Consequently, porphyrin deposits form in the bloodstream and cause neuropathic pain, leading to the acute neurological crises experienced by some patients. Additionally. SA can function to inhibit renal tubular function, the synthesis of heme, and the immune system.The accumulation of unprocessed tyrosine itself in the blood stream as a consequence of deficient catabolism can also lead to disruption of hormonal signaling and neurotransmission. Tyrosine is a precursor molecule required for synthesis of several neurotransmitters and hormones, mainly Dopamine, norepinephrine, and thryoxine. Excessive synthesis of these molecules due to elevated tyrosine levels can impair physical growth, motor function, and speech development. Diagnosis
Beyond the identification of physical clinical symptoms outlined above, the definitive criterion for diagnostic assessment of Tyrosinemia Type I is elevated succinylacetone (SA) in blood and urine. Elevated SA levels are not associated with any other known medical condition, so there is minimal risk of misdiagnosis. Quantitation of tyrosine levels is also used as a diagnostic but is less reliable due to high false positive and false negative rates. Newborns are not generally screened for HT1 due to rarity of the condition and lack of apparent symptoms at time of birth. However, prompt assessment upon the manifestation of physical symptoms such as fever, vomiting, increased tendency to bleed, diarrhea along with bloody feces, and jaundice is critical for improving long term prognosis. Management
The primary treatment for type 1 tyrosinemia is nitisinone and restriction of tyrosine in the diet.
When considering taking these medicines, it is important to note the variations in their ability to offset the nongenomic effects of aldosterone.Currently, there is not enough evidence available from the randomized controlled trials on side effects of eplerenone to do a benefit versus risk assessment in people with primary hypertension. Interactions
Eplerenone is primarily metabolized by the cytochrome P450 enzyme CYP3A4. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4. Specifically, the concomitant use of the CYP3A4 potent inhibitors ketoconazole and itraconazole is contraindicated. Other CYP3A4 inhibitors including erythromycin, saquinavir, and verapamil should be used with caution. Other drugs that increase potassium concentrations may increase the risk of hyperkalemia associated with eplerenone therapy, including salt substitutes, potassium supplements and other potassium-sparing diuretics. Pharmacology
Eplerenone is an antimineralocorticoid, or an antagonist of the mineralocorticoid receptor (MR). Eplerenone is also known chemically as 9,11α-epoxy-7α-methoxycarbonyl-3-oxo-17α-pregn-4-ene-21,17-carbolactone and "was derived from spironolactone by the introduction of a 9α,11α-epoxy bridge and by substitution of the 17α-thoacetyl group of spironolactone with a carbomethoxy group." The drug controls high blood pressure by blocking the binding of aldosterone to the mineralocorticoid receptor (MR) in epithelial tissues, such as the kidney. Blocking the action of aldosterone decreases blood volume and lowers blood pressure. It has 10- to 20-fold lower affinity for the MR relative to spironolactone, and is less potent in vivo as an antimineralocorticoid. However, in contrast to spironolactone, eplerenone has little affinity for the androgen, progesterone, and glucocorticoid receptors.