October University for Modern Sciences and Arts PO512

Faculty of Pharmacy Clinical Pharmacology & Drug Interactions

Mid-Term Exam, Fall 2020 Model Answer Time allowed 1.5 hours

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

Case I: (30 Marks)

Mrs. A.G. is 61 years old, complaining of dyspnea on exertion, orthopnea and peripheral edema.
She has a history of diabetes mellitus type II and is well controlled with oral anti diabetic, metformin.
On examination her blood pressure measurement is 125/85 mm Hg and heart rate is 75 beats /minute.
Laboratory investigations show normal renal and hepatic functions with increased and disturbed
cholesterol and triglycerides levels. She is diagnosed as a case of congestive heart failure and prescribed
hydrochlorothiazide, captopril, gemfibrozil and atorvastatin.

Questions:
1. Comment on the patient’s blood pressure. Does she need treatment? (4 Marks)
The patient is pre-hypertensive and diabetic. She should start treatment and the best are ACEI or
receptor blockers.

2. Evaluate the prescription for gemfibrozil and atorvastatin. (8 Marks)

Atorvastatin
Mechanism : Inhibit the synthesis of cholesterol   LDL &  HDL.
Side Effects :
a- Hepatotoxic   Serum transaminases.
b- Myositis   Serum creatine kinase.
c- Contraindicated during pregnancy and lactation.
Gemfibrozil (Lopid).
Mechanism:
a-  Lipoprotein lipase enzyme.
b-  Hepatic synthesis of triglycerides.
c-  Triglycerides   VLDL.
Side Effects:
a- GIT upset. b- Gall stones. c- Gain weight.
d- Myositis   Creatine kinase. e- Hepatotoxic   Transaminases.
f- Skin rash, alopecia, impotence. g- Displace anticoagulants.
h- Contraindicated in :
- Liver & kidney diseases. - pregnancy & lactation.
- Not combined with HMG Co-A R   Severe Liver & Muscle damage

3. What is the rationale for the use of hydrochlorothiazide? Mention its side effects.
(5 Marks)
Hydrochlorothiazide
Mechanism of Anti-Hypertensive Effect:
a- Initial  Bl.p. is due to their diuretic effect   Blood volume.
b- Sustained  Bl.p is Mainly due to Direct Art. VD   TPR   DBP &  SBP:
- Activation of K+-channels  Hyperpolarization.
- Depletion of Na+ & H2O from arterial wall   Edema of arterial wall &
 V.C. of Noradrenaline & Angio II.
- V.D. may be through PGs # by NSAID.

Side Effects:
a-  RBF &  GFR.

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October University for Modern Sciences and Arts PO512
Faculty of Pharmacy Clinical Pharmacology & Drug Interactions
Mid-Term Exam, Fall 2020 Model Answer Time allowed 1.5 hours

b- Hypokalemia. c- Hyponatremia. c- Hypchloremic alkalosis. d- Hypomagnesemia.

e- Hypercalcemia. f- Hyperglycemia. g- Hyperuricemia. g- Hyperlipidemia.
h- Hypersensitivity reactions. I- G.I.T. upsets j- Fetotoxic

4. What are the advantages of the use of Captopril in this case? Describe its main side effects.
(5 Marks)
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).

- Advantages:
- NO  COP, even it may  COP in HF.
Less Veno-dilator
- 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).
Side Effects of ACE.I:
a- Dry irritant Cough due to  Bk &  PGs. Treat by NASID.
b- First dose hypotension especially in Na+-depleted patients by diuretics.
Treat by NaCl orally or Infusion (Saline). Stop diuretics before the use of ACE.I.
c- Hyperkalemia, especially if accompanied with K+-retaining diuretics e.g. Spironolactone, -Blockers
& NSAID.
d- C.I. in Bilateral Renal Artery stenosis  Fatal Renal Failure.
e- C.I. in 2nd - 3rd trimester of pregnancy  Fetal hypotension, renal failure, Oligohydramnios 
Malformation or DEATH.
f- Proteinuria: Do frequent urine analysis.
g- Neutropenia: Do frequent blood count.
h-  Taste (Dysgeusia).
i- Allergic manifestations (Especially S-H containing e.g. Captopril)  Angioedema.

5. Explain the non-pharmacologic lines of treatment that help for better control of the disease.
(4 Marks)
Non-pharmacologic Therapy:
1- Dietary sodium restriction. 2- Weight reduction in obese.
3- Cessation of smoking. 4- Alcohol restriction.
5- Physical exercise. 6- Relaxation therapy.

6. Does aliskiren have a role in the management of this case? Explain your answer.
(4 Marks)
Yes it is an anti-renin that inhibit the renin angiotensin system like ACEI and receptor blockers.
It is good in cases of hypertension and HF.

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October University for Modern Sciences and Arts PO512
Faculty of Pharmacy Clinical Pharmacology & Drug Interactions
Mid-Term Exam, Fall 2020 Model Answer Time allowed 1.5 hours

Case II: (30 Marks)

Mr. A.R. is a 48 years old with a long history of bronchial asthma. He takes oral Zafirlukast and
a beclometasone inhaler daily to treat this condition. He uses a salbutamol inhaler when breathless. He
was admitted to hospital with chest pain. Cardiovascular investigations indicated stable angina. The
physician added diltiazem daily and sub-lingual Nitroglycerine, when needed, to control his condition.

Questions:
1. What is the rationale of use of Zafirlukast? Discuss its possible side effects. (5 marks)
Cysteinyl LT1-receptor blockers: Zafirlukast (Accolate) Hepatotoxic → Routine monitoring of liver
function tests.

2. Explain the main lines of patient education in this case. (3 marks)

1- Stop Smoking.
2- Identify the antigen →Avoid Antigen if possible &/or Immuno-therapy.
3- Treat upper respiratory tract Infection e.g. sinusitis.
4- Yearly administration of Influenza vaccine every winter.
5- Change the Job if possible.
6- Avoid Stress & Emotions.
7- Avoid severe muscle Exercise.
8- Avoid the following Drugs:
a- NSAID e.g. Aspirin:
- If an Anti-pyretic analgesic is required  Use Paracetamol.
- If an Anti-inflammatory is required  Use Corticosteroid.
b- Non-selective -Blockers e.g. Propranolol & even Timolol eye drops.
- If a -Blocker is required  Use small dose of Cardio-selective 1-blockers e.g. Atenolol.
c- Parasympathomimetics.
d- Parasympatholytics e.g. Atropine  Dry bronchial secretions. Ipratropium is allowed.
e- Histamine, Histamine-like & Histamine-Releasers.
f- Anti-histaminics  Not very effective & Atropine-like.
g- Barbiturates   R.C. Allow Benzodiazepines e.g. Diazepam.
h- Narcotic Analgesics e.g. Morphine   R.C.,  Cough center, Histamine release & dry bronchial
secretions.
i- ACE-Inhibitors e.g. Captopril   Bk & PG. Allow AT1-blockers e.g. Losartan.

3. Evaluate the prescription for diltiazem in this patient. (5 marks)

POWERFUL CARDIAC DEPRESSANT: and bronchodilator.
a- -ve Chronotropic Effect =  SAN = Bradycardia:
- Long Diastolic Perfusion Time for the coronaries.
- Antagonizes Tachycardia induced by Nitrates.
b- -ve Inotropic Effect =  Contractility:
-  Cardiac work &  Oxygen consumption.
- Contraindicated in Heart Failure.
c- -ve Dromotropic effect =  AV Conduction: VD
- Contraindicated in Heart Block.
Side effects

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October University for Modern Sciences and Arts PO512
Faculty of Pharmacy Clinical Pharmacology & Drug Interactions
Mid-Term Exam, Fall 2020 Model Answer Time allowed 1.5 hours

1- Headache & flush.

2- Heart:
Diltiazem 
- -ve Inotropic  Heart failure.
- -ve Chronotropic  Bradycardia.
- -ve Dromotropic  Heart Block.
3- Hypotension.
4- Constipation specially Verapamil.
5- Reversible liver impairment.

4. Would you advise to replace diltiazem with nifedipine or propranolol? Explain your answer.
(6 marks)
Nifedipine is better and of the same group. It produces Broncho dilatation but might lead to harmful
tachycardia.
Propranolol is contraindicated. It produces bronco-spasm.

5. Criticize the use of Nitroglycerine. (6 marks)

It is denitrated by Glutathione transferase enzyme (consuming S-H group)  Release of Nitric
Oxide (NO)   Soluble Guanylate Cyclase enzyme   cGMP:
a- Dephosphorylation of Myosin light chain  Smooth muscle relaxation  V.D.
b-  Platelet aggregation.
Excellent in angina.
Adverse Effects of Nitrates:
1- Headache, Flush &  I.O.P.
2- Postural hypotension & Syncope. Sit while taking rapidly acting nitrate.
3- Hypotension  Reflex  Sympathetic  Tachycardia  Short Diastolic Coronary perfusion # by -
Blockers or Verapamil (CCB).
4- Tolerance & cross-tolerance between nitrites & nitrates:
a- Due to depletion of S-H group required for denitration & activation.
b- Avoid by daily 8-10 hours nitrate free or alternate with other Anti-anginals every 2 weeks.
5- Coronary Dependence after prolonged exposure to nitrates.
Sudden stop of Nitrates  Rebound coronary V.C.  Ischemia & Infarction.
6- Hypersensitivity reactions.
7- Met-Hb especially by Nitrites > Nitrates.
8- Nitrites & Nitrates + Amino group  Nitrosamines  Carcinogenic.

6. What are the adverse effects of beclometasone inhaler? Discuss how to avoid them.
(5 marks)
Side Effects:
- Most (80-90%) of the dose is deposited in mouth and pharynx to be swallowed.
- Oropharyngeal Candidiasis (Thrush). Can be avoided by the use of Spacing device.
- Dysphonia  Change in voice.
NB) Most of theses side effects can be avoided by the use of spacers & rinsing the mouth after
each administration.

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