A drug which has gained currency is dexamethasone. This drug, dexamethasone, has proven effective in COVID-19 patients that are seriously ill, hospitalized and on ventilators, reducing deaths by a third, and by a fifth in COVID-19 patients receiving other kinds of breathing support. These findings are from the Recovery (Randomized Evaluation of COVID-19 therapy) trial, conducted by the University of Oxford. The trial only included people who had been hospitalized and for those who did not require breathing support no benefit was found. Dexamethasone is used as part of interventions to curb “cytokine storm” in COVID-19 which is a situation of overreaction of the immune system to the invasion of the lungs by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This overreaction is perceived to be a key cause of lung injury and subsequent multi-organ failure in COVID-19. A check in Medscape shows that methylprednisolone is used in a similar manner. Locally though, methylprednisolone is far more expensive.
Other uses of dexamethasone are in allergic and inflammatory conditions such as asthma.Glucocorticoids, such as dexamethasone and methylprednisolone, decrease local inflammation by blocking the chemical mediators of inflammation and subsequently have analgesic properties. They also possess antiemetic properties. They may exert their antiemetic action via prostaglandin antagonism, release of endorphins, and reduction of serotonin level in the gut and neural tissue. Also, they enhance the effect of other antiemetics by sensitizing their pharmacological receptors. Practitioners find it useful in cancer therapy either to prevent nausea and vomiting or reduction of oedema particularly in brain tumour. If the size of a brain metastasis (BM) exceeds a certain threshold, occurrence of a vasogenic cerebral oedema due to tumor-induced disruption of the blood-brain-barrier is a well-known phenomenon. During this process, fluid leakage from defective capillaries into the extracellular space contributes significantly to overall mass effect. In this setting, application of systemic (oral or intravenous) glucocorticoids (GC) to reduce BM capillary permeability is the first-line treatment.
Dexamethasone has a lower mineralocorticoid (salt retaining) activity and a longer plasma half-life than other synthetic GC and is thus the most commonly used drug. Practice guidelines from a systematic review including two studies recommended a starting dose of 4–8 mg/day for patients with mild symptoms and 16 mg/day for those with moderate and severe symptoms attributed to mass effect from brain metastasis (BM) and vasogenic cerebral oedema. (Schroeder et al.Efficiency of Dexamethasone for Treatment of Vasogenic Edema in Brain Metastasis Patients: A Radiographic Approach. Front. Oncol., 30 July 2019 | https://doi.org/10.3389/fonc.2019.00695).
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body’s immune responses to diverse stimuli. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone. In terms of duration of action, betamethasone and dexamethasone are considered long acting, methylprednisolone, prednisolone and triamcinolone are intermediate-acting. Hydrocortisone is short-acting. In equipotent doses 1.2mg betamethasone = 1.5mg dexamethasone=8mg methylprednisolone= 8mg triamcinolone=10mg prednisolone=40mg hydrocortisone.
Even though COVID-19 has given prominence to glucocorticoids such as dexamethasone and methylprednisolone, steroids have wide therapeutic applications. For endocrine disorders they are used to manage primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance). Preoperatively, and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful. Hypercalcemia associated with cancer. Rheumatic Disorders- as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in, post-traumatic osteoarthritis, synovitis of osteoarthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis. Acute and subacute bursitis. Acute nonspecific tenosynovitis. Acute gouty arthritis. Psoriatic arthritis. Ankylosing spondylitis. Dermatologic Diseases- severe erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, severe seborrheic dermatitis, severe psoriasis. Allergic States- control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, drug hypersensitivity reactions. Ophthalmic Diseases- severe acute and chronic allergic and inflammatory processes involving the eye. Gastrointestinal Diseases- to tide the patient over a critical period of the disease in ulcerative colitis, regional enteritis. Haematologic Disorders- acquired (autoimmune) hemolytic anemia, idiopathic thrombocytopenic purpura in adults. Neoplastic Diseases- for palliative management of leukemias and lymphomas in adults, acute leukemia of childhood. Oedematous states- to induce diuresis or remission of proteinuria in the nephrotic syndrome. Cerebral oedema associated with primary or metastatic brain tumor, craniotomy, or head injury. The therapeutic applications are broad. The adverse reactions include fluid and electrolyte disturbances, muscle weakness, loss of muscle mass, osteoporosis, and pathologic fracture of long bones. Others include tendon rupture, peptic ulcer disease, ulcerative esophagitis. There could be impaired wound healing, thin fragile skin, increased sweating, burning or tingling, especially in the perineal area (after IV injection). Others are cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic edema. There could be convulsions, headache, psychic disturbances, endocrine disorders such as menstrual irregularities, suppression of growth in children, decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, and increased requirements for insulin or oral hypoglycemic agents in persons with diabetes. There could be weight gain, increased appetite and hiccups.
As a pharmacist you will need to get your pharmacovigilance forms at hand to record any unintended outcomes of steroid therapy. Pharmacovigilance, also known as drug safety relates to the collection, detection, assessment, monitoring, and prevention of adverse effects of pharmaceutical products. There is a lot for you to do as a Pharmacist in these times (COVID-19).
DR. EDWARD O. AMPORFUL