Clinical Drug Safety Chapter 8: Renal Impairment and Drug Safety

Play an AI-generated podcast conversation about this lesson

What is the main topic of Chapter 8?

Renal impairment and its impact on drug safety

What is one of the mechanisms of renal excretion of drugs that students will be able to describe after completing this chapter?

Different mechanisms of renal excretion of drugs

What are some examples of drugs that require special consideration in chronic kidney disease?

Lithium, antidiabetics, and oral anticoagulants

What is the importance of optimizing dosing regimens in patients with renal impairment?

To minimize toxicity and ensure efficacy Signup and view all the answers

What is chronic kidney disease?

A condition that will be defined in the chapter Signup and view all the answers

Why is it important to calculate glomerular filtration rate in patients with renal impairment?

To adjust drug dosing and minimize toxicity Signup and view all the answers

What is the purpose of using different types of equations to calculate drug dosing in case of renal impairment?

To ensure accurate dosing and minimize toxicity Signup and view all the answers

How can renal disease affect the effects of drugs?

It can either decrease or increase the effects, leading to potential toxicity Signup and view all the answers

What is the result of increased drug clearance?

Lower drug concentrations Signup and view all the answers

In patients with renal disease, what should be done to avoid harm when drug clearance is significantly reduced?

The dose of renally cleared drugs should be reduced Signup and view all the answers

How does renal disease affect a drug's effect?

By one of three ways: patient susceptibility, pharmacodynamic properties, or pharmacokinetic properties Signup and view all the answers

What is the maximum drug clearance via glomerular filtration alone?

The glomerular filtration rate (GFR), around 90 ml/min Signup and view all the answers

How does protein binding affect drug clearance via glomerular filtration?

It restricts clearance in proportion to the percentage protein bound Signup and view all the answers

What is the formula for drug filtration rate?

GFR x fu x [drug] Signup and view all the answers

What is the effect of decreased drug clearance on drug concentrations?

Higher drug concentrations Signup and view all the answers

How should the medication dose be adjusted in patients with renal disease?

It should be decreased equivalently to the calculated reduction of drug clearance Signup and view all the answers

What is the mechanism that enables renal clearance to be larger than the GFR?

Active transport Signup and view all the answers

What type of drugs are actively transported from the blood to the tubular lumen?

Acids, such as penicillins, NSAIDs, probenecid, and methotrexate Signup and view all the answers

What is the mechanism that affects weak acids and weak bases?

Reabsorption by non-ionic diffusion Signup and view all the answers

What is an example of a weak acid that is affected by reabsorption by non-ionic diffusion?

Phenobarbital Signup and view all the answers

What is an example of a weak base that is affected by reabsorption by non-ionic diffusion?

Quinidine Signup and view all the answers

What is the mechanism that involves the active reabsorption of high threshold endogenous substances or nutrients?

Active reabsorption Signup and view all the answers

What is an example of a substance that is actively re-absorbed?

Uric acid Signup and view all the answers

What is the rate of renal blood flow that active transport can theoretically achieve?

Up to 1500 ml/min Signup and view all the answers

What fraction of a drug with fu = 0.5 is excreted unchanged through the kidneys?

50% Signup and view all the answers

How should the dose of a drug be adjusted if CrCl is half normal?

The dose should be halved. Signup and view all the answers

What is the recommended approach to calculating CrCl in pregnant women?

Measuring the creatinine clearance using the classical way of 24 hours urine. Signup and view all the answers

What happens to the dose-rate (DR) of drugs excreted 100% unchanged by the kidneys in cases of renal impairment?

The dose-rate (DR) is decreased in direct proportion to the impairment in renal function. Signup and view all the answers

What fraction of the dose should be halved if CrCl is half normal?

The fraction of the dose that is excreted unchanged through the kidneys. Signup and view all the answers

Why is it necessary to adjust the dose of certain drugs in patients with renal impairment?

Because the kidneys play a significant role in the excretion of these drugs. Signup and view all the answers

What is the significance of fu in determining drug dosing in patients with renal impairment?

fu determines the fraction of the drug that is excreted unchanged through the kidneys. Signup and view all the answers

What is the consequence of not adjusting the dose of a drug in patients with renal impairment?

Toxicity or inadequate treatment. Signup and view all the answers

What is the best overall index of kidney function?

Glomerular filtration rate (GFR) Signup and view all the answers

Why does the Cockcroft and Gault equation assume a 15% lower creatinine clearance for women?

Due to lesser muscle mass Signup and view all the answers

At what age does creatinine clearance normally start to decrease?

20 years old Signup and view all the answers

What is the purpose of the CKD-EPI Creatinine Equation?

To estimate GFR Signup and view all the answers

How does the CKD-EPI equation improve on the MDRD Study equation?

By reducing bias at eGFR >60 Signup and view all the answers

What is the recommended approach for dose adjustment in renal diseases for drugs with free fraction fu=1?

Reduce doses in direct proportion to the degree of impairment in CrCl Signup and view all the answers

Why is the age term in the Cockcroft and Gault equation (140 - age)?

To show how dependent the estimation of Crcl is based on age Signup and view all the answers

What is the correction factor for obese patients in the Cockcroft and Gault equation?

Ideal body weight Signup and view all the answers