Drug Interactions- Elimination

Sponsored Links

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.
Topic: 

About the Author

Prof. J. Vijaya Ratna's picture

Dr. Vijaya Ratna Jayanthi serving Andhra University College of Pharmaceutical Sciences as Chairman, Pharmaceutical Technology Department.

Dr. J. Vijaya Ratna did her B.Pharm (1977), M.Pharm (1979), PGDAS (1981) and Ph.D (1998) at Andhra University Campus and won "M.L. Khorana Gold Medal" for standing University FIRST in graduation.

Comments

TK Indira's picture

Quite important concept. Can you please explain the excretory pathway for lipid soluble and lipid insoluble drugs.

T.K. Indira. http://www.pharmainfo.net/tkindira

-- "Our greatest glory is not in never falling, but in rising every time we fall..." Team 'Char'minar.

Prof. J. Vijaya Ratna's picture

Indira Sorry, I cannot straightaway answer that question.
Uma Pratyusha's picture

Dear madam, You said that use of NSAID's increases the levels of lithium in blood by inhibiting the prostaglandins and reducing the function of glomeruli. Now, if lithium concentrations increases, isn't it toxic to us? Then, do we need to administer any other drugs to prevent it along with NSAID's?

Regards

Uma Prathyusha

Prof. J. Vijaya Ratna's picture

Dear Uma Yes, if the lithium levels increase to unexpected levels, it may be toxic. My understanding is that we must not use NSAID at the same time as lithium to prevent this interaction.
Uma Pratyusha's picture

Dear madam, May I know how does lithium enter our body/ I mean the sources of it.

Regards

Uma Prathyusha

Prof. J. Vijaya Ratna's picture

Dear Uma Lithium is used in Psychiatry as a medicine. Vijaya Ratna
Uma Pratyusha's picture

Dear madam, Can you name a few?

Regards

Uma Prathyusha

V.B.S.Aishwarya's picture

Dear madam, Does the drug gets excreted only through urine? why not through sweat as water and salts gets excreted through urine and sweat and along with this only know, the drug too gets excreted?

Regards

V.B.S.Aishwarya

 

 

 

Prof. J. Vijaya Ratna's picture

Dear Aishwarya Yes, drugs get excreted through different routes. But here I am talking about the interactions that may happen at the place of urinary excretion. Vijaya Ratna

You May Also Like..