Liver active substances

Digoxin-like immunore active substances (found in patients with chronic heart failure, end stage renal disease, liver disease, or third trimester of pregnancy) may cross-react with certain digoxin immunoassays and may result in a false elevation of levels... 

The smoke is 1% to 2% nicotine and approximately 1-3 mg of the drug reaches the smoker s bloodstream per cigarette. Half of the nicotine is eliminated from the blood in 30 to 120 minutes. This short half-life is the result of a portion of nicotine in the blood being metabolized (broken down or changed into other substances) in the liver, lungs, and other organs. Primarily, it is oxidized into cotinine, a less active substance. The kidney then rapidly removes nicotine and cotinine from the body. 

In order to obtain a clinical effect by an orally administered drug, it is, for example, required that the drug is (i) dissolved and released from its formulation, (ii) transported over the mucosal barrier, and (iii) has passed from the lumen to the systemic blood circulation without being metabolized by, for example, the lumen or the liver. The drug dissolution rate and the rate of absorption of the dissolved active substance as well as the relation between these processes are important, in particular the dissolution process since the absorption of undissolved drug particles can be disregarded. 

The formation of an active substance as well as its inactivation or breakdown depend on the individual functional capacity of the liver. 

I have been told that raw goat s milk (2 x 0.25 1/day, stored in the refrigerator) is used successfully to treat liver cirrhosis in some regions. Ubiquinone ( ) is thought to be the active substance — this agent is also said to have prevented the occurrence of cirrhosis in animal experiments. 

Some medicaments with special indications are used in various liver diseases or in certain complications. They are not found in the special category of liver therapeutics (pharmacopoeia), but are listed according to their main indication. Treatment with some of these active substances may possibly be accompanied by side effects, (s. tab. 40.4)... 

A great number of different active substances have been discussed in connection with the treatment of the various liver diseases or their complications in the respective chapters. The effectiveness of these substances has either been statistically confirmed in controlled trials, or they have been tested empirically, or they seem to be pharmacologically plausible for a specific application. Some of these therapeutic substances and their uses are presented in more detail in the following section. 

Liver and renal function tests should be monitored in symptomatic patients or patients on chronic usage of the herb. Individuals using kava regularly should be cautioned about the potential for adverse interactions with other pharmacologically active substances, including ethanol, barbiturates, and some benzodiazepines. A toxic dose has not yet been established. 

Table 3.6 Transformation (%) from prodrug 15 to active substance 14a and 14i by liver S9 fractions from rats, monkeys and humans, pharmacokinetics parameters for active substances, 14a and 14i, after oral dosing (lOmg/kg) of 14a, 14i, and prodrug 15 to rats and monkeys, and antidepressant-like activity of 14a and its prodrug 15a (MCS0210)... 

Their acute toxicity to mammals is low, but the two active substances may cause dermatitis. In rats fed daily on a diet containing quinomethionate a high cumulative toxicity was observed. A dietary level of 500 mg/kg for 90 days reduced body-weight, caused hypertrophy of the liver, and inhibited acetoacetate synthesis and the microsomal enzymes. It primarily inhibited the function of the HS-enzymes (pyruvate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and a-ketoglutarate oxidase) (Carlson and DuBois, 1970). 

Liver Extract Kyer89 prepared a concentrated liver extract by precipitating the proteins with lead acetate and then adsorbing the active principle on carbon. The use of the lead salt had certain disadvantages in a later method, calcium chloride and sodium carbonate were added to form a precipitate of calcium carbonate which removed the protein as did lead acetate. The filtrate adjusted to pH 5 is treated with activated carbon, and the filtrate from this is treated with an additional quantity of carbon. The carbon cakes are extracted with hot 50% alcohol and the eluate is concentrated in vacuo. Tyrosine also is adsorbed and eluted with the active substance, although, with some carbons, the adsorption of tyrosine is incomplete. 

Precipitate Factor Elvehjem90 and coworkers found a dietary factor in liver, yeast, and milk, which they called the alcohol-ether precipitate factor. This factor can be adsorbed by activated carbon, but difficulty has been experienced in eluting the active substance. However, when carbon that contained the adsorbed factor was fed to vitamin-deficient animals, good growth was obtained. This suggests that elution In vitro could be accomplished under appropriate conditions. 

On the other hand, the inhibitory actions of oleic acid on metastasis in the liver and metastatic tumor growth in the liver, cannot be explained by the effects of DNA synthesis in LLC cells, and microvascular endothelial cells, or the adherence of LLC cells to the microvascular endothelium rather, these inhibitory actions by oleic acid are partly attributable to the inhibition of the angiogenesis induced by tumors. In conclusion, it seems likely that the antitumor and antimetastatic activities of carp oil may be partly ascribed to a fatty acid, oleic acid, as an active substance. However, the antitumor and antimetastatic effects of carp oil are insufficiently by themselves to explain the action of oleic acid. Further work is in progress to identify the active substance(s) in carp oil. 

The two relevant constituents of nutmeg, elemicine and myristicine, become centrally active substances by transamination in die liver. The effects of the biogenic products 3,4,5-trimethoxyamphetamine and MMDA have been known for a long time. After consumption of these drugs, the urine also contains various methoxypropenylphenols, especially 2,6-dimethoxy-4-(2-propenyl)-phenol (Fig. 8-26). 

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