ACTH acts through membrane receptors, leading to activation of adenylyl cyclase, enhanced formation of intracellular 3’-5’ cyclic adenosine monophosphate (cAMP), and increased phosphorylation by protein kinase type A, which ultimately stimulates cortisol synthesis and secretion. Cholesterol is stored esterified to long-chain fatty acids, which must be cleaved and transported to the inner mitochondrial membrane, where the enzymatic processes leading to steroid synthesis reside. This transport step through the outer mitochondrial membrane is the actual rate-limiting process in overall steroid synthesis and requires the participation of the steroidogenic acute regulatory protein (StAR). ACTH rapidly stimulates StAR synthesis in the adrenals (as the gonadotropins do in the testes and ovaries), which facilitates cholesterol transport through the mitochondria, leading to initiation of steroid synthesis. Mutations in StAR have been associated with congenital lipoid adrenal hyperplasia, an autosomal recessive disorder that leads to deficiencies of adrenal and gonadal hormones and life-compromising pathology associated with salt loss, hyperkalemic acidosis, and dehydration, unless treated with adrenal steroids.
Isoniazid should not be administered with food. Studies have shown that the bioavailability of isoniazid is reduced significantly when administered with food. Tyramine- and histamine -containing foods should be avoided in patients receiving isoniazid. Because isoniazid has some monoamine oxidase inhibiting activity, an interaction with tyramine-containing foods (cheese, red wine) may occur. Diamine oxidase may also be inhibited, causing exaggerated response (., headache, sweating, palpitations , flushing, hypotension ) to foods containing histamine (., skipjack, tuna , other tropical fish).