Podcast
Questions and Answers
Which of the following impacts drug clearance in patients with kidney disease?
Which of the following impacts drug clearance in patients with kidney disease?
Chronic kidney disease (CKD) leads to an increase in the volume of drug distribution consistently.
Chronic kidney disease (CKD) leads to an increase in the volume of drug distribution consistently.
False
What is the primary physiological change in drug clearance that occurs in acute kidney injury (AKI)?
What is the primary physiological change in drug clearance that occurs in acute kidney injury (AKI)?
Decreased drug clearance
The nephron primarily facilitates the ________ process of drugs during kidney function.
The nephron primarily facilitates the ________ process of drugs during kidney function.
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Match the following nephron functions with their descriptions:
Match the following nephron functions with their descriptions:
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Which factor is NOT typically considered in designing dosing regimens for kidney disease patients?
Which factor is NOT typically considered in designing dosing regimens for kidney disease patients?
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Guidelines for drug dosing in kidney disease are always reliable and applicable to all patients.
Guidelines for drug dosing in kidney disease are always reliable and applicable to all patients.
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What is a common challenge when prescribing medications to patients with impaired kidney function?
What is a common challenge when prescribing medications to patients with impaired kidney function?
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What percentage of patients with data in kidney impairment are evaluated on hemodialysis?
What percentage of patients with data in kidney impairment are evaluated on hemodialysis?
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Drug dosing for patients with kidney disease does not require particular caution due to the lack of impact by kidney function.
Drug dosing for patients with kidney disease does not require particular caution due to the lack of impact by kidney function.
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Name one factor that determines the effect of kidney disease on pharmacokinetics?
Name one factor that determines the effect of kidney disease on pharmacokinetics?
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In cases where the drug has a wide therapeutic index, it may be reasonable to simply prescribe the ______ recommended by the manufacturer.
In cases where the drug has a wide therapeutic index, it may be reasonable to simply prescribe the ______ recommended by the manufacturer.
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Match the following kidney conditions with their effects on drug pharmacokinetics:
Match the following kidney conditions with their effects on drug pharmacokinetics:
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What is one reason why prescribing can be complicated for patients with kidney disease?
What is one reason why prescribing can be complicated for patients with kidney disease?
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Prescribing a dose based on clinical progression is a valid approach when dealing with kidney disease patients.
Prescribing a dose based on clinical progression is a valid approach when dealing with kidney disease patients.
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What is a recommended source for additional dosing guidance in kidney impairment?
What is a recommended source for additional dosing guidance in kidney impairment?
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Which of the following factors can lead to the prolonged half-life (t1/2) of drugs in patients with kidney impairment?
Which of the following factors can lead to the prolonged half-life (t1/2) of drugs in patients with kidney impairment?
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Active secretion in nephrons leads to increased drug accumulation in cases of kidney dysfunction.
Active secretion in nephrons leads to increased drug accumulation in cases of kidney dysfunction.
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What is the significance of dose adjustments for drugs like metformin in patients with chronic kidney disease?
What is the significance of dose adjustments for drugs like metformin in patients with chronic kidney disease?
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Phenolic acid glucuronide is an example of an ____________ metabolite that may accumulate in renal impairment.
Phenolic acid glucuronide is an example of an ____________ metabolite that may accumulate in renal impairment.
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Match the following drugs to their classifications based on toxicity and treatment duration:
Match the following drugs to their classifications based on toxicity and treatment duration:
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Which drug requires dose adjustments due to its long elimination half-life and higher intrinsic toxicity?
Which drug requires dose adjustments due to its long elimination half-life and higher intrinsic toxicity?
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Short courses of treatment reduce the risk of drug accumulation in patients with kidney dysfunction.
Short courses of treatment reduce the risk of drug accumulation in patients with kidney dysfunction.
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What clinical complications can arise from drug accumulation in patients with chronic kidney disease?
What clinical complications can arise from drug accumulation in patients with chronic kidney disease?
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Study Notes
Clinical Pharmacokinetics in Kidney Disease
- Kidney disease is a common comorbidity, altering drug pharmacokinetics
- Prescribing to patients with kidney disease requires knowledge of the drug, patient physiology, and pharmacokinetic principles
- Impaired kidney function affects drug clearance and volume of distribution
- Acute kidney injury (AKI) has dynamic changes in drug clearance, unlike chronic kidney disease (CKD), which has slower progression
- Recovery is possible in AKI based on the cause and treatment
- Kidney replacement therapies in AKI further complicate drug clearance quantification
- Adjusting dosing regimens can personalize care and minimize adverse effects
- Principles of pharmacokinetics guide rational dosing strategies
Introduction
- Drugs are crucial treatments for kidney disease
- Knowledge of basic pharmacokinetic principles is essential for all prescribers, especially nephrologists
- Kidney disease impacts drug handling in various ways, including chronic (slow progression) and acute (rapid changes) conditions
- Understanding how physiological changes affect drug pharmacokinetics is vital for rational drug use and treatment optimization
Relationship between Dosing Regimen and Drug Effect
- A drug's effect depends on both its pharmacokinetics (body's effect on the drug) and pharmacodynamics (drug's effect on the body)
- Pharmacokinetics includes absorption, distribution, metabolism, and excretion (ADME), each of which can be altered in kidney disease affecting therapeutic outcomes
- Drug concentration-time profiles reflect how ADME processes affect drug action, and drug exposure (e.g., maximal concentration, and area under the curve [AUC]) is associated with drug effects
Reasons to Optimize Dosing Regimens
- Sub- and supra-therapeutic drug exposures can result in treatment failure, morbidity, prolonged hospitalizations, and potentially, death
- Risks increase in drugs with narrow therapeutic indices (for example, digoxin or lithium), where even small changes in exposure can lead to toxicity
Selected Examples of Drugs Requiring Special Consideration in Kidney Disease
- Antibiotics' efficacy depends on their concentration relative to a bacteria's minimum inhibitory concentration (MIC).
- Factors that maximize antibiotic efficacy include the ratio of peak to MIC (concentration-dependent agents), the ratio of AUC to MIC, and the duration of time the plasma concentration exceeds the MIC (time-dependent agents)
- Lithium excretion is dependent on kidney function; chronic poisoning is an adverse effect in impaired kidney function
- Digoxin has a narrow therapeutic index and accumulates with impaired kidney function, requiring dose adjustments
- Cyclophosphamide and its metabolites are cleared by the kidneys, thus dosage needs to be adjusted for patients with impaired kidney function and considerations of the presence of glomerulonephritis
Novel/Direct Acting Oral Anticoagulants (NOACs/DOACs)
- NOACs/DOACs clearance varies with kidney function
- Some NOACs have dose adjustments in patients with kidney disease, and others are contraindicated
- Dabigatran exposure increased in patients with impaired kidney function due to dependence of clearance on kidney function and P-glycoprotein transporters
- Apixaban clearance less reduced and appropriate dose adjustment determined
Pharmacokinetic Principles and Parameters
- Volume of distribution (Vd) describes the drug distribution in the body
- Clearance (CL) measures the volume of blood cleared of a drug per unit time
- Elimination half-life (t1/2) measures the time required for the drug concentration to decrease by 50%
- AUC (area under the curve) is proportional to the decrease in CL
- Changes in both CL and Vd influence drug concentration-time profiles
Kidney Clearance
- Kidney clearance is influenced by glomerular filtration, active tubular secretion, and passive tubular reabsorption.
- Several factors, including individual variability and the interplay of several processes (especially nonrenal CL) in addition to kidney-related CL, can alter expected drug clearance, and dose adjustment is often required
Other Considerations
- Factors like drug-drug interactions might affect clearance, requiring dosing adjustments
- Protein binding influences drug action and may change in kidney disease, affecting free drug concentration and impacting dosing
- Dose adjustments are usually not required for drugs of low toxicity administered for a short duration, but they are essential for drugs with long elimination half-lives
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Description
This quiz covers the crucial principles of clinical pharmacokinetics specifically related to kidney disease. It highlights the importance of understanding drug clearance, dosing regimens, and patient physiology for effective prescribing. Tailored strategies for managing drug therapies in acute and chronic kidney conditions are emphasized.
