Digitalis products

Glandular products, drugs of vegetable origin, such as quinine, strychnine and brucine, emetine, and digitalis glycosides ... 

There is an additive bone marrow depression when methimazole or propylthiouracil is administered with otiier bone marrow depressants, such as the antineo-plastic drugs, or witii radiation therapy. When methimazole is administered with digitalis, there is an increased effectiveness of the digitalis and increased risk of toxicity. There is an additive effect of propylthiouracil when the drug is administered with lithium, potassium iodide, or sodium iodide When iodine products are administered with litiiium products, synergistic hypotiiyroid activity is likely to occur. 

Good manufacturing practices (GMPs) ensure that products meet specific quality standards, are not adulterated or misbranded, and contain the correct ingredients and doses stated on the label. GMPs specifically for dietary supplements are being proposed from the FDA. Cases of adulteration have been reported to the FDA, and examples include a plantain product adulterated with digitalis and hibiscus tea adulterated with warfarin [29]. 

The product usually extracted from both types of Digitalis is made up of already partially hydrolyzed glycosides, namely digitoxin and digoxin. 

Withering s discovery of the clinical use of digitalis was important, but it may well be that his contribution to the methodology of pharmacology and therapeutics was of even greater importance. His rejection of polypharmacy, his attention to pharmaceutical product quality and to the standardization of his remedy, and his development of the technique of dose-titration enabling a drug with the narrowest of therapeutic ratios to be used safely - were recorded in a way that seems as fresh today as it ever was. These aspects of his work, the careful and detailed nature of his clinical observations, and the aphoristic nature of his splendid Inferences continue to excite one s admiration today (see Mann, 1985). 

Historically, plant-based natural products have been a source of useful drugs. The analgesic opiates come from the poppy plant. Digitalis for congestive heart failure was first isolated from the foxglove plant. Various antibiotics (penicillin) and anticancer agents (taxol) are derived from natural product sources. There are numerous other examples. 

The enzyme catalyzing the transfer of D-apiose from UDP-apiose to 4, 5-dihydroxyflavon-7-yl /3-D-glucopyranoside is commonly called apiin synthetase.7 Activity is measured by the formation of [14C]apiin from UDP-[U-14C]apiose. Apiin synthetase can be measured by the rapid separation and isolation, by poly(ethylenimine)-paper chromatography, of a product of the reaction, namely, [14C] apiin, from UDP-D-[U-14C]xylose and degradation products of UDP-[U-14C]apiose.31 There are reports of the isolation and purification of apiin synthetase from parsley leaves,31 from cell-suspension cultures of parsley,121 and from foxglove (Digitalis purpurea).31 Apiin synthetase isolated from parsley does not require metal ions, NAD+, or other cofactors, and is soluble. It is inhibited by several heavy metals, but not by tetra-N-... 

D. Chemical Use Classes. This includes the toxicology aspects of the development of new chemicals for commercial use. In some of these use classes, toxicity, at least to some organisms, is a desirable trait in others, it is an undesirable side effect. Use classes are not composed entirely of synthetic chemicals many natural products are isolated and used for commercial and other purposes and must be subjected to the same toxicity testing as that required for synthetic chemicals. Examples of such natural products include the insecticide, pyrethrin, the clinical drug, digitalis, and the drug of abuse, cocaine. 

In the first place, they provide a number of extremely useful drugs that are difficult, if not impossible, to produce commercially by synthetic means. These include diverse groups of compounds such as the alkaloids of opium poppy, ergot, and solanaceous plants the cardiotonic glycosides of digitalis most of the antibiotics and all of the serums, vaccines, and related products. 

In the process of observing the pharmacological effects of Digitalis, Withering identified desired endpoints to include increased urine production (now believed to be the result of increased cardiac output and increased blood flow through the kidneys) and a decreased pulse rate. He also noted the toxic central and cardiac effects... 

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