Adverse Effects of Retinoids

Abstract

Oral retinoids, synthetic derivatives of vitamin A, have been used in the treatment of various dermatoses over the last decade. The most useful drugs have been isotretinoin (13-cis-retinoic acid) for nodulocystic acne and etretinate for psoriasis vulgaris. Retinoids are also effective in the treatment of papulosquamous dermatoses other than psoriasis (i.e. inherited disorders of keratinisation), cutaneous T-cell lymphoma and in chemotherapy and chemoprevention of cancer. However, systemic administration of these compounds is frequently associated with mucocutaneous side effects, liver toxicity and abnormalities of serum lipid profiles, which might be related to an increased risk of coronary heart disease. Of particular concern is the teratogenic effect of all retinoids, which limits their use in women of child-bearing potential. Chronic toxicities from long term therapy with retinoids may result in skeletal abnormalities, usually mimicking diffuse idiopathic hyperostosis syndrome. Furthermore, the chronic use of retinoids in children may inhibit their growth due to premature epiphyseal closure. In contrast to other side effects of retinoids which are dose dependent and reversible upon withdrawal of the drug, it seems unlikely that bone abnormalities will resolve after discontinuation of the medication. In view of the wide spectrum of toxicities, treatment with retinoids requires appropriate selection of patients, careful consideration of the benefit to risk ratio for each individual, periodic monitoring of clinical response and laboratory tests. Clinicians should use special management techniques in order to prevent or minimize slide effects. Extensive investigations are currently being conducted in an attempt to develop new retinoids which will improve the therapeutic efficacy and reduce unwanted reactions.

Retinoic Acid Regulates Arterial Smooth Muscle Cell Proliferation and Phenotypic Features In Vivo and In Vitro Through an RARα-Dependent Signaling Pathway

“…Clinical applications of tRA have had some success in the treatment of human diseases such as cancer, psoriasis, and leukemia, but its therapeutic use has been precluded by serious adverse effects such as skin or liver toxicity and teratogenesis. 52 Moreover, the biological efficacy of tRA is greatly impaired by a hypercatabolism of the drug accompanied by rapid development of resistance. 53 The development of new retinoic acid derivatives targeted against RAR-␣ exhibiting higher activity and lower toxicity than tRA could be one of the promising strategies for therapeutic intervention in arterial disease.…”

Synthesis, anticancer activities and molecular modeling studies of novel indole retinoid derivatives

“…Nevertheless, due to the observation of numerous undesirable side effects i.e. teratogenic activity [14,15], liver and bone toxicity [16], hypervitaminosis A syndrome [17], the short and long term applications of retinoids are limited for the treatment of above-mentioned diseases [18]. Synthesized new retinoid derivatives are required that have increased beneficial properties and reduced adverse effects.…”

Natural Products and Dermatological Hypersensitivity Diseases

“…Retinoids require careful consideration before use due to side effects including local effects, systemic, psychological but more importantly teratogenic effects (David et al, 1988).…”