Weak acids gastrointestinal absorption

Absorption. Absorption of cyanide across the gastrointestinal mucosa depends on the pH of the gut and the pKa and lipid solubility of the particular cyanide compound. Hydrogen cyanide is a weak acid with a pKa of 9.2 at 25 °C. The acidic environment in the stomach favors the non-ionized form of hydrogen cyanide and facilitates absorption. Information regarding the rapid lethal effects following oral intake of cyanide in humans (Gosselin et al. 1976) indicates that cyanide is rapidly absorbed from the gastrointestinal tract. 

Our gastrointestinal tract is lined with epithelial cells, and drugs have to cross the cell membrane (see Exhibit 5.2). In the stomach, where pH is low, drugs that are weak acids are absorbed faster. In the intestine, where pH is high, weak basic drugs are absorbed preferentially. Figure 5.6 shows the absorption of drugs under different pH environments. 

FIGURE 2-3 Effect of phi and ionization on absorption of drugs from the gastrointestinal tract. Weak acids and bases are absorbed from the stomach and duodenum, respectively, when they are in their neutral, nonionized form. 

Among factors that may modify gastrointestinal absorption of ingested chemicals, the presence of food in the tract is one of the most important. The presence of food in the stomach will delay the absorption of weak organic acids at that site. The presence of lipid-rich food will delay the emptying of the gastric content into the intestine and thus also delay the absorption of chemicals. Conversely, an empty stomach facilitates absorption, a situation that is almost always beneficial in drug therapy. 

Per Oral Toxicity. Molar toxicities for HCN, NaCN, and KCN are similar. For HCN and NaCN, lethal toxicity is somewhat greater for starved than unstarved animals, but the reverse situation is obtained with KCN (Ballantyne, 1984). Time to onset of signs is around 1-8 min and time to death from 7 to 26 min. When cyanide is given per orally the gastric environment favors the formation of HCN, which facilitates absorption. In addition, favoring the absorption of HCN across the gastrointestinal mucosa is its weak acidity, with a pKa of 9.2. 

Oral absorption depends partially on the pH of the gastrointestinal tract which is known to vary between species, as shown in table 5,3. Clearly, therefore, considerable differences in the absorption of weak acids from the stomach may occur between species. Similarly, differences might be seen in compounds which are susceptible to the acidic conditions... 

D. Enhancement of Elimination Enhancement of elimination is possible for a number of toxins, including manipulation of urine pH to accelerate renal excretion of weak acids and bases. For example, alkaline diuresis is effective in toxicity due to fluoride, isoniazid, fluoroquinolones, phenobarbital, and salicylates. Urinary acidiflcation may be useful in toxicity due to weak bases, including amphetamines, nicotine, and phencyclidine, but care must be taken to avoid acidosis and renal failure in rhabdomyolysis. Hemodialysis or hemoperfusion enhances the elimination of many toxic compounds, including acetaminophen, ethylene glycol, formaldehyde, lithium, methanol, procainamide, quinidine, salicylates, and theophylline. Cathartics such as sorbitol (70%) may decrease absorption and hasten removal of toxins from the gastrointestinal tract. 

The degree of ionization of many therapeutic drugs, which are usually weak electrolytes, is directly dependent upon the pH of the gastrointestinal content. The pH will therefore have considerable influence on the absorption of such chemicals absorption will occur at sites where the drugs are present as neutral molecules. At the low acidic pH of the stomach (1-3), most weak organic acids such as... 

For drugs administered oraUy, impaired gastrointestinal (GI) absorption is an important consideration. For example, aluminum ions in certain antacids or ferrous ions in oral iron supplements form insoluble chelates of tetracycline antibiotics, thereby preventing their absorption. The antifungal ketoconazole is a weak base that is only soluble at acid pH. Drugs that inhibit gastric acidity, such as the proton pump inhibitors and histamine Hj receptor antagonists, impair the dissolution and absorption of ketoconazole. 

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