Clinical and pharmacological group: & nbsp

Mineralocorticosteroids

Included in the formulation
  • Cortineff
    pills inwards 
  • Fludrocortisone
    pills inwards 
  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    ONLS

    АТХ:

    H.02.A.A.02   Fludrocortisone

    Pharmacodynamics:

    Corticosteroid with a pronounced mineralocorticoid activity and glucocorticoid activity.

    Mineralocorticoid action is due to binding to mineralocorticoid receptors in the cytoplasm of target cells, primarily in the cells of the collecting tubules of the kidneys. As a result, there is an increase in sodium reabsorption, removal of potassium and hydrogen, while water retention is observed. The reabsorption of sodium in the sweat and salivary glands, the mucous membrane of the gastrointestinal tract and through the cell membranes also increases.

    Possessing glucocorticoid activity, fludrocortisone suppresses the function of leukocytes and tissue macrophages. Limits the migration of leukocytes to the area of ​​inflammation. Violates the ability of macrophages to phagocytosis, as well as to the formation of interleukin-1. Promotes the stabilization of lysosomal membranes, thereby reducing the concentration of proteolytic enzymes in the area of ​​inflammation. Reduces the permeability of capillaries due to the release of histamine.Suppresses the activity of fibroblasts and the formation of collagen.

    Fludrocortisone inhibits the activity of phospholipase A2, which leads to suppression of the synthesis of prostaglandins and leukotrienes; inhibits the release of cyclooxygenase (mainly COX-2), which also contributes to a decrease in the production of prostaglandins.

    Reduces the number of circulating lymphocytes (T- and B-cells), monocytes, eosinophils and basophils due to their movement from the vascular bed into the lymphoid tissue; suppresses the formation of antibodies.

    Fludrocortisone suppresses pituitary release of ACTH and β-lipotropin, but does not reduce the level of circulating β-endorphin; oppresses the secretion of TSH and FSH.

    With direct application on the vessels causes a vasoconstrictor effect.

    Stimulates gluconeogenesis, promotes the capture of amino acids by the liver and kidneys and increases the activity of gluconeogenesis enzymes. In the liver fludrocortisone enhances the storage of glycogen, stimulating the activity of glycogen synthetase and the synthesis of glucose from protein metabolism products. Increasing the glucose level in the blood activates the release of insulin.

    Suppresses the capture of glucose by fat cells, which leads to activation of lipolysis.However, due to increased secretion of insulin, lipogenesis stimulation occurs, which leads to fat accumulation.

    Has catabolic effect in lymphoid and connective tissue, muscles, fatty tissue, skin, bone tissue. As a result of catabolic action, growth can be suppressed in children.

    In high doses fludrocortisone can increase the excitability of brain tissue and helps lower the threshold of convulsive readiness. Stimulates excess production of hydrochloric acid and pepsin in the stomach, which contributes to the development of peptic ulcers.

    In comparison with hydrocortisone, the ability of fludrocortisone to retain sodium ions in the body is expressed 250 times more, the anti-inflammatory activity is 10 times stronger.

    Pharmacokinetics:

    After oral administration, it is quickly and completely absorbed from the digestive tract. The maximum concentration of fludrocortisone in plasma is reached after approximately 2 hours. Binding to plasma proteins - 42%.

    Metabolised in the liver. The half-life is about 3.5 hours. It is excreted by the kidneys in the form of inactive metabolites.

    Indications:Primary insufficiency of the adrenal cortex (Addison's disease, condition after complete adrenalectomy), secondary adrenocortical insufficiency, adrenogenitalth syndrome (congenital adrenal hyperplasia), hypovolemia and arterial hypotension of various genesis.

    IV.E20-E35.E25   Adrenogenital disorders

    IV.E20-E35.E27.1   Primary insufficiency of the adrenal cortex

    IV.E20-E35.E27.4   Other and unspecified adrenocortical insufficiency

    IV.E70-E90.E86   Reduction of the volume of the liquid

    IX.I95-I99.I95   Hypotension

    IX.I95-I99.I95.9   Hypotension, unspecified

    VII.H10-H13.H10.1   Acute atopic conjunctivitis

    VII.H15-H22.H16   Keratite

    XIX.S00-S09.S05   Injury of the eye and orbit

    Contraindications:Hypersensitivityand systemic fungal infections.
    Carefully:Nonspecific ulcerative colitis, intestinal diverticulosis, stomach ulcer or duodenal ulcerosteoporosis, myasthenia gravis, hypoalbuminemia, and conditions predisposing to the intestinal anesthesia, esophagitis, gastritis, gastrointestinal surgery, abnormal liver function, renal failure, arterial hypertension, osteoporosis, myasthenia gravis, hypoalbuminemiae to its occurrence, hyperlipidemia; diabetes mellitus (including a violation of carbohydrate tolerance), hypothyroidism, Itenko-Cushing's disease, thyrotoxicosis, obesity (III-IV century), acute psychosis and mental disorders, poliomyelitis (with the exception of the form of bulbar encephalitis); cardiovascular systemincluding those with recent myocardial infarction (in patients with acute and subacute myocardial infarction it is possible to spread the focus of necrosis, slow the formation of scar tissue and, as a result, break the heart muscle), decompensatedchronic heart failure; parasitic and infectious diseases of bacterial nature (currently or recently transferred, including contact with the patient) - herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amebiasis, strongyloidiasis (established or suspected); active and latent tuberculosis; severe infectious diseases (permissible only against the background of specific therapy); a period of 8 weeks before and 2 weeks after vaccination, lymphadenitis after BCG vaccination; HIV infection and AIDS (the decision on the use of corticosteroids should be taken after a careful consideration of the benefit and risk to the patient).
    Pregnancy and lactation:

    Acceptance of corticosteroids by women of childbearing age and pregnant women is allowed only if their potential benefit to the mother exceeds the potential risk to the fetus.If the adrenal cortex is deficient, fludrocortisone should be taken during pregnancy, but the dose may increase.

    Action category for the fetus by FDA - C.

    If it is necessary to use the drug during breastfeeding, it is recommended to stop breastfeeding.

    Dosing and Administration:

    When taken orally depending on the clinical situation, the dose varies from 100 mcg 3 times a week to 200 mcg once a day.

    Locally applied 1-3 times a day. Duration of treatment - no more than 2 weeks.

    Side effects:

    From the side cardiovascular system and blood (hematopoiesis, hemostasis): arterial hypertension, peripheral edema, left ventricular hypertrophy of the heart, circulatory insufficiency, arrhythmia, bradycardia (up to cardiac arrest), ECG changes characteristic of hypokalemia; hypercoagulation, thrombosis, obliterating endarteritis; in patients with acute and subacute myocardial infarction - the spread of the focus of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle.

    From the side organs of the digestive tract: steroid ulcer with possible perforation and bleeding,pancreatitis, flatulence, ulcerative esophagitis, indigestion, nausea, increased or decreased appetite, vomiting, hiccough; in rare cases - increased activity of hepatic transaminases and alkaline phosphatase.

    From the side skin integument: atrophic bands, acne, delayed wound healing, thinning of the skin, petechiae and hematomas, erythema, excessive sweating, ecchymosis, hyper- or hypopigmentation, propensity to develop pyoderma and candidiasis.

    From the side nervous system and sense organs: increase in intracranial pressure with the syndrome of the congestive nipple of the optic nerve (pseudotumor of the brain - most often in children, usually after too rapid reduction of the dose, symptoms - headache, reduced visual acuity or double vision), convulsions, dizziness, headache, sleep disturbance, mental disorders (most often appear within the first 2 weeks of treatment, symptoms can mimic schizophrenia, mania or delirious syndrome; women are most susceptible), posterior subcapsular cataract (usually occurs after discontinuing Nia treatment but may require surgical treatment), increased intraocular pressure,glaucoma (usually after treatment for at least a year), exophthalmos, a tendency to develop secondary bacterial, fungal or viral eye infections, trophic corneal changes.

    From the side endocrine system: secondary adrenal and hypothalamic-pituitary insufficiency (especially in stressful situations such as illness, trauma, surgery), Itenko-Cushing's syndrome, growth inhibition in children, menstrual irregularities, decreased glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus , hirsutism.

    From the side metabolism: hypocalcemia, negative nitrogen balance due to protein catabolism, hyperglycemia, glucosuria, increased excretion of Ca2 +; caused by mineralocorticoid activity - hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

    From the side musculoskeletal system: muscle weakness, steroid myopathy (more often in women), loss of muscle mass, rupture of tendons, osteoporosis, compression fracture of the spine, aseptic necrosis of femoral and humerus head, pathological fractures of long tubular bones.

    Allergic reactions: Allergic dermatitis, urticaria, anaphylactic reactions, angioedema.

    Other: weight gain, masking of symptoms of infectious diseases, syncope, development or exacerbation of infections (this side effect is promoted by jointly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome.

    Overdose:

    Symptoms: arrhythmia, hypokalemia, arterial hypertension, peripheral edema, a significant increase in body weight, hypertrophy of the heart muscle.

    Treatment: cancellation of the drug (symptoms usually last for several days), symptomatic therapy. Then the treatment should be continued, reducing the dose of the drug.

    Interaction:

    Alcohol, NSAIDs - increased risk of bleeding (including hemorrhagic stroke) and ulceration of the gastric mucosa.

    Aminoglutethimide - suppression of adrenal function (additional administration of glucocorticoids and mineral corticoids is required).

    Amphotericin B (parenterally), inhibitors of carbonic anhydrase - the risk of severe hypokalemia.

    Antiglaucoma means - dosage correction due to proglacomial action glucocorticoids.

    Anticholinergics, especially atropine - risk of intraocular hypertension.

    Acetazolamide - the risk of hypernatremia, edema, hypocalcemia (osteoporosis).

    Anabolic steroids, androgens - the risk of edema, severe acne.

    Tricyclic antidepressants - exacerbate steroid-dependent disorders of the psyche (do not apply).

    Anticoagulants indirect (coumarin and indanedione derivatives), anticoagulants direct, thrombolytics - risk of hemorrhagic stroke.

    Antithyroid drugs, thyroid hormones - dose adjustment glucocorticoids due to reduced clearance in hypothyroidism and increased in hyperthyroid condition.

    Asparaginase - increased toxic effects of asparaginase.

    Vaccines, live viruses or other immunization - pharmacological (immunosuppressive) doses glucocorticoids lead to stimulation of replication of live viruses, an increase in the risk of developing viral diseases, a decrease in the formation of antibodies to the vaccine.

    Diuretics - reduction of their natriuretic and diuretic effects, hypokalemia.

    Inhibitors of acetylcholinesterase - a risk of severe weakness in myasthenia gravis (cancel for 24 hours before the start of therapy glucocorticoids).

    Isoniazid, mexiletine - Increase in clearance of isoniazid, mexiletine, decrease in plasma concentration (dose adjustment).

    Immunosuppressants, others - the risk of infection.

    Carbamazepine, ephedrine, phenobarbital, phenytoin, rifampin - increased clearance glucocorticoids.

    Ketoconazole - reduced clearance glucocorticoids (increased risk of side effects).

    Contact lenses - increased risk of infection.

    Macrolides - reduced clearance glucocorticoids.

    Mitotan - increased dose glucocorticoids.

    Non-depolarizing muscle relaxants - the risk of respiratory depression (due to hypokalemia, inducible glucocorticoids).

    Oral antidiabetic agents and insulin - dose adjustment of one or both drugs in combination. Correction of an antidiabetic remedy after cessation of glucocorticoid therapy.

    Cardiac glycosides - the risk of their overdose and arrhythmia due to hypokalemia.

    Somatropin - oppression of the growth stimulating response to somatropin (prednisolone inside at a daily dose> 2.5-3.75 mg / m2 body surface, parenterally in a dose and 1.25-1.88 mg / m2).

    Means or products containing high amounts of sodium - the risk of edema and hypertension.

    Means that induce liver enzymes - increased clearance glucocorticoids.

    Means stimulating the activity of liver enzymes - reducing effects glucocorticoids by increasing their metabolism.

    Folic acid - increased demand for folate with prolonged therapy.glucocorticoids

    Estrogen-containing oral contraceptives - increased clearance and reduced half-life glucocorticoids (dose adjustment).

    Special instructions:

    Regular monitoring of blood pressure, potassium and glucose levels in the blood is necessary. It is necessary to limit the intake of salt, prophylactically prescribe potassium preparations, control the functions of the adrenal cortex. Lengthening of the course is possible only with a lower dose. After a long reception, cancellation is made gradually (the risk of adrenal insufficiency).

    The frequency and severity of side effects depend on the duration of the application, the amount of dose used and the possibility of observing the circadian rhythm of the appointment.

    A powerful synthetic fluorinated mineralocorticoid (125 times more active than hydrocortisone) with marked glucocorticoid activity (10 times more active than hydrocortisone). Is taken internally. In the doses used for replacement mineralocorticoid therapy,practically does not show glucocorticoid activity.

    Reduces the risk of developing ischemic complications in aneurysmal subarachnoid hemorrhage.

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