Iatrogenic Cushing's syndrome in a adolescent with AIDSs on ritonavir and inhaled fluticasone. case report and literature review

Pessanha, Tatiana Melino; Campos, João Maurício Scarpellini; Barros, Ana Cláudia Mamede Wiering de; Pone, Marcos V.S.; Garrido, José Roberto; Pone, Sheila Moura

doi:10.1097/qad.0b013e328013d9c7

Cited by 21 publications

(16 citation statements)

References 17 publications

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“…Indeed, even the development of iatrogenic Cushing's syndrome due to topical ocular steroids has been reported [1,2]. Another interesting example of iatrogenic Cushing's syndrome are HIV-infected patients on inhaled corticosteroids, such as fluticasone, and protease-inhibiting antiretroviral drugs, such as ritonavir [3]. This association inhibits steroid hepatic metabolism and increases steroid bioavailability, thereby causing Cushingoid features and secondary adrenal insufficiency.…”

Section: Synthetic Glucocorticoidsmentioning

confidence: 96%

Drugs and HPA axis

2008

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Section: Synthetic Glucocorticoidsmentioning

confidence: 96%

Drugs and HPA axis

2008

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“…Consequently, even if FP itself lacks oral activity because high hepatic first-pass metabolism to the corresponding (inactive) 17-carboxylic acid, it has systemic effects if given subcutaneously [232]. In a few cases, even severe systemic sideeffects have been seen with inhaled or intranasal FP especially when coadministered with CYP3A4 inhibitors [233][234][235][236], and since 2004, the combination of inhaled fluticasone and ritonavir is no longer recommended by GlaxoSmithKline, because of the risk of Cushing's syndrome, unless the benefits overcome the risks [236]. FP was found to have a terminal half-life of $8 h in 12 healthy male subjects after inhaled administration of 500, 1000, and 2000 mg of drug using a metered-dose inhaler (MDI).…”

Section: Softmentioning

confidence: 99%

Retrometabolism‐Based Drug Design and Targeting

Bodor

Buchwald

2010

Burger's Medicinal Chemistry and Drug Discovery

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Retrometabolic drug design (RMDD) approaches are systematic methodologies aimed to design safe compounds with an improved therapeutic index. RMDDs thoroughly integrate structure– activity and structure‐metabolism considerations into the entire design process and incorporate two major concepts aimed to design soft drugs and chemical delivery systems, respectively. Soft drugs (SDs) are new, active therapeutic agents designed to undergo predictable metabolism resulting in inactive metabolites after exerting their desired therapeutic effect(s). Chemical delivery systems (CDSs) are biologically inert molecules that provide enhanced and targeted delivery of an active drug to a particular organ or site through a designed sequential metabolism that involves several steps. Here, we present a comprehensive review including a general overview of the RMDD principles and a large number of specific examples from various pharmacological areas, including many recent developments, to illustrate RMDD concepts. Whenever possible, the rationale for the design as well as the pharmacokinetic and pharmacodynamic properties of the new therapeutic agents are briefly summarized and compared to those of the other compounds used in the same field.

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“…Fluticasone, given by nasal or oral inhalation for management of seasonal allergies or asthma, has minimal systemic exposure when given alone. In recent years, a number of reports have identified Cushing's syndrome and other corticosteroid-associated toxicities occurring in association with use of fluticasone in combination with ritonavir (a potent CYP3A4 inhibitor), caused by significant systemic accumulation of fluticasone [28,29 ]. Another example of an unexpected interaction is the increase in didanosine concentration and resultant increased toxicities (e.g.…”

Section: Clinical Significance Of Pharmacokinetic Drug Interactionsmentioning

confidence: 99%