Tolerance
After long-term use for chronic conditions, nitrate tolerance—tolerance to agents such as GTN— may develop in a patient, reducing its effectiveness. Tolerance is defined as the loss of symptomatic and hemodynamic effects of GTN and/or the need for higher doses of the drug to achieve the same effects, and was first described soon after the introduction of GTN in cardiovascular therapy. Studies have shown that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients prognosis. These include endothelial and autonomic dysfunction.The mechanisms of nitrate tolerance have been investigated over the last 30 years, and several hypotheses to explain tolerance have been offered, including: 

plasma volume expansion
impaired transformation of GTN into NO or related species
counteraction of GTN vasodilation by neurohormonal activation
oxidative stressRecent evidence suggests that deleterious GTN-induced production of oxygen free radicals might induce a number of abnormalities, include those described above, so that the oxidative stress hypothesis might represent a unifying principle. Adverse events
Glyceryl trinitrate can cause severe hypotension, reflex tachycardia, and severe headaches that necessitate analgesic intervention for pain relief, the painful nature of which can have a marked negative effect on patient compliance. GTN also can cause severe hypotension, circulatory collapse, and death if used together with vasodilator drugs that are used for erectile dysfunction, such as sildenafil, tadalafil, and vardenafil.GTN transdermal patches should be removed before defibrillation due to the risk of explosion and/or burns, but investigations have concluded that GTN patch explosions during defibrillation were due to voltage breakdown involving the metal mesh in some patches.
An intraneural perineurioma is a rare benign tumor within the sheath of a single nerve that grows but typically does not recur or metastasize. These lesions are only composed of perineurial cells, cloned from a single cell. They are distinct from schwannoma and neurofibroma. Intraneural perineurioma is a neoplastic proliferation of perineurial cells with unique immunohistochemistry and ultrastructural features, and it is distinct from other onion bulb Schwann cell-derived entities. Despite harboring molecular abnormalities of the long arm of chromosome 22, intraneural perineurioma has not been associated with neurofibromatosis.Due to the involvement of one or more nerve fascicles, intraneural perineuriomas are distinguished by a localized, solitary expansion of peripheral nerves. These tumors develop slowly or stay stable over time. References
Further reading
Macarenco RS, Ellinger F, Oliveira AM (2007). "Perineurioma: a distinctive and underrecognized peripheral nerve sheath neoplasm". Archives of Pathology & Laboratory Medicine. 131 (4): 625–36. doi:10.1043/1543-2165(2007)131[625:PADAUP]2.0.CO;2. PMID 17425397. Kum YS, Kim JK, Cho CH, Kim HK (2009). "Intraneural reticular perineurioma of the hypoglossal nerve". Head Neck. 31 (6): 833–7. doi:10.1002/hed.20965. PMID 18972430. Chung JH, Jeong SH, Dhong ES, Han SK (2014). "Surgical removal of intraneural perineurioma arising in the brachial plexus using an interfascicular dissection technique". Arch Plast Surg. 41 (3): 296–9. doi:10.5999/aps.2014.41.3.296. PMC 4037780. PMID 24883285. Emory TS, Scheithauer BW, Hirose T, Wood M, Onofrio BM, Jenkins RB (1995). "Intraneural perineurioma. A clonal neoplasm associated with abnormalities of chromosome 22". Am J Clin Pathol. 103 (6): 696–704. doi:10.1093/ajcp/103.6.696. PMID 7785653.