Common side effects may include cataracts, bone loss, easy bruising, muscle weakness, and thrush.[3] Other side effects include weight gain, swelling, high blood sugar, increased risk of infection, and psychosis.[4][3] It is generally considered safe in pregnancy and low doses appear to be safe while the user is breastfeeding.[5] After prolonged use, prednisone must be stopped gradually.[3]
Prednisone can be used in the treatment of decompensated heart failure to increase renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large doses of loop diuretics.[17][18][19][20][21][22] In terms of the mechanism of action for this purpose: prednisone, a glucocorticoid, can improve renal responsiveness to atrial natriuretic peptide by increasing the density of natriuretic peptide receptor type A in the renal inner medullary collecting duct, thereby inducing a potent diuresis.[23]
At high doses, it may be used to prevent rejection following an organ transplant.[3]
Short-term side effects, as with all glucocorticoids, include high blood glucose levels (especially in patients with diabetes mellitus or on other medications that increase blood glucose, such as tacrolimus) and mineralocorticoid effects such as fluid retention.[24] The mineralocorticoid effects of prednisone are minor, which is why it is not used in the management of adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly.
Adrenal suppression will begin to occur if prednisone is taken for longer than seven days. Eventually, this may cause the body to temporarily lose the ability to manufacture natural corticosteroids (especially cortisol), which results in dependence on prednisone. For this reason, prednisone should not be abruptly stopped if taken for more than seven days; instead, the dosage should be gradually reduced. This weaning process may be over a few days if the course of prednisone is short but may take weeks or months[33] if the patient had been on long-term treatment. Abrupt withdrawal may lead to an Addisonian crisis. For those on chronic therapy, alternate-day dosing may preserve adrenal function and thereby reduce side effects.[34]
Glucocorticoids act to inhibit feedback of both the hypothalamus, decreasing corticotropin-releasing hormone (CRH), and corticotrophs in the anterior pituitary gland, decreasing the amount of adrenocorticotropic hormone (ACTH). For this reason, glucocorticoid analogue drugs such as prednisone down-regulate the natural synthesis of glucocorticoids. This mechanism leads to dependence in a short time and can be dangerous if medications are withdrawn too quickly. The body must have time to begin synthesis of CRH and ACTH and for the adrenal glands to begin functioning normally again.
Prednisone may start to result in the suppression of the hypothalamic–pituitary–adrenal (HPA) axis if used at doses 7–10 mg or higher for several weeks. This is approximately equal to the amount of endogenous cortisol produced by the body every day. As such, the HPA axis starts to become suppressed and atrophy. If this occurs the patient should be tapered off prednisone slowly to give the adrenal gland enough time to regain its function and endogenous production of steroids.
Withdrawal
The magnitude and speed of dose reduction in corticosteroid withdrawal should be determined on a case-by-case basis, taking into consideration the underlying condition being treated, and individual patient factors such as the likelihood of relapse and the duration of corticosteroid treatment. Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have:
received more than 40 mg prednisone (or equivalent) daily for more than one week
been given repeat doses in the evening
received more than three weeks of treatment
recently received repeated courses (particularly if taken for longer than three weeks)
taken a short course within one year of stopping long-term therapy
other possible causes of adrenal suppression
Systemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse who have received treatment for three weeks or less and who are not included in the patient groups described above.
During corticosteroid withdrawal, the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily) and then reduced more slowly. Assessment of the disease may be needed during withdrawal to ensure that relapse does not occur.[35]
Prednisone is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive properties.[36][37] Prednisone is a prodrug; it is metabolised in the liver by 11-β-HSD to prednisolone, the active drug. Prednisone has no substantial biological effects until converted via hepatic metabolism to prednisolone.[38]
Pharmacokinetics
Prednisone is absorbed in the gastrointestinal tract and has a half-life of 2–3 hours.[37] it has a volume of distribution of 0.4–1 L/kg.[39] The drug is cleared by hepatic metabolism using cytochrome P450 enzymes. Metabolites are excreted in the bile and urine.[39]
Lodotra
"Lodotra" is the brand name of an oral formulation, which releases prednisone four hours after ingestion. It is indicated for rheumatoid arthritis with morning stiffness. Taken at 10 p.m., it releases the drug at around 2 a.m. The plasmic peak level is reached at 4 a.m., which is considered to be the optimal time for relieving morning stiffness. The drug was approved in the European Union, in January 2009.[40][41]
The first isolation and structure identifications of prednisone and prednisolone were done in 1950 by Arthur Nobile.[44][45][46] The first commercially feasible synthesis of prednisone was carried out in 1955 in the laboratories of Schering Corporation, which later became Schering-Plough Corporation, by Arthur Nobile and coworkers.[47] They discovered that cortisone could be microbiologically oxidized to prednisone by the bacterium Corynebacterium simplex. The same process was used to prepare prednisolone from hydrocortisone.[48]
The enhanced adrenocorticoid activity of these compounds over cortisone and hydrocortisone was demonstrated in mice.[48]
Prednisone and prednisolone were introduced in 1955 by Schering and Upjohn, under the brand names Meticorten[49] and Delta-Cortef,[50] respectively.
^World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^Riemer AD (April 1958). "Application of the newer corticosteroids to augment diuresis in congestive heart failure". The American Journal of Cardiology. 1 (4): 488–496. doi:10.1016/0002-9149(58)90120-6. PMID13520608.
^Newman DA (February 1959). "Reversal of intractable cardiac edema with prednisone". New York State Journal of Medicine. 59 (4): 625–633. PMID13632954.
^Massari F, Mastropasqua F, Iacoviello M, Nuzzolese V, Torres D, Parrinello G (March 2012). "The glucocorticoid in acute decompensated heart failure: Dr Jekyll or Mr Hyde?". The American Journal of Emergency Medicine. 30 (3): 517.e5–517.10. doi:10.1016/j.ajem.2011.01.023. PMID21406321.
^Liu C, Chen Y, Kang Y, Ni Z, Xiu H, Guan J, et al. (October 2011). "Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up-regulating natriuretic peptide receptor-A expression in the renal inner medullary collecting duct in decompensated heart failure". The Journal of Pharmacology and Experimental Therapeutics. 339 (1): 203–209. doi:10.1124/jpet.111.184796. PMID21737535. S2CID1892149.
^Wolkowitz OM, Lupien SJ, Bigler ED (June 2007). "The "steroid dementia syndrome": a possible model of human glucocorticoid neurotoxicity". Neurocase. 13 (3): 189–200. doi:10.1080/13554790701475468. PMID17786779. S2CID39340010.
^"Steroids". Australian Department of Health & Human Services. April 2016. Retrieved 14 June 2018.
^Schakman O, Gilson H, Kalista S, Thissen JP (November 2009). "Mechanisms of muscle atrophy induced by glucocorticoids". Hormone Research. 72 (Suppl 1): 36–41. doi:10.1159/000229762 (inactive 9 December 2024). PMID19940494. S2CID21997662.{{cite journal}}: CS1 maint: DOI inactive as of December 2024 (link)
^Iliopoulou A, Abbas A, Murray R (19 May 2013). "How to manage withdrawal of glucocorticoid therapy". Prescriber. 24 (10): 23–29. doi:10.1002/psb.1060. S2CID72082017.
^Buttgereit F, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, et al. (January 2008). "Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial". Lancet. 371 (9608): 205–214. doi:10.1016/S0140-6736(08)60132-4. PMID18207016. S2CID6197980.
^Wainwright M (1998). "The secret of success: Arthur Nobile's discovery of the steroids prednisone and prednisolone in the 1950s revolutionised the treatment of arthritis". Chemistry in Britain. 34 (1): 46. OCLC106716069.
