1. CARDIOVASCULAR PHARMACOLOGY
Dr A.SHYAM SUNDAR.,M.Pharm.,Ph.D
Associate Professor in Pharmacology,
University of Nizwa,
Sultanate of Oman

3. 4 BASIC POINTS & 4 MAIN DISEASES
Heart Failure is a condition in which the heart is unable to meet the metabolic demands of the body.
Hypertension is a clinical condition in which there will be persistent increase in
arteriolar blood pressure.
Cardiac Arrhythmias, a group of disorders in which there will be abnormality
either in the impulse generation or impulse conduction.
Angina is the hearts way of signaling that it doesn't receive sufficient blood supply and Myocardial Infarction occurs when oxygen deprived myocardial cells start dying.
James Olson, Clinical Pharmacology Made Ridiculously Simple, Second Edition, MedMaster Series,

4. ANS & CVS CORRELATIONS M2 receptors activated and causes
When sympathetic nervous system is stimulated...
When parasympathetic nervous system is stimulated...
β1 receptors activated and causes
Increase in heart rate,
Increase in conduction velocity Increase in force of contraction
M2 receptors activated and causes
Decrease in heart rate,
Decrease in conduction velocity Decrease in force of contraction
α1 receptors activated and causes
vasoconstriction
Secretion of Catacholamines and α1and β1 actions occur.

5. UNIT 1: CONGESTIVE HEART FAILURE
UNIT INSTRUCTIONAL OUTCOMES:
At the end of this unit, the student should be able to,
Differentiate the types of heart failure
List compensatory mechanisms of heart failure
Describe the physiology of cardiac contraction and ionic movement during cardiac contraction
List the classes of drugs used to treat cardiac failure and their mechanism of action
Recall vital information about the drugs used in CHF.
Apply pharmacological knowledge gained in the clinical scenario.

6. Types of heart failure...
Low-output heart failure vs High-output heart failure
In LOHF, the metabolic demands of the body is normal and heart will not be able to supply the normal demand.
In HOHF, the metabolic demands may be very high (due to anemia or hyperthyroidism),and the heart will not be able to supply blood to meet this increase in demand.
Left sided heart failure vs Right sided heart failure
LSHF leads to pulmonary edema and RSHF leads to systemic edema
Systolic Failure vs Diastolic Failure
Systolic failure : Abnormality in cardiac contraction (As seen in IHD)
Diastolic failure: Abnormality in Ventricular relaxation (As seen in HTN)

7. COMPENSATORY MECHANISMS OF HEART FAILURE
Increased sympathetic activity.
Retention of sodium and water.
Myocardial hypertrophy.
Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

8. Physiology of cardiac contraction
Actin and myosin
Tropomyosin
Troponin complex
Ca++ Ions

9. Ionic Movement during cardiac contraction
Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

10. Therapeutic Goals in CHF
Acute/Decompensated Heart Failure:
Decrease congestive symptoms (Diuretics)
Increase Myocardial Contractility (Inotropes)
Chronic/Compensated Heart Failure:
Decrease Workload of Heart (Vasodialators)
Decrease mortality by reversing cardiac remodeling (Aldosterone Antagonists)

11. Classification of drugs
Review Questions:
1. What are the therapeutic goals for a CHF patient?
2. List the rationale why the above mentioned drugs
are used in CHF
Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

12. MOA OF CARDIAC GLYCOSIDES
Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

13. Cardiac Glycosides Examples:
Digoxin, Digitoxin, Strophanthin and Ouabain
Used for acute treatment of CHF, Atrial Fibrillation, Atrial Flutter and Supraventricular tachycardia.
Used for acute treatment CHF ( Digoxin is an exception which is given orally as maintenance)
MOA in CHF: Inhibition of Na+-K+ ATPase.
MOA in Atrial Flutter: Vagomimitic action (AV conduction rate is decreased)
Unlike other inotropes, CG’s do not increase heart rate and Oxygen consumption. (Rather O2 consumption and HR decreases)

14. Cardiac Glycosides- Adverse Effects and Toxicity
First symptoms are Nausea and Vomitting
Causes visual disturbances and Gynacomastia.
Mild toxicity can be treated with KCl( KCl is contraindicated in severe toxicity)
Digitalis induced vetricular Arrhythmias can be treated with Lignocaine(DOC)/ Phenytoin.
Digitalis induced Atrial Tachycardia can be treated with propanolol
Digibind (Digoxin antibody) is preferred in case of severe toxicity

15. Contraindications and Interactions of Digitalis
METABOLIC:
1. Hypokalemia
2. Hypomagnesemia
3. Hypercalcemia
DRUGS:
1. Thiazides and Furosemide: (Results in Hypokalemia and Hypomagnesemia
2. Quinidine and Ca++ channel blockers (Results in Decreased Renal Clearance and hence toxicity).
DISEASES:
1. Hypothyroidism and Hyperthyroidism
2. Myocarditis
3. Digoxin precipitates toxicity in Renal Failure and Digitoxin precipitates toxicity in Hepatic Failure.

16. MOA OF BETA ADRENERGIC AGONISTS AND PHOSPHODIESTERASE INHIBITORS
Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

17. DOPAMINE and DOBUTAMINE
Selective Beta-1 receptor agonist.
MOA:
Increases cAMP
Increases Cardiac Contraction
Increases Cardiac Output
Acts on Dopamine, Beta and Alpha receptors based on the dose administered
1-2 µg/kg/min Stimulates Dopamine receptors Increased Vasodilation.
2-10 µg/kg/min Stimulates Beta 1 receptors Increased Cardiac Contraction.
>10 µg/kg/min Stimulates Alpha receptors Increased Vasoconstriction.
Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

18. Inodialators Examples: Inamrinone, Milrinone and Vesnarinone.
They act as Inotropes as well as Vasodilators.
Acts by inhibiting the enzyme Phosphodiesterase and thereby increasing the level of cAMP in heart and blood vessels.
Short term use of severe and refractory CHF.
Milrinone is preferred as inamrinone causes thrombocytopenia.
Both Inamrinone and Milrinone may result in arrhythmias.

19. DIRECT ACTING VASODILATORS
Vasodilators reduces both preload and afterload.
Venodilation reduces preload and Arterial dilation reduces afterload.
Minoxidil is used to treat male pattern bladness.
Nitrates
Hydralazine
Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

20. MOA OF ACE INHIBITORS CONTRAINDICATED IN PREGNANCY
Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

21. BETA-BLOCKERS IN CHF
β-blockers decrease sympathetic activity by blocking the β-receptors on the excitable cells in the myocardium and blood vessels.
A blockade of these receptors results in decreased cardiac contractile activity and heart rate, decreased blood pressure, and decreased peripheral circulation.
All these effects reduce the oxygen demand of myocytes. β-blockers such as bisoprolol, carvedilol, metoprolol are used in treatment of heart failure in addition to the treatment of diuretics and ACE-inhibitors

22. DIURETICS IN CHF
Diuretics increase excretion of Na+ ions from the kidney.
As a result water is excreted as well, which lowers plasma volume, extra cellular fluid, cardiac output and ultimately relieve edema and dyspnea. Two classes of diuretics are applied in the treatment of the symptoms of heart failure.
Loop diuretics act in the ascending loop of Henle. Example: Furosemide.
Thiazide diurietics act in the distal tubule. Example: Hydrochlorothiazide.
Spironolactone is also used in maintenance of severe heart failure since it slows down the remodeling of the heart by antagonising the aldosterone receptors of the heart.

23. CHF- Updates Vasopeptidase Inhibitors:
Examples: Omapatrilat and Sampatrilat
These drugs inhibit ACE and NEP(Neutral Endo Peptidase)
Orally administered for the treatment of chronic CHF.
Same properties as ACE inhibitors PLUS natriuresis.
Angioedema is the major adverse effects.

24. CHF- Updates
Levosimenden is an agent that sensitizes the myocardium to Ca++ apart from inhibiting phosphodiesterase.
Nesiritide:
Is an rBNP (Brain Derived Natriuretic Peptide)
Increases cGNP and causes vasodilation
Treatment acute CHF associated with dyspnea at rest.

25. CONGESTIVE HEART FAILURE - Summary
Therapeutic goals:
1)Reduce workload of the heart
2)Improve myocardial contractility
James Olson, Clinical Pharmacology Made Ridiculously Simple, Second Edition, MedMaster Series,