October University for Modern Sciences and Arts PO512

Faculty of Pharmacy Clinical Pharmacology & Drug Interactions

Mid-Term Exam, Fall 2019, Model answer Time allowed 1,5 hours

Answer all of the following questions: (Total 60/4 marks)

Case I: (30 Marks)

Mr. S.L. is 64 years old. He has a past medical history of hypertension, angina and dyslipidemia.
He lives alone and smokes 30-40 cigarettes per day. Mr. SL's medication history is as follows: Aspirin
75 mg daily, ramipril 5 mg twice a day, amlodipine 5 mg each morning, isosorbide mononitrate MR 30
mg each morning and simvastatin 40 mg at night. He presents at the clinic complaining of aches and
pains in his legs over the past 10 days. On questioning he reveals that over recent months he has been
eating fresh grapefruit and consuming the occasional glass of grapefruit juice. A tentative diagnosis of
myopathy is initially made.
Questions:
1. What is the likelihood that grapefruit juice has contributed to Mr. SL's problem?
(4 marks)
Grapefruit inhibits cytochrome P-450 leads to increase serum concentration of Simvastatin and its side
effects on the muscles (myopathy)
2. Evaluate the use of simvastatin in this case. (6 marks)
1- Hydroxy-Methyl-Glutaryl (HMG) Co-A Reductase Inhibitors
Inhibit the synthesis of cholesterol   LDL &  HDL.
Side Effects :
a- Hepatotoxic   Serum transaminases.
b- Myositis   Serum creatine kinase.
c- Contraindicated during pregnancy and lactation.

3. Explain the rationale behind the use of ramipril and amlodipine. (8 marks)
Ramipril
Inhibit Angiotensin Converting Enzyme:
a-  Conversion of inactive Angio I to active Angio II   Synthesis of Angio II:
-  VC. -  Aldosterone. -  Sympathetic.
-  Hypertrophy & Remodeling of heart & BV. -  Renin &  Angio I.
b-  Inactivation of Bradykinin   Bradykinin  VD (Directly & by  PGs).
So it will lead to:
a- Mixed VD Arterial > Venous.
b- Art. VD   T.P.R.   After-load &  Bl.p.
c- Weak Vein. VD   V.R.   E.D.V.   Pre-load &  Bl.p.
d- C.O.P. is maintained or even  in cases of H.F.
e-  RBF BUT  GFR (Efferent VD)   Glomerular hypertension.
- NO postural hypotension NO reflex tachycardia ( Baroreceptors reflex &  Sympathetic
activity).
- NO abnormality in Glucose or Lipid or Cholesterol or Uric acid metabolism (Better than
diuretics).

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October University for Modern Sciences and Arts PO512
Faculty of Pharmacy Clinical Pharmacology & Drug Interactions
Mid-Term Exam, Fall 2019, Model answer Time allowed 1,5 hours

Amlodipine - POWERFUL V.D. (ARTERIAL > Vein in contrast to Nitrates):

a- Potent Arterio-Dilator   TPR   AFTER-LOAD.  Cardiac Work &
b- Weak Veno-dilator Less  VR   Preload.  O2 - Consumption.
c- Coronary VD: BUT VD of SMALL coronaries on the non-ischemic area may steal the blood from
the atherosclerosed area  Coronary Steal Phenomenon.
d- Hypotension  Reflex  Sympathetic  Tachycardia  Short Diastolic Filling. Better ADD -
Blocker. Better not used ALONE with Nitrates.
2- Very Weak Myocardial Depressant:
a- Does NOT  SAN. It even causes TACHYCARDIA.
b- Does NOT  AVN. Allowed in Heart Block.
c- Minimal -ve Inotropic  COP is maintained or may increase  Allowed in HF.

CCB in combination of ACEI is very effective in controlling blood pressure when one drug is not
sufficient. Moreover, CCB will keep both HTN and angina under control as it more vascular selective
CCB, leading to reduce after-load and reduce both blood pressure and anginal attacks.
4. Mr. S.L. asks if he could stop the intake of isosorbide mononitrate. What is your advice?
Explain your answer. (6 marks)
Yes, he can stop the intake of isosorbide mononitrate but with close monitoring with his cardiologist.
The rational will be to avoid tolerance as the nitrate is the only drug class that shows high efficacy in
acute anginal attack. With an additional advice for stop or reduce smoking to improve both his oxygen
demand and supply.

5. Discuss the importance of the administration of Aspirin in this dose. (6 marks)

Small dose Aspirin has an effective antiplatelet action which is very important as a prophylactic effect
against the conversion of stable angina into unstable angina.

Case II: (30 marks)

Mrs. H.M. is, 66 years old with chronic asthma and mild heart failure. She has been prescribed
naproxen 250mg three times daily to treat her painful knee. On inspection of her medication record, it
is discovered that she is also receiving: furosemide 40 mg each morning. ramipril 5 mg in the morning,
prednisolone 5 mg daily, salbutamol inhaler two puffs when required, salmeterol 50 micrograms
inhaler one puff twice daily and beclometasone 250 micrograms inhaler two puffs twice daily.
Questions:
1. Do you think Mrs. H.M. should be taking naproxen? Explain your answer. (5 marks)
No, naproxen is a NSAID, that inhibit PG release in the kidney leading to vasoconstriction in the
afferent arteriole and ends with reduction of renal filtration. The later will increase salt and water
retention and activation of renin angiotensin aldosterone system and worsen her heart condition.
Moreover, naproxen as NSAID will shift toward increasing the production of leukotriene, which
will cause bronchospasm and worsen her asthma.

2. Criticize the use of furosemide. (5 marks)

Co-administration of furosemide (loop diuretic) and prednisolone may lead to hypokalemia.
Addition of potassium sparing diuretic can be an option to balance K+ levels is this patient.

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October University for Modern Sciences and Arts PO512
Faculty of Pharmacy Clinical Pharmacology & Drug Interactions
Mid-Term Exam, Fall 2019, Model answer Time allowed 1,5 hours

3. Explain the likely effect of the prescribed therapy on serum potassium concentration.
(6 marks)
Naproxen and ramipril: increase K+ level
Furosemide and prednisolone: decrease K+ level

4. Do you recommend the combined administration of salmetrol and beclometasone? Justify your
answer (4 marks)
Yes, the co-administration of corticosteroid together with beta agonist leads to increase the receptor
sensitivity and improve the beta agonist mode of action.

5. Describe the rationale for use of salbutamol and salmeterol. (4 marks)

Both are selective beta 2 agonists that lead to bronchial relaxation. Salbutamol is prescribed when
required due to its quick onset but it has short acting effect. While salmeterol has long acting effect so it
is used for prophylactic treatment in the current case.

6. Give Mrs. H.M. some advises for non-pharmacologic lines of treatment. (6 marks)
Mrs. H.M needs to follow non-pharmacological treatment of heart failure in order to improve her
condition:
1- Restriction of physical activity + bed rest
2- Weight reduction in obese patients
3- Diet:
a- Restriction of dietary salt (sodium chloride)
b- Low caloric diet
c- Small frequent light meals (4-6 times / day)
As well as her lung condition (asthma):
1- Identify the antigen →Avoid Antigen if possible &/or Immuno-therapy.
2- Treat upper respiratory tract infection e.g. sinusitis if present.
3- Yearly administration of influenza vaccine every winter.
4- Avoid stress & emotions.
5- Avoid severe muscle exercise.

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