- 1. Clinical Cases for CCF Prof. Dr. Talat Ahmed
2. Case Scenario for Clinical pharmacokinetics A 64 yrs old male
had heart failure was put on digoxin therapy in tabletform,
formulated by XY pharmaceutical. Initially he was given 0.5 mg
8hourly for three days followed by 0.125 mg/day. Simultaneously he
wassuffering from severe cough, fever and malaise, the physician
afterthorough investigations diagnosed as a case of lower
respiratory tractinfection and prescribed 100mg/d doxycycline
initially for one weekwhich was further extended to 10 days. The
patient suffered fromdiarrhea, doxycycline was discontinued, a
course of metronidazole wasgiven and patient got cured. After few
days patient complaint of fatigue, palpitations and dyspnea.The
dose of digoxin was increased to 0.25mg/ day and he felt better.
After several years he was diagnosed for chronic renal failure,
blood ureaand creatinine is raised. He developed heart sinking and
palpitation. ECGshowed pulses bigeminy. Serum digoxin was 2.8ng/ml.
Digoxin therapywas stopped for three days. KCl was administered for
few days Theplasma level was now 1ng/ml and the dose of digoxin was
adjusted to0.125mg digoxin/day. 3. Case Scenario for Clinical
pharmacokinetics1. What is form?2. Why patient was asked to take
the digoxin formulated by XY pharmaceutical only?3. Why he suffered
from diarrhea?4. Why he was given high doses of digoxin
initially?5. Why the patient complaint of fatigue, palpitations and
dyspnea.6. Why the physician had to increase the dose of digoxin?7.
Therapeutic blood monitoring is required, at which time you will
take blood sample?8. Plasma concentration is found to be 0.35
ng/ml. How will you calculate the new dose? 4. 8. What is the first
symptom of digoxin toxicity leadingto diagnosis?9. Why patient
developed cardiac toxicity?10. Enumerate the formulas applied for
Estimation ofGFR & Creatinin clearance11.What is the normal
range of serum digoxin level?12. After increasing the dose to 0.25
mg/day how longit took to improve the patients condition and
wasstabilized?13. What is the mechanism of development of
pulsesbigeminy?14. What will be effect of chronic renal failure
onplasma half life of digoxin?15. Later, on reducing the dose from
0.25 to 0.125 mg,how long will it take to reach Css? 5. Clinical
EvidencesDoxycycline Antibiotics might increase digoxin
absorptionby inactivating intestinal bacteria John R Horn, Pharmacy
times 2004Azole Derivatives Antifungal Agents (Azole
Derivatives,Systemic): May increase the serumconcentration of
Cardiac Glycosides.(UpToDate) 6. Doxycycline Unlike many
tetracyclines, doxycycline doesnot appear to accumulate in patients
withimpaired renal function, and aggravation ofimpairment may be
less likely. Similarly, thereis also no evidence that doxycycline
causessevere hepatitis (BMJ) 7. Metronidazole DOSING: RENAL
IMPAIRMENT To reduce possible accumulation in patients
receivingmultiple doses, consider reduction to 50% of dose orevery
12 hours; Note: Dosage reduction is unnecessary inshort courses of
therapy. Some references do notrecommend reduction at any level of
renal impairment(Lamp, 1999). DOSING: HEPATIC IMPAIRMENT Unchanged
in mildliver disease; reduce dosage in severe liver disease. 8.
4-variable MDRD," (Modification of Diet in RenalDisease Study
Group) serum creatinine, agerace, & Gender.CKD-EPI including
urinary albumin 9. NSR=normal sinus rhythemPVB= premature
ventricular beat 10. Therapeutic Dose Toxic dose 11. Thank you
