Dexamethasone

Dexamethasone is a synthetic corticosteroid used from many years in clinical practice for its anti-inflammatory, anti-allergic and immunosuppressive properties.
Dexamethasone was first synthesized in 1957 and was approved for medical use in 1961. It is in the WHO: World Health Organization’s list of essential medicines and is available both as generic and brand medicines.
It doesn’t have mineralocorticoid activity.

Mechanism of Action of dexamethasone

Figure- Mechanism of action of dexamethasone

Dexamethasone is a corticosteroid hormone receptor agonist. It binds to glucocorticoid receptor which are widely distributed throughout the body.
The steroid-receptor complex translocate to the nucleus where it binds to glucocorticosteroid response elements (GREs) in DNA and acts as transcription factor.
The interaction is responsible for genomic effect. It turns gene on or activate DNA transcription (when complexed with co-activators) and turns gene off or repress DNA transcription (when complexed with co-repressors).
Repression of DNA transcription is responsible for its anti-inflammatory actions and upregulation of DNA transcription is responsible for various side effects.

It is used to treat various inflammatory and autoimmune conditions such as asthma, active inflammatory bowel disease, rheumatoid arthritis. Also helps to prevent homograft rejection.
It is also useful in treating allergic rhinitis, drug and transfusion allergic reactions and allergic anaphylactic shock (if used in large doses).
Dexamethasone can prevent or suppress signs of inflammation. It suppresses both early phenomena (edema, fibrin deposition, migration of leucocytes into inflamed area) as well as late manifestation (capillary and fibroblastic proliferation and collagen deposition).
The mechanism responsible for anti-inflammatory action are inhibition of release of arachidonic acid and leucocyte migration in inflamed tissue, suppression of pro-inflammatory cytokines and chemokines, decrease of capillary permeability.
In large doses, suppress cell mediated hypersensitivity.

Addison’s disease is caused by adrenal cortex dysfunction.
Normally, hydrocortisone (similar to natural cortisol), prednisolone or methylprednisolone are preferred. Dexamethasone is used when patients doesn’t respond well to these medicines.

Respiratory distress syndrome is a major problem and main cause of mortality in premature infants.
Dexamethasone, when given to pregnant women at risk of delivering prematurely (before due date), helps in accelerating lung maturation in fetus. It should be administered through IM route within the 48 hours of proceeding premature delivery.

It is used to counteract certain side effects of anti-tumor treatment in cancer patients who are in chemotherapy and is used for prophylaxis and treatment of chemotherapy induced nausea and vomiting.
It is also used as direct chemotherapeutic agent alone or in combination with other chemotherapeutic agents to treat hematological malignancies like multiple myeloma.

It is approved as standard for prophylaxis and treatment of post-operative nausea and vomiting. It increases anti-emetic effect of 5-HT₃ receptor antagonist like ondansetron.

It is commonly carried by mountain climbers as it helps in treatment of high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE).

Dexamethasone in low dose is found to be breakthrough in the fight against COVID-19.
It is studied in the large clinical trial in the United Kingdom known as RECOVERY, or Randomized Evaluation of COVID-19 Therapy. In the trial, 2,105 randomly selected COVID-19 patients were administered 6 milligrams of dexamethasone per day for 10 days and result was compared with 4,321 patients who received the usual care alone.
The results showed that dexamethasone reduce deaths by one-third in ventilated patients and by one-fifth in patients receiving oxygen only.
As the drug possess anti-inflammatory and immunosuppressive properties, it prevents damage that can happen to our body, when our immune system goes into overdrive to fight against COVID-19. This over reaction, a cytokine storm can be deadly.
It is not helpful in patients who don’t require respiratory help.
The detailed report has not been published yet.

Given through oral, IV, IM or local route.
It is metabolized by liver and excreted in urine mainly. It has a half-life of approximately 3 hours.

Prolonged therapy with high dose may produce various adverse effects.

Common adverse effects include stomach upset, dizziness, headache, vomiting, amnesia, increased risk of infection, hypertension, increased appetite and weight gain.
Some serious side effects are osteoporosis (due to suppression of intestinal calcium absorption), unusual tiredness and dizziness, euphoria, insomnia, myopathy, retardation of linear growth in children (who receive higher doses), hyperglycemia which can lead to diabetes mellitus and glaucoma and cataract.

Drugs which increase dexamethasone level in blood when used together includes:
- Antifungal drugs like ketoconazole, itraconazole.
- Antibiotics like erythromycin.
Drugs which decrease dexamethasone level include:
- Antiepileptic drugs like phenytoin, fosphenytoin.
- Anti-tuberculosis drugs like rifampin, rifabutin.
Dexamethasone reduce the level of HIV drugs like ritonavir, indinavir and maraviroc, blood thinners like warfarin and apixaban, anti-TB drugs like isoniazid.
It increases risk of stomach upset when used together with NSAIDs like aspirin.
Combining with thalidomide can cause toxic epidermal necrolysis which is life-threatening.
Combination of cyclosporine could increase risk of prolong suppression of immune system which raise risk of other infection.

https://www.healthline.com/health/dexamethasone-oral-tablet#other-warnings
https://www.bbc.com/news/health-53061281
https://www.usatoday.com/story/news/health/2020/06/16/dexamethasone-what-we-know-drug-may-help-covid-19-survival/3198841001/
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