2. DRUG-INDUCED PERIPHERAL EDEMA
Various drugs can induce or worsen peripheral edema by disrupting the
delicate homeostasis between transcapillary flow, edema safety factors
and lymphatic drainage capacity (Figure 2 ). Although most often
pitting and bilateral, some drugs are involved in the development of
peripheral edema that is readily erythematous (e.g., dopaminergic
agonists (Wood, 2010), pemetrexed (D’Angelo, Kris, Pietanza, Rizvi, &
Azzoli, 2011)) or unilateral (e.g., sirolimus (Rashid-Farokhi & Afshar,
2017)). In addition to aggressive fluid resuscitation and preparation
providing a significant amount of sodium, drug-induced edema entails
four mechanisms, namely precapillary arteriolar vasodilation
(vasodilatory edema), sodium and water retention (renal edema),
lymphatic insufficiency (lymphedema) and increased capillary
permeability (permeability edema). In most situations, several
mechanisms occur and contribute synergistically to edema genesis. The
underlying mechanism directly affects treatment efficacy.
The aim of this review is to raise awareness on the mechanisms involved
in drug-induced peripheral edema. Each of these mechanisms is
illustrated through an example of the most notable drug. Drug-induced
angioedema, whether mediated by bradykinin (e.g., angiotensin-converting
enzyme inhibitors), histamine (e.g., beta-lactams) or leukotrienes
(e.g., non-steroidal anti-inflammatory drugs), is regarded as
permeability edema. However, given its predominantly non-peripheral
location (e.g., facial, laryngeal or gastrointestinal involvement), it
will not be discussed in this review. This review does not cover drugs
that may cause edema by a primary indirect mechanism, such as heart
failure (Page et al., 2016) or hypoalbuminemia as in glomerular injury
(Markowitz, Bomback, & Perazella, 2015) and liver injury (European
Association for the Study of the Liver. Electronic address:
easloffice@easloffice.eu, Clinical Practice Guideline Panel: Chair:,
Panel members, & EASL Governing Board representative:, 2019).