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 tablet
form, formulated by XY pharmaceutical. Initially he was given 0.5 mg 8
hourly for three days followed by 0.125 mg/day. Simultaneously he was
suffering from severe cough, fever and malaise, the physician after
thorough investigations diagnosed as a case of lower respiratory tract
infection and prescribed 100mg/d doxycycline initially for one week
which was further extended to 10 days. The patient suffered from
diarrhea, doxycycline was discontinued, a course of metronidazole was
given 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 urea
and creatinine is raised. He developed heart sinking and palpitation. ECG
showed pulses bigeminy. Serum digoxin was 2.8ng/ml. Digoxin therapy
was stopped for three days. KCl was administered for few days The
plasma level was now 1ng/ml and the dose of digoxin was adjusted to
0.125mg digoxin/day.

3. Case Scenario for Clinical pharmacokinetics
1. 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 leading
to diagnosis?
9. Why patient developed cardiac toxicity?
10. Enumerate the formulas applied for Estimation of
GFR & Creatinin clearance
11.What is the normal range of serum digoxin level?
12. After increasing the dose to 0.25 mg/day how long
it took to improve the patients condition and was
stabilized?
13. What is the mechanism of development of pulses
bigeminy?
14. What will be effect of chronic renal failure on
plasma 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 Evidences
Doxycycline
• Antibiotics might increase digoxin absorption
by inactivating intestinal bacteria
• John R Horn, Pharmacy times 2004
Azole Derivatives
• Antifungal Agents (Azole Derivatives,
Systemic): May increase the serum
concentration of Cardiac Glycosides.
(UpToDate)

6. Doxycycline
• Unlike many tetracyclines, doxycycline does
not appear to accumulate in patients with
impaired renal function, and aggravation of
impairment may be less likely. Similarly, there
is also no evidence that doxycycline causes
severe hepatitis (BMJ)

7. Metronidazole
• DOSING: RENAL IMPAIRMENT
• To reduce possible accumulation in patients receiving
multiple doses, consider reduction to 50% of dose or
every 12 hours; Note: Dosage reduction is unnecessary in
short courses of therapy. Some references do not
recommend reduction at any level of renal impairment
(Lamp, 1999).
• DOSING: HEPATIC IMPAIRMENT — Unchanged in mild
liver disease; reduce dosage in severe liver disease.

8. 4-variable MDRD," (Modification of Diet in Renal
Disease Study Group) serum creatinine, age
race, & Gender.
CKD-EPI including urinary albumin

9. NSR=normal sinus rhythem
PVB= premature ventricular beat

10. Therapeutic Dose Toxic dose

11. Thank you