: 6-methylmercaptopurine
    • HPRT: hypoxanthine-guanine phosphoribosyltransferase
    • TIMP: thioinosine monophosphate, thioinosinic acid
    • MeTIMP: methyl-thioinosine monophosphate
    • TGTP: thioguanosine triphosphate
    • TdGTP: thio-deoxyguanosine triphosphate

    Azathioprine is absorbed from the gut to about 88%. Bioavailability varies greatly between individual patients, between 30 and 90%, because the drug is partly inactivated in the liver. Highest blood plasma concentrations, counting not only the drug itself but also its metabolites, are reached after one to two hours; and the average plasma half-life is 26 to 80 minutes for azathioprine and three to five hours for drug plus metabolites. 20 to 30% are bound to plasma proteins while circulating in the bloodstream.[9][28][66][67]

    Azathioprine is a prodrug, a substance that is not an active drug itself but is activated in the body. This happens in several steps; at first it is slowly and almost completely converted to 6-mercaptopurine (6-MP) by reductive cleavage of the thioether (–S–). This is mediated by glutathione and similar compounds in the intestinal wall, the liver and on red blood cells, without the aid of enzymes. 6-MP is metabolized analogously to natural purines, giving thioguanosine triphosphate (TGTP) and thio-deoxyguanosine triphosphate (TdGTP) via thioinosine monophosphate (TIMP) and several further intermediates. On a second path, the sulfur atom of 6-MP and TIMP is methylated. The end products of azathioprine metabolism are thiouric acid (38%) and various methylated and hydroxylated purines, which are excreted via the urine.[36][66][67]

    Mechanism of action[edit]

    Azathioprine inhibits purine synthesis. Purines are needed to produce DNA and RNA. By inhibiting purine synthesis, less DNA and RNA are produced for the synthesis of white blood cells, thus causing immunosuppression.

    Azathioprine is converted within tissues to 6-mercaptopurine (6-MP). Some 6-MP is converted in turn to 6-thioguanine by the addition of an amino group. Both 6-MP and 6-thioguanine are conjugated with ribose, and then phosphorylated to form the nucleotides thioinosinic acid and thioguanylic acid respectively.[10] These nucleotides masquerade, respectively, as inosinic acid and guanylic acid: the former is the starting point for purine nucleotide biosynthesis, while the latter is one of the building blocks of DNA and RNA.

    • The nucleotides are incorporated into newly synthesized (but non-functional) DNA, halting replication.
    • The nucleotides act to inhibit glutamine-phosphoribosyl pyrophosphate amidotransferase (GPAT), one of the enzymes involved in purine biosynthesis, one of the earlier steps in the synthesis of DNA and RNA. They achieve GPAT inhibition through a form of negative feedback called product inhibition.[68] Because actively replicating cells (such as cancer cells and the T cells and B cells of the immune system) are most active in synthesizing purine making new DNA, these cells are most strongly affected. ].[69][9]
    • A portion of the nucleotides is additionally phosphorylated to the triphosphate forms. These bind to GTP-binding protein Rac1, blocking synthesis of the protein Bcl-xL and thus sending activated T cells and mononuclear cells into apoptosis (a kind of programmed cell death). Increased apoptosis of mononuclear cells is seen in inflammatory bowel disease patients treated with azathioprine.[69]

    Chemistry[edit]

    Azathioprine is a thiopurine linked to a second heterocycle (an imidazole derivative) via a thioether. It is a pale yellow solid with a slightly bitter taste and a melting point of 238–245 °C. It is practically insoluble in water and only slightly soluble in lipophilic solvents such as chloroform, ethanol and diethylether. It dissolves in alkaline aqueous solutions, where it hydrolyzes to 6-mercaptopurine.[66]

    Azathioprine is synthesized from 5-chloro-1-methyl-4-nitro-1H-imidazole and 6-mercaptopurine in dimethyl sulfoxide (DMSO).[70] The synthesis of the former starts with an amide from methylamine and diethyl oxalate, which is then cyclizised and chlorinated with phosphorus pentachloride;[71] the nitro group is introduced with nitric and sulfuric acid.

    History[edit]

    Azathioprine was synthesized by George Herbert Hitchings and Gertrude Elion in 1957 (named BW 57-322) to produce 6-mercaptopurine (6-MP) in a metabolically active but masked form, and at first used as a chemotherapy drug.[72][73][74]

    Robert Schwartz investigated the effect of 6-MP on the immune response in 1958 and discovered that it profoundly suppresses the formation of antibodies when given to rabbits together with antigens.[75] Following the work done by Sir Peter Medawar and Gertrude Elion in discovering the immunological basis of rejection of transplanted tissues and organs, and Schwartz’s researches on 6-MP, Sir Roy Calne, the British pioneer in transplantation, introduced 6-MP as an experimental immunosuppressant for kidney and heart transplants.[76] When Calne asked Elion for related compounds to investigate, she suggested azathioprine, which was subsequently found out to be superior (as effective and less toxic to the bone marrow) by Calne.[72][9] On 5 April 1962, with regimens consisting of azathioprine and prednisone, the transplantation of kidneys to unrelated recipients (allotransplantation) was successful for the first time.[9][77] For many years, this kind of dual therapy with azathioprine and glucocorticoids was the standard antirejection regimen, until ciclosporin was introduced into clinical practice (by Calne as well) in 1978.

    Ciclosporin has now replaced some of the azathioprine use due to a longer survival time, especially in heart-related transplantations.[78][79][80] Moreover, despite being considerably more expensive, mycophenolate mofetil is also increasingly being used in place of azathioprine in organ transplantation, as it is associated with less bone marrow suppression, fewer opportunistic infections, and a lower incidence of acute rejection.[13][81]

    References[edit]

  • ^ “Azathioprine”. Merriam-Webster Dictionary. 
  • ^ a b c d e f g h i “Azathioprine”. The American Society of Health-System Pharmacists. Archived from the original on 20 August 2016. Retrieved 8 December 2016. 
  • ^ Axelrad, JE; Lichtiger, S; Yajnik, V (28 May 2016). “Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment”. World Journal of Gastroenterology (Review). 22 (20): 4794–801. doi:10.3748/wjg.v22.i20.4794. PMC 4873872 . PMID 27239106. 
  • ^ a b Singer, O; McCune, WJ (May 2017). “Update on maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis”. Current Opinion in Rheumatology. 29 (3): 248–253. doi:10.1097/BOR.0000000000000382. PMID 28306595. 
  • ^ a b c Sami, Naveed (2016). Autoimmune Bullous Diseases: Approach and Management. Springer. p. 83. ISBN 9783319267289. Archived from the original on 2016-12-21. 
  • ^ “WHO Model List of Essential Medicines (19th List)” (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016. 
  • ^ “Azathioprine”. International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  • ^ “NADAC as of 2016-12-07 | Data.Medicaid.gov”. Centers for Medicare and Medicaid Services. Archived from the original on 21 December 2016. Retrieved 20 December 2016. 
  • ^ a b c d e f g Patel, A. A.; Swerlick, R. A.; McCall, C. O. (2006). “Azathioprine in dermatology: The past, the present, and the future”. Journal of the American Academy of Dermatology. 55 (3): 369–389. doi:10.1016/j.jaad.2005.07.059. PMID 16908341. 
  • ^ a b Evans WE. (2004). “Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy”. Ther Drug Monit. 26 (2): 186–91. doi:10.1097/00007691-200404000-00018. PMID 15228163. 
  • ^ a b c d American Society of Health-System Pharmacists (January 2012). “Azathioprine, Azathioprine Sodium”. AHFS Drug Information 2012. American Society of Health-System Pharmacists. ISBN 978-1-58528-267-8. 
  • ^ Nuyttens, J. J.; Harper, J.; Jenrette, J. M.; Turrisi, A. T. (2005). “Outcome of radiation therapy for renal transplant rejection refractory to chemical immunosuppression”. Radiotherapy and Oncology. 74 (1): 17–19. doi:10.1016/j.radonc.2004.08.011. PMID 15683663. 
  • ^ a b Remuzzi, G.; Lesti, M.; Gotti, E.; Ganeva, M.; Dimitrov, B.; Ene-Iordache, B.; Gherardi, G.; Donati, D.; et al. (August 2004). “Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial”. The Lancet. 364 (9433): 503–12. doi:10.1016/S0140-6736(04)16808-6. PMID 15302193. 
  • ^ Suarez-Almazor, M. E.; Spooner, C.; Belseck, E. (2000). Suarez-Almazor, Maria E, ed. “Azathioprine for treating rheumatoid arthritis”. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD001461. 
  • ^ a b Sandborn, W. J. (1998). “Azathioprine: State of the art in inflammatory bowel disease”. Scandinavian journal of gastroenterology. Supplement. 225: 92–99. PMID 9515759. 
  • ^ Biancone, L.; Tosti, C.; Fina, D.; Fantini, M.; De Nigris, F.; Geremia, A.; Pallone, F. (2003). “Maintenance treatment of Crohn’s disease”. Alimentary Pharmacology & Therapeutics. 17: 31–37. doi:10.1046/j.1365-2036.17.s2.20.x. PMID 12786610. 
  • ^ Rutgeerts, P. (2004). “Treatment of perianal fistulizing Crohn’s disease”. Alimentary Pharmacology & Therapeutics. 20: 106–110. doi:10.1111/j.1365-2036.2004.02060.x. PMID 15352905. 
  • ^ Kandiel, A; Fraser, AG; Korelitz, BI; Brensinger, C; Lewis, JD (Aug 2005). “Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine”. Gut. 54 (8): 1121–5. doi:10.1136/gut.2004.049460. PMC 1774897 . PMID 16009685. 
  • ^ Kirschner, B. S. (1998). “Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease”. Gastroenterology. 115 (4): 813–821. doi:10.1016/S0016-5085(98)70251-3. PMID 9753482. 
  • ^ Cosnes, J. (2013). “Early Administration of Azathioprine vs Conventional Management of Crohn’s Disease: A Randomized Controlled Trial”. Gastroenterology. 145 (4): 758–774. doi:10.1053/j.gastro.2013.04.048. 
  • ^ Timmer, A; Patton, PH; Chande, N; McDonald, JW; MacDonald, JK (18 May 2016). “Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis”. The Cochrane Database of Systematic Reviews (5): CD000478. doi:10.1002/14651858.CD000478.pub4. PMID 27192092. 
  • ^ Abu-Shakra, M.; Shoenfeld, Y. (2001). “Azathioprine therapy for patients with systemic lupus erythematosus”. Lupus. 10 (3): 152–153. doi:10.1191/096120301676669495. PMID 11315344. 
  • ^ Olszewska, M.; Kolacinska-Strasz, Z.; Sulej, J.; Labecka, H.; Cwikla, J.; Natorska, U.; Blaszczyk, M. (2007). “Efficacy and safety of cyclophosphamide, azathioprine, and cyclosporine (ciclosporin) as adjuvant drugs in pemphigus vulgaris”. American journal of clinical dermatology. 8 (2): 85–92. doi:10.2165/00128071-200708020-00004. PMID 17428113. 
  • ^ Richman, D. P.; Agius, M. A. (2003). “Treatment of autoimmune myasthenia gravis”. Neurology. 61 (12): 1652–1661. doi:10.1212/01.wnl.0000098887.24618.a0. PMID 14694025. 
  • ^ Meggitt, S. J.; Gray, J. C.; Reynolds, N. J. (2006). “Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: A double-blind, randomised controlled trial”. The Lancet. 367 (9513): 839–846. doi:10.1016/S0140-6736(06)68340-2. PMID 16530578. 
  • ^ Casetta, I.; Iuliano, G.; Filippini, G. (2009). “Azathioprine for multiple sclerosis”. Journal of Neurology, Neurosurgery & Psychiatry. 80 (2): 131–132; discussion 132. doi:10.1136/jnnp.2008.144972. PMID 19151017. 
  • ^ The Idiopathic Pulmonary Fibrosis Clinical Research Network (2012). “Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis”. N Engl J Med. 366 (21): 1968–1977. doi:10.1056/NEJMoa1113354. PMC 3422642 . PMID 22607134. 
  • ^ a b c d Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 4103–9. ISBN 978-3-85200-181-4. 
  • ^ Weersma, R. K.; Peters, F. T. M.; Oostenbrug, L. E.; van den Berg, A. P.; van Haastert, M.; Ploeg, R. J.; Posthumus, M. D.; Homan van der Heide, J. J.; Jansen, P. L. M. & van Dullemen, H. M. (October 2004). “Increased incidence of azathioprine-induced pancreatitis in Crohn’s disease compared with other diseases”. Alimentary Pharmacology & Therapeutics. 20 (8): 843–850. doi:10.1111/j.1365-2036.2004.02197.x. PMID 15479355. 
  • ^ Carol Eustice (October 23, 2005). “Blood Donation – Are rheumatoid arthritis patients able to donate blood?”. About.com. Archived from the original on March 5, 2012. Retrieved November 29, 2011. 
  • ^ a b International Agency for Research on Cancer (IARC) (1987). “Azathioprine”. Summaries & Evaluations. World Health Organization. suppl. 7: 119. Archived from the original on 2006-06-04. 
  • ^ a b Zaza G, Cheok M, Krynetskaia N, Thorn C, Stocco G, Hebert JM, McLeod H, Weinshilboum RM, Relling MV, Evans WE, Klein TE, Altman RB (September 2010). “Thiopurine pathway”. Pharmcogenet Genomics. 20 (9): 573–4. doi:10.1097/FPC.0b013e328334338f. PMC 3098750 . PMID 19952870. 
  • ^ Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G (April 2014). “Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase?”. World J Gastroenterol. 20 (13): 3534–41. doi:10.3748/wjg.v20.i13.3534. PMC 3974520 . PMID 24707136. 
  • ^ Fujita K, Sasaki Y (August 2007). “Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy”. Curr. Drug Metab. 8 (6): 554–62. doi:10.2174/138920007781368890. PMID 17691917. Archived from the original on 2013-01-12. 
  • ^ a b c Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE (March 2011). Clinical Pharmacogenetics Implementation Consortium. “Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing”. Clin Pharmacol Ther. 89 (3): 387–91. doi:10.1038/clpt.2010.320. PMC 3098761 . PMID 21270794. 
  • ^ a b Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 107, 936. ISBN 3-8047-1763-2. 
  • ^ Payne, K.; Newman, W.; Fargher, E.; Tricker, K.; Bruce, I. N.; Ollier, W. E. R. (2007). “TPMT testing in rheumatology: Any better than routine monitoring?”. Rheumatology. 46 (5): 727–729. doi:10.1093/rheumatology/kel427. PMID 17255139. 
  • ^ “Label: Imuran – azathioprine tablet”. Archived from the original on 20 October 2014. Retrieved 19 October 2014. 
  • ^ Wang L, Pelleymounter L, Weinshilboum R, Johnson JA, Hebert JM, Altman RB, Klein TE (June 2010). “Very important pharmacogene summary: thiopurine S-methyltransferase”. Pharmacogenet Genomics. 20 (6): 401–5. doi:10.1097/FPC.0b013e3283352860. PMC 3086840 . PMID 20154640. 
  • ^ Yang SK, Hong M, Baek J, Choi H, Zhao W, Jung Y, et al. (September 2014). “A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia”. Nature Genetics. 46 (9): 1017–20. doi:10.1038/ng.3060. PMC 4999337 . PMID 25108385. 
  • ^ National Toxicology Program (10 June 2011). “Report On Carcinogens – Twelfth Edition – 2011” (PDF). National Toxicology Program. Archived (PDF) from the original on 16 July 2012. Retrieved June 20, 2012. 
  • ^ “FDA: Cancer Warnings Required for TNF Blockers”. FDA. August 4, 2009. Archived from the original on July 3, 2012. Retrieved June 20, 2012. 
  • ^ International Agency for Research on Cancer (IARC) (1981). “Azathioprine – 5. Summary of Data Reported and Evaluation”. Summaries & Evaluations. World Health Organization. 26: 47. Archived from the original on 2006-09-06. 
  • ^ Gombar V, Enslein K, Blake B, Einstein K (1993). “Carcinogenicity of azathioprine: an S-AR investigation”. Mutat Res. 302 (1): 7–12. doi:10.1016/0165-7992(93)90083-8. PMID 7683109. 
  • ^ McGovern, D. P. B.; Jewell, D. P. (2005). “Risks and benefits of azathioprine therapy”. Gut. 54 (8): 1055–1059. doi:10.1136/gut.2004.053231. PMC 1774869 . PMID 16009676. 
  • ^ “Imuran (azathioprine) Tablets and Injection”. FDA. May 2011. Archived from the original on March 2, 2012. Retrieved June 20, 2012. 
  • ^ “Skin cancer alert for organ drug”. BBC Online. BBC news. September 15, 2005. Archived from the original on October 14, 2012. Retrieved June 10, 2012. 
  • ^ O’Donovan, P.; Perrett, C. M.; Zhang, X.; Montaner, B.; Xu, Y.-Z.; Harwood, C. A.; McGregor, J. M.; Walker, S. L.; Hanaoka, F.; Karran, P. (2005). “Azathioprine and UVA Light Generate Mutagenic Oxidative DNA Damage”. Science. 309 (5742): 1871–1874. doi:10.1126/science.1114233. PMC 2426755 . PMID 16166520. 
  • ^ Sahasranaman, S.; Howard, D.; Roy, S. (2008). “Clinical pharmacology and pharmacogenetics of thiopurines”. European Journal of Clinical Pharmacology. 64 (8): 753–767. doi:10.1007/s00228-008-0478-6. PMID 18506437. 
  • ^ Chocair P, Duley J, Simmonds HA, et al. (1993). “Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen”. Lancet. 342 (8863): 83–84. doi:10.1016/0140-6736(93)91287-V. PMID 8100914. 
  • ^ Sparrow MP, Hande SA, Friedman S, et al. (2005). “Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine”. Aliment Pharmacol Ther. 22 (5): 441–6. doi:10.1111/j.1365-2036.2005.02583.x. PMID 16128682. 
  • ^ Sparrow, M. P.; Hande, S. A.; Friedman, S.; Cao, D.; Hanauer, S. B. (2007). “Effect of Allopurinol on Clinical Outcomes in Inflammatory Bowel Disease Nonresponders to Azathioprine or 6-Mercaptopurine”. Clinical Gastroenterology and Hepatology. 5 (2): 209–214. doi:10.1016/j.cgh.2006.11.020. PMID 17296529. 
  • ^ Govani SM, Higgins PD (2010). “Combination of thiopurines and allopurinol: adverse events and clinical benefit in IBD”. J Crohns Colitis. 4 (4): 444–9. doi:10.1016/j.crohns.2010.02.009. PMC 3157326 . PMID 21122542. 
  • ^ Ansari AR, Patel N, Sanderson J, et al. (2010). “Low dose azathioprine or 6-mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease”. Aliment Pharmacol Ther. 31 (6): 640–647. doi:10.1111/j.1365-2036.2009.04221.x. PMID 20015102. 
  • ^ Oliveria A, Sanches M, Selores M (2011). “Azathioprine-induced pellagra”. J Dermatol. 38 (10): 1035–7. doi:10.1111/j.1346-8138.2010.01189.x. PMID 21658113. 
  • ^ Kim CJ, Park K, Inoue H, et al. (1998). “Azathioprine-Induced megaloblastic anemia with pancytopenia 22 years after living-related renal transplantation”. Int J Urol. 5 (1): 100–102. doi:10.1111/j.1442-2042.1998.tb00250.x. PMID 9535611. 
  • ^ a b Dinesh K. Mehta (March 2003). British National Formulary, Issue 45. Pharmaceutical Society of Great Britain. London: British Medical Association. ISBN 0-85369-555-5. 
  • ^ Cleary, B. J.; Källén, B. (2009). “Early pregnancy azathioprine use and pregnancy outcomes”. Birth Defects Research Part A: Clinical and Molecular Teratology. 85 (7): 647–654. doi:10.1002/bdra.20583. PMID 19343728. 
  • ^ Tagatz, G. E.; Simmons, R. L. (1975). “Pregnancy after renal transplantation”. Annals of Internal Medicine. 82 (1): 113–114. doi:10.7326/0003-4819-82-1-113. PMID 799904. 
  • ^ Nørgård, B.; L. Pedersen; K. Fonager; S. Rasmussen; H. Sørensen (March 2003). “Azathioprine, mercaptopurine and birth outcome: a population-based cohort study”. Alimentary Pharmacology & Therapeutics. 17 (6): 827–834. doi:10.1046/j.1365-2036.2003.01537.x. PMID 12641505. 
  • ^ Tallent, M. B.; Simmons, R. L.; Najarian, J. S. (1970). “Birth defects in child of male recipient of kidney transplant”. JAMA: the Journal of the American Medical Association. 211 (11): 1854–1855. doi:10.1001/jama.211.11.1854. PMID 4905893. 
  • ^ Polifka, J. E.; Friedman, J. M. (2002). “Teratogen update: Azathioprine and 6-mercaptopurine”. Teratology. 65 (5): 240–261. doi:10.1002/tera.10043. PMID 11967923. 
  • ^ Thomas W. Hale (April 2010). Medications and Mothers’ Milk: A Manual of Lactational Pharmacology. Hale Pub. ISBN 978-0-9823379-9-8. 
  • ^ Cronstein, B. N. (2004). “Pharmacogenetics in the rheumatic diseases”. Annals of the Rheumatic Diseases. 63 (Suppl 2): ii25–ii27. doi:10.1136/ard.2004.028217. PMC 1766779 . PMID 15479867. 
  • ^ Karran, P.; Attard, N. (2008). “Thiopurines in current medical practice: Molecular mechanisms and contributions to therapy-related cancer”. Nature Reviews Cancer. 8 (1): 24–36. doi:10.1038/nrc2292. PMID 18097462. 
  • ^ a b c Dinnendahl, V; Fricke, U, eds. (2011). Arzneistoff-Profile (in German). 2 (25th ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3. 
  • ^ a b Steinhilber, D; Schubert-Zsilavecz, M; Roth, HJ (2005). Medizinische Chemie (in German). Stuttgart: Deutscher Apotheker Verlag. p. 340. ISBN 3-7692-3483-9. 
  • ^ “Azathioprine Pathway”. Small Molecule Pathway Database. Archived from the original on 2 July 2012. Retrieved 31 August 2012. 
  • ^ a b Maltzman, J. S.; Koretzky, G. A. (2003). “Azathioprine: Old drug, new actions”. Journal of Clinical Investigation. 111 (8): 1122–1124. doi:10.1172/JCI18384. PMC 152947 . PMID 12697731. 
  • ^ US Patent 3056785, G. H. Hitchings; Yonkers & G. B. Elion, “Purine Derivatives”, issued 1962-10-06 .
  • ^ Blicke, F. F.; Godt, H. C. (1954). “Diuretics. I. 3-Substituted Paraxanthines”. Journal of the American Chemical Society. 76 (14): 3653–3655. doi:10.1021/ja01643a015. 
  • ^ a b Elion, G. (1989). “The purine path to chemotherapy”. Science. 244 (4900): 41–47. doi:10.1126/science.2649979. PMID 2649979. 
  • ^ Elion, G. B.; Callahan, S. W.; Hitchings, G. H.; Rundles, R. W. (1960). “The metabolism of 2-amino-6-(1-methyl-4-nitro-5-imidazolyl)thiopurine (B.W. 57-323) in man”. Cancer Chemotherapy Reports. Part 1. 8: 47–52. PMID 13849699. 
  • ^ Thiersch, J. B. (1962). “Effect of 6-(1′-methyl-4′-nitro-5′-imidazolyl)-mercaptopurine and 2-amino-6-(1′-methyl-4′-nitro-5′-imidazolyl)-mercaptopurine on the rat litter in utero”. Journal of reproduction and fertility. 4 (3): 297–302. doi:10.1530/jrf.0.0040297. PMID 13980986. 
  • ^ Schwartz, R.; Stack, J.; Dameshek, W. (1958). “Effect of 6-mercaptopurine on antibody production”. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine. 99 (1): 164–167. doi:10.3181/00379727-99-24281. PMID 13601801. 
  • ^ Calne, R. Y. (1960). “The rejection of renal homografts”. The Lancet. 275 (7121): 417–418. doi:10.1016/S0140-6736(60)90343-3. 
  • ^ Murray, J. E.; Merrill, J. P.; Harrison, J. H.; Wilson, R. E.; Dammin, G. J. (1963). “Prolonged Survival of Human-Kidney Homografts by Immunosuppressive Drug Therapy”. New England Journal of Medicine. 268 (24): 1315–1323. doi:10.1056/NEJM196306132682401. PMID 13936775. 
  • ^ Bakker, R. C.; Hollander, A. A. M. J.; Mallat, M. J. K.; Bruijn, J. A.; Paul, L. C.; De Fijter, J. W. (2003). “Conversion from cyclosporine to azathioprine at three months reduces the incidence of chronic allograft nephropathy”. Kidney International. 64 (3): 1027–1034. doi:10.1046/j.1523-1755.2003.00175.x. PMID 12911553. 
  • ^ Henry, M. L.; Sommer, B. G.; Ferguson, R. M. (1985). “Beneficial effects of cyclosporine compared with azathioprine in cadaveric renal transplantation”. The American Journal of Surgery. 150 (5): 533–536. doi:10.1016/0002-9610(85)90431-3. 
  • ^ Modry, D. L.; Oyer, P. E.; Jamieson, S. W.; Stinson, E. B.; Baldwin, J. C.; Reitz, B. A.; Dawkins, K. D.; McGregor, C. G.; Hunt, S. A.; Moran, M. (1985). “Cyclosporine in heart and heart-lung transplantation”. Canadian Journal of Surgery. 28 (3): 274–280, 282. PMID 3922606. 
  • ^ Woodroffe R; Yao G; Meads C; Bayliss S; Ready A; Raftery J; Taylor R (2005). “Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study”. Health Technol Assess. 9 (21): 1–194. PMID 15899149. 
  • External links[edit]

    • Imuran
    • Azasan (manufacturer’s website)
    • U.S. National Library of Medicine: Drug Information Portal – Azathioprine

    Intracellular
    (reception)

    Extracellular

    Polyclonal

    • Anti-thymocyte globulin
    • Anti-lymphocyte globulin

    -cept (Fusion)

    • CTLA-4
      • Abatacept
      • Belatacept
    • TNF inhibitor
      • Etanercept
      • Pegsunercept
    • Aflibercept
    • Alefacept
    • Rilonacept
    • Pharmacy and pharmacology portal
    • Medicine portal


    Source: https://en.wikipedia.org/wiki/Azathioprine