People reporting headache as a side effect often report comorbid neuropsychiatric symptoms, especially depression; a statistically significant relationship between headache and depression has been established. It is suggested that people sensitive to isotretinoin-induced CNS effects may also be susceptible to other psychiatric side effects such as depression.Studies in mice and rats have found that retinoids, including isotretinoin, bind to dopaminergic receptors in the central nervous system. Isotretinoin may affect dopaminergic neurotransmission by disrupting the structure of dopamine receptors and decreasing dopaminergic activity. The dopaminergic system is implicated in numerous psychological disorders, including depression. Isotretinoin is also thought to affect the serotonergic system – it increases expression of 5-HT1A receptors in the pre-synaptic neuron, which inhibit serotonin secretion. Isotretinoin also directly and indirectly increases the translation of the serotonin transporter protein (SERT), leading to increased reuptake and consequently reduced synaptic availability of serotonin.Inhibition of hippocampal neurogenesis may also play a role in the development of isotretinoin-induced depression. A further effect of isotretinoin on the brain involves retinoic acid function in the hypothalamus, the hormone regulatory centre of the brain and part of the hypothalamus-pituitary-adrenal axis, a key part of the bodys stress response. Other brain regions regulated by retinoic acid and potentially disrupted by isotretinoin include the frontal cortex and the striatum. Pharmacokinetics and pharmacodynamics
Oral isotretinoin is best absorbed when taken with a high-fat meal, because it has a high level of lipophilicity. The efficacy of isotretinoin doubles when taken after a high-fat meal compared to when taken without food.
Bizarre parosteal osteochondromatous proliferation (BPOP), also known as Noras lesion, is a type of non-cancerous bone tumor belonging to the group of cartilage tumors. It is generally seen in the tubular bones of the hands and feet, where it presents with a rapidly enlarging painless lump in a finger or toe.It is composed of bone, cartilage and spindle cells. Some people report previous trauma.Diagnosis is by medical imaging. Treatment is by surgical excision. Up to 50% recur after surgery.It is rare, and occurs more often in the 20s and 30s. Combined with subungal exostosis, it accounts for less than 5% of cartilage tumors. Males and females are affected equally. The condition was first described by Frederick E. Nora in 1983. Signs and symptoms
BPOP generally presents with a 1–3 cm painless lump in a finger or more frequently a toe. Growth can be rapid. Mechanism
It is composed of bone, cartilage and spindle cells. A small number of people have reported previous trauma. Diagnosis
Medical imaging usually shows a well-defined wide-based bony growth on the surface of bone. Differential diagnosis
BPOP is distinct from subungal exostosis. Conditions that may appear similar to BPOP include: myositis ossficans, ostechondroma, surface osteosarcoma and granulomatous infection. Treatment
Treatment is by surgical excision. Outcomes
Up to 50% recur after surgery. Epidemiology
BPOP is rare. It is most often seen in people in their 20s and 30s. Combined with subungal exostosis, it accounts for less than 5% of cartilage tumors. Males and females are affected equally.