Hello everyone, I hope you are enjoying your day. We started a series on pharmacology, looking at pharmacokinetics. In this series, I explained the process of drug absorption which is basically meant for drugs that aren't taken via the intravenous method. It explains how the drugs get into the gastrointestinal tract after which it is taken from the intestinal tract into the bloodstream. After absorption has been done, the next step is the distribution phase which has to do with sharing drugs from the blood to other parts of the body would include where the drug will be used (site of action), site of metabolism, excretion sites, and other various tissues. Metabolism has to do with converting an active drug to an inactive one before it is excreted or from a prodrug to an active drug. These are possible using phase 1 Biotransformation and phase 2 Biotransformation. In today's post, I will be discussing Drug Excretion.
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When I say excretion of the drug, I literally mean taking the drug out of the body, and there are several organs that can be used to excrete drugs but it is primarily done by the kidney via urination, other organs for excretions would include the Bile (If the drug is absorbed into the GI tract to reach the Bile system where it then excreted through the hepatic circulation), the Lungs where it is exhaled out (in anesthetics), and through the feces. While all other organs are important in excreting drugs, the kidney is the most important and common organ for excretion, so your kidney needs to function properly. When a person has kidney disease or problems, then drugs will not be excreted which could become toxic to the body.
In the Kidney, there are factors that can affect the excretion of drugs. We will be looking at the various kidney function that relates to excretion which is filtration, secretion, and reabsorption, and then look at the factors that could affect the excretion of drugs.
In Filtration, the drug goes from the afferent arteriole to the glomerulus where drugs are filtered into the Bowman's capsule through Glomerular hydrostatic pressure. From the Bowman's capsule, the drug gets into the proximal convoluted tubule. Remember that filtration is dependent on the Glomerular filtration rate. This means that patients who have certain kidney diseases that affect the glomerular filtration rate of the glomerulus thereby causing plasma filtration to be less, means that drug filtration will be less, causing higher blood drug concentration. Also, filtration is dependent on the proteins to be filtered. Proteins such as Albumin can be very big and if drugs are bound to albumin in the kidney, the ability to filter them will be very poor, keeping the drug in the blood. Increase protein binding of drugs will reduce the filtration of the drugs across the glomerulus and into the bowman's capsule, thereby increasing the Blood Drug Concentration.
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With secretion in the Kidney, it is no news that not all substances are filtered into the Bowman's capsule, which also includes drugs. Some of them move through the Efferent Arterioles to the Peri Tubular capillaries where they are then supplied to the lumen of the kidney tubules for excretion. In the case of drugs, it is dependent on the solubility of the drug and the concentration gradient of the drug. When a drug is polar, water-soluble, and large, it will require Organic Anion Transporters and Organic Cation Transporters to move the drug from the Basolateral membrane into the lumen of the kidney tubules if not completely filtered in the glomerulus. When a drug is non-polar, hydrophobic, and small, there is a high possibility of not being filtered in the glomerulus due to its characteristics which I explained in my previous post, it means there will be more drug concentration in the peritubular capillary blood, and low concentration in the tubules but in the easy for the drug to be secreted into the lumen through the Peri Tubular capillaries into the lumen without transporters as it is taking it from a higher concentration region to a lower concentration region which will help for the drug to be excreted through urine.
After filtration, drugs could get into the lumen through the Peri Tubular capillaries depending on the concentration gradient of the drug, solubility of the drug, and transporters. When this drug is in the lumen, it moves to the distal convoluted tubule where there is a high contraction of the drug. At this point, small nonpolar, and hydrophobic (lipid soluble) drugs can be reabsorbed into the bloodstream through diffusion without any transporter but in other for the drug to be excreted, it is sent back to the liver where it undergoes phase 1 biotransformation and or phase 2 biotransformation metabolism to make it more polar, so it will not be reabsorbed in the distal convoluted tubule when it gets back, then it can be excreted out of the body. In cases of a drug overdose, it is very important that the drug is in a charged form so it can be excreted very fast without being reabsorbed back into the bloodstream because it would need a transporter to get it out of the tubule. In other, for this to be possible, non-polar drugs can be trapped in the urine by decreasing the proton in the drug by alkalinizing the urine decreasing the proton and allowing the drug to be trapped and excreted out with urine. Sodium Bicarbonates do a good job of alkalinizing the urine and trapping the drug in the urine. In the case where the drug is completely polar, there won't be reabsorption of the drug in the distal convoluted tubule, increasing the proton concentration will make the drug less polar, which means increasing the acidity of the urine. In other to acidify the during, Ammonium chloride is introduced trapping the ions in the kidney tubules and helping them get excreted.