MD 3105 Basic Pharmacology

Question:

Assessment of drug clearance in patients suffering from acute kidney injury.

Answer:

Introduction

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The Kidneys excrete drug into urine through renal clearance.

It is actually the direct result of active tubular production, tubular absorption, and glomerularfiltration.

This paper will focus on the various methods of measuring renal clearance.

For the dosing drugs of medication during dialysis or acute kidney injuries, renal clearance is normal.

Clearance of Drugs In The Renal System

A kidney’s ability to eliminate a drug from the blood can be defined as its capacity to remove the drug in one unit.

Acute Kidney Injury (AKI), patients who have had to undergo renal clearance of drugs.

Dialysis and drug dosing is required for acute kidney injury patients.

To do this, it is necessary that the kidney rate of drug clearance by the kidney be determined.

The body may accumulate harmful metabolites if drugs are not cleared by the kidneys after an acute kidney injury.

An enhanced drug response could be caused by the accumulation of a pharmacologically activated drug.

Hypersensitive drug reaction can occur when drugs such as codeine, allopurinol, and meperidine cause anxiety, agitation, or depression in the central nervous system.

The renal function of a renal is a key factor in determining the drug’s renal clearance.

For patients with acute kidney disease, the renal clearance of drugs is required to determine the dosage of drugs.

Drug clearance is the removal of drug from the body by the kidney.

To be eliminated, the drug must be channeled to the kidney via the plasma flow.

It can thus be said that drug elimination rates are proportional to plasma concentration.

The drugs that are ionized and cannot cross the liver membrane don’t undergo hepatic metabolism. They are more likely to be cleared by the kidneys.

The primary organ that excretes water soluble substances is the kidneys.

The kidneys are responsible for removing drugs from the body that are not absorbed into the gastrointestinal system.

The majority of drugs are expelled through renal filtration.

The pores of the glomerulus tubule’s endothelium filter about one-fifth of plasma.

To determine whether dosing rates of drugs should be changed, it is necessary to know the renal clearance rate and whether there has been any increase in drug level that can cause adverse side effects.

Sometimes the renal clearance can be used to determine which mechanism is responsible for drug clearance by the kidney.

If the renal clearance equals the product of the rate of glomerular filtration and the unbound fraction, then filtration is happening.

If the renal clearance equals the product glomerular rate and unbound drug fraction, then renal resorption can be considered. On the other hand, if renal clearance is higher than the product glomerular rate by unbound drug fraction, then it is possible to consider that secretion is still taking place.

There are several methods that aid in the removal drugs from the kidney.

They include Glomerular Filtration, renal drug metabolism, tubular secretion and tubular secretion.

It is difficult to evaluate the renal clearance of drugs

Acute kidney injury patients have kidney function tests that determine the need for dialysis, adjustments to the medication, or nutritional therapy.

A kidney function is determined by the rate at which drugs are cleared from the kidney. This rate can also be calculated by estimating the glomerularfiltration rate.

Because of fluctuations in creatine production, kidney function and fluid imbalance, it can be difficult to evaluate the different methods for renal clearance.

To determine kidney function, the GFR (glomerular filtration rate) is calculated.

Clearance of inulin is the best method but is more labor-intensive than the other methods.

Glomerular filtration rates are the amounts of plasma filtered out by the glomerulus per minute7.

GFR is measured by the Fructose-polymer inulin.

However, it is very difficult to test in clinical practice.

It is difficult to calculate the plasma clearance accurately. The procedure can also be cumbersome and may give incorrect results8.

GFR is primarily determined by urine creatinine levels.

There are also the possibility of erroneous results. The procedure must be initiated with 24-hour urine.

An error in urine collection, especially if it is not completed within a short time frame, can lead to erroneous results.

GFR is measured by measuring serum creatinine and applying the equations.

Clearance of Equation Of Renal

The renal extraction ratio and renal blood flow can be used to estimate renal clearance

CLrenal= QxE

CL renal = renal clearance

Q = Renal perfusion

E = extraction rate

fe is the excreted fraction

Cockcroft & Gault equation8

CLcr=(140 (years), x weight (kg), x 0.85 [female Scr, (mg/dl), x 72

MDRD (four variable) Study equation 8

MDRD (fourvariable) Study equation to IDMS serum creatinine 8

Abbreviations CKD-EPI = Chronic Kidney Disease-Epidemiology Collaborative; CLcr= creatinine filtration; GFR= glomerular filter rate; IDMS= isotope-dilution mass spectrumcopy; MDRD= Modification Of Diet in Renal Disease

Here, k = 0.75 (females), and 0.9 (males).

a = –0.329 (females), & –0.411 (males).

Min denotes the minimum amount of Scr/k, or 1; max denotes the maximum amount of Scr/k/ 1, and age is in years.

CLcr = 98-0.8 (A–20) / SCr

CLcr = 88-0.7 (A – 20) / SCr

A is the age in years

CLcr = creatinine clearance measured in mL/min/1.73m2

Conclusion

This means that renal clearance can be used to evaluate drug dosing in acute kidney injury patients.

A drug’s clearance can be directly correlated with the patient’s renal function.

The ability of the kidney to expel the drug determines whether it should be adjusted.

A variety of procedures are needed to determine the renal clearance. Many of them can be difficult or time-consuming.

However, the report proposes some equations to help determine the rate renal clearance in patients with acute kidney injury.

References

Bouchard. Josee, EtienneMacedo. Sharon Soroko. Glenn M. Chertow. Jonathan Himmelfarb. Talat.Alp Ikizler. Emil P. Paganini. Ravindra. L. Mehta.

“Comparative comparison of methods for estimating the glomerular filtration rates in critically ill people with acute kidney injury.”

Nephrology Dialysis Transplantation 25, No.

“Glomerular rate-estimating equations to patients with advanced chronic kidney disease.”

Nephrology Dialysis Transplantation 28, no.

KDIGO clinical guidelines for acute renal injury.

Nephron Clinical Practice, 120(4). pp.c179-c184.

“Drug Dosing Considerations in Patients with Acute and Chronic Kidney Disease–A Clinical Update from Kidney Disease International: Improving Global Outcomes.

Kidney international 80.

Morrissey Kari M., Sophie L. Stocker and Matthias B. Wittwer. Lu Xu and Kathleen M. Giacomini.

Annual review in pharmacology & toxicology 53 (2013), 503-529.

Two new equations for estimating kidney function in individuals aged 70 years and older.

Annals of internal Medicine, 157(7) pp. 471-481.

“Continuous renal replacement therapy for acute kidney damage.”

New England Journal of Medicine 367.

Vilay A. Mary, Mariann Dr. Churchwell, Bruce A. Mueller.

“Clinical review: Drug metabolism in acute kidney damage.

Critical Care 12, no.

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