Aphthasolone - General Information
An anti-inflammatory 9-fluoro-glucocorticoid.
Pharmacology of Aphthasolone
Aphthasolone and its derivatives, dexamethasone sodium phosphate and dexamethasone acetate, are synthetic glucocorticoids. Used for its antiinflammatory or immunosuppressive properties and ability to penetrate the CNS, dexamethasone is used alone to manage cerebral edema and with tobramycin to treat corticosteroid-responsive inflammatory ocular conditions.
Aphthasolone for patients
Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision. As prolonged use may cause adrenal insufficiency and make patients dependent on corticosteroids, they should advise any medical attendants that they are taking corticosteroids and they should seek medical advice at once should they develop an acute illness including fever or other signs of infection. Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including, myalgia, arthralgia, and malaise. Persons who are on corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.
Aminoglutethimide: Aminoglutethimide may diminish adrenal suppression by corticosteroids.
Amphotericin B injection and potassium-depleting agents: When corticosteroids are administered concomitantly with potassium-depleting agents (e.g., amphotericin B, diuretics), patients should be observed closely for development of hypokalemia. In addition, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.
Antibiotics: Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance.
Anticholinesterases: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.
Anticoagulants, oral: Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.
Antidiabetics: Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.
Antitubercular drugs: Serum concentrations of isoniazid may be decreased. Cholestyramine: Cholestyramine may increase the clearance of corticosteroids. Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.
Dexamethasone suppression test (DST): False-negative results in the dexamethasone suppression test (DST) in patients being treated with indomethacin have been reported. Thus, results of the DST should be interpreted with caution in these patients.
Digitalis glycosides: Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.
Ephedrine: Ephedrine may enhance the metabolic clearance of corticosteroids, resulting in decreased blood levels and lessened physiologic activity, thus requiring an increase in corticosteroid dosage.
Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.
Hepatic Enzyme Inducers, Inhibitors and Substrates: Drugs which induce cytochrome P450 3A4 (CYP 3A4) enzyme activity (e.g., barbiturates, phenytoin, carbamazepine, rifampin) may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. Drugs which inhibit CYP 3A4 (e.g., ketoconazole, macrolide antibiotics such as erythromycin) have the potential to result in increased plasma concentrations of corticosteroids. Dexamethasone is a moderate inducer of CYP 3A4. Co-administration with other drugs that are metabolized by CYP 3A4 (e.g., indinavir, erythromycin) may increase their clearance, resulting in decreased plasma concentration.
Ketoconazole: Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects. In addition, ketoconazole alone can inhibit adrenal corticosteroid synthesis and may cause adrenal insufficiency during corticosteroid withdrawal.
Nonsteroidal anti-inflammatory agents (NSAIDS): Concomitant use of aspirin (or other nonsteroidal antiinflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.
Phenytoin: In post-marketing experience, there have been reports of both increases and decreases in phenytoin levels with dexamethasone co-administration, leading to alterations in seizure control.
Skin tests: Corticosteroids may suppress reactions to skin tests.
Thalidomide: Co-administration with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use.
Vaccines: Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible.
Systemic fungal infections.
DECADRON tablets are contraindicated in patients who are hypersensitive to any components of this product.
Additional information about Aphthasolone
Aphthasolone Indication: Injection: for the treatment of endocrine disorders, rheumatic D=disorders, collagen diseases, dermatologic diseases, allergic statesc, ophthalmic diseases, gastrointestinal diseases, respiratory diseases, hematologic disorders, neoplastic diseases, edematous states, cerebral edema.
Ophthalmic ointment and solution: for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe.
Ophthalmic solution only: for the treatment of steroid responsive inflammatory conditions of the external auditory meatus
Topic cream: for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses
Oral aerosol: for the treatment of bronchial asthma and related corticosteroid responsive bronchospastic states intractable to adequate trial of conventional therapy
Intranasal aerosol: for the treatment of allergic ot inflammatory nasal conditions, and nasal polyps
Mechanism Of Action: Aphthasolone is a glucocorticoid agonist. Unbound dexamethasone crosses cell membranes and binds with high affinity to specific cytoplasmic receptors. This results in a modification of transcription and, hence, protein synthesis in order to achieve inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, suppression of humoral immune responses, and reduction in edema or scar tissue. The antiinflammatory actions of dexamethasone are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.
Drug Interactions: Ambenonium The corticosteroid decreases the effect of anticholinesterases
Aminoglutethimide Aminogluthetimide decreases the effect of dexamethasone
Amobarbital The barbiturate decreases the effect of the corticosteroid
Anisindione The corticosteroid alters the anticoagulant effect
Aprepitant Aprepitant increases the effect and toxicity of dexamethasone
Aprobarbital The barbiturate decreases the effect of the corticosteroid
Aspirin The corticosteroid decreases the effect of salicylates
Butabarbital The barbiturate decreases the effect of the corticosteroid
Butalbital The barbiturate decreases the effect of the corticosteroid
Butethal The barbiturate decreases the effect of the corticosteroid
Dicumarol The corticosteroid alters the anticoagulant effect
Dihydroquinidine barbiturate The barbiturate decreases the effect of the corticosteroid
Edrophonium The corticosteroid decreases the effect of anticholinesterases
Ethotoin The enzyme inducer decreases the effect of the corticosteroid
Fosphenytoin The enzyme inducer decreases the effect of the corticosteroid
Heptabarbital The barbiturate decreases the effect of the corticosteroid
Hexobarbital The barbiturate decreases the effect of the corticosteroid
Imatinib Decreases levels of imatinib
Mephenytoin The enzyme inducer decreases the effect of the corticosteroid
Methohexital The barbiturate decreases the effect of the corticosteroid
Methylphenobarbital The barbiturate decreases the effect of the corticosteroid
Midodrine Increased arterial pressure
Neostigmine The corticosteroid decreases the effect of anticholinesterases
Pentobarbital The barbiturate decreases the effect of the corticosteroid
Phenobarbital The barbiturate decreases the effect of the corticosteroid
Phenytoin The enzyme inducer decreases the effect of the corticosteroid
Primidone The barbiturate decreases the effect of the corticosteroid
Pyridostigmine The corticosteroid decreases the effect of anticholinesterases
Quinidine barbiturate The barbiturate decreases the effect of the corticosteroid
Rifampin The enzyme inducer decreases the effect of the corticosteroid
Secobarbital The barbiturate decreases the effect of the corticosteroid
Sunitinib Possible decrease in sunitinib levels
Talbutal The barbiturate decreases the effect of the corticosteroid
Warfarin The corticosteroid alters the anticoagulant effect
Bismuth The corticosteroid decreases the effect of salicylates
Acenocoumarol The corticosteroid alters the anticoagulant effect
Salicylate-magnesium The corticosteroid decreases the effect of salicylates
Salsalate The corticosteroid decreases the effect of salicylates
Food Interactions: Avoid alcohol.
Take with food to reduce irritation.
Avoid taking with grapefruit juice.
Generic Name: Dexamethasone
Synonyms: Desametasone [Dcit]; Desametasone; Desamethasone; DEX; Dexametasona [Inn-Spanish]; Dexamethasone Acetate; Dexamethasone Alcohol; Dexamethasone Base; Dexamethasone Sodium Phosphate; Dexamethasonum [Inn-Latin]; Dexamethazone; DXM; Dxms; Fluormethylprednisolone
Drug Category: Antineoplastic Agents, Hormonal; Glucocorticoids; Antiemetics; Anti-inflammatory Agents; Adrenergic Agents
Drug Type: Small Molecule; Approved; Investigational
Toxicity (Overdose): Oral, rat LD50: >3 gm/kg. Signs of overdose include retinal toxicity, glaucoma, subcapsular cataract, gastrointestinal bleeding, pancreatitis, aseptic bone necrosis, osteoporosis, myopathies, obesity, edemas, hypertension, proteinuria, diabetes, sleep disturbances, psychiatric syndromes, delayed wound healing, atrophy and fragility of the skin, ecchymosis, and pseudotumor cerebri.
Protein Binding: 70%
Half Life: 36-54 hours
Dosage Forms of Aphthasolone: Solution Intravenous
Solution / drops Ophthalmic
Chemical 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
Chemical Formula: C22H29FO5
Dexamethasone on Wikipedia: https://en.wikipedia.org/wiki/Dexamethasone
Organisms Affected: Humans and other mammals