Late pregnancy
In late pregnancy liver function decreases significantly, which can be easily monitored by blood tests. Early clinical manifestations of ALF in late pregnancy include hypodynamia, decrease in appetite, dark amber urine, deep jaundice, nausea, vomiting, and abdominal distention. Among patients whose deaths were attributed to ALF in late pregnancy, the majority had experienced vaginal deliveries. Causes
Common causes for acute liver failure are paracetamol (acetaminophen) overdose, idiosyncratic reaction to medication (e.g. tetracycline, troglitazone), excessive alcohol consumption (severe alcoholic hepatitis), viral hepatitis (hepatitis A or B—it is extremely uncommon in hepatitis C), acute fatty liver of pregnancy, and idiopathic (without an obvious cause). Reye syndrome is acute liver failure in a child with a viral infection (e.g. chickenpox); it appears that aspirin use may play a significant role. Wilsons disease (hereditary copper accumulation) may infrequently present with acute liver failure. Acute liver failure also results from poisoning by the death cap mushroom (Amanita phalloides) as well as other amatoxin-producing fungus species. Certain strains of Bacillus cereus—a common species of bacterium implicated as a frequent cause of food poisoning—can cause fulminant liver failure through the production of cereulide, a toxin which destroys the mitochondria in affected hepatocytes, resulting in cell death. While most instances of B. cereus infection are resolved by the bodys immune system and do not affect the liver, severe cases resulting in liver damage can be fatal without immediate treatment or liver transplantation.
The dihydropyridine ring of the nimodipine is dehydrogenated in the hepatic cells of the liver, a process governed by cytochrome P450 isoform 3A (CYP3A). This can be completely inhibited however, by troleandomycin (an antibiotic) or ketoconazole (an antifungal drug). Excretion
Studies in non-human mammals using radioactive labeling have found that 40–50% of the dose is excreted via urine. The residue level in the body was never more than 1.5% in monkeys. Mode of action
Nimodipine binds specifically to L-type voltage-gated calcium channels. There are numerous theories about its mechanism in preventing vasospasm, but none are conclusive.Nimodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid. Synthesis
The key acetoacetate (2) for the synthesis of nimodipine (5) is obtained by alkylation of sodium acetoacetate  with 2-methoxyethyl chloride, Aldol condensation of meta-nitrobenzene (1) and the subsequent reaction of the intermediate with enamine (4) gives nimodipine. Stereochemistry
Nimodipine contains a stereocenter and can exist as either of two enantiomers. The pharmaceutical drug is a racemate, an equal mixture of the (R)- and (S)- forms. References
Further reading
Pharmacology: R. Towart, S. Kazda, Br. J. Pharmacol. 67, 409P (1979). Use as cerebral vasodilator: H. Meyer et al., GB 2018134 ; eidem, U.S. Patent 4,406,906 (1979, 1983 to Bayer). Effect on associative learning in aging rabbits: R. A. Deyo et al., Science 243, 809 (1989). External links
"Nimodipine". Drug Information Portal. U.S. National Library of Medicine.