Dexamethasone

Dexamethasone

Systematic (IUPAC) name
(8S,9R,10S,11S,13S,14S,16R,17R)-9- Fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17- dodecahydro-3H-cyclopenta[a]phenanthren-3-one
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682792
Pregnancy category	AU: A US: C (Risk not ruled out)
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral, IV, IM, SC and IO
Pharmacokinetic data
Bioavailability	80-90%
Protein binding	77%
Metabolism	hepatic
Biological half-life	190 minutes
Excretion	Urine (65%)
Identifiers
CAS Number	50-02-2 Y
ATC code	A01AC02 (WHO) C05AA09, D07AB19, D10AA03, H02AB02, R01AD03, S01BA01,S02BA06, S03BA01
PubChem	CID: 5743
IUPHAR/BPS	2768
DrugBank	DB01234 N
ChemSpider	5541 Y
UNII	7S5I7G3JQL Y
KEGG	D00292 Y
ChEBI	CHEBI:41879 Y
ChEMBL	CHEMBL384467 Y
Chemical data
Formula	C22H29FO5
Molecular mass	392.461 g/mol
SMILES O=C(CO)[C@]3(O)[C@]2(C[C@H](O)[C@]4(F)[C@@]/1(\C(=C/C(=O)\C=C\1)CC[C@H]4[C@@H]2C[C@H]3C)C)C
InChI InChI=1S/C22H29FO5/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,23)17(26)10-20(16,3)22(12,28)18(27)11-24/h6-7,9,12,15-17,24,26,28H,4-5,8,10-11H2,1-3H3/t12-,15+,16+,17+,19+,20+,21+,22+/m1/s1 Y Key:UREBDLICKHMUKA-CXSFZGCWSA-N Y
Physical data
Melting point	262 °C (504 °F)
NY (what is this?)  (verify)

Dexamethasone is a type of steroid medication. It is used in the treatment of rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, and along with antibiotics in tuberculosis, among others. In adrenocortical insufficiency it should be used together with a medication that has greater mineralocorticoid effects such as fludrocortisone. In preterm labor it may be used to improve outcomes in the baby. It may be taken by mouth, as an injection into a muscle, or intravenously. The effects of dexamethasone are frequently seen within a day and last for about three days.

The long term use of dexamethasone may result in thrush, bone loss, cataracts, easy bruising, or muscle weakness. It is pregnancy category C in the United States and class A in Australia, meaning it has been frequently used in pregnancy and not been found to cause problems to the baby. It should not be taken when breastfeeding. Dexamethasone has anti-inflammatory and immunosuppressant effects.

Dexamethasone was first made in 1957. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. Dexamethasone is not expensive. In the United States a month of medication typically costs less than 25 USD. In India a course of treatment for preterm labor is about 0.5 USD. It is available in most areas of the world.

Medical use

Anti-inflammatory

Dexamethasone is used to treat many inflammatory and autoimmune conditions, such as rheumatoid arthritis and bronchospasm. Idiopathic thrombocytopenic purpura, a decrease in numbers of platelets due to an immune problem, responds to 40 mg daily for four days; it may be administered in 14-day cycles. It is unclear whether dexamethasone in this condition is significantly better than other glucocorticoids.

It is also given in small amounts 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 – particularly after eye surgery – and as a nasal spray (trade name Dexacort), and certain ear drops (Sofradex, when combined with an antibiotic and an antifungal).

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 proinflammatory mediators that can cause a response which is harmful to the patient), thus improving prognosis and outcome.

Dexamethasone phosphate for injection

Cancer

Cancer patients undergoing chemotherapy are given dexamethasone to counteract certain side effects of their antitumor treatments. Dexamethasone can augment the antiemetic effect of 5-HT₃ receptor antagonists, such as ondansetron.

In brain tumors (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures. It is also given in cord compression, where a tumor is compressing the spinal cord.

Dexamethasone is also used as a direct chemotherapeutic agent in certain haematological malignancies, especially in the treatment of multiple myeloma, in which dexamethasone is given alone or in combination with other chemotherapeutic drugs, including most commonly with thalidomide (Thal-dex), lenalidomide, bortezomib (Velcade, Vel-dex), or a combination of doxorubicin (Adriamycin) and vincristine or bortezomib/lenalidomide/dexamethasone.

Endocrine

Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.

In adrenal insufficiency and Addison's disease, dexamethasone is prescribed when the patient does not respond well to prednisone or methylprednisolone.

It can be used in congenital adrenal hyperplasia in older adolescents and adults to suppress ACTH production. It is typically given at night.

Pregnancy

Dexamethasone may be given to women at risk of delivering prematurely to promote maturation of the fetus' lungs. This has been associated with low birth weight, although not with increased rates of neonatal death.

Dexamethasone has been also been used during pregnancy as an off-label prenatal treatment for the symptoms of congenital adrenal hyperplasia (CAH) in female fetuses. CAH causes a variety of physical abnormalities, notably ambiguous genitalia in girls. Early prenatal CAH treatment has been shown to reduce some CAH symptoms, but it does not treat the underlying congenital disorder.

A small clinical trial found long-term effects on verbal working memory among the small group of children treated prenatally, but the small number of test subjects means the study cannot be considered definitive. Administration of prenatal dexamethasone has been the subject of controversy over issues of informed consent and because treatment must predate a clinical diagnosis of CAH in the female fetus.

High-altitude illnesses

Dexamethasone is used in the treatment of high-altitude cerebral edema (HACE), as well as high-altitude pulmonary edema (HAPE). It is commonly carried on mountain-climbing expeditions to help climbers deal with complications of altitude sickness.

Synergism

Dexamethasone and ondansetron are more effective than ondansetron alone in preventing postoperative nausea and vomiting.

Adverse effects

The exact incidence of the adverse effects of dexamethasone are not available, hence estimates have been made as to the incidence of the adverse effects below based on the adverse effects of related corticosteroids and on available documentation on dexamethasone.

Common:

• Acne
• Insomnia
• Vertigo
• Increased appetite
• Weight gain
• Impaired skin healing
• Depression
• Euphoria
• Hypertension
• Increased risk of infection
• Raised intraocular pressure
• Vomiting
• Dyspepsia
• Confusion
• Amnesia
• Irritability
• Nausea
• Malaise
• Headaches
• Cataract (in cases of long-term treatment it occurs in about 10% of patients)

Unknown incidence:

• Papilloedema
• Adrenal suppression
• Growth stunting (in children)
• Cushing's syndrome
• Peptic ulcer
• Osteoporosis
• Myopathy
• Diabetes mellitus type 2
• Hyperglycaemia
• Pancreatitis (inflammation of the pancreas)
• Sodium and water retention
• Mania
• Psychosis
• Glaucoma
• Cardiomyopathy
• Abdominal distention
• Corneal or scleral thinning
• Candidiasis
• Skin atrophy
• Bruising
• Telangiectasia
• Striae
• Leukocytosis
• Thromboembolism
• Psychological dependence
• Vertebral collapse
• Oesophageal ulcer
• Seizures
• Hypertriglyceridaemia
• Intracranial hypertension (long-term treatment)
• Facial plethora
• Hypokalaemia
• Hypocalcaemia
• Muscular atrophy
• Nitrogen depletion due to protein catabolism
• Allergic reactions including anaphylaxis

Withdrawal

Sudden withdrawal after long-term treatment with corticosteroids can lead to:

• Adrenal insufficiency
• Hypotension
• Fever
• Myalgia
• Arthralgia
• Rhinitis
• Conjunctivitis
• Painful itchy skin nodules
• Weight loss
• Death

Contraindications

Contraindications include:

• Uncontrolled infections
• Known hypersensitivity to dexamethasone
• Cerebral malaria
• Systemic fungal infection
• Concurrent treatment with live virus vaccines (including smallpox)

Interactions

Known drug interactions include:

• Inducers of hepatic microsomal enzymes such as barbiturates, phenytoin, and rifampicin can reduce the half-life of dexamethasone.
• Cotreatment with oral contraceptives can increase its volume of distribution.

Synthesis

To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative. This is then reacted with a source of hypobromite, such as basic N-bromosuccinimide, to form the 9α-bromo-11β-hydrin derivative, which is then ring-closed to an epoxide. A ring-opening reaction with hydrogen fluoride in tetrahydrofuran gives dexamethasone.

Dexamethasone synthesis:

Society and culture

Cost

Dexamethasone is not expensive. In the United States a month of medication typically costs less than 25 USD. In India a course of treatment for preterm labor is about 0.5 USD. It is available in most areas of the world.

Nonmedical use

Dexamethasone is given in legal Bangladeshi brothels to prostitutes not yet of legal age, causing weight gain aimed at making them appear healthier and older to customers and police.

Dexamethasone is a banned substance by some sporting bodies. In November 2014, the world's number one badminton player Lee Chong Wei was banned by the Badminton World Federation for testing positive for the drug, although he denied using any banned substances.

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.

See also

• Dexamethasone suppression test