Drugs and Therapeutics
James Sherifi in General Practice Under the NHS, 2023
They vary in potency from cortisone to dexamethasone. There is a sense that more recent generations of GPs are less familiar and confident regarding the relative potency and potential side effects, both short and long term, of this invaluable class of compounds and are thus misguidedly limiting their use. Fludrocortisone—1953Addison’s Disease, Nocturnal Enuresis Fludrocortisone, the first of the synthetic corticosteroids, was used as a hormone replacement for Addison’s disease. Since its actions mimicked naturally occurring aldosterone, it could cause electrolyte imbalance and fluid retention resulting in oedema, cardiac failure, and cardiac arrhythmia. Urea and electrolytes required regular monitoring.
Syncope
Henry J. Woodford in Essential Geriatrics, 2022
Fludrocortisone is a synthetic mineralocorticoid. Its main mechanism of action is by promoting renal sodium retention (in exchange for potassium) thus expanding fluid volume. Its dose is usually started at 50 mcg once daily and can be titrated up to 300 mcg. However, the evidence of a significant clinical benefit is lacking. A trial in younger people (n = 210; mean age 30 [range 21–47]) found that 12-month syncope event rates were not significantly lower with fludrocortisone (HR 0.69; 95% CI 0.46–1.03; 44% v 61%).44 There is no reliable evidence of efficacy in older people. Main adverse effects are provocation of oedema, congestive cardiac failure, hypertension (due to fluid retention) and hypokalaemia. It is contraindicated in people on diuretic medications or with clinical evidence of fluid overload.
Answers
Andrew Schofield, Paul Schofield in The Complete SAQ Study Guide, 2019
Falls are common in the elderly, and the number of causes is vast. Arthritis, reduced cognition, polypharmacy, reduced visual input, reduced muscle strength, reduced proprioception and an increased reaction time all contribute to the increased risk of falling. As a junior doctor, you will be asked to assess numerous patients who have been admitted with falls, or who have fallen during their admission. It is important to take a full history to establish the mechanism of the fall, whether consciousness was lost, what injuries have been sustained, etc. A collateral history from someone who witnessed the fall can be extremely helpful. Postural hypotension is a fall in blood pressure on standing. Antihypertensives are commonly responsible, and stopping them often resolves the problem. However, in many cases no cause will be found. Non-pharmacological measures should be tried first, such as full-length compression hosiery, tilting the bed so it is more upright and increasing salt in the diet. Fludrocortisone is a synthetic mineralocorticoid and acts to increase the intravascular volume, hence raising the blood pressure. Midodrine is a locally acting vascular bed vasoconstrictor, and is contraindicated in those with peripheral vascular disease and coronary artery disease.
Transient Visual Loss in Young Females with Crowded Optic Discs: A Proposed Aetiology
Published in Neuro-Ophthalmology, 2021
Stephen A. Madill
I have to explain the mechanism by which fludrocortisone reduced the frequency of the TVL episodes in Patients 1 and 3. If optic nerve head autoregulation is fully functional then both the pre- and post-treatment BPs of Patient 1 should maintain OPPs within the normal autoregulatory plateau. The effect of fludrocortisone can therefore not be explained by an iatrogenic increase in BP alone if associated with normal autoregulation. I note again studies demonstrating impaired autoregulation in a subgroup of healthy individuals,13,22 specifically a linear relationship between increasing OPP and tissue blood flow.13 This effectively suggests zero functioning of optic nerve head autoregulation in some subjects. If Patient 1 had autoregulatory dysfunction to this degree then a small increase in OPP could manifest as an augmented improvement in optic nerve head perfusion, explaining the benefit of fludrocortisone. The improvement in symptomatology with fludrocortisone could therefore also be considered evidence for autoregulatory dysfunction.
Pharmacological management of sepsis in adults with a focus on the current gold standard treatments and promising adjunctive strategies: evidence from the last five years
Published in Expert Opinion on Pharmacotherapy, 2019
Evdoxia Kyriazopoulou, Evangelos J. Giamarellos-Bourboulis
Two RCTs have recently been published shedding more light to this controversy; the ADRENAL trial [52] and the APROCCHSS trial [53]. ADRENAL is a pragmatic large-scale trial in five countries allocating patients at septic shock to treatment with placebo (n = 1,860) or hydrocortisone (n = 1,853). The primary outcome, 90-day mortality, did not differ between the two groups (27.9% versus 28.8%, p: 0.50). However, patients who had been assigned to hydrocortisone had faster resolution of shock than those assigned to placebo (median duration 3 versus 4 days, p < 0.001); less days on initial mechanical ventilation (median 6 versus 7 days, p < 0.001) and required fewer blood transfusions (37% vs 41.7%, p: 0.004) [54]. In the APROCCHSS trial conducted in France, patients at septic shock were randomly assigned to placebo or hydrocortisone for seven days [53]. The hydrocortisone group was also administered 50μg fludrocortisone daily. Intervention was accompanied by a substantial decrease of all-cause 90-mortality (43% versus 49.1% of the placebo group) and this was accompanied by a decrease of vasopressor-free days (median 19 versus 23 days in the placebo group, p < 0.001). The time to weaning from vasopressors, the time to weaning from mechanical ventilation and the time to reaching a SOFA score less than 6 was shorter in the intervention group than the placebo group. The parallel administration of fludrocortisone is a possible explanation for the survival benefit observed in this trial compared to others.
Non-antibiotic therapies for sepsis: an update
Published in Expert Review of Anti-infective Therapy, 2019
Jean-Louis Vincent, Wasineenart Mongkolpun
Corticosteroids have long been proposed for the treatment of patients with sepsis for their anti-inflammatory properties. The SSC guidelines [4] give a weak recommendation that use of intravenous hydrocortisone should be avoided in patients with septic shock if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability, but if that is not possible then intravenous hydrocortisone should be given at a dose of 200 mg per day. The results from two trials that have been published since the most recent SSC guidelines support this recommendation [33]. In 1241 patients with severe septic shock (Sequential Organ Failure Assessment [SOFA] score 12 ± 3; Simplified Acute Physiology Score [SAPS] 56 ± 19), Annane et al. [34] reported that 90-day mortality was significantly lower in patients treated with hydrocortisone plus fludrocortisone than in placebo-treated patients (43.0% vs 49.1%; p = 0.03) giving a relative risk of death in the treated group of 0.88 (95% CI, 0.78–0.99). Another trial from Australia, the ADRENAL (ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock) trial [35] did not show a decrease in mortality rate, but the patients were less severely ill. The addition of fludrocortisone, as used in the study by Annane et al. [34] is probably not necessary.
Related Knowledge Centers
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- Hydrocortisone
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- Immunosuppression
- Corticosteroid
- Hypertension
- Orthostatic Hypotension
- Heart Failure