Drugs Affecting the cardiovascular system

Drugs Affecting the cardiovascular systemLec. No. 10ByDina Abdel-Azim Ghazy GhorabaLecturer of medical science

Cardiovascular agents affect the action of the circulatory system. Most of these agents are highly specialized.

1-Antihypertensive drugs A. Diuretics a) Thiazide diuretics: initial therapy in most cases, used in mild to moderate hypertension.b) Loop diuretics: in sever and resistant hypertension and hypertension of renal failure. c) K-sparing diuretics: in hyperaldosteronism.B. Beta blockers Nonselective: propranolol, timolol, pindolol. Cardio selective (1 selective): atenolol, esmolol, metoprolol

C. Calcium channel blockers (CCBs) a) More selective on heart: Verapamil & Diltiazemb) More selective on blood vessels: NifedipineD. Drugs affecting angiotensin systemAngiotensin converting enzyme inhibitors(ACE Is):E.g.: Captopril, Alcepril, Enalapril, Lisinopril2. Angiotensin-1 receptors antagonists (AT-1 antagonists):E.g.: Saralasin, Losartan

VASOCONSTRICTIONVASODILATATION KininogenKallikreinInactive FragmentsAngiotensinogenAngiotensin IRENIN

Kininase II

Inhibitor

ALDOSTERONESYMPATHETICVASOPRESSINPROSTAGLANDINStPA

ANGIOTENSIN II

BRADYKININACE-i. Mechanism of Action

A.C.E.

5Treatment of Heart FailureAngiotensin Converting-Enzyme Inhibitors (ACEI) :Mechanisms of actionACE-inhibitors competitively block the converting enzyme that transforms angiotensin I into angiotensin II. The reduction in angiotensin II levels explains its arteriovenous vasodilatory actions, as angiotensin II is a potent vasoconstrictor that augments sympathetic tone in the arteriovenous system. Additionally, angiotensin causes vasopressin release and produces sodium and water retention, both through a direct renal effect and through the liberation of aldosterone. Since converting enzyme has a similar structure to kinase II that degrades bradykinin, ACE-inhibitors increase kinin levels that are potent vasodilators (E2 and F2) and increase release of fibrinolytic substances such as tPA.

RENINAngiotensinogenAngiotensin I

ANGIOTENSIN II

ACE

Other pathwaysVasoconstrictionProliferative Action

Vasodilatation Antiproliferative Action

AT1 AT2

AT1 Receptor Blockers

RECEPTORSAngiotensin II Receptor Blockers (ARB)

6Treatment of congestive heart failure.Angiotensin II inhibitors

Angiotensin II has different effects mediated via specific receptors. There are two types of tissue receptors for angiotensin: AT1 and AT2. Stimulation of AT1 receptors has a proliferative and vasoconstrictor effect, while stimulation of AT2 receptors has the opposite effects, that is, vasodilatory and antiproliferative. In the treatment of heart failure, specific blockade of the AT1 receptors is desirable. Drugs which create a selective and competitive block of the AT1 receptors include:losartan, valsartan, irbersartan and candersartan.

E. Direct acting vasodilators

F. 1 adrenergic blockers: eg. Prazosin HCl

Antihypertensive drugs in special cases

Angina Heart failureDiabetes

Possible combinations between some classes of antihypertensive drugsThiazide diureticsACE inhibitors-blockersAngiotensin receptor antagonistsCalcium antagonists- blockersThe preferred combinations in the general hypertensive population are represented as thick lines. The frames indicate classes of agents proven to be beneficial in controlled intervention trials

Hypertensive emergencies

These include: hypertensive encephalopathy, cerebral stroke, severe renal failure. Patient should be hospitalized and reduction of blood pressure should be in hours and not in minutes. Drugs that can be used:

Sublingual nifedipine or captoprilParentral therapy Diuretics (furosemide, bumetanide) I.V.Diazoxid 300 mg I.V. very rapidly.Nitroprusside infusion 2-5mcg/kg/min. according to blood pressure. Beta blocker (propranolol) l-2mg I.V. slowly dilutedNefedipine I.V. diluted

2- Drugs used in the treatment of congestive heart failure (CHF)Heart failure is a condition in which:Cardiac output is less than the body needsPositive Inotropic drugs : Cardiac glycosides2. Vasodilators; a- Calcium channel blockers e.g amlodipine b- Angiotensin converting enzyme inhibitors e.g.:(Captopril, enalapril )c- Other vasodilators e.g.:(hydralazine, nitroprusside) 3. Diuretics

Cardiac Glycoside

DigitoxinDigoxin(lanoxin)

3- Drugs used in the treatment ofArrhythmia

Arrhythmia is any abnormal heartbeat. Disorders of Impulse formation, impulse conduction, or a combination

1.Na+ blockers (Class I):3.-blockers (Class II):4.K+ channel blockers (Class III):2. Ca2+ channel blockers (Class IV):5. Unclassified:

Quinidine. Lidocaine (I.V)Propranolol, Atenolol, SotalolAmiodarone, BretyliumVerapamil, Diltiazem.Adenosine, Digoxin, Atropine, Adrenalin & Isoprenaline

4- Drugs used in treatment of Angina:

Angina pectoris is an acute chest pain that occurs when coronary blood flowis inadequate to supply the oxygen required by the heart.

During the acute attack: Short acting Nitrates: Glyceryl Trinitrate (Nitroglycerin) [sublingual /I.V /infusion]Amyl nitrite [inhalation]Isosorbide dinitrate [sublingual]

- In between the attacks : Long acting Nitrates Isosorbide mononitrate, Isosorbide dinitrate [oral]2. Beta adrenergic blockers3. Calcium channel blockers4. Antiplatelets (aspirin, dipyridamol): used to incidence of coronary thrombosis.

Nitrates ToleranceTolerance for the vasodilating action may develop with continuous exposure to Nitrates without interruption.

5- Drugs used in the treatment of hyperlipidemia

Hyperlipidemia is a condition of high levels of Cholesterol, Triglycerides, and /or Lipoprotein in the blood.

Antihyperlipidemic agents may

prevent cholesterol synthesis or promote the breakdown of internal cholesterol.

1. Resins (Bile acid sequestrants): e.g. cholestyramine, colestipol2. Statins: e.g. lovastatin, simvastatin3. Nicotinic acid and its derivatives 4. Fibrates (Lipoprotein lipase stimulators): e.g. gemfibrozil, clofibrate

6- Thrombolytic drugs

To dissolve blood clotse.g.: Streptokinase

7- Anticoagulants

To prevent blood clotting.HeparinWarfarin (Caumadin)