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DRUGS USED IN THE CARDIO-VASCULAR SYSTEM

MR. ABDOU MARAM PANNEH

(RM ,FWACN,NT, RN)

INTRODUCTIONCardio vascular drugs are very diverse and can therefore be broadly classified according to their pharmacological action.These are:-Angiotensin Converting Enzyme inhibitors (ACE). Adrenergic Neuron Blockers Alpha Blockers Angiotensin II receptor Antagonists Beta Blockers Calcium Channel Blockers DiureticsNitratesLipid Regulating AgentsCardiac GlycosidesCentrally Acting AgentsAnticoagulantsAntiplatelets

1. ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORSGENERAL CHARACTERISTICS:-ACE inhibitors block the conversion of angiotensin l to angiotensin ll.Angiotensin ll is a vasoconstrictor and promotes release of aldosterone, causing salt and water retention, K+ loss and reduces peripheral resistance.ACE inhibitors thus lower blood pressure by vasodilatation and promote loss of salt and water, thereby, elevate serum K+.They produce both preload and after load in patients with heart failure.CLINICAL USES:- Hypertension, Heart Failure and Myocardial Infarction

1. ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS ContdADR:- Dry mouth, acute renal failure, allergic skin rash, taste changes, Angioedema, agranulocytosis, cough, hypostatic hypotension, etcINTERACTION:- NSAIDs ( Ibuprofen, Indomethacin, Aspirin, etc)--These drugs inhibits their hypotensive effect.

1. ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS ContdDRUGS COMMONLY USED:Captopril (capoten) 25mg, 50mg, 100mgCilazapril (vascace) 500mcgEnalapril (innonace,vasotec) 2.5mg, 5mg,10mg,20mg Lisinopril (carace,zestril) 2.5mg, 5mg, 20mg, 40mgRamipril (tritace) 1.25mg, 2.5mg, 5mg, 1omg, 20mgFosinopril (staril)10mg, 40mgPeridonpril (coversyl) 2mg, 4mg, 8mgTrandolapril (gopten,odrik, tarka) 2mg, 4mg

2. ANGIOTENSIN II RECEPTOR ANTAGONISTS:

GENERAL CHARACTERISTICS:-These drugs compete with angiotensin II for tissue binding sites. They mainly act by selective blockage of angiotensin I thus, reducing the pressure effects of angiotensin II.CLINICAL USES:- Treatment of hypertension.ADR:- Nausea, diarrhea, abdominal pain, dizziness, cough renal dysfunction, insomnia, sinusitis, CONTRA-INDICATION:- Pregnancy & breastfeeding (may cause malformation)

2. ANGIOTENSIN II RECEPTOR ANTAGONISTS Contd:DRUGS COMMONLY USED:-Losartan (cozaar) 25mg, 50mg Valsartan (Divon, Tareg) 20mg. 40mg, 80mg Telmisartan (micardis) 40mg, 80mgEprosartan (Teveten) 300mg, 600mg

3. ADRENERGIC NEURON BLOCKERS:-

GENERAL CHARACTERISTICSThese drugs act by selectively inhibiting the transmission in the adrenergic nerve endings.CLINICAL USES:- They have been used in hypertension but are now superceeded by other antihypertensives.Open-angle glaucoma treatment due to hypertension.ADR:- nausea, diarrhea, dizziness, muscle weakness, etcINTERACTION:- Anti histamines inhibit their effectiveness.CONTRA INDICATIONS:- Avoid in pregnancy.

3. ADRENERGIC NEURON BLOCKERS Contd..:-

DRUGS USED:-GuanethidineBetanidineGuanoxan

3. ALPHA ADRENERGIC BLOCKERS / ALPHA ADRENERGIC RECEPTOR ANTAGONISTS:

These drugs do block the effect of alpha1. Blockage of alpha1 adrenoreceptors inhibits vaso constriction caused by the endogenous catecholamines (hormones, histamines).This causes both arteriolar and venous vasodilation resulting in a fall in blood pressure due to decrease peripheral resistance.CLINICAL USES:- Hypertension, urinary obstruction in Benign prostate hyperplasia.ADR:- headache, dizziness, palpitations, priapism.INTERACTION:- Diclofenac & Warfarin (hastens the excretion of alpha blockers)PRECAUTION:- avoid in pregnancy & breast feeding. Use in men preferably.

ALPHA ADRENERGIC BLOCKERS / ALPHA ADRENERGIC RECEPTOR ANTAGONISTS:DRUGS USED:Doxazosin (cardular, cardura) 1mg, 2mg, 4mg, 8mgTamsulosin (tamurex) 400mcgPrazosin (hypovase) 500mcgTerazosin (hytrin) 2mg, 5mg, 10mgIndiramin (baratol, doralese) 25mg, 50mg.

5. BETA ADRENERGIC BLOCKERS

These drugs are competitive antagonists at beta-adrenergic receptor sites.They reduce cardiac contractibility, thereby reducing arterial pressure pulses.They interrupt the renin-angiotensin-aldosterone system, and decrease renin release from the kidneys.Beta Blockers also block sympathetic stimulation at the sinus node, which decreases the heart rate and cardiac output, thereby lowering the blood pressure.

5. BETA ADRENERGIC BLOCKERS Contd.

CLINICAL USES BETA ADRENERGIC BLOCKERS:-Treatment of Hypertension & is often combined with diuretics or other Antihypertensives.Angina pectoris, Cardiac arrhythmias, myocardial infarction, Heart Failure.Control of sympathetic over activity in alcohol withdrawal, anxiety states, hyperthyroidism, etc.As eye drop in raised intra-ocular pressure of Glaucoma & ocular hypertension.ADR OF BETA ADRENERGIC BLOCKERS:- Depression, sinusitis, Bradycardia, nervousness, fatigue, impotence, headache, dizziness, nightmares, mood changes, nausea.INTERACTION:- Insulin, Hydralazine, Prostaglandins (interfere with the action of B/blockers)

5. BETA ADRENERGIC BLOCKERS Contd.COMMON DRUGS USED:-Atenolol (tenoretic, atenol) 25mg, 50mg, 100mgBisoproprol (cardiocor, emcor, zebeta) 5mg, 10mg, 20mgMetoprolol (betaloc, lopresor) 50mg 100mg, 200mgPropranolol (inderal, inderex) 10mg, 40mg, 80mg,Acebutolol (sectral secadrex) 100mg, 200mgCarvedilol (eucardic) 3.125mg 6,25mg, 12.5mg,Timolol (betim) 5mg, 10mg

6. CALCIUM CHANNEL BLOCKERS / CALCIUM ANTAGONISTS

These drugs inhibit cellular influx of calcium, which is responsible for maintenance of the plateau phase of the action potentials.These affects the tissues that depend on calcium for action.Calcium Channel Blockers dilate coronary, peripheral arteries and arterioles with little effect on venous tone.CLINICAL USES:- Treatment & control of hypertension, angina pectoris & cardiac arrhythmias.ADR: same as beta blockers.

6. CALCIUM CHANNEL BLOCKERS / CALCIUM ANTAGONISTS Contd

DRUGS USED:Calcium Channel Blockers can be further classified into 3 major groups.A. Benzothiazepines- These group have less vasodilator activity.- They have direct effect on the myocardium causing depression of SA & AV nodal conduction.- They are basically used in angina, hypertension and arrhythmia.Examples:- Diltiazem (tildiem) 60mgB. Phenylalkylamines- They have similar effect as benzothiazepines- They are widely used because of their anti arrhythmic, anti hypertensive & anti anginal properties.Examples: Verapamil (cordilox, securon) 40mg, 80mg, 120mg

CALCIUM CHANNEL BLOCKERS / CALCIUM ANTAGONISTS Contd

C. DihydrophyridinesThese of Calcium channel blockers have greater selectivity on the vascular smooth muscles than for the myocardium. Their main effect is on vaso dilation.They also have both antihypertensive, anti arrhythmic and anti anginal properties. They are the ones that are more commonly used.Examples:Amlodipine (amlor, istin) 5mg, 10mg, 20mgNifedipine (adalat, nifelat) 2.5mg, 5mg, 10mg, 20mg, 30mgFelodipine (plendil) 2,5mg, 5mg, 10mgNisoldipine (syscor) 10mg, 20mg, 30mgNicardipine (cardene)20mg, 30mg

7. DIURETICSGENERAL CHARACTERISTICS:-They lower B/P by depleting the volume of sodium and blood volume.Some have vasodilator effects.Others can block the transport function of the renal tubules and prevent water reabsorption.There are several types of diuretics. These are:-Loop DiureticsThiazides DiureticsCarbonic Anhydrase inhibitors DiureticsPotassium Sparing Diuretics Others:- osmotic diuretics - Anti diuretic hormone antagonists.

7. DIURETICS Contd.A. Loop DiureticsThese products selectively inhibit the reabsorption of sodium chloride in the Loop of Henle.They are the most powerful and efficacious diuretics.They are usually employed in hypertensive crises.CLINICAL USES:Pulmonary edema with congestive heart failureEdema that does not respond to less powerful diuretics and is caused by hepatic, renal or cardiac conditionsHypertension that cannot be controlled with other types of diureticsADR - ototoxicity, allergic reactions, GIT disorders(nausea, vomiting,etc), dehydration, hypokalemia, hypocalcemia, hypotension, hyperglycemia, photosensitivity.PRECAUTION: allergy to sulphonamides, anuria, hypovolemia, B/feeding, infants.INTERACTIONS:-Digtalis:- increase risk of digitalis toxicityNSAIDs:- inhibits the effect of loop diureticsLithium:- reduces the excretion of lithium.

7. DIURETICSLOOP DIURETICS DRUGS USED:-Furosemide/Frusemide (lasix) 20mg, 40mg tabsBumetanide (burinex) 1mg, 2.5mg, 5mg tabsTorasemide (torem) 2.5mg, 5mg tabs

7. DIURETICS ContdThiazides DiureticsThese drugs are chemically related to the sulfonamides and similar effects to the loop diuretics.They products block the transport function of renal tubules and also inhibit water re-absorptionThey are well absorbed when given orally and are excreted through the kidneys via urine. CLINICAL USES:- treatment of essential Hypertension, Fluid retention due to heart failure, hepatic or renal disease.ADR:impotence due to loss of electrolytesDehydration, photosensitivity, paresthesias, hyperglycemia, etc..

7. DIURETICS ContdTHIAZIDES DRUGS USED:_Chlorothiazide (diuril) 25mgmg, 50mg tabsBendroflumethiazide/Bendrofluazide (naturetin) 2.5mg, 5mg, 10mg tabsHydrochlorothiazide 25mg, 50mg tabsMetolazone (zaroxolyn, mykrox, metenix-5) 5mg tabsPolythiazide (nephril) 1mg tabsMethyclothiazide (enduron)Indapamide (lozol, natrilix) 2.5mg tabs

7. DIURETICS ContdC. Potassium Sparing DiureticsThese products inhibits the elimination of potassium form the renal tubules.CLINICAL USE:- Treat hypertension and edema. Prevent hypokalemiaADR:- Gynaecomastia, menstrual irregularities, erectile dysfunction, deepening of voice, leg cramps, dizziness, acute renal failure, kidney stonesINTERACTION: ACE inhibitors, potassium supplements, Indomethacin- can all cause increase risk of hyperkalemia.Aspirin blocks the effects of diuretics.Examples of Drugs Used:-Spironolactone (aldactone) 25mg, 50mg, 100mg tabsAmiloride(midamor) 5mg tabsTriamterene (dytac, dyrenium) 50mg caps

7. DIURETICS ContdD. Osmotic DiureticsThese products raised the osmolality of plasma and renal tubules fluid.They maintain urine output and prevent renal failure as in hypovolemic shock.They reduce intracranial pressure caused by cerebral oedema.Reduces intraocular pressure by drawing fluid from the eyes.Eliminates toxins through the kidneys.ADR: Edema, fluid & electrolyte imbalance, nausea & vomiting, headache, rebound ICP.PRECAUTION:_ in renal failureExamples:Mannitol 5%, 10%, 15%, 20%, etc infusion.

7. DIURETICS ContdE. Carbonic Anhydrate Inhibitors DiureticsThese are weak diuretics and are used mainly to reduce raised intra-ocular pressure.CLINICAL USES: open-angle glaucoma, epilepsy, acute mountain sickness.ADR: fatigue, drowsiness, depression, excitement, hypokalemia, paraesthesia. Aplastic anemia, rash, pruritis, tinnitus, etcINTERACTION: Aspirin may cause acidosis.Examples:-BrinzolamideDiclofenamideDorzolamideMethazolamide.

8. NITRATES

These drugs are peripheral and coronary vasodilators.They relax smooth muscles in the blood vessel walls, and thus, help reduce pain of anginal attacks..They redistribute blood flow to ischemic areas of the myocardium, which improves perfusion of the heart.They dilate the veins, reducing venous pressure and venous return.They reduce blood volume and pressure within the heart, thereby reducing preload-which is the distending force that stretches the ventricular muscle prior to electrical excitation and contraction of the heart muscles.They dilate arterioles, which lowers peripheral vascular resistance.CLINICAL USES:- Acute, Stable & unstable angina, acute & chronic heart failure.ADR:- dizziness, hypotension, weakness, nausea & vomiting, pulsating headache.

8. NITRATES Contd

PRECAUTION:- avoid IV administration to clients with hypovolemia or severe hypertension.Administer with caution to clients with carotid disease, constrictive pericarditis, cardiac tamponade, severe hypertension.Examples of Drugs used:NGT/Nitroglycerin (Nitro-Bid, Nitrostat, Nitrodisc, Nitrogard) tabs (oral / sublingually) Glycerin trinitrate- sublingual tabs 300mcg, 600mcgIsosorbide dinitrate(isordil, isocard) 5mg, 10mg tabsIsosorbide Mononitrate(isotrate, ismo, monit) 10mg, 20mg, 40mg tabs

9. LIPID REGULATING AGENTSThese drugs are used to modify blood lipid concentration in the management of hyperlipidaemia.They are also used in the reduction of cardiovascular arrest.These drugs are grouped into five:-A- The StatinsB- The FibratesC- Bile-acid binding resinsD- NicotinatesE- Omega-3 Triglycerides

9. LIPID REGULATING AGENTS ContdA. The StatinsThese drugs help to reduce cholesterol by stimulating an increase in the Low Density Lipoproteins (LDL), or hapocytes memnrane, causing an increase clearance in LDL from the circulation.This reduces LDL cholesterol and some triglyceride.CLINICAL USES:- Coronary artery bypass, cerebrovascular disease, peripheral vascular disease, high total serum-cholesterol level, etcADR:- Headache, altered liver function tests, abdominal Pain, flatulence, nausea & vomiting, rash.CONTRA_INDICATION:- Pregnancy, active liver disease.

9. LIPID REGULATING AGENTS ContdExamples of Statins Used:-Atorvastatin (lipitor)10mg, 20mg, 40mg tabsSimvastatin (zocor) 5mg, 10mg, 20mg, 40mg tabsFluvastatin (lescol) 10mg, 20mg, 40mg tabs/ capsPravastatin (lipostat) 10mg, 20mg, 40mg tabs/capsOthers include:- Lovastatin, Cervastatin, Mevastatin, rosuvastatin, .

9. LIPID REGULATING AGENTS ContdB. The FibratesThese are derivatives of fibric acid.They inhibit the synthesis of cholesteroland bile acids thereby enhancing their secretion.They are broad spectrum lipid regulating agents. Their main action is to decrease serum triglycerides and LDL cholesterol level and to raise the High Density Lipoproteins (HDL)- cholesterol level.USES:- To treat clients with hyperlipideamia who fail to respond to treatment or at risk of pancreatitis.ADR:- Abdominal pains, headache, eczema, fatigue, liver tumorsExamples:-Bezafibrate (Bzalip) 200mg tabsCiprofibrate (modalim) 100mg tabsFenafibrate (lipantil) 67mg, 200mg 267mg caps

9. LIPID REGULATING AGENTS ContdC. Bile-Acid Binding ResinsThese products lower cholesterol by combining with bile acids in the GIT and preventing their reabsorption.They increase the oxidation of cholesterol to replace bile acids loss.USES:- Treatment of hypercholesterolemia in adults.ADR:- constipation, pruritis, headache, nausea, bloating and flatulence.Examples:colestipol (colestid)Cholestyramine (questran, prevalite powder)Colesevelam, Divistyramine.

9. LIPID REGULATING AGENTS ContdD. NicotinesThese drugs reduce triglycerides level and increase the LDL cholesterol.They are mainly used in hypertriglyceridaemia.Examples:-NiceritrolAcipimox (olbetam) 520mgSorbinicate Nicotinic acid 50mg

9. LIPID REGULATING AGENTS ContdE. Omega-3 TriglyceridesThese are long chain polyunsaturated fatty acids that primarily reduce triglycerides.They reduce plasma triglycerides in clients with severe hypertriglyceridaemia with risk of ischemic heart disease. ADR: occasional nausea and belching.Examples:-Omega-3 Fish oil.

10. CARDIAC GLYCOSIDES.

These products increase cardiac output especially when the heart is failing.They inhibit sodium-potassium adenosine trphosphate.They also reduce conductivity in the heart, especially through the atrio-ventricular node and therefore, have a negative chronotropic effect.They are used to slow the heart rate in supraventricular arrhythmias in heart failure.ADR:- nausea & vomiting, fatigue, drowsiness, confusion, arrhythmias,gynaecomastia.Examples:-Digoxin (lanoxin) 62.5cmg, 125mcg, 250mcgDigitalis lanata, Digitalis Leaf, Digitoxin,etc.

11. CENTRALLY ACTING AGENTS:These products act like alpha2 adreno-receptor antagonists.They act by stimulating alpha2 adrenocptors in the CNS causing a reduction in sympathetic tone and a resultant fall in blood pressure.They also reduce the heart rate.However, they have been superceeded by other antihypertensive drugs because of their adverse effects.ADR:- dry mouth, paraesthesia, stomatitis, Bradycardia, depression, nightmares, impotence, gynaecomastia, mild psychosis, decreased libido.Examples:Methyldopa (aldomet) 125mg,250mg, 500mgMoxonidine (physiotens) 200mcg, tabsClonidine, Brimonidine, Triamenidine, Guanfacine, Apraclonidine.

12. ANTICOAGULANTS:-

These products are used in the treatment and prophylaxis of thromboembolic disorders.ADR:- bleeding, local pain at injection site, Osteoporosis, alopeciaINTERACTION:- Tetracyclines, Nicotine, Digitalis glycosides these drug decreases the effect of anticoagulants.They can be divided into two types:-Direct anticoagulantsIndirect anticoagulants.

12. ANTICOAGULANTS Contd:-A. Direct Anti coagulantsThese group of anti coagulants act by inhibiting the cloting of blood in vitro and in vivo by enhancing the action of antithrombin III.Antithrombin III is present in plasma and inhibit the activity of activated clotting factors.CLINICAL USES:- Prophylaxis and treatment of thromboembolic disorders, maintains patency of IV catheters, Useful DIC, Prevention of blood clotting in cardiac and vascular surgery.DRUGSVOMMONLY USED:-Heparin1000Iu/ml, 5000Iu/ml, 25000Iu/ml injectionCetoparin (alphaparin)3000IU injectionDalteparin 12500UI/ml injectionReviparin (clivarin) 1432IU/0.25mlTinzaparin 10000IU/mlDanaparoid sodium (orgaran) 1250IU/ml injection

12. ANTICOAGULANTS Contd:-B. Indirect Anti-coagulants:-The products act by depressing the hepatic vitamin K-dependant synthesis of coagulation factors II (prothrombin), VII, IX and X.They also suppress the anticoagulant protein C and its co-factor proteins.DRUGS USED:Warfarin 0.5mg, 1mg, 3mg, 5mg tabsAcenocoumarol (sinthrome) 1mg tabsPhenindione (Dindevan) 10mg, 25mg, 50mg tabs

13. ANTI-PLATELET AGENTS

Platelet aggregation is very important in homeostatis.It is also involved in thrombos formation especially in arterial circulation.Antiplatelet drugs reduce platelet aggregation and are used to prevent thromembolic events in patients who have suffered myocardial infarction, ischemic stroke or transient ischemic attack or unstable angina.They are also used for primary prevention of thromboembolic events in patients at risk,Antiplatelet drugs act by inhibiting platelet cyclo-oxygenase and thus preventing synthesis of thromboxanes A2.ADR:- bleeding manifestation, hypotension, Bradycardia, headache, fever, chest pain, CONTRA-INDICATION: pregnancy, breastfeeding.

13. Contd

DRUGS USED:Aspirin 75mg tabsClopidogrel (Plavix) 75mg tabs dly(prefable in PM).Aciximab (Reo-pro) 2mg/ml injectionDipyridamole (Persantin)25mg, 59mg, 100mg or 5mg/ml tabs or injectionTirofiban (aggrastat) 250mcgsLamifiban, Cilostazol, Sibrafiban, Ditazole, Indobufen.

QUESTIONS, CONTRIBUTIONS, CLARIFICATIONS & CONSTRUCTIVE CRITICISMS?????