Drug Interactions--Excretion Some drug- drug interactions happen due to alterations in excretion. When drugs are absorbed into blood, the biological defence systems like distribution, metabolism and elimination immediately start happening. The body perceives the drug as a 'xenobiotic' or stranger and devices various strategies to remove it from the bloodstream. The most important strategy to remove a drug is to eliminate it through urine, which is called as renal excretion. Renal excretion: There are three processes happening in renal excretion, glomerular filtration, tubular secretion and tubular reabsorption. In the first step, most of the low molecular weight drugs are filtered. If they are bound to plasma proteins, they cannot be filtered. In the second step, some reabsorption of water and some secretion of weak electrolytes and weak acids takes place (1). Competitive inhibition of reabsorption: This is an active process and needs energy and carrier. As such two compounds may compete for the same carrier and cause inhibition of secretion of the other. This mechanism operates in the case of penicillin and probenecid. Probenecid is intentionally coadministered with penicillin so that probenecid competes with penicillin and preferentially gets eliminated. As a result more penicillin is kept back in the plasma. The same mechanism may be used for the prevention of elimination of cephalosporins(1). Urinary excretion and pH: Passive excretion and reabsorption of lipid soluble drugs happens in distal tubules. Unionized drugs are readily reabsorbed from the distal tubule. Drugs are either weak acids or weak bases. In acidic urine, weakly acidic drugs are reabsorbed. When it is basic. weakly basic drugs get reabsorbed. Alternatively, if we make urine acidic, alkaline drugs are better excreted. Urine pH can vary between 4.5 to 8.0 depending on what type of foods and drugs are consumed. This property of the body may be utilized in handling cases of drug poisoning. For example, poisoning with the weak acid, pentobarbital, may be handled by causing the urine to become alkaline , by giving sodium bicarbonate injection and causing elimination of pentobarbital.If a drug overdose happens, we can increase the excretion of the drugs by suitable adjustment of urine pH (1). Some urinary alkalinisers: Acetazolamide Diuretics Potassium Citrate Sodium Acetate Sodium Bicarbonate Sodium Citrate Some urinary acidifiers: p-amino salicylate Ascorbic acid Fatty acids Phenyl butazone Ammonium Chloride Calcium Chloride (2) Some prominent examples of altered urinary excretion: 1. Thiazide diuretics increase reabsorption of lithium and may cause lithium toxicity. 2. NSAIDs inhibit prostaglandins , and thus reduce the functioning of glomeruli and thus less lithium is filtered and more of it is made available in blood. 3. Sodium citrate is an alkaliniser used to treat urinary tract infections. 4. Sodium citrate interacts with acidic drugs like acyclovir, cephalosporins, penicillins, and thiazide diuretics. Sodium citrate makes these drugs more ionized, less reabsorbed and hence more excreted (3). So, we can see that some drugs alter the excretion rate and extent of other drugs through competitive inhibiton of reabsorption and through alteration of pH. References:1. www.boomer.org/c/p3/c27/c2702.html , Boomer manual and download, accessed on 30.10.2010. 2. Biopharmaceutics and Pharmacokinetics, A treatise, D.M.Brahmankar, and Sunil B.Jaiswal, pages 204- 211, Vallabh Prakashan ,1995. 3. A textbook of Clinical Pharmacy Practice, Essential Concepts and Skills, by G.parthasarathi, Karin Nyfort-Hansen and Milap C Nahata (Editors), Orient Longman Publishers, page 107. This blog does not contain plagiarized material.