Exam 3 - Hussein Flashcards
What is the major organ for drug elimination?
Kidneys
What factors contribute to renal clearance?
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
How is renal clearance calculated?
Renal Cl = Glomerular filtration + Tubular secretion - Tubular reabsorption
The kidneys receive what % of cardiac output?
25%
What is the normal GFR for a healthy adult?
125 mL/min
The glomerulus can filter what small molecules with a molecular weight of?
MW
How does a GFR correlate with an individual’s BSA and free fraction of drug in their plasma?
Proportionally
How is GFR assessed?
Calculation of CrCl over 24 hours of urine collection
What is the equation for CrCl?
CrCl (mL/min) = Cr excretion rate (mg/dL) / [serum concentration (0.8-1.2 mg/dL) * 1440]
How can CrCl be practically calculated to quickly estimate kidney function in clinical practice?
Using ONLY ONE measurement of serum creatinine, CrCl can be calculated via several equations
What is the Cockcroft-Gault equation for CrCl?
CrCl (mL/min) = [(140 - Age)(Weight)] / [(72)(SCr)]
**Multiply entire right side of equation by 0.85 for female over 18 years
In the assessment of active tubular secretion, a transport process AGAINST a concentration gradient, requires what?
Energy
When assessing tubular reabsorption, can be influenced by what?
Tubular pH
pKa of the drug
Unionized drugs are:
More lipid soluble and easily reabsorbed
Ionized drugs are:
More water soluble, not easily reabsorbed, and eliminated more quickly in urine
Is amphetamine a weak acid or weak base?
Amphetamine is a weak base
What should be done to the urine in order to keep or remove acids?
Acidify to keep
Alkalinize to remove
What is commonly used to alkalinize urine, and what is a common indication for this agent?
Sodium bicarbonate; drug overdose with weak acids
What is the Henderson-Hesselbalch equation for a urine-plasma ratio?
(U/P)= [1 + (10 pH urine - pKa )] / [1 + (10 pH plasma- pKa )]
Renal Clearance is mathematically equal to?
a) Filtration + Secretion + reabsorption
b) Filtration + Secretion – reabsorption
c) Filtration - Secretion – reabsorption
b) Filtration + Secretion – reabsorption
With regard to glomerular filtration, which of the following is true?
a) Filtration rate in healthy adult is > 80 ml/min
b) Filtration rate is NOT related to body surface
area
c) Molecules >500 Dalton are filtered
a) Filtration rate in healthy adult is > 80 ml/min
With regard to tubular reabsorption, which of the following is true?
a) Alkalinization of urine will increase the elimination of acidic drugs
b) Acidifying the urine will increase the elimination of acidic drugs
a) Alkalinization of urine will increase the elimination of acidic drugs
What is used as a practical assessment of renal function?
CrCl; CrCl (mL/min) is about = GFR (mg/dL)
What CrCl (or GFR) is considered renal dysfunction?
CrCl 1.2 mg/dL
When do we use ideal body weight (IBW) or actual body weight? What is the calculation for IBW?
Use IBW if ABW is 80-120% of IBW
Use ABW if ABW > 120% of IBW
IBW (male) in kg = 50 + [2.3 * height in inches over 5 feet]
IBW (female) in kg = 45 + [2.3 * height in inches over 5 feet]
How do we assess kidney function in children 1-18 years?
CKiD Schwartz and Bedside Schwartz
CrCl (mL/min/1.73 m^2) = 0.48 * [height in cm / SCr)]
What are indicators of renal impairment?
Increased:
SCr > 1.3
BUN > 21-24
Hyperkalemia > 5.3
Decreased:
CrCl
Which of the following is a flag for a declined kidney function?
a) Calculated creatinine clearance of 180 ml/min
b) Measured serum creatinine of 1.8 mg/dl
c) Age in years of 50
d) Serum potassium of 3.5
b)Measured serum creatinine of 1.8 mg/dl
How can renal impairment alter the BA of some drugs?
It can either increase of decrease the BA of some drugs
Alpha-1-acid glycoprotein binds to acidic or basic drugs?
Basic drugs
Albumin binds to acidic or basic drugs?
Acidic drugs
What was the resulting impact of individualized doses?
Improved patient outcomes and cost-savings
Is it possible to, when assessing liver function, quantitatively measure the liver’s ability to metabolize drugs in a way that is similar to renal dysfunction in clinical practice?
No
What SINGLE tests are used to predict the degree of hepatic impairment or ability to eliminate drugs?
No single tests are available; several factors must be considered to properly assess liver function
What are some common Liver Function tests (LFTs)?
- Albumin
- Alpha-1 antitrypsin
- ALP
- ALT
- AST
- Gamma-glutamyl transpeptidase (GGT)
- Prothrombin time
- Serum bilirubin
- Urine bilirubin
What is MELD?
Estimated 3-Month Survival as a Function of Model for End-Stage Liver Disease (MELD)
MELD = 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4
What LFT uses the least number of variables?
APRI, which uses AST and platelets
What LFT model uses the most variables?
FibroSure
What classification system is used to assess liver function for severity of cirrhosis?
The Pugh’s Modification of Child’s Classification of liver diseases was developed (Child-Turcotte-Pugh Classification) utilizing 3 laboratory parameters and 2 clinical measures
What do scores of 5-6, 7-9, and > 9 on Pugh’s Modification scale indicate?
5-6: mild dysfunction (class A) 7-9: moderate dysfunction (class B) > 9: severe dysfunction (class C)
What are the main CYP enzymes inhibited in liver disease?
- 2C19: most profoundly affected
- 1A2
- 2D6
- 2E1
Inhibition of each respective enzyme can result in hepatic decompensation and eventually to hepatic-renal syndrome
