Glucorticoids include - Short acting- Cortisone, Hydrocortisone Intermediate acting - Prednisone, Prednisolone, Triamcinolone, Methylprednisolone Long acting- Dexamethasone, Betamethasone Refer- Dexamethasone

Interacting drugs - summary 

+Corticosteroids 

Aminoglutethimide                                                                                                     possible loss of dexamethosone-induced adrenal suppression dexamethosone 

  Barbiturates                                                                                                                 decreased pharmacolgic effects of the corticosteroids metabolism through the           induction of hepatic microsomal enzymes 

 Contraceptives                                                                                                               Hepatic metabolism decreased by OCs, resulting in  increased therapeutic                           effects or toxicity 

Ephedrine                                                                                                                              decreased half-life and increased clearance of dexamethsone may occur 

Estrogens                                                                                                                     estrogen coadministration reduce the clearance and increase the elimination                  half-life of corticosteroids 

Hydantoins                                                                                                                corticosteroids clearance decreased and the AUC increased resulting                                  in reduced therapeutic effects 

Ketoconazole                                                                                                       corticosteroid clearance decreased and the AUC increased 

Macrolide antibiotic                                                                                                         significant decrease in methylprednisolone clearance 

Rifampicin                                                                                                                      corticosteroid clearance increased resulting in decreased therapeutic effects

Corticosteroids +  Anticholinesterases                                                      anticholinesterase effect antagonised in myasthenia gravis 

Anticoagulants                                                                                                                    oral  anticoagulant dose requirements reduced. Conversely, corticosteroids may           oppose the anticoagulant action.

Cyclosporine                                                                                                                      although this combination is therapeutically beneficial for organ transplant, toxicity          may be enhanced 

Digitalis glycosides                                                                                                 coadministration enhance the possibility ofdigitalis toxicity associated with           hypokalemia 

Isoniazid                                                                                                                              isoniazid serum concentration decreased 

Nondepolarising  muscle relaxants                                                                          corticosteroids potentiate, counteract or have no effect on the neuromuscular           blocking action

Poatssium deleting  diuretics                                                                                                  observe patients for hypokalemia agents eg.diuretics 

Salicylates                                                                                                               corticosteroids will reduce serum salicylate levels and decrease their                  effectiveness 

Somatrem                                                                                                                       growth-promoting effect of somatrem inhibited 

Theophyllines                                                                                                                alterations in the pharmacologic activity of either agent occur

Approved by (DCI) Drug Controller  GENERAL -  India  For Marketing                                                                                   (Ref- IDMA Publication)

Anti-inflammatory conditions.

Glucorticoids include - Short acting- Cortisone, Hydrocortisone Intermediate acting - Prednisolone, Triamcinolone, Methylprednisolone Long acting- Dexamethasone, Betamethasone Refer- Dexamethasone

Mineral corticosteroids adverse effects are - Manifest in water retention with odema and hypertension and increased excretion of potassium with possibility of hypokalemia, alkolosis CHF in susceptible patients, hypotension or shock -like reactions, hypertension.

In susceptible patients - cardiac failure may be induced Disturbances of electroltyte balance are common with naturally occuring corticosteroids such as cortisone and hydrocortisone, but less frequent with many synthetic glucocorticosteroids which have little or no mineralocortiocosteroid activity

Adverse glucocorticosteroids effects leads to - Mobilisation of calcium and phosphorus, with osteoporosis and spontaneous fractures, muscle wasting and nitrogen depletion, hyperglycemia, with accentuation or precipitation of diabetic state. Insulin requirements of diabetes patients are increased Increased appetite often reported.

Impaired tissue repair and immune function can lead to delayed wound healing, and increased susceptibility to infection, including septicemia, tuberculosis, fungal infections and viral infections Infections may also be masked by anti-inflammatory , analgesic, and antipyretic effects of glucocorticoids. Increased severity of varicella and measles may lead to fatal outcome in non-immune patients receiving systemic corticosteroids therapy

Other adverse effects include- menstrual irregularities, amenorrhea, hyperhirrosis, skin thinning, ocular changes including development of glaucoma, and cataract Development of Cushingoid state (eg, moon face, buffalo hump, supraventricular fat enlargement, central obesity) suppresion of growth in children

Mental and neurological disturbances, benign intracranial hypertension, acute pancreatitis, and avascular necrosis of bone Increase in caogulability of blood may lead to tromboembolic complications Peptic ulceration reported review do not always agree Large doses of corticosteroids -

Hyperactivity - moon face, hirsutism, buffalo hump, flushing, increased bruising Abrupt withdrawal can cause hypoadrenal crisis if daily dose not increased during stress. Growth retardation, osteoporosis, peptic ulcer, glaucoma and subcapsular catarats, vertebral compression fractures.

Topical appication- Corneal ulcers, raised intra-occular pressure, reduced visual function

Appln to skin - lead to collagen and sub cutaneous atrophy local hypopigmentation, dryness, irritation, epistaxis Hoarseness and candidiasis of the mouth or throat may occur with inhaled corticosteroids

For replacement therapy no contraindiaction except allergy. For non endocrinal use pregnancy,ocular herpex, GI ulcer, infection, diabetes, hypertension, immunization.

Special precautions:

Precautions- Used with caution in presence of heart failure, recent myocardial infarction, diabetes mellitus, eilepsy, glaucoma, hypothyroidism, hepatic failure, oseteoporosis, pepticulceration, psychoses, renal impairment

Contraindicated in presence of acute infections uncontrolled by appropiate antimicrobial therapy Risk of chicken pox and severe herpes zoster increasd Increased in non-immune patients receiving therapeutic doses of systemic corticosteroids Patients should avoid close personal contact with either infection

Examine regularly - sodium intake may be need to be reduced and calcium and potassium supplements may be necessary Monitor fluid intake and output, and daily weight records give early warning of fluid retention Back pain signify osteoporosis

Observe patients for weight increase ,edema, hypertension, and excessive potassium excretion as well as for less obivious signs of adrenocortical steroid-induced untoward efects. Monitor for a negative nitrogen balance due to protein catabolism Renal disease,osteoporosis, children and adolescent, lactation and elderly.

Use the lowest possible dose- make a benefit/risk decison in each individual case as to the size of the dose, duration of treatment, and the use of daily or intermittent therapy, since complications of treatment are dependent on these factors.

Use with caution in- GI- nonspecific ulcerative colitis, if there is a probabilty of impending peforation, abcess, or other pyogenic infection, diverticulitis, fresh intestinal anastomases, active or latent peptic ulcer

Cardiovascular- hypertension, CHF, thromboembolic tendencies, thrombophlebitis. Miscellaneous- osteoporosis, exanthema, Cushings syndrome,antibiotic resistent infections, convulsive disorders, metastatic carcinoma, myasthenia gravis, vaccina, varicella , diabetes mellitus, hypothyroidism, cirrhosis

Multiple sclerosis- relatively high doses of coticostroids are necessary

Repatrtory- injections- to minimise the likelihood and severity of atrophy , do not inject SC avoid injection into the deltoid and avoid repeated IM injection s in the same site, if possible Local injections- avoid local injection into an infected site and into unstable joints.

Warnings-

Infections- Coticosteroids may mask signs of infection and new infections may appear during use. If an infection occurs during therapy it shold be controlled by suitable antimicrobial therapy.

Tuberculosis- restrict use in active tuberculosis to cases of fulminating or disseminated disease in which the corticosteroid is used for disease management with tuberculin reactivity, observe closely.

Fungal- corticosteroids may exacerbate systemic fungal infections, do not use in such infections, except to control drug reactions due to amphotericin B. Concomittant use of Amphotericin B and hydrocortisone has been followed by cardiac enlargement and CHF.

Amebias- rule out amebiasis before giving to a patient who has been in the tropics or has unexplained diarrhea

Cerbral malaria- a double-blind trial has shown corticosteroid use is associated with prolongation of coma and a higher incidence of pneumonia and GI bleeding.

Hepatitis- corticosteroids may be harmful in chronic active hepatitis positive for hepatitis B surface antigen.

Ocular effects- use cautiously in ocular herpes simplex because of possible corneal perforation.

Fluid and electrolyte balance- average and large doses of hydrocotisone orcotisone can cause elevation of blood pressure, salt and water retension and increased excretion of potassium. Dietary salt restriction may be necessary.

Peptic ulcer- patients who appear to be at risk are those being treated for nephrotic syndrome or liver disease or who are comatose postcraniotomy. It may desirable to use prophylactic antacids.

Immunosuppression- corticosteroids may suppress reactions to skin tests.

Adrenal suppression- prolonged therapy of pharmacologic doses may lead to hypothalmic-pituitary -asrenal suppression.

Following prolonged therrapy, Abrupt discontinuation may result in withdrawal symptoms without evidence of adrenal insufficiency Stress- in patients receiving or recently withdrawn from corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroid is necessary.

Cardiovascular- use with caution in these patients.

Hypersentivity- anaphylactoid reactions have occured with corticosteroid therapy.

Renal function impairment- use with caution in renal insufficiency ,acute glomerulonephritis and in chronic patients Elderly- consider the risk/benefit factors of steroid use. Consider lower doses because of body changes caused by aging.

Monitor blood pressure, blood glucose and electrolytes

Pregnancy- if used in pregnancy or in women of child bearing potential, weigh benefits against the potential hazards to the mother.

Lactation- advice mothers taking phsarmacologic corticosteroid doses not to nurse.

Children- carefully observe growth and development of infants on prolonged corticosteroid therapy .

Approved by (DCI) Drug Controller  GENERAL -  India  For Marketing                                                                                   (Ref- IDMA Publication)

Indications: Anti-inflammatory conditions.

Dosage: Initial - 0.75 to 9mg/day.

Overdosage- Symptoms There are two categories of toxic effects from therapeutic use of glucocorticoids-

Acute adrenal insufficiency- due to too rapid withdrawal after long term use resulting in- fever, myalgia, arthalgia, anorexia, nausea, skin desquamation, orthostatic hypotension, dizziness, fainting, dyspnea, and hypoglycemia

Cushingold changes from continued long use of long doses resulting in - moonface, central obesity, straie,hirsutism, acne, ecchymoses, hypertension, osteoporosis, myopathy, sexual dysfunction, diabetes, hyperlipidemia, peptic ulcer, increased susceptibility to infection and electrlyte and fluid imbalance.

Reports of acute toxicity or death are rare. Treatment

1. Recovery of adrenal and pituitary function may require up to 9 months.

2. Gradually taper the steroid under the supervision of a physician completely

3. Frequent lab tests are necessary.

4. Supplementaion is required during periods of stress (eg, illness, surgery, injury)

5. Eventually reduce the lowest dose that will control the symptoms or discontinue the corticosteroid completely

6. For large acute overdoses, treatment includes gastric lavage or emesis, and usual suppotive measures

Missed dose

1. If you miss a dose of this medicine, take it as soon as you remember.

2. However, if you do not remember until later, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

For Availability/supplies 

Purpura- ( Thrombocytopenia ) ( 1558 ) 

The term thrombocytopenia refers to sustained elevation of platelet count usually above 800, 000 per cubic meterrs . In this condition, which is generally considered to be a myeloproliferative dosorder the spleen is palpablly enlarged Drugs causing adverse Reactions- ( 385 ) 

1. Corticosteroids

2. Aspirin

CORTICOSTEROIDS- REFER DEXAMETHASONE

1. May cause GI upset; take with meals or snacks.

2. Take single daily or alternate day doses in the morning prior to 9 am. Take in multiple doses at evenly spread intervals through out the day.

3. Patients on chronic steroid therapy should wear or carry identification to that effect.

4. Notify physician if unusual weight gain, swelling of the lower extremities, muscle weakness,black tarry stools, vomiting of blood, puffing of the face, menstrual irregularties, prolonged sore throat, fever, cold or infection occurs.

5. Avoid abrupt withdrawal of the therapy.

6. Allergies- Tell your doctor if you have ever had any unusual or allergic raections to coticosteroids or other related medicines. Also tell your doctor if you are allergic to any other substances such as foods, preservatives or dyes.

7. Diet- if you will be using this medicine for a long time your doctor may want you to- Follow a lowsalt diet Watch your calories to prevent gain Add extra protein to your diet. Make certain your doctor knows if you are already on a special diet, such as low sugar diet.

8. Pregnancy- too much use of corticosteroids during pregnancy may cause the baby to have problems after birth, such as slower growth. Also studies in animals have shown that corticosteroids cause birth defects.

9. Breast feeding- depending on amount of medicine younare taking it may be necessary for you to take another medicine or to stop breast-feeding during treatment.

10.Children- before this medicine is given to teenagers you should discuss its use with your childs doctor and then carefully follow the doctors instructions.

11. Elderly- older patients asre more likely to develop high blood pressure or bone disease from corticosteroids. Women are more likely to develop bone disease.

12. Other medicines- tell your doctor if you are taking any of the following- Aminoglutethimide or Antacids or Barbiturates or Carbamazepine or Griseofluvin or Mitotane or Phenylbutazone or Phenytoin or Primidone or Rifampin - use of these medicines may make certain corticosteroids less efective. Amphotericin B by injection- corticosteroids and this medicine decrease the amount of potassium in the blood.

13. Other medical problems- tell your doctor if you have any other medical problems- Bone disease - these medicines may worsen bone disease because they cause the body to lose calcium Chicken pox or Measles - risk of severe disease affecting other parts of the body Colitis or Diverticulitis or Stomach ulcer or other stomach or interstine problems - these medicines may cover up symptoms of a worsening stomach or intestinal condition.

14.Kidney stones - these medicines cause the body to retain more salt and water. These conditions may be made worse bythis extra body water High cholesterol levels - corticosteroids may increase blood cholesterol levels Liver disease or Overactive thyroid - with these conditions the body may not eliminate the corticosteroids at the usual rate, which may change themedicines effect.

15.Myastthenia gravis - whennthese medicines are first started muscle weaknees may occur. Your doctor may want you to take special precautions because this could cause problems with breathing Sytemic lupus erythematous SLE- this condition may cause side effects of corticosteroids to occur more easily.

16. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

Pharmacology:

These include Short acting- Cortisone

Intermediate acting- Prednisone, Prednisolone, Triamcinolone, Methyl Prednisone

Long acting- Dexamethasone, Betamethasone The naturally occuring adrenal cortical steroids have both anti-inflammatory (glucocorticoid) and salt retaining (mineralocorticoid) properties.

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the bodys immune responses to diverse stimuli.. These compounds including hydrocortisone(cortisol) and cortisone, are used as replacement therapy in adrenocortical deficiency states and for their anti-inflammatory effects. The synthetic steroid compounds prednisone, prednisolone and fludrocortisone also have glucocorticoid and mineral corticocoid activity.

Prednisone and prednisolone are used primarily for their glucocorticoid effects. In addition, a group of synthetic compounds with marked glucocorticoid activity are distinguished by the absence of any significant salt-retaining activity. These include triamcinolone, dexamethasone, methyl prednisone and betamethasone.. These agents are used for their potent anti-inflammatory effects.

Pharmacokinetics:

Hydrocortisone and most of the congeners are readily absorbed from GI tract. Hydrocortisone is reversibly bound to corticosteroid-binding globulin(CBG) or corticosteroid binding albumin(CBA). Hydrocortisone is metabolized by the liver, which is the rate-limiting step in its clearance.

Can be taken with food.

Pregnancy:

If used in pregnancy, or in women of child bearing potential, weigh benefits against the potential hazards to the mother and fetus.

Lactation:

Corticosteroids appear in breast milk and could supress growth. Advise mothers taking pharmacological corticosteroid doses not to nurse.

Children:

Carefully observe growth and development of infants on prolonged corticosteroid therapy .