Non-exertional heatstroke is a much greater danger: even the healthiest person, if left in a heatstroke-inducing environment without medical attention, will continue to deteriorate to the point of death, and 65% of the most severe cases are fatal even with treatment. Signs and symptoms
Heat stroke generally presents with a hyperthermia of greater than 40.6 °C (105.1 °F) in combination with disorientation. However, high body temperature does not necessarily indicate that heat stroke is present, such as with people in high-performance endurance sports or with people experiencing fevers. Exertional heat stroke is more accurately diagnosed based on a constellation of symptoms rather than just a specific temperature threshold. There is generally a lack of sweating in classic heatstroke, while sweating is generally present in exertional heatstroke.Early symptoms of heat stroke include behavioral changes, confusion, delirium, dizziness, weakness, agitation, combativeness, slurred speech, nausea, and vomiting. In some individuals with exertional heatstroke, seizures and sphincter incontinence have also been reported. Additionally, in exertional heat stroke, the affected person may sweat excessively. If treatment is delayed, patients could develop vital organ damage, unconsciousness and even organ failure. In the absence of prompt and adequate treatment, heatstroke can be fatal. Causes
Heat stroke occurs when thermoregulation is overwhelmed by a combination of excessive metabolic production of heat (exertion), excessive heat in the physical environment, and insufficient or impaired heat loss, resulting in an abnormally high body temperature.
Nitisinone, sold under the brand name Nityr and Orfadin among others, is a medication used to slow the effects of hereditary tyrosinemia type 1 (HT-1). Uses
Nitisinone is used to treat hereditary tyrosinemia type 1 (HT-1) in patients from all ages, in combination with dietary restriction of tyrosine and phenylalanine.Since its first use for this indication in 1991, it has replaced liver transplantation as the first-line treatment for this ultra rare condition. Adverse effects
The most common adverse reactions (>1%)  for nitisinone are elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash and alopecia.has several negative side effects; these include but are not limited to: bloated abdomen, dark urine, abdominal pain, feeling of tiredness or weakness, headache, light-colored stools, loss of appetite, weight loss, vomiting, and yellow-colored eyes or skin. Mechanism of action
The mechanism of action of nitisinone involves inhibition of 4-Hydroxyphenylpyruvate dioxygenase (HPPD). This is a treatment for patients with Tyrosinemia type 1 as it prevents the formation of 4-Maleylacetoacetic acid and fumarylacetoacetic acid, which have the potential to be converted to succinyl acetone, a toxin that damages the liver and kidneys. This causes the symptoms of Tyrosinemia type 1 experienced by untreated patients.Alkaptonuria is caused when an enzyme called homogentisic dioxygenase (HGD) is faulty, leading to a buildup of homogenisate. Alkaptonuria patients treated with nitisinone produce far less HGA than those not treated (95% less in the urine),  because nitisinone inhibits HPPD, resulting in less homogenisate accumulation.