**4.1 Nitrates**

The mechanism of nitrates is based on the release of nitric oxide, which influences the relaxation of the internal anal sphincter muscle [13, 14]. Its commonly used form is glyceryl trinitrate (GTN) in 0.2–0.4% doses, and it is applied topically two to three times a day. The topical application of GTN has been reported to decrease anal resting pressures and promote healing in anal fissure compared to placebo; however, 50% of patients' disease has recurred in the long term [11]. Major side-effects and reasons for discontinuing the treatment are headaches and light-headedness [15, 16].
