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What categories are used to judge liver dysfunction?
Bilirubin, Albumin, Ascites, Encephalopathy, Prothrombin Time
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What does the Child-Pugh classification system do?
Assigns a grade of liver dysfuncation (A, B or C)
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A person with a Child-Pugh total of 7-9 will have what grade?
B
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A person with a Child-Pugh total of <7 will have what grade?
A
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A person with a Child-Pugh total of 10-15 will have what grade?
C
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What does Child-Pugh grade A indicate?
Mild to moderate liver dysfunction
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What does Child-Pugh grade B indicate?
Mild to moderate liver dysfunction
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What does Child-Pugh grade C indicate?
Severe liver dysfunction
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What is the validated method for quantifying liver dysfunction severity and capacity to metabolize drugs?
None
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Is there a clear correlation between liver dysfunction severity and drug metabolism?
No
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Where is the best place to look information on dosage adjustment for liver disease?
Package insert, though often absent
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Other than Child-Pugh, what other classification/severity systems are used?
Discriminant Function and MELD (Mayo End Stage Liver Disease) Score
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What numerical value determined by the Discriminant Function describes a poor prognosis and higher risk of death?
>32
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What is the MELD score used for?
To determine the need for transplantation
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Generally, the higher the discriminant function score, the ________ the patient’s ability to metabolize certain drugs.
Lower
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Does a Child-Pugh score give the pharmacist an idea of how much to alter a dose?
No, not quantifiable or relatable to dose
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What factors impact the pharmacokinetic activity of the liver?
Hepatic blood flow, Metabolizing enzymes and Protein binding
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(True/False) Ascites is effected by protein binding.
True
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What is the route of an oral drug after leaving the intestine until it reaches the heart?
Portal vein, Liver, Hepatic Vein, heart
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What is the equation for Hepatic Clearance (Cl H)
Cl(H)= Qh x fu(B) x Cl(int)/ Qh + fu(B) x Cl(int) OR Cl(H)= Qh x ER(H)
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What does Hepatic Clearance depend on?
Qh = hepatic blood flow, fu(B) = unbound fraction in blood and Cl(int) = intrinsic metabolic activity OR ER(H) = hepatic extraction ratio
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What is ER(H) = heptic extraction ratio?
Fraction of the drug removed from the blood during a single pass through the liver
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What is the range of values you can have for the ER(H) = heptic extraction ratio?
0-1
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Define Cl(int) = intrinsic metabolic activity:
Ability of the hepatocyte to eliminate a drug independent of blood flow or protein binding
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Drugs with high hepatic extraction ratio may have ___________ bioavailability.
Increased
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What does a portacaval shunt do?
Reduced blood flow through the liver, affecting the clearance of high extraction ratio drugs
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What type of drugs are not usually as effected by altered hepatic blood flow?
Drugs with low hepatic extraction
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What value is considered a High Extraction Ratio?
> 0.7
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What drugs were given as an example of a high extraction ratio?
Metoprolol, Propranolol, Labetalol, Nitroglycerin, Verapamil, Midazolam, Morphine
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What value is considered a Low Extraction Ratio?
< 0.3
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What drugs were given as an example of a Low extraction ratio?
Warfarin, Diazepam, Valproic acid, Phenytoin, Theophylline, Erythromycin
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What extraction ratio would indicate a drug that has metabolism that is independent of Hepatic blood flow?
< 0.3
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What extraction ratio would indicate a drug that has metabolism that is dependent on Hepatic blood flow?
> 0.7
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After first pass extraction, the bioavailability of a drug with an extraction ratio of 0.7 would be what?
30%
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(True/False) CYP enzyme activity will be similar across patients with the same severity of liver dysfunction.
False, vary widely
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Is phase I oxidative metabolism or phase II conjugation more sensitive to cirrhosis of the liver?
Phase I oxidative metabolism
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In a patient with cirrhosis, what relative level of function would you expect for CYP2C9?
Mild or no change in function
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