Gastrointestinal tract essential drugs

Labetalol is almost completely absorbed from the gastrointestinal tract. However, it is subject to considerable first-pass metabolism, which occurs in both the gastrointestinal tract and the liver, so that only about 25% of an administered dose reaches the systemic circulation. While traces of unchanged labetalol are recovered in the urine, most of the drug is metabolized to inactive glucuronide conjugates. The plasma half-life of labetalol is 6 to 8 hours, and the elimination kinetics are essentially unchanged in patients with impaired renal failure. 

It acts by inhibiting dihydrofolate reductase. It inhibits conversion of dihydrofolic acid to tetrahydrofolic which is essential for purine synthesis and amino acid interconversions. It primarily affects DNA synthesis but also RNA and protein synthesis. It has cell cycle specific action and kills cells in S phase. It is readily absorbed from gastrointestinal tract but larger doses are absorbed incompletely, little drug is metabolised and it is excreted largely unchanged in urine. 

Medicinal chemists have used isosterism for the design of safe, effective drug substances for many years. During the development of anti-ulcer medications, for example, it was found that metiamide (38) greatly reduced acid secretion in the gastrointestinal tract by antagonizing H2-receptor sites. Its potential as auseful anti-ulcer medication was lessened by adverse effects caused by the thiourea moiety, a toxicophore (Table 4.1). This moiety is essential for H2-receptor blockade, but bestows toxicity. 

Sink conditions refer to a special case where there is essentially no buildup of the solute, which is assumed to be the case forthe absorption of a drug from the gastrointestinal tract. Two ramiLcations for this special case are that the concentration gradient ft) described in Equation 17.9 is not... 

Zopiclone. Zopiclone is well absorbed from the gastrointestinal tract with peak plasma concentration reached within 2 h after administration. It has a half-life of 4-6 h and a duration of action of 6-8 h. It is metabolized in the liver to N-desmethylzopiclone and zopicloneN-oxide, and these two metabolites constitute about 36%of the dose excreted in the urine along with small amounts of zopiclone. Excretion of drug and metabolites was essentially complete 48 h after the final dose. 

Niclosamide, which is not absorbed from the gastrointestinal tract, is the safest effective drug in cestode infestations. It inhibits anaerobic metabolism and glucose uptake in Taenia solium, against which it is highly effective. As lethal doses of niclosamide in adult worms do not destroy the ova, purgation 1 to 2 horns after niclosamide is essential, or the risk of cysUcercosis is likely. 

Some very weak acidic drugs (plCa 7 or higher) such as barbiturates, phenytoin (Dilantin) and theophylline remain, essentially, in unionized form throughout the gastrointestinal tract. 

Shanahan F (2010) Gut microbes from bugs to drugs. Am J Gastroenterol 105 275-279 Sivropoulou A, Papanikolaou E, Nikolaou C et al (1996) Antimicrobial and cytotoxic activities of Origanum essential oils. J Agric Food Chem 44 1202-1205 Smith AH, Mackie RI (2004) Effect of condensed tannins on bacterial diversity and metabolic activity in the rat gastrointestinal tract. Appl Environ Microbiol 70 1104-1115 Smith AH, Zoetendal EG, Mackie RI (2005) Bacterial mechanisms to overcome inhibitory effects of dietary tannins. Microb Ecol 50 197-205... 

Parenteral administration of drugs by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes is now an established and essential part of medical practice. Advantages for parenterally administered drugs include the following rapid onset, predictable effect, predictable and nearly complete bioavailability, and avoidance of the gastrointestinal (GI) tract and, hence, the problems of variable absorption, drug inactivation, and GI distress. In addition, the parenteral route provides reliable drug administration in very ill or comatose patients. 

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