Mineralocorticosteroids

hydrocortisone

(cortisol) hydrocortisone is secreted by the adrenal cortex and has both glucocorticoid and mineralocorticoid effects anti-inflammatory and immunomodulatory effects

indications

- Addisons - replacing mineralocorticoids - adrenocortical insufficiency = septic shock (combined with hydrocortisone) - congenital adrenal hyperplasia - neuropathic postural hypotension (unlicensed use)

use of corticosteroids in pregnancy

- Corticosteroids vary in their ability to cross the placenta. Prednisolone is mostly inactivated as it crosses the placenta, whereas betamethasone and dexamethasone cross readily. - Although corticosteroids can cause abnormalities in fetal development in animals, this has not been shown in humans (for example, cleft lip and palate). - Prolonged or repeated corticosteroid administration in pregnancy increases the risk of intrauterine growth restriction (IUGR). Short-term treatment carries no such risk. - The theoretical risk of adrenal suppression in neonates after prenatal exposure to corticosteroids is not clinically important and resolves spontaneously after birth. - Prednisolone is excreted in small amounts in breast milk and is unlikely to cause systemic effects in the infant unless doses exceed 40 mg daily. Above this dose, infants should be monitored for adrenal suppression. No data are available on other corticosteroids.

endocrine/metabolic side effects of corticosteroids

- adrenal suppression - growth failure in children - insulin resistance - diabetes - disturbance of thyroid function - hypokalaemia - metabolic alkalosis

side effects

- adrenal suppression - inf risk - psychiatric reactions - chorioretinopathy - anxiety - increased appetite - hypertension - fluid retention - Cushing's syndrome - hypokalaemia - impaired diabetes control

examples of mineralocorticoids

- aldosterone - fludrocortisone

possible interactions

- anti-fungal: amphotericin B - furosemide - digoxin --> exacerbation of hypokalaemia with digoxin, diuretics, theophyllines and beta-2 agonists - NSAIDs --> exacerbation of GI side effects, peptic ulcer - warfarin - enhanced anticoagulant effects - diabetic drugs antagonism - phenobarbital and phenytoin - rifampicin - anabolic steroids - oestrogens - vaccines --> impaired immune response of vaccines - antagonism of anti-hypertensives

conditions where corticosteroids have been used with evidence-based benefits

- asthma - croup - crohn's disease - UC - giant cell arteritis (temporal arteritis) - polymyalgia rheumatica - RA - SLE - polyarteritis nodosa - Wegener's granulomatosis - sarcoidosis - eczema - otitis externa - pemphigus - dermatomyositis - minimal change glomerulonephritis - acute leukaemia - acquired haemolytic anaemia - idiopathic thrombocytopenic purpura - cerebral oedema - cluster headache - congenital adrenal hyperplasia - anaphylaxis and allergic reactions

ophthalmic side effects of corticosteroids

- cataracts (more common in children) - elevation of intraocular pressure - glaucoma

specific side effects of fludrocortisone

- conjunctivitis - idiopathic intracranial hypertension - muscle weakness - thrombophlebitis

contraindications

- diabetes - pregnancy - hepatic/renal impairment caution

GI side effects of corticosteroids

- gastric effects (peptic ulceration etc) - fatty liver

cardiovascular side effects of corticosteroids

- hypertension - congestive cardiac failure

CNS side effects of corticosteroids

- mood disturbance (including mania) - psychosis - sleep disturbance

side effects of corticosteroids for the skin and other systems

- moon face - truncal obesity - dorsolumbar hump - acne - thin skin - skin striae (violaceous) - impotence - irregular periods

musculoskeletal side effects of corticosteroids

- myopathy (especially proximal muscles) - osteoporosis - avascular necrosis of bone

types of steroids

- short-acting - intermediate-acting - long-acting - mineralocorticosteroids

immunological side effects of corticosteroids

- suppression type IV hypersensitivity (interferes with Mantoux test) - inhibitory effects (leukocytes, macrophages, cytokines) - suppression of primary antigen response (important with vaccines)

structure of the adrenal cortex

-About 90% of the adrenal gland is composed of the cortex. -It consists of three layers (zones): zona fasiculata --> glucocorticoids zona glomerulosa --> mineralocorticoids zona reticularis --> androgens

deflazacort

Deflazacort (steroid) to help build muscle to prolong mobility and therefore, prolong life it is an oral steroid with high glucocorticoid and low mineralocorticoid activity derived from prednisolone

effect of glucocorticoids

anti-inflammatory and immunosuppressive effects also involved in increasing blood sugar by: - stimulating gluconeogenesis in the liver - mobilising amino acids from extrahepatic tissues - reducing glucose usage by inhibiting uptake in muscle and fat - stimulating fat breakdown

patient information - what to tell the patient

avoid abrupt withdrawal = adrenal insufficiency/hypotension/death increase dose in intercurrent illness, trauma/surgery taken orally corticosteroid therapy is a major risk factor for osteoporosis

half-life and examples of intermediate-acting steroids

biological half-life --> 18-36 hours - prednisolone - triamcinolone - methylprednisolone

half-life and examples of long-acting steroids

biological half-life --> 36-54 hours - dexamethasone - betamethasone

half-life and examples of short-acting steroids

biological half-life --> 8-12 hours - cortisol - hydrocortisone

generic/trade name

generic name --> fludrocortisone (fludrocortisone acetate in BNF)

Mantoux test

intradermal test to determine tuberculin sensitivity based on a positive reaction where the area around the test site becomes red and swollen

haematopoietic side effects of corticosteroids

leukocytosis and other effects (e.g. reduced eosinophils and monocytes)

androgens

male sex hormones

elimination

metabolised by liver

note

only stuff relevant in this relates to the mineralocorticoid component (don't need to know corticosteroid and glucocorticoid stuff I don't think)

class of drug

steroid

how does it work?

taken orally high mineralocorticoid activity and insignificant glucocorticoid activity binds to min receptor/aldosterone = distal tubules to increased sodium ions absorption into blood + potassium and H+ into urine