Clinical Pharmokinetics

Question 1

Bioavailability

Answer 1

Fraction of administered drug that reaches the systemic circulation

Question 2

Where are most drugs absorbed?

Answer 2

Stomach or 1st part of the duodenum

Question 3

Where do lipophilic drugs tend to distribute?

Answer 3

Adipose

Question 4

Where do hydrophilic drugs tend to distribute?

Answer 4

ECF

Question 5

If a drug has low protein binding, what will it’s Vd be like?

Answer 5

Large

Question 6

If a drug has high protein binding, what will it’s Vd be like?

Answer 6

Small

Question 7

What is the steady state dependent upon?

Answer 7

Half-life

Question 8

Where does elimination of most drugs occur?

Answer 8

Kidneys

Question 9

What is different with neonates for topical drugs?

Answer 9

Increased skin hydration will increase absorption of topical products

Question 10

What is different with neonates for Vd?

Answer 10

Neonates have increased ECF which will increase Vd of hydrophilic drugs

Question 11

What happens to the elderly with hydrophilic and hydrophobic drugs?

Answer 11

Hydrophilic - 􏰁decreased extracellular fluid leads to decreased Vd of H2O soluble drugs

Lipophilic - increased adipose tissue will increase Vd of lipid soluble drugs

Question 12

LC is a 41 year old female who is being treated for E. Coli urosepsis. She is allergic to many medications and her only treatment option at this time is an aminoglycoside agent, tobramycin. She is 64inches tall and weighs 60kg on admission. Her usual weight is 57kg (IBW 55kg). Renal function is within normal limit with BUN of 10 and Cr of 0.8mg/dl. She has marked edema and has not yet received any diuretic. Based on this information, her estimated CrCl is 78.3ml/min using her actual weight.

You use her usual weight and recommend starting tobramycin 120 mg.

Later weight is now 64kg & she has 3+ pitting edema. What happened?

Answer 12

Aminoglycosides readily distribute into extracellular fluid. When dosing was initiated in this patient, she was dosed based on a euvolemic status. However, she was fluid overloaded at the time of medication initiation and is even more fluid loaded at present. The tobramycin readily distributed into the extracellular fluid resulting in lower serum levels. Slightly increasing the milligram amount of the dose would have accounted for some of the extracellular shifting. However, if the patient were to have been given a diuretic to help remove the extra water, the levels would have been right on target.

Question 13

36yo F s/p gastric bypass surgery seen today in the nutrition clinic for iron deficient anemia.
She has been taking oral iron sulfate 324mg 3x/day as prescribed for 2 months. Repeat Hgb is 8.2mg/dl, CBC & iron studies c/w iron deficiency
She states she is compliant with the iron and that she has been taking a Vitamin C tablet with the iron to boost absorption.

What do you think best explains what is
going on?

Answer 13

Gastric bypass surgery usually involves minimization of the stomach and reconnecting of the small intestines, often decreasing the surface area of the duodenum.

Iron is generally absorbed in the first part of the duodenum. Despite her compliance, the bypass surgery resulted in decreased absorption of the iron due to anatomical changes. She may require long term intravenous iron administration to treat the ongoing deficit.

Question 14

69yo M with a PMH including CVA resulting in paralysis, PVD, DM, CHF, seizure disorder, CAD. He was recently admitted for Pseudomonas UTI. He was treated with piperacillin/tazobactam (Zosyn􏰃) IV while admitted x 3 days and was discharged on oral ciprofloxacin (Cipro 􏰃) per sensitivities to complete a 14 day total
treatment course. He was readmitted 4 days after discharge for urosepsis. Blood and urine cultures reveal the same strain of pseudomonas. The daughter states she has been giving her Dad the medications. You reconcile his home medications from a chart she provided and note the following:

– Ciprofloxacin 500mg: 1 tab at 8am 8pm
– MVI+ minerals: 1 tab daily 8am
– Calcium Carbonate 500mg: 2 tablets at 8am
– Enalapril 20mg tab: 8am 8pm
– Pheyntoin 300mg tab at 10pm

What is your assessment of the clinical failure?
A. The daughter is not giving her father the medications as prescribed.
B. The patient has a new infection.
C. There is a drug interaction present: Ciprofloxacin, multivitamins and calcium.
D. There is a drug interaction present: Ciprofloxacin and enalapril.
E. There is a drug interaction present: Ciprofloxacin and phenytoin.

Answer 14

C. There is a drug interaction present: Ciprofloxacin, multivitamins and calcium.

Decreased absorption
– Chelation of Ciprofloxacin with divalent cations present in dairy products and Calcium Carbonate results in significantly decreased absorption
Space Ciprofloxacin& dairy products/nutritional supplements/divalent cations by 2h—dose antibiotic first!

Question 15

SU is a 60yo F with Type II diabetes (medically managed) and severe osteoarthritis of knees and ankles. She recently fell down the stairs and further injured her knee. Her internal medicine physician prescribed a prednisone (corticosteroid) taper for 5 days to decrease the inflammation. Day 2 of therapy, she complains of increased thirst and urination and reports her blood sugars to be in the 300’s despite no diet or other medication changes.

What can explain her symptoms?
A. The patient is not truthful about her diet intake.
B. The prednisone can increase blood glucose.
C. The patient is not taking her diabetes medications.
D. The joint is now infected.

Answer 15

B. The prednisone can increase blood glucose.