Therapeutic Drug Monitoring - Pharmacokinetics in Special Populations Lecture

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

How does renal disease impact the elimination or metabolism of the majority of drugs?

Renal disease decreases the elimination or metabolism of the majority of drugs.

What effect does dialysis have on drug removal in patients with renal failure?

Dialysis procedures remove some medications from the body while leaving the pharmacokinetics of other drugs unchanged.

How does heart failure impact drug clearance rates?

Heart failure results in low cardiac output, reducing blood flow to eliminating organs and affecting the clearance rate of drugs.

What effect does obesity have on drug distribution in the body?

Obesity can alter the way drugs distribute in the body by adding excessive adipose tissue, which in turn affects the volume of distribution for the medication. Signup and view all the answers

How can drug interactions impact drug metabolism?

Drug interactions can inhibit or induce drug metabolism, leading to changes in how drugs are broken down in the body. Signup and view all the answers

What is the functional unit responsible for waste product removal from the body?

The nephron is the functional unit of the kidney responsible for waste product removal and drug elimination. Signup and view all the answers

Which organ's blood flow is affected by heart failure, impacting drug clearance?

Heart failure decreases blood flow to eliminating organs, affecting drug clearance. Signup and view all the answers

Why do drugs with moderate-to-high extraction ratios show sensitivity to alterations in organ blood flow?

Drugs with moderate-to-high extraction ratios are sensitive to alterations in organ blood flow due to their dependence on adequate blood flow for effective clearance. Signup and view all the answers

What is the equation that describes hepatic drug metabolism?

Hepatic drug metabolism is described by the equation: LBF = fB * Cl'int Signup and view all the answers

For drugs with a low hepatic extraction ratio (≤30%), how does the numeric value of liver blood flow compare to the product of unbound fraction of drug in the blood and intrinsic clearance of the compound?

The numeric value of liver blood flow is much greater than LBF>>fB * Cl'int Signup and view all the answers

What is hepatic clearance equal to for a drug with a low hepatic extraction ratio?

Hepatic clearance is equal to the product of free fraction in the blood and the intrinsic clearance of the drug Signup and view all the answers

For drugs with a high hepatic extraction ratio (≥70%), how does the numeric value of liver blood flow compare to the product of unbound fraction of drug in the blood and intrinsic clearance of the agent?

The numeric value of liver blood flow is much less than LBF << fB * Cl'int Signup and view all the answers

What enzyme system is often responsible for Phase I type reactions in drug metabolism?

Cytochrome P-450 enzyme system (CYP) Signup and view all the answers

Where in the hepatocytes is the cytochrome P-450 enzyme system located?

Bound to the membrane of the endoplasmic reticulum Signup and view all the answers

What is the purpose of Phase II type reactions in drug metabolism?

Conjugation to form glucuronides, acetates, or sulfates Signup and view all the answers

What type of reactions generally result in drug metabolites that are more water-soluble?

Phase I and Phase II reactions Signup and view all the answers

Which transport protein actively secretes drug molecules into the bile?

P-glycoprotein Signup and view all the answers

What are the two major types of liver disease mentioned in the text?

Hepatitis and cirrhosis Signup and view all the answers

What happens to hepatocytes in patients with cirrhosis?

Permanent loss of functional hepatocytes Signup and view all the answers

What laboratory tests or clinical symptoms are included in the Child-Pugh score?

Serum albumin, total bilirubin, prothrombin time, ascites, and hepatic encephalopathy Signup and view all the answers

What is the Child-Pugh score for a patient with normal liver function?

5 Signup and view all the answers

What is the Child-Pugh score for a patient with grossly abnormal serum albumin, total bilirubin, and prothrombin time values, in addition to severe ascites and hepatic encephalopathy?

15 Signup and view all the answers

What is the threshold Child-Pugh score that indicates a moderate decrease (~ 25%) in initial daily drug dose for agents that are primarily (≥60%) hepatically metabolized?

8-9 Signup and view all the answers

What is the threshold Child-Pugh score that indicates a significant decrease (~ 50%) in initial daily dose for drugs that are mostly liver metabolized?

10 or greater Signup and view all the answers

For a medication that is 95% liver metabolized with a usual dose of 500 mg every 6 hours (2000 mg/d), what would be the appropriate initial dose for a hepatic cirrhosis patient with a Child-Pugh score of 12?

1000 mg/d Signup and view all the answers

How could the 1000 mg/d dose for the patient with a Child-Pugh score of 12 be prescribed?

The drug could be prescribed as 250 mg every 6 hours or 500 mg every 12 hours. Signup and view all the answers

What is the purpose of the initial doses mentioned in the text?

Initial doses are meant as starting points for dosage titration based on patient response and avoidance of adverse effects. Signup and view all the answers

What is the usual total daily dose of a medication that is 95% liver metabolized?

2000 mg/d Signup and view all the answers

What is the expected glomerular filtration rate (GFR) range for otherwise healthy 80-year-old adults?

30-40 mL/min Signup and view all the answers

What is the normal range for glomerular filtration rate considered by most clinical laboratories?

80-120 mL/min Signup and view all the answers

In patients with renal disease, what is the underlying cause of the functional loss of nephrons?

Depending on the etiology of the renal disease Signup and view all the answers

For patients with acute renal failure due to sudden decrease in renal blood flow or nephrotoxic drug therapy, what is the likelihood of their kidney function returning to pre-insult levels?

Their kidney function can return to pre-insult levels if they survive the underlying causes Signup and view all the answers

What is the key difference between acute renal failure and chronic renal failure in terms of the potential for recovery of kidney function?

Patients with chronic renal failure sustain permanent loss of functional nephrons and do not recover lost kidney function Signup and view all the answers

What is the formula used to calculate creatinine clearance rate (CrCl) from urine and serum creatinine measurements?

CrCl (in mL/min) = (UCr * Vurine) / (SCr * T) Signup and view all the answers

What are the units used for the variables in the creatinine clearance rate formula?

UCr in mg/dL, Vurine in mL, SCr in mg/dL, T in minutes Signup and view all the answers

At what point during the urine collection period is the serum creatinine sample collected for the creatinine clearance rate calculation?

At the midpoint of the urine collection time Signup and view all the answers

Study Notes

Introduction to Pharmacokinetics in Special Populations

Most medications require dosage modification due to specific disease states and conditions that alter their pharmacokinetics.
Factors that alter pharmacokinetics include renal or hepatic disease, dialysis, heart failure, obesity, and drug interactions.

Renal Disease

The nephron is the functional unit of the kidney responsible for waste product removal and drug elimination.
Normal glomerular filtration rate (GFR) is 80-120 mL/min, and a GFR of 30-40 mL/min is expected for otherwise healthy 80-year-old adults.
Renal failure can be acute or chronic, with acute failure potentially reversible and chronic failure causing permanent loss of functional nephrons.
Creatinine clearance (CrCl) can be measured using urine and blood samples, and is calculated using the formula: CrCl (in mL/min) = (UCr * Vurine) / (SCr * T)

Hepatic Disease

Phase I reactions (oxidation, hydrolysis, reduction) are mediated by the cytochrome P-450 enzyme system in the liver.
Phase II reactions (conjugation) are also mediated in the liver by cytosolic enzymes.
Liver disease can be classified into two types: hepatitis and cirrhosis.
Hepatitis is an inflammation of the liver, which can cause mild, transient decreases in drug metabolism.
Cirrhosis is a permanent loss of functional hepatocytes, requiring dosage changes.
The Child-Pugh score is used to assess liver function, with a score of 5 indicating normal liver function and a score of 15 indicating grossly abnormal liver function.

Implications of Hepatic Disease on Drug Effects

Hepatic drug metabolism is described by the equation: hepatic clearance = LBF * fB * Cl'int
For drugs with a low hepatic extraction ratio (≤30%), hepatic clearance is equal to the product of free fraction in the blood and the intrinsic clearance of the drug.
For drugs with a high hepatic extraction ratio (≥70%), liver blood flow is much less than the product of unbound fraction of drug in the blood and the intrinsic clearance of the agent.
A Child-Pugh score of 8-9 indicates a moderate decrease (~ 25%) in initial daily drug dose, and a score of 10 or greater indicates a significant decrease (~ 50%) is required for drugs that are mostly liver metabolized.
Initial doses are meant as starting points for dosage titration based on patient response and avoidance of adverse effects.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Explore the impacts of renal and hepatic diseases on the pharmacokinetics of drugs in special populations with this quiz from the Department of Clinical Pharmacy. Understand how diseases can alter drug clearance and metabolism, leading to necessary dosage adjustments.