HomeHealth articleskidney healthHow Is Kidney Function Linked to Drug Pharmacology?

Relation Between Drug Pharmacology and Kidney Function

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Kidney function can alter the relationship between the drug dosage and the clinical effect of the drugs in several ways. To know more, read the content below.

Medically reviewed by

Dr. Manzoor Ahmad Parry

Published At December 13, 2022
Reviewed AtJune 14, 2023

Introduction:

Kidneys are a pair of bean-shaped organs located in the retroperitoneal area on either side of the body. Each kidney measures about four to five inches in size. The main function of the kidney is to filter blood. It is estimated that the whole blood in the body passes through the kidneys about forty times a day to get filtered. Other functions include maintaining the water-electrolyte balance and acid-base balance in the body. Once the blood reaches the kidney, along with filtration of the wastes, the salt, water, and electrolyte levels are adjusted, after which the blood re-enters circulation. The drugs and the medications that are taken for various reasons will alter kidney function.

Any drug administered goes through the following mechanism; initially, it gets absorbed by the body, which is then distributed in the blood, undergoes metabolism, reaches the kidneys, gets filtered, and the rest is excreted in the urine.

Based on the dosing interval, the concentration of the drug in the blood varies. The drug will be effective till its half-life and lose its action after that period. Hence, the half-life period of the drug is important for the duration of the effectiveness of the drug.

What Are the Determinants of the Dose and Concentration of the Drug in the Blood?

The factors that determine the dose and concentration of the drug are as follows:

1. Rate of Absorption: It is the pharmacokinetic property of the drug that denotes the way the drug is absorbed from the bloodstream into circulation. It is an important parameter as it determines the time and magnitude at which the drug reaches its peak concentration in the blood. The factors that influence drug absorption include:

  • Diseases That Cause Delayed Drug Emptying - The rate of absorption of the drug is determined by the rapidity with which the stomach empties the drug.

  • Physicochemical Properties of the Drug - The pharmacological effect of the drug depends on the physical and chemical properties of the other chemical agent that it interacts with in the gastrointestinal tract.

  • Intestinal Motility - Increased intestinal motility will accelerate the rate of drug absorption. But in the case of slowly absorbed drugs like Digoxin, increased intestinal motility would result in poor absorption.

  • Renal Dysfunction - Studies report that renal dysfunction affects the rate of drug absorption by the intestine and intestinal motility.

2. Rate of Distribution: The rate of distribution of the drug is an important factor, as it determines the amount of drug available in the blood to elicit the drug's effect. The factors that influence drug distribution include:

  • Systemic pH - An increase in the systemic pH would decrease the solubility of the drug.

  • Disease States - This may decrease the binding of the drug to the plasma proteins such as albumin and alpha-1 acid glycoprotein.

  • Protein Binding - It is the amount of drug that binds with the plasma proteins present in the blood.

  • Renal Dysfunction - Studies report that renal dysfunction affects drug distribution by inducing and altering the systemic pH.

3. Elimination: The drug is eliminated from the body by three mechanisms: metabolism, excretion, or dialysis.

  • Metabolism- It mainly takes place in the liver and the proximal convoluted tubules of the kidney.

  • Excretion - This is mainly through the bile juices, and a few drugs like anesthetic gases and paraldehyde are eliminated through the lungs.

  • Dialysis - This is a special mode of drug excretion; the water-soluble drugs of low molecular weight will be eliminated by this process.

How Does Renal Dysfunction Affect the Pharmacological Properties of the Drug?

The normal functioning of the kidneys is essential for the effectiveness of the drugs, as renal dysfunction has an impact on all the pharmacokinetic properties of the drug, such as absorption, distribution, and elimination.

Renal Dysfunction and Drug Absorption: Absorption is the first and prime step for the drug to reach blood circulation. In the case of renal dysfunction, the normal absorption of the drug is affected. It is because, in patients with renal failure, there will be decreased mesenteric blood flow. Mesenteric arteries are the main blood vessels that carry blood and oxygen to the intestine. As the intestines are responsible for drug absorption, the decreased mesenteric blood flow would decrease the absorption of the drug in the intestine.

Renal Dysfunction and Drug Distribution: The main component of the serum that helps in drug distribution is the plasma proteins. Once the drug is absorbed into the circulation, it binds with the plasma proteins, namely, albumin, beta-globulin, and acid glycoprotein. In renal diseases, the degree of drug binding to the plasma protein is decreased due to uremia (increased uric acid level in the blood) and hypoalbuminemia (decreased serum albumin), thereby affecting the half-life of the administered drug.

Renal dysfunction would result in systemic acidosis as a result of uremia or renal tubular acidosis, thereby altering the systemic pH. In this condition, the binding of drugs to the plasma protein is not affected, but the distribution of the drug to the target tissue is considerably reduced.

Renal Dysfunction and Drug Elimination: Eliminating the drugs from circulation is one of the key roles of the kidneys, as their main function is filtration. In patients with renal diseases, this process is affected due to the poorly functioning glomeruli and the number of nephrons (functional unit of the kidney), resulting in poor elimination of the drugs. As a consequence of this, the drug gets deposited in the kidneys leading to drug toxicity.

Can Changes Occur in the Properties of Drugs Due to Kidney Problems or Kidney Failure?

The drugs that show changes in their normal pharmacological behavior are as follows:

  • Propranolol is normally eliminated by the metabolic transformation in the liver and excreted in the urine. In patients with renal failure, the hepatic elimination of Propranolol is decreased, thereby increasing the bioavailability of the drug.

  • Drugs such as Cloxacillin, Chlorpropamide, and Pindolol show decreased intestinal absorption in patients with renal failure.

  • In patients with renal tubular acidosis and renal failure, there is decreased calcium absorption in the intestine due to the inadequate hydroxylation of vitamin D3.

  • Drugs such as Warfarin, Phenytoin, Salicylates, Tthiopentone, and Diazoxide, show distribution-related changes in patients with renal failure. As in such patients, the degree of plasma protein binding is poor, causing the decreased distribution of drugs in the blood and to the target tissues.

  • Hypoalbuminemia caused due to renal failure can affect the binding of drugs, such as Warfarin and Phenytoin, thereby increasing the amount of free drugs in plasma.

  • An antiarrhythmic agent such as Procainamide is usually eliminated by the kidneys. In patients with renal failure, Procainamide settles in the kidney causing toxicity.

  • Pain-relieving medication such as Pethidine, usually eliminated by the kidneys, can accumulate in the kidney due to its poor elimination capacity resulting in seizures.

  • Drugs such as Iodipamide, Probenecid, and high-dose salicylates induce uricosuria (excretion of uric acid in the urine) in patients with renal dysfunction by decreasing the reabsorption of uric acid by the kidneys.

Conclusion:

Renal dysfunction can affect the pharmacological property of the drug by affecting its rate of absorption, distribution, and excretion. Proper knowledge about the changes in the drug properties in patients with renal dysfunction would help alter the drug dosage accordingly and decrease the advent of complications and drug toxicity.

Frequently Asked Questions

1.

What Is the Pharmacological Role of the Kidney?

Kidney functioning can determine drug dosage and its clinical effect. The organ plays a role in medication absorption, distribution, and elimination depending on the drug’s concentration in the blood.

2.

How Can Renal Function Affect Pharmacokinetics?

 
Pharmacokinetics is described as the effect of the body on the drug. The kidney's functioning of absorption, distribution, metabolism, and excretion is included in the assessment of the kidney’s pharmacokinetics. There may be disruption to the kidney’s pharmacokinetics if there is the development of renal disease.

3.

What Is the Effect of Kidney Function on Drug Absorption?

Some of the drugs that are present in the filtered blood in kidneys are reabsorbed from the tubules. The reabsorbed drugs and water enter the blood circulation. This reabsorption is called passive diffusion, as it does not require energy.

4.

What Is the Pharmacological Consideration in Kidney Failure?

 
Individuals with renal failure react abnormally to the drugs. Small doses of drugs in patients with renal failure may cause severe and fatal complications. Therefore, modification of drugs becomes necessary. There is also the risk of drug retention leading to drug toxicity.

5.

What Are the Factors Affecting Drug Absorption?

Drug absorption depends on the drug’s chemical composition, solubility, and route of administration. The drug’s particle size, disintegration time (dissolving in fluids), or gastric emptying time can also be other factors that affect drug absorption. The drugs that are in solution form can be easily reabsorbed.

6.

Can Kidney Failure Affect Drug Distribution?

Renal failure can affect the plasma protein binding, which causes an increase in the volume distribution of the drug.  It is one of the main effects of renal failure. However, a reduction in renal blood flow can reduce volume distribution in blood.

7.

What Are the Drugs That Support Kidney Function?

Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARB) are two types of medication that support kidney function. The drugs are blood pressure medicine that slows kidney function loss and delays renal failure.

8.

What Are the Drugs Metabolized in the Kidneys?

The kidney contains many enzymes that are needed for drug metabolism. Drugs like Morphine (pain medicine), Paracetamol, and P-Aminobenzoic acid (a chemical compound naturally occurring in the body) undergo metabolism in the kidneys. In renal disease, the metabolizing function of the kidney is reduced.

9.

What Are the Factors Affecting Drug Pharmacodynamics?

The factors that can affect drug action are age, sex, and body size of the patient. The drug dose, route of administration, time of administration, and associated renal diseases can affect the pharmacodynamics of the drug in the body.

10.

What Are the Drugs That Are Harmful to Kidneys?

Drugs such as antibiotics, diuretics, non-steroidal anti-inflammatory drugs, proton pump inhibitors, specific supplements, and laxatives harm kidneys. These drugs can disrupt the normal functioning of kidneys.

11.

What Is the Role of the Kidney in the Detoxification of Drugs?

Kidneys detoxify the body by secreting or filtering the toxins from the blood. These toxins are then excreted from urine. The toxins are excreted from the kidneys in three mechanisms. They are through filtration from glomeruli (loop of blood vessels in the kidney), passive diffusion from distal tubules (nephron segment), and active process (filtration of toxins from blood and excretion).

12.

Which Organ Is Responsible for the First-Pass Effect?

The first-pass effect is a process in which a drug is metabolized in the specific organ that causes a reduction in drug concentration. This happens before the drug reaches the site of action. The liver is the most common site for the first-pass effect, as the organ is responsible for drug metabolism.

13.

What Is Drug Bioavailability?

Drug bioavailability is the rate and extent to which the drug enters the body’s blood circulation to reach the site of action. The bioavailability depends on the drug dosage and route of administration.

14.

How Is the Drug Excreted From the Body?

 
Drug excretion is the removal of unchanged drugs or metabolites from the body. The drugs can be excreted from the body through urine, bile, saliva, sweat, tears, and stool. The non-soluble drugs are metabolized to form soluble drugs for excretion from the body.
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Dr. Manzoor Ahmad Parry
Dr. Manzoor Ahmad Parry

Nephrology

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