Dexamethasone

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Dexamethasone
Systematic (IUPAC) name
(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
Identifiers
CAS number	50-02-2
ATC code	?
PubChem	5743
DrugBank	APRD00674
ChemSpider	5541
Chemical data
Formula	?
Mol. mass	392.461 g/mol
Physical data
Solubility in water	89(EXP) at 25^oC mg/mL
Pharmacokinetic data
Bioavailability	80-90%
Protein binding	70%
Metabolism	hepatic
Half life	36-54 hours
Excretion	renal
Therapeutic considerations
Pregnancy cat.	C(US)
Legal status	Template:Unicode Prescription only
Routes	Oral, IV, IM, SC and IO

An anti-inflammatory 9-fluoro-glucocorticoid.Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. It acts as an anti-inflammatory and immunosuppressant. Its potency is about 20-30 times that of hydrocortisone and 4-5 times of prednisone.

[edit] General Properties

*Molecular Weight

392.46

*Molecular Formula

C₂₂H₂₉FO₅

*IUPAC NAME

(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one

*Canonical Smiles

CC1CC2C3CCC4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)CO)O)C)O)F)C

*Isomeric Smiles

C[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@@]4([C@]3([C@H](C[C@@]2([C@]1(C(=O)CO)O)C)O)F)C

[edit] PhysioChemical Properties

*Melting Point

262(EXP)

*LogP

1.83(EXP)

*Water Solubility

89(EXP) at 25C

[edit] Therapeutic use

[edit] Anti-inflammatory

Dexamethasone is used to treat many inflammatory and autoimmune conditions, e.g., rheumatoid arthritis.

It is also given in small amounts (usually 5-6 tablets) before and/or after some forms of dental surgery, such as the extraction of the wisdom teeth, an operation which often leaves the patient with puffy, swollen cheeks.

It is injected into the heel when treating plantar fasciitis, sometimes in conjunction with triamcinolone acetonide.

It is useful to counteract allergic anaphylactic shock, if given in high doses. It is present in certain eye drops and as a nasal spray (trade name Dexacort).

Dexamethasone is used in transvenous screw-in cardiac pacing leads to minimize the inflammatory response of the myocardium. The steroid is released into the myocardium as soon as the screw is extended and can play a significant role in minimizing the acute pacing threshold due to the reduction of inflammatory response. The typical quantity present in a lead tip is less than 1.0 mg.

Dexamethasone is often administered before antibiotics in cases of bacterial meningitis. It then acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics (bacterial death releases pro-inflammatory mediators that can cause a response which is harmful to the patient), thus improving prognosis and outcome.<ref>van de Beek D, de Gans J, McIntyre P, Prasad K (2007). "Corticosteroids for acute bacterial meningitis". Cochrane Database Syst Rev (1): CD004405. doi:10.1002/14651858.CD004405.pub2. PMID 17253505. </ref>

[edit] Oncologic uses

In oncology, it is given to cancer patients undergoing chemotherapy, to counteract certain side-effects of their antitumor treatment. Dexamethasone can augment the antiemetic effect of 5-HT₃ receptor antagonists like ondansetron. Dexamethasone is also used in certain hematological malignancies, especially in the treatment of multiple myeloma, in which dexamethasone is given alone or together with thalidomide (thal-dex) or a combination of Adriamycin (doxorubicin) and vincristine (VAD). In brain tumours (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures. Dexamethasone is also given in cord compression where a tumor is compressing the spinal cord.

[edit] Endocrine

Dexamethasone can be used in the context of congenital adrenal hyperplasia, to prevent virilisation of a female fetus. If one or both parents are carriers of mutations to the CYP21A gene, the mother may start dexamethasone treatment within 7 weeks of conception. At the 12th week, a chorionic villus sample will determine whether the fetus is male (in which case the dexamethasone is stopped) or female. Subsequent DNA analysis can then reveal whether the female fetus is a carrier of the mutation, in which case dexamethasone treatment must continue until birth. The side-effects for the mother can be severe and the long-term impact on the child is not clear.

In adrenal insufficiency and Addison's disease, dexamethasone is prescribed when the person doesn't respond well to prednisone or methylprednisone.

[edit] Obstetrics

Dexamethasone may be given to women at risk of delivering prematurely in order to promote maturation of the fetus' lungs. This has been associated with low birth weight, although not with increased rates of neonatal death.<ref>Bloom SL, Sheffield JS, McIntire DD, Leveno KJ (2001). "Antenatal dexamethasone and decreased birth weight". Obstet Gynecol 97 (4): 485–90. doi:10.1016/S0029-7844(00)01206-0. PMID 11275014. </ref>

[edit] High altitude illnesses

Dexamethasone is used in the treatment of high altitude cerebral edema as well as pulmonary edema. It is commonly carried on mountain climbing expeditions to help climbers deal with altitude sickness. <ref>COMMENTS AND RESPONSES Reducing the Incidence of High-Altitude Pulmonary Edema Annals of Internal Medicine PDF</ref>

[edit] Diagnostic use

Dexamethasone is also used in a diagnostic context, namely in its property to suppress the natural pituitary-adrenal axis. Patients presenting with clinical signs of glucocorticoid excess (Cushing's syndrome) are generally diagnosed by a 24-hour urine collection for cortisol or by a dexamethasone suppression test. During the latter, the response of the body to a high dose of glucocorticoids is monitored. Various forms are performed. In the most common form, a patient takes a nighttime dose of either 1 or 4 mg of dexamethasone, and the serum cortisol levels are measured in the morning. If the levels are relatively high (over 5 µg/dl or 150 nmol/l), then the test is positive and the patient has an autonomous source of either cortisol or ACTH, indicating Cushing's syndrome where the tumor does not have a feedback mechanism. If ACTH levels are lowered by at least 50%, this would indicate Cushing's Disease, since the pituitary adenoma has a feedback mechanism that has been reset to a higher level of cortisol. Longer versions rely on urine collections on oral dexamethasone over various days.

[edit] Veterinary use

Combined with marbofloxacin and clotrimazole, dexamethasone is available under the name Aurizon , CAS number 115550-35-1, and used to treat difficult ear infections, especially in dogs. It can also be combined with Trichlormethiazide to treat horses with swelling of distal limbs and general bruising.<ref name="wedgewood">Template:Cite web</ref>

[edit] Contraindications

Some of these contraindications are relative:

Existing gastrointestinal ulceration
Cushing's syndrome
Severe forms of heart insufficiency
Severe hypertension
Uncontrolled diabetes mellitus
Systemic tuberculosis
Severe systemic viral, bacterial, and fungal infections
Preexisting wide angle glaucoma
Osteoporosis

[edit] Side effects

If dexamethasone is given orally or by injection (parenteral) over a period of more than a few days, side-effects common to systemic glucocorticoids may occur. These may include:

Stomach upset, increased sensitivity to stomach acid to the point of ulceration of esophagus, stomach, and duodenum
Increased appetite leading to significant weight gain
A latent diabetes mellitus often becomes manifest. Glucose intolerance is worsened in patients with preexisting diabetes.
Immunsuppressant action, particularly if given together with other immunosuppressants such as ciclosporine. Bacterial, viral, and fungal disease may progress more easily and can become life-threatening. Fever as a warning symptom is often suppressed.
Psychiatric disturbances, including personality changes, irritability, euphoria, mania
Osteoporosis under long term treatment, pathologic fractures (e.g., hip)
Muscle atrophy, negative protein balance (catabolism)
Elevated liver enzymes, fatty liver degeneration (usually reversible)
Cushingoid (syndrome resembling hyperactive adrenal cortex with increase in adiposity, hypertension, bone demineralization, etc.)
Depression of the adrenal gland is usually seen, if more than 1.5 mg daily are given for more than three weeks to a month.
Hypertension, fluid and sodium retention, edema, worsening of heart insufficiency (due to mineral corticoid activity)
Dependence with withdrawal syndrome is frequently seen.
Increased intraocular pressure, certain types of glaucoma, cataract (serious clouding of eye lenses)
Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound-healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
Allergic reactions (though infrequently): Anaphylactoid reaction, anaphylaxis, angioedema. (Highly unlikely, since dexamethasone is given to prevent anaphylactoid reactions.)

Other side-effects have been noted, and should cause concern if they are more than mild.

The short time treatment for allergic reaction, shock, and diagnostic purposes usually does not cause serious side effects.

[edit] Interactions

NSAIDs and alcohol: increased risk of gastrointestinal ulceration
Mineralocorticoids: increased risk of hypertension, edema and heart problems
Oral antidiabetic drugs and insulin: antidiabetic therapy may have to be adjusted

Other interactions (with certain antibiotics, estrogens, ephedrine, digoxin) are known.

[edit] Dosage

Shock: 4 to 8 mg intravenously initially, repeat if necessary to a total dose of 24 mg.
Autoimmune diseases and inflammations: longterm therapy with 0.5 to 1.5 mg oral per day. Avoid more than 1.5 mg daily, because serious side effects are more frequently encountered with higher doses.
Adjuvant to or part of chemotherapy: individual schedule
Diagnostic purposes: special schedule

[edit] Sports doping

In 2005, Polish cross country skier Justyna Kowalczyk was disqualified from the Under 23 (U23) OPA (Alpine nations) Intercontinential Competition in Germany and issued a 2-year suspension for her doping offenses on dexamethasone.<ref>June 13, 2005 FIS Doping Control statement on Kowalcyzk (Digitized version). - Accessed July 30, 2006</ref> This was eventually reduced to one year during 2005 and later rescinded by the Court of Arbitration for Sport in December 2005.<ref>December 14, 2005 FIS Newsflash on her overturned suspension (Digitized version). - Accessed July 30, 2006</ref> She would later earn a bronze in the women's 30 km freestyle mass start at the 2006 Winter Olympics in Turin.

[edit] External Links

[1]Pubchem
[2]]KEGG Drug
[3]Human Metabolome DataBase
[4]Drugbank
Understanding Dexamethasone and Other Steroids

@@ Line 1: / Line 1: @@
 <table align='right' border=1>
 <tr><td>
@@ Line 11: / Line 9: @@
 </jmol>
 </td></tr></table>
-==Description==
-An anti-inflammatory 9-fluoro-glucocorticoid.
+[http://crdd.osdd.net/raghava/hmrbase/test_extract.php?db=arun&table=nphormonet&id=1042&show=SHOW-3D Show 3-D Structure]
+{{drugbox
+| IUPAC_name = (8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
+| CAS_number = 50-02-2
+| ChemSpiderID = 5541
+| ATC_suffix = AC02
+| ATC_supplemental=
+| PubChem = 5743
+| DrugBank = APRD00674
+| formula=C<sub>2</sub><sub>2</sub>H<sub>2</sub><sub>9</sub>FO<sub>5</sub>
+| molecular_weight = 392.461 g/mol
+| melting point = 262(EXP)
+|solubility = 89(EXP) at 25<sup>o</sup>C
+| bioavailability = 80-90%
+| protein_bound = 70%
+| metabolism = [[hepatic]]
+| elimination_half-life = 36-54 hours
+| excretion = renal
+| pregnancy_AU =
+| pregnancy_US = C
+| pregnancy_category =
+| legal_status = Rx-only
+| routes_of_administration = Oral, [[Intravenous therapy|IV]], [[Intramuscular injection|IM]], [[Subcutaneous injection|SC]] and [[Intraosseous|IO]]
+}}
+An anti-inflammatory 9-fluoro-glucocorticoid.'''Dexamethasone''' is a potent synthetic member of the glucocorticoid class of [[steroid]] [[hormone]]s. It acts as an [[anti-inflammatory]] and [[immunosuppressive drug|immunosuppressant]]. Its potency is about 20-30 times that of [[hydrocortisone]] and 4-5 times of [[prednisone]].
 ==General Properties==
@@ Line 41: / Line 64: @@
 (EXP)
 <b>*LogP</b>
@@ Line 49: / Line 73: @@
 (EXP) at 25C
+==Therapeutic use==
+===Anti-inflammatory===
+Dexamethasone is used to treat many [[inflammation|inflammatory]] and [[autoimmune disease|autoimmune]] conditions, e.g., [[rheumatoid arthritis]].
+It is also given in small amounts (usually 5-6 tablets) before and/or after some forms of [[dental surgery]], such as the extraction of the [[wisdom teeth]], an operation which often leaves the patient with puffy, swollen cheeks.
+It is injected into the heel when treating [[plantar fasciitis]], sometimes in conjunction with [[triamcinolone acetonide]].
+It is useful to counteract allergic anaphylactic shock, if given in high doses.  It is present in certain [[eye drop]]s and as a [[nasal spray]] (trade name Dexacort).
+Dexamethasone is used in transvenous screw-in cardiac pacing leads to minimize the inflammatory response of the myocardium. The steroid is released into the myocardium as soon as the screw is extended and can play a significant role in minimizing the acute pacing threshold due to the reduction of inflammatory response. The typical quantity present in a lead tip is less than 1.0&nbsp;mg.
+Dexamethasone is often administered before antibiotics in cases of bacterial meningitis. It then acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics (bacterial death releases pro-inflammatory mediators that can cause a response which is harmful to the patient), thus improving prognosis and outcome.<ref>{{cite journal |author=van de Beek D, de Gans J, McIntyre P, Prasad K |title=Corticosteroids for acute bacterial meningitis |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD004405 |year=2007 |pmid=17253505 |doi=10.1002/14651858.CD004405.pub2 |url=http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD004405/frame.html}}</ref>
+===Oncologic uses===
+In oncology, it is given to [[cancer]] patients undergoing [[chemotherapy]], to counteract certain [[Adverse drug reaction|side-effects]] of their antitumor treatment. Dexamethasone can augment the [[antiemetic]] effect of [[5-HT3 antagonist|5-HT<sub>3</sub> receptor antagonists]] like [[ondansetron]].  Dexamethasone is also used in certain [[hematological malignancy|hematological malignancies]], especially in the treatment of [[multiple myeloma]], in which dexamethasone is given alone or together with [[thalidomide]] (thal-dex) or a combination of [[Adriamycin]] (doxorubicin) and [[vincristine]] (VAD).  In [[brain tumour]]s (primary or metastatic), dexamethasone is used to counteract the development of [[edema]], which could eventually compress other brain structures.  Dexamethasone is also given in [[cord compression]] where a tumor is compressing the spinal cord.
+===Endocrine===
+Dexamethasone can be used in the context of [[congenital adrenal hyperplasia]], to prevent [[virilisation]] of a female fetus.  If one or both parents are carriers of mutations to the CYP21A gene, the mother may start dexamethasone treatment within 7 weeks of [[Conception (biology)|conception]].  At the 12th week, a [[chorionic villus sampling|chorionic villus sample]] will determine whether the fetus is male (in which case the dexamethasone is stopped) or female. Subsequent DNA analysis can then reveal whether the female fetus is a carrier of the mutation, in which case dexamethasone treatment must continue until birth. The side-effects for the mother can be severe and the long-term impact on the child is not clear.
+In adrenal insufficiency and Addison's disease, dexamethasone is prescribed when the person doesn't respond well to prednisone or methylprednisone.
+===Obstetrics===
+Dexamethasone may be given to women at risk of delivering prematurely in order to promote [[Respiratory system#Development|maturation]] of the fetus' lungs. This has been associated with [[low birth weight]], although not with increased rates of neonatal death.<ref>{{cite journal |author=Bloom SL, Sheffield JS, McIntire DD, Leveno KJ |title=Antenatal dexamethasone and decreased birth weight |journal=Obstet Gynecol |volume=97 |issue=4 |pages=485–90 |year=2001 |pmid=11275014 |url=http://www.greenjournal.org/cgi/content/full/97/4/485 |doi=10.1016/S0029-7844(00)01206-0}}</ref>
+===High altitude illnesses===
+Dexamethasone is used in the treatment of [[high altitude cerebral edema]] as well as pulmonary edema.  It is commonly carried on mountain climbing expeditions to help climbers deal with altitude sickness. <ref>COMMENTS AND RESPONSES Reducing the Incidence of High-Altitude Pulmonary Edema
+Annals of Internal Medicine [http://www.annals.org/cgi/reprint/146/8/615.pdf PDF]</ref>
+==Diagnostic use==
+Dexamethasone is also used in a ''diagnostic'' context, namely in its property to suppress the natural [[Hypothalamic-pituitary-adrenal axis|pituitary-adrenal axis]].
+Patients presenting with clinical signs of glucocorticoid excess ([[Cushing's syndrome]]) are generally diagnosed by a 24-hour urine collection for cortisol or by a ''[[dexamethasone suppression test]]''. During the latter, the response of the body to a high dose of glucocorticoids is monitored. Various forms are performed. In the most common form, a patient takes a nighttime dose of either 1 or 4&nbsp;mg of dexamethasone, and the serum cortisol levels are measured in the morning. If the levels are relatively high (over 5&nbsp;µg/dl or 150 nmol/l), then the test is positive and the patient has an autonomous source of either [[cortisol]] or [[ACTH]], indicating Cushing's syndrome where the tumor does not have a feedback mechanism. If ACTH levels are lowered by at least 50%, this would indicate [[Cushing's Disease]], since the [[pituitary adenoma]] has a feedback mechanism that has been reset to a higher level of cortisol.  Longer versions rely on urine collections on oral dexamethasone over various days.
+==Veterinary use==
+Combined with [[marbofloxacin]] and [[clotrimazole]], dexamethasone is available under the name ''Aurizon '', [[CAS number]] 115550-35-1, and used to treat difficult ear infections, especially in dogs. It can also be combined with [[Trichlormethiazide]] to treat horses with swelling of [[distal]] limbs and general [[bruising]].<ref name="wedgewood">{{cite web |url=http://www.wedgewoodpharmacy.com/monographs/trichlormethiazide.asp |title=Trichlormethiazide and Dexamethasone for veterinary use | author= | publisher=Wedgewood Pharmacy |accessdate=2008-01-23 |format= |work=}}</ref>
+==Contraindications==
+Some of these [[contraindications]] are relative:
+* Existing gastrointestinal [[Peptic ulcer|ulceration]]
+* Cushing's syndrome
+* Severe forms of heart insufficiency
+* Severe [[hypertension]]
+* Uncontrolled [[diabetes mellitus]]
+* Systemic [[tuberculosis]]
+* Severe systemic viral, bacterial, and fungal infections
+* Preexisting wide angle [[glaucoma]]
+* [[Osteoporosis]]
+==Side effects==
+If dexamethasone is given orally or by injection (parenteral) over a period of more than a few days, side-effects common to systemic glucocorticoids may occur. These may include:
+* Stomach upset, increased sensitivity to stomach acid to the point of ulceration of esophagus, stomach, and duodenum
+* Increased appetite leading to significant weight gain
+* A latent diabetes mellitus often becomes manifest.  Glucose intolerance is worsened in patients with preexisting diabetes.
+* Immunsuppressant action, particularly if given together with other immunosuppressants such as ciclosporine. Bacterial, viral, and fungal disease may progress more easily and can become life-threatening. Fever as a warning symptom is often suppressed.
+* Psychiatric disturbances, including personality changes, irritability, euphoria, mania
+* Osteoporosis under long term treatment, pathologic fractures (e.g., hip)
+* Muscle atrophy, negative protein balance (catabolism)
+* Elevated liver enzymes, fatty liver degeneration (usually reversible)
+* Cushingoid (syndrome resembling hyperactive adrenal cortex with increase in adiposity, hypertension, bone demineralization, etc.)
+* Depression of the adrenal gland is usually seen, if more than 1.5&nbsp;mg daily are given for more than three weeks to a month.
+* Hypertension, fluid and sodium retention, edema, worsening of heart insufficiency (due to mineral corticoid activity)
+* Dependence with withdrawal syndrome is frequently seen.
+* Increased intraocular pressure, certain types of glaucoma, cataract (serious clouding of eye lenses)
+* Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound-healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
+* Allergic reactions (though infrequently): [[Anaphylactoid reactions|Anaphylactoid reaction]], [[anaphylaxis]], [[angioedema]].  (Highly unlikely, since dexamethasone is given to ''prevent'' anaphylactoid reactions.)
+Other side-effects have been noted, and should cause concern if they are more than mild.
+The short time treatment for allergic reaction, shock, and diagnostic purposes usually does not cause serious side effects.
+==Interactions==
+* NSAIDs and alcohol: increased risk of gastrointestinal ulceration
+* Mineralocorticoids: increased risk of hypertension, edema and heart problems
+* Oral antidiabetic drugs and insulin: antidiabetic therapy may have to be adjusted
+Other interactions (with certain antibiotics, estrogens, ephedrine, digoxin) are known.
+==Dosage==
+* Shock: 4 to 8&nbsp;mg intravenously initially, repeat if necessary to a total dose of 24&nbsp;mg.
+* Autoimmune diseases and inflammations: longterm therapy with 0.5 to 1.5&nbsp;mg oral per day. Avoid more than 1.5&nbsp;mg daily, because serious side effects are more frequently encountered with higher doses.
+* Adjuvant to or part of chemotherapy: individual schedule
+* Diagnostic purposes: special schedule
+==Sports doping==
+In [[2005]], [[Poland|Polish]] [[cross country skier]] [[Justyna Kowalczyk]] was disqualified from the Under 23 (U23) OPA (Alpine nations) Intercontinential Competition in [[Germany]] and issued a 2-year suspension for her doping offenses on dexamethasone.<ref>[http://www.fis-ski.com/data/document/info-kowalczyk.pdf June 13, 2005 FIS Doping Control statement on Kowalcyzk (Digitized version).] - Accessed [[July 30]], [[2006]]</ref> This was eventually reduced to one year during 2005 and later rescinded by the [[Court of Arbitration for Sport]] in December 2005.<ref>[http://www.fis-ski.com/data/document/fisnewsflash2005_12_14.pdf December 14, 2005 FIS Newsflash on her overturned suspension (Digitized version).] - Accessed July 30, 2006</ref> She would later earn a bronze in the women's 30&nbsp;km freestyle mass start at the [[2006 Winter Olympics]] in [[Turin]].
 ==External Links==
@@ Line 55: / Line 164: @@
 *[http://www.hmdb.ca/metabolites/]Human Metabolome DataBase
 *[http://www.drugbank.ca/drugs/DB01234]Drugbank
+* [http://www.myeloma.org/main.jsp?source=link&source_link_id=2117&type=article&tab_id=13&menu_id=94&id=1749 Understanding Dexamethasone and Other Steroids]
-[[Categories:Hormones]]
+[[Category:Hormones]]
+[[Category:Glucocorticoids]]
+[[Category:Organofluorides]]
+[[Category:World Health Organization essential medicines]]