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Dexamethasone: Uses, Dosage, Mechanism of action and Side effects

Reading time: 7 minutes, 44 seconds

Dexamethasone is a synthetic corticosteroid medication that is widely used in the treatment of a range of conditions. Dexamethasone is a derivative of cortisol (hydrocortisone). It is also known as 1-dehydro-9α-fluoro-16α-methylhydrocortisone

When compared to other corticosteroids, dexamethasone has powerful anti-inflammatory properties but devoid of mineralocorticoid activity.

Dexamethasone was approved by the Food and Drug Authority for use in October 1958.

This agent is sold under the brand names: Decadron, Deronil, Hexadrol and Spersadex.

Dexamethasone belongs to pregnancy category C,meaning use should be based on benefits being predicted to be greater than risks.

Recently, The UK Recovery Trial study has reported that Dexamethasone has shown to be of importance in patients with severe complications of COVID-19. This has been looked at at the end of this article.

What is a corticosteroid?

Corticosteroids are naturally-occurring chemicals that are synthesized by the adrenal glands. Adrenal glands are located one above each kidney. Adrenal glands are also known as suprarenal glands.

These corticosteroids are known to suppress the immune system and also blocks inflammation.

The most important corticosteroid in the body is cortisol.

Indications of dexamethasone

Dexamethasone is generally reserved for a few distinct indications, such as:

  1. As a diagnostic agent to aid in the diagnosis of suspected Cushing’s syndromein a test known as dexamethasone suppression tests. This is because it does not cross react with endogenous cortisol in conventional radioimmunoassays. This test measures the suppression of cortisol in plasma after the administration of dexamethasone that normally binds to the growth hormone in the pituitary gland inhibiting adreocorticotrophin hormone Failure to suppress cortisol may indicate primary Cushing syndrome or ectopic ACTH production.
  2. This drug is also used in the symptomatic treatment of cerebral oedema secondary tobrain tumours;
  3. It is also used to prevent respiratory distress syndrome in babies who are born prematurely by promoting maturation of the fetal lungs. In these cases, it is administered topregnant mothers who are at risk of giving birth to preterm babies.
  4. Dexamethasone is also used in combination with other anti-emeticdrugs  to prevent cytotoxic chemotherapy-induced nausea and vomiting in patients with cancer. It is known to increase the antiemetic effect of 5-HT3 receptor antagonist drugs, such as ondansetron .
  5. It is used in patients who require corticocteroids but with problematic fluid retention.
  6. Dexamethasone provides significant pain relief from inflammationin patients with chronic adjuvant-induced arthritis.
  7. Dexamethasone is also used in the treatment of a number of inflammatory and autoimmune such as, such as rheumatoid arthritis and bronchospasms. 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.
  8. Dexamethasone is also commonly given as a treatmentof choice for croup in children.
  9. It is also used in conjunction with triamcinolone acetonide to treat plantar fascitis. It is injected into the inflammed heel.
  10. This drug hasalso been employed during pregnancy for prenatal treatment for the symptoms of congenital adrenal hyperplasia (CAH) in female babies.This condition is associated with a variety of physical abnormalities, with the most common feature being ambiguous genitalia.
  11. This agent is also used in the treatment of a condition known as high-altitude pulmonary edema (HAPE), as well as high-altitude cerebral edema (HACE).
  12. When given intravenously, it is effective in preventing nausea and vomiting in individuals who had surgery and whose post-operative pain was treated with long-acting spinal or epidural spinal opioids.
  13. Dexamethasonetablets are also used in certain adult haematological malignancies such as multiple myeloma,as a direct chemotherapeutic agent. Here it is given alone or in combination with other chemotherapeutic agents such as thalidomide, bortezomib, lenalidomide, or a combination of doxorubicin  and vincristine or bortezomib/lenalidomide/dexamethasone.
  14. A single dose of dexamethasone is known to speed improvement of a sore throat.
  15. This drugis the treatment for the very rare disorder of glucocorticoid resistance.
  16. It is also used in the management of leukemias and lymphomas in adults and acute leukemia in childrenand also to induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome without uremia or nephrotic syndrome caused by systemic lupus erythematosus.
  17. Dexamethasone is also used to provide palliative therapy during acute exacerbations of GI diseases, such as ulcerative colitis and regional enteritis

Mechanism of action of dexamethasone

Dexamethasone is a potent glucocorticoid with no mineracorticoid property. It exerts is action in decreasing inflammation by suppressing the migration of cells known as polymorphonuclear leukocytes of PMN and reducing capillary permeability.

Through this activity, it stabilizes the cell and lysosomal membrane. Dexamethasone also stimulated increased surfactant production in the lungs of premature infants. It also has the ability to inhibit proinflammatory cytokines and prostaglandin synthesis.

Dexamethasone also suppresses proliferation of lymphocytes through direct cytolysis and has the ability to inhibit mitosis process of cell division and

Dexamethasone binds to intracellular glucocorticoid receptors and suppresses inflammatory and immune responses by: inhibiting neutrophil and monocyte accumulation at inflammation site and suppressing phagocytic and bactericidal action stabilizing lysosomal membranes suppressing antigen response of macrophages and helper T cells inhibiting synthesis of inflammatory response mediators, such as cytokines, interleukins, and prostaglandins.

Pharmacodynamics

Dexamethasone has a high anti-inflamatoty relative potency of between 25-30, a metabolic potency of 1 and a low sodium retaining potency of 0.05.

Long-acting agents such as dexamethasone are active for 39–54 hours.

Adverse drug reactions

Dexamethasone is associated with various mild adverse drug reactions including;

Acne, Insomnia, weight gain, depression or euphoria, Vertigo, Increased appetite, Impaired skin healing, Hypertension, vomiting, confusion, amnesia, dyspepsia, Increased risk of infection

Raised intraocular pressure, Vomiting, irritability, Nausea, headache and Malaise

Contraindications

Dexamethasone use in contraindicated but not limited to the following scenarios:

  • Patients with uncontrolled infections
  • Individuals with known corticosteroid hypersensitivity
  • Individuals with cerebral malaria
  • People with systemic fungal infectionand
  • Concurrent treatment with live virus vaccines

Drug-Drug interactions

The following drug interactions with dexamethasone have been selected on the basis of their potential significance.

Using this drug together with any of the following medicines is not recommended due to interactions. These drugs include;

  • Artemether
  • Praziquantel
  • Desmopressin
  • Rotavirus Vaccine, Live
  • Rilpivirine

Dexamethasone has relative mild interactions hen used together with

  • Aceclofenac,Acemetacin, Clonixin, Daclatasvir, Dexibuprofen, Diflunisal
  • Aldesleukin, Alfentanil, Amiodarone, , Apalutamide, Balofloxacin, Benzhydrocodone
  • Besifloxacin, Boceprevir, Bromfenac, Bufexamac, Buprenorphine, Carbamazepine, Celecoxib
  • Ceritinib, Cholestyramine, Conivaptan, Diclofenac, Dexketoprofen, Guacil
  • Choline Salicylate, Codeine, Etoricoxib, Ciprofloxacin, Dexibuprofen,
  • Clarithromycin, Etofenamate, Fosamprenavir, Desogestrel, Indinavir
  • Dronedarone, Felbinac, Enoxacin, Idelalisib, Doxorubicin, Flufenamic Acid, Ibuprofen
  • Floctafenine, Flurbiprofen, Dienogest, Estradiol, Gemifloxacin, Gestodene
  • Dihydrocodeine, Hydrocodone
  • Dipyrone, Elvitegravir, Doxorubicin Hydrochloride Liposome, Etodolac, Fenoprofen, Fentanyl
  • Fosphenytoin, Gatifloxacin, Etonogestrel, Etravirine, Drospirenone, Droxicam, Ethinyl Estradiol, Fleroxacin
  • Ethynodiol,Flumequine, Efavirenz, Enzalutamide,  Fepradinol, Feprazone, Indomethaci, Itraconazole, Ixabepilone, Ketoconazole
  • Ketoprofen, Ketorolac, Lapatinib, Levofloxac, Levonorgestrel, Lomefloxacin, Lopinavir, Lornoxicam
  • Loxoprofen, Lumacaftor, Lumateperone, Lumiracoxib, Macimorelin, Meclofenamate
  • Mefenamic Acid, Meloxicam, Meperidine, Mestranol, Methadone, Mitotane, Morniflumate, Moxifloxacin, Nabumetone
  • Nadifloxacin, Nadroparin, Naproxen, Nefazodone, Nelfinavir, Nepafenac
  • Nevirapine, Nifedipine, Niflumic Acid, Nilotinib, Nimesulide
  • Nimesulide Beta Cyclodextrin, Nimodipine, Norethindrone, Norfloxacin, Norgestimate, Norgestrel, Ofloxacin, Oxaprozin, Oxycodone, Oxyphenbutazone, Parecoxib
  • Pazufloxacin, Pefloxacin, Pentazocine, Phenylbutazone, Phenytoin, Piketoprofen, Piperaquine, Piroxicam, Posaconazole, Pranoprofen, Proglumetacin, Propyphenazone, Proquazone
  • Prulifloxacin, Rifampin, Ritonavir, Rofecoxib, Rufloxacin, Salicylic Acid, Salsalate, Saquinavir
  • Sargramostim
  • Sodium Salicylate, Sparfloxacin, St John's Wort, Sufentanil, Sulindac, Sunitinib, Tacrolimus, Telaprevir
  • Telithromycin, Tenoxicam, Thalidomide, Tiaprofenic Acid, Ticagrelor, Tolfenamic Acid
  • Tolmetin, Tosufloxacin, Tramadol, Ubrogepant, Ulipristal, Valdecoxib, Velpatasvir, Vincristine Sulfate Liposome, Voriconazole, Vortioxetine, Voxilaprevir

Dexamethasone and COVID-19

From the recent study that was carried out by United Kingdom’s Recovery Trial between the month of March and April, it has been found that dexamethasone reduces COVID-19 deaths by up to a third in what is being described as a "groundbreaking development" in the fight against the virus.

Dexamethasone was one of several drugs that was being tested by the UK's Recovery trial between March and June.

More than 2,100 COVID-19 patients were treated with a low-dose of the steroid once per day for 10 days and results were compared with 4,321 patients receiving only the usual care.

Researchers found that dexamethasone reduced death by one-third in mechanically ventilated patients with complications secondary to COVID-19 and by one fifth in other patients receiving oxygen only

On 16 June 2020, the Oxford University RECOVERY Trial in the United Kingdom, announced findings that low-dose dexamethasone treatment (6 mg per day either through oral administration or by intravenous injection) can reduce the death rate by 35% in COVID-19 patients on ventilators and by 20% in COVID-19 patients on oxygen. This is due to its effect of inhibiting cytokine storm.

However there were no benefits reported to patients not requiring respiratory support was observed.

Although prolonged use of dexamethasone may result in thrush, bone loss, cataracts, easy bruising, or muscle weakness. It is pregnancy category C in the United States meaning use should be based on benefits being predicted to be greater than risks. In Australia, it is category A, meaning it has been frequently used in pregnancy and not been found to cause problems to the baby.

Dexamethasone should not be taken when breastfeeding.

Researchers estimated that the drug would prevent one death for every eight patients treated while on breathing machines and one for every 25 patients on extra oxygen alone


Post References

  • Revised on: 2021-07-10 03:24:44