CVS AND BLOOD

Q. Explain the mechanism of action of Furosemide with the help of a diagram.

Q. What is the rationale of using it in Pulmonary edema?

They cause a brisk natriuresis which reduces left -ventricular filling pressure along with a
rapid increase in venous capacitance leading to a rapid relief in pulmonary edema.

Q. Tabulate the effect of Loop and potassium sparing diuretics on the urinary
excretion of NaCl, NaHCO3 and K+.

Q. What is the rationale of using nitrates in Angina pectoris?

1. Decrease O2 demand
Venodilation: dec venous return, dec Preload, dec diastolic heart size and fibre tension
Arteriolar Dilation: Dec PVR, Dec afterload, Dec fibre tension & double product
2. Increase O2 supply: increase in coronary flow via collateral vessels in ischemic areas
Q. Briefly explain the Coronary Steal Phenomenon with an example.

It is a phenomenon where physiological or pharmacological vasodilation of myocardial

segment’s vasculature is associated with “steal” of blood from another myocardial
segment, which is already significantly vasodilated due to the presence of a significant
stenosis in a large epicardial artery. This alteration of circulation patterns leads to
reduction in the blood flow directed to the coronary circulation leading to the worsening of
classical angina.
Drugs that cause coronary steal phenomenon:
• Hydralazine
• Isoflurane / Enflurane
• Dipyridamole

Q. Enlist any SIX clinical uses of calcium channel blockers.

1. Hypertension
2. Angina
3. Arrhythmias
4. Hypertrophic cardiomyopathy
5. Stroke
6. Subarachnoid hemorrhage
7. Migraine Prophylaxis
8. Raynaud’s phenomenon
9. Preterm labor
10. To reverse resistance of cancer cells to cancer chemotherapy

Q. Tabulate the electrical effects of Digoxin on heart.

OR
Q. Write down the mechanism of action of Digoxin. Enumerate its adverse effects.

Mechanism of action
Digoxin inhibits Na+/K+ ATPase pump of the cell membranes. This results in increased
intracellular sodium which alters the driving force for sodium calcium exchange by NCX
exchanger leading to decreased removal of calcium from cell. The increased intracellular
calcium stored in sarcoplasmic reticulum is released which results in increased contractile
force. Digoxin also modifies autonomic outflow thus having effects on electrical properties
of heart.

Adverse Effects of Digoxin:

1. GIT: Decreased appetite, nausea, vomiting, diarrhea

2. CNS: Confusion, hallucinations, visual disturbances
3. CVS: Arrythmias e.g., bigeminy, tachycardia, fibrillation, cardiac arrest/ depression
(extreme toxicity)
4. Others: endocrine aberration, Potassium & Magnesium deficiency.

Q. A 50-year-old man was being treated with Thiazide diuretics and ACE
inhibitors for chronic congestive heart failure. Enumerate the adverse effects of

Hypokalemic Metabolic Alkalosis

Hyperuricemia
Hyperglycemia
Hyperlipidemia
Hyponatremia
Allergic reactions

Q. Classify Anti-arrhythmic drugs.

Class I, Na Channel Blockers:

Ia: Disopyramide, Procainamide, Quinidine
Ib: Lidocaine, Mexilitine, Phenytoin
Ic: Flecainide, Propofenone, Moricizine
Class II, Beta Blockers: Propranolol, Esmolol
Class III, K+ Channels Blockers: Amiodarone, Dronedarone, Sotalol, Ibutilide,
Dofetilide, Vernakalant
Class IV, Ca Channel Blockers: Verapamil, Diltiazem, Bepridil
Class V, Miscellaneous: Adenosine, Magnesium, Potassium, Digoxin
Q.A 25-year-old lady was on warfarin for the treatment of her DVT (deep venous
thrombosis). After few months of her treatment, she conceived. What would be
the treatment strategy for this lady now and why?

She would be shifted on heparin

Since heparin has a large molecular size and negative charge, it cannot cross placental
barrier and doesn’t cause teratogenic effects in the newborn.

Q. Name two direct thrombin inhibitors. How do LMW heparin differ from the
unfractionated heparin?

Hirudin, Lepirudin, Argatroban, Bivalirudin, Dabigatran

S.no Unfractionated heparin LMW heparin

1. Large molecular weight Low
2. Less bioavailability 20% More 80%
3. Glycosaminoglycan Chemical/enzymatic
depolymerization of unfractionated
heparin
4. Plasma half-life 3 hours T ½ is 4 hours
3. Response unpredictable Predictable
4. More heparin induced Less occurrence of HIT
thrombocytopenia
(HIT)
5. Requires hospital administration Can be given in OPD
6. MOA: binds to antithrombin III and Inactivates only factor X
inactivates clotting factor II and X

Q. A 45-year-old female with Atrial fibrillation is admitted in CCU; Heparin is

started immediately to reduce the risk of thromboembolism. How will it produce
its anticoagulant effect and what are its toxic effects.

Unfractionated heparin binds to endogenous antithrombin III (ATIII) via a key

pentasaccharide sequence. The heparin–ATIII complex combines with and irreversibly
inactivates thrombin and several other factors, particularly factor Xa.

In the presence of heparin, ATIII proteolyzes thrombin and factor Xa approximately 1000-
fold faster than in its absence. Because it acts on preformed blood components, heparin
provides anticoagulation immediately after administration.

Toxic effects:

· Increased bleeding
· Heparin-induced thrombocytopenia (HIT) in a small percentage of patients who produce
an antibody that binds to a complex of heparin and platelet factor
· Osteoporosis with chronic use
Q. How does Streptokinase produce its effect in thromboembolism?

Streptokinase forms a complex with endogenous plasminogen; the plasminogen in this

complex undergoes a conformational change that allows it to rapidly convert free
plasminogen into plasmin.

Q. A 42-year-old obese, hypertensive man presents to you in OPD for routine

checkup. His fasting lipid panel showed raised serum concentrations of total
cholesterol, LDL cholesterol, triglyceride, Lp(a), and reduced HDL cholesterol.
Name the most appropriate drug to treat this patient. Write down its mechanism
of action and enlist its adverse effects.

Niacin
MOA:

• Inhibits lipolysis in adipose tissue (producer of FFA)

• Liver utilizes fatty acids for TG synthesis; required for VLDL production
• LDL is derived from VLDL in plasma
• Catabolic rate for HDL is decreased

Adverse effects:

1. Harmless cutaneous flush

2. Pruritus, rash, dry skin, acanthosis nigricans
3. Nausea, abdominal discomfort
4. Hepatotoxicity
5. Hyperuricemia
6. Impair CHO tolerance (increase in insulin resistance)
7. Red cell macrocytosis with higher doses
8. Reversible platelet deficiency
9. Atrial arrhythmia
10. Macular edema

Q. Write down the mechanism of action of Statins as anti-hyperlipidemic.

The rate-limiting step in hepatic cholesterol synthesis is conversion of

hydroxymethylglutaryl coenzyme (HMG-CoA) to mevalonate by HMG-CoA reductase. The
statins are structural analogs of HMG-CoA that competitively inhibit the enzyme
Q. Explain different pharmacokinetic and pharmacodynamic drug interactions of
Warfarin.

Q. Enlist parenteral iron preparations used to treat iron deficiency anemia.

Iron dextran
Sodium ferric gluconate complex
Iron sucrose