Kinetics Exam #1

Cl= 0.288 (CrCl)

What is the lithium clearance in a NON-manic state?

Cl= 0.432(CrCl)

What is the lithium clearance in a manic state?

0.6-0.8 mmol/L

What is the recommended therapeutic serum concentration of lithium for long term maintenance use?

0.8-1 mmol/L

What is the therapeutic serum concentration recommended for lithium during acute mania?

8.12 mmol of Li/ 300 mg of lithium carbonate

What is the conversion factor of lithium ions to lithium carbonate?

7-12 mL/h/kg

What is the clearance of valproic acid in adults not taking hepatic metabolism-inducing drugs?

15-18 mL/h/kg

What is the clearance of valproic acid in adults taking hepatic metabolism-inducing drugs?

20-30 mL/h/kg

What is the clearance of valproic acid in children taking hepatic metabolism-inducing drugs?

3-4 mL/h/kg

What is the clearance of valproic acid in the presence of other disease states, such as liver cirrhosis and acute hepatitis?

0.15 L/kg

What is the estimated volume of distribution of valproic acid in adults?

0.2 L/kg

What is the estimated volume of distribution of valproic acid in children under 12?

(0.693 * V)/Cl

How is the elimination half-life calculated?

0.693/t1/2

How is the elimination rate constant (k) calculated?

10 mg/kg/day

What is the recommended maintenance dose of valproic acid in children?

20 mg/kg/day

What is the recommended maintenance dose of valproic acid in children that are enzyme inducers?

7.5 mg/kg/day

What is the recommended maintenance dose of valproic acid in adults?

15 mg/kg/day

What is the recommended maintenance dose of valproic acid in adults that are enzyme inducers?

phenytoin, phenobarbital, carbamazepine, rifampin

What drugs induce the metabolism of valproic acid?

c. CKD may cause a decrease in hepatic metabolism

Which of the following statements best describes hepatic metabolism in patients with chronic kidney disease?

a. CKD does not affect hepatic metabolism

b. CKD may cause an increase in hepatic metabolism

c. CKD may cause a decrease in hepatic metabolism

a. The free drug level of phenytoin will increase if the dose is not adjusted to account for changes in albumin

Serum albumin levels may be low in older adults. Phenytoin is highly bound to plasma proteins. Which of the following may occur when administering phenytoin to an older adult with low serum albumin levels?

a. The free drug level of phenytoin will increase if the dose is not adjusted to account for changes in albumin

b. The free drug level of phenytoin will decrease if the dose is not adjusted to account for changes in albumin

c. Changes in serum albumin levels do not affect medications that are highly plasma protein

a. use actual body weight to calculate CrCl

If actual body weight = 60 kg and ideal body weight = 80

a. use actual body weight to calculate CrCl

b. use adjusted body weight to calculate CrCl

c. use ideal body weight to calculate CrCl

b. use adjusted body weight to calculate CrCl

If actual body weight = 90 kg and ideal body weight = 65

a. use actual body weight to calculate CrCl

b. use adjusted body weight to calculate CrCl

c. use ideal body weight to calculate CrCl

c. use ideal body weight to calculate CrCl

If ideal body weight = 70 kg and actual body weight = 80

a. use actual body weight to calculate CrCl

b. use adjusted body weight to calculate CrCl

c. use ideal body weight to calculate CrCl

Age (decreased renal fx), renal disease (decreased drug clearance, increased t1/2), genetic factors, obesity, pregnancy (increased renal clearance), DDIs

What factors can cause changes in renal function?

Greater body fat increases the volume of distribution (Vd) of highly lipophilic drugs

What changes in drug distribution occur with aging? (diazepam, chlordiazepoxide)

↓ CYP 450 activity = high drug concentration with conventional dosing

What changes in metabolism occur with aging? (propranolol, phenobarbital, nifedipine)

Decreased GFR, which increases drug serum levels

What changes in renal elimination occur with aging?

Present at birth

What age do pediatric patients begin to detect sweetness?

2 years

What age do pediatric patients begin to detect sour, bitter, saltiness?

5-7 years

What age do pediatric patients begin to have an affective response to odor?

6-8, but will decrease to 1-3 within 24-72 hrs

What is the gastric pH of a full-term neonate?

No, due to decreased acid secretion

Does the gastric pH of a pre-mature neonate fall as quickly as a full-term neonate?

↑ bioavailability in small intestine because the pH is basic and the drug can be absorbed more readily; therefore, decrease dose

How is absorption of acid-labile drugs (e.g. penicillins) affected in neonates?

↓ bioavailability in small intestine due to basic environment and dose must be increased

How is absorption of weak acid drugs (e.g. phenobarbital, phenytoin) affected in neonates?

a. Higher Cmax

b. Delayed Tmax

Select all that apply:

Differences in gastric emptying for pediatric patients can lead to which of the following?

a. Higher Cmax

b. Delayed Tmax

c. Faster Cl

d. Reduced F

Children have slower gastric emptying and drugs will remain in the GI tract for a longer period of time, which increases the time at the absorptive site

Why may Cmax be elevated in pediatric patients?

Topical due to rapid absorption within first 2 weeks, suppositories because they have high-amplitude pulsatile contractions of the lower GI tract that cannot be controlled, IM because absorption is unpredictable

What routes of administration should be avoided in neonates/infants?

a. 2 week-old

Which of the following would experience the greatest topical medication absorption?

a. 2 week-old

b. 3 month-old

c. 6 month-old

d. 6 year-old

a. Total body water is increased compared to adults

Which of the following statements about drug distribution in pediatric patients is true?

a. Total body water is increased compared to adults

b. Extracellular water is decreased compared to adults

c. Protein binding is increased compared to adults

d. Percentage of body fat is increased compared to adults

Increased due to high level of total body water

Should the dose of hydrophilic drugs be increased or decreased in neonates and infants?

There is less albumin due to an immature liver (at birth), and this leads to increased concentrations of unbound drugs in children <6 months old

What binding protein is low in neonates?

Bilirubin, free fatty acids

What product is highly bound to proteins in neonates?

ceftriaxone, phenytoin, phenobarbital, Bactrim

What drugs are greater than 70% protein bound in pediatric patients and need to be dose adjusted?

Glucuronidation, which develops by 1 year and is why chloramphenicol is CI

What metabolic pathway is significantly underdeveloped in neonates and infants?

Sulfation, which compensates for APAP

What metabolic pathway is completely developed in neonates?

First 3 months of life

When does the greatest risk of accumulation of renally-cleared medications occur in pediatric patients?