Cardiovascular drugs

Antihypertensive
Blood pressure is the force created as the heart pumps blood through the blood vessels. When the blood pressure goes beyond the prescribed normal range, an individual is diagnosed as having high blood pressure. (hypertension)

Types of Antihypertensives:
1. Diuretics help kidneys eliminate excess salt and water from bodys tissues and fluids a. Loop diuretics act on ascending loop of Henle in the kidney. i. Burinex bumetanide ii. Edemann furosemide iii. Frusema furosemide iv. Lasix furosemide b. Thiazide diuretics inhibit thiazide-sensitive Na+, Cl- symporter. Inhibit reabsorption of Na,Cl from distal convulated tubules in kidneys. i. Hytaz HCTZ (hydrochlorothiazide) ii. Diuzid HCTZ (hydrochlorothiazide) c. Thiazide-like diuretics similar action with thiazide diuretics but does not have thiazide structure. i. Natrilix SR - indapamide ii. Vazamide SR indapamide d. Potassium sparing diuretics do not promote secretion of potassium in urine. i. Aldactone spinorolactone ii. Triamterene e. Carbonic anhydrase inhibitor i. Cetamid acetazolamide 2. Sympatholytic Sympathetic adrenergic nervous system plays a major role in respiration of arterial pressure. Activation of the nerves to heart increases heart rate, contractility, and velocity of electrical impulse conduction. Sympatholytic drugs can block sympathetic adrenergic system in these different levels. 2.1 Peripheral sympatholytic drugs block influence of norepinephrine. a. Alpha-adrenergic blocker (1-adrenergic antagonist)

i. phentolamine b. Selective Alpha- adrenergic blockers(1-adrenergic antagonist) (-sin) i. Hytrin terazosin ii. Minpress - prazosin c. Beta-adrenergic blockers (-olol) i. Cardioten/Durabeta/Tenormin/Therabloc atenolol ii. Concore bisoprolol iii. Ziac bisoprolol and HCTZ iv. Angionorm/Angiobloc/Betaloc/Cardiosel/Cardiostat/Neobloc-metoprolol v. Logimax metoprolol and felodipine vi. Visken pindolol vii. Inderal propanolol viii. Timoptol timolol (Anti-glaucoma) d. Alpha and beta adrenergic blockers i. Betacard carvedilol ii. Cardipres carvedilol iii. Dilatrend carvedilol 2.2 Centrally acting sympatholytics stimulate alpha-receptors in brain. These drugs are administered usually in combination of diuretic. (2-adrenergic agonist) i. Catapres clonidine ii. Aldomet methyldopa Physiotens moxonidine 2.3 Adrenergic neuron blocker used for most resistant form of hypertension i. guanethidine ii. reserpine 3. Calcium channel blocker blocks entry of calcium in muscle cell of arterial wall. 3.1 Dihydropyridine (L-type calcium channel blockers) i. Amvasc/Norvasc/Provasc/Vasalat amlodipine ii. Plendil ER/Versant XR felodipine iii. Logimax metoprolol and felodipine iv. Lacipil lacidipine v. Zanidip lercanidipine vi. Cardepine/ Perpidine - nicardipine vii. Adalat/ Calcibloc nifedipine viii. Nimotop nimodipine 3.2 Non-dihydropyridine

a. Benzodiazepine i. Angiozem - diltiazem ii. Dilzem diltiazem b. Phenylalkyamines i. Isoptin verapamil 4. ACE inhibitor inhibits activity of the angiotensin converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin (to angiotensin II, potent vasoconstrictor)(-pril) i. Capoten - captopril ii. Renitec/Vasotec enalapril iii. BPNorm fosinopril iv. Vascor/Norten imidapril v. Vascoride/Norplus imidapril + HCTZ vi. Zestril lisinopril vii. Coversyl/Coveram perindopril viii. Accupril quinapril ix. Tritace ramipril 5. Angiotensin II receptor antagonist antagonize the activation of angiotensin receptors (ARBS) (sartan). i. Blopress candesartan ii. Teveten eprosartan iii. Aprovel irbesartan iv. Co-aprovel irbesartan + HCTZ v. Cozaar losartan vi. Combizar losartan + HCTZ vii. Hyzaar losartan +HCTZ viii. Lifezar losartan ix. Olmetec olmesartan x. Olmetec plus olmesartan +HCTZ xi. Micardis/Pritor telmisartan xii. Micardis Plus/Pritor Plus telmisartan + HCTZ xiii. Diovan valsartan xiv. Exforge valsartan + amlodipine 6. Other vasodilators 6.1 Arterial and venous Sodium Nitroprusside unlike organic nitrates, dilates arterial resistance vessels more than venous vessels rapid onset of action

 used to treat severe hypertensive emergencies and heart failure IV, continuous infusion is required 6.2 Arterial Apresoline - hydralazine 6.3 Peripheral minoxidil

Anti-anginal
Angina pectoris Principal symptom of ischemic heart disease Caused by transient episodes of myocardial ischemia that results from a reduction of oxygen supply/demand ratio Characterized by a severe constricting pain in the chest, often radiating from precordium to the left shoulder and down the arm.

Drug action in angina Lower myocardial requirement by decreasing determinants of oxygen demand (heart rate, ventricular volume, blood pressure, and contractility)

Types of Anti-anginal drugs:

1. Coronary vasodilators a. Nitrates/ Nitrites i. Amyl nitrate (inhalant) ii. Nitroglycerin >Deponit >Nitrolingual >Nitronal iii. Isosorbide dinitrate >Isoket >Isordil iv. Isosorbide 5-mononitrate >Elantan >Imdur durules b. Calcium channel blockers (refer to antihypertensives) 2. Beta-blocking agents (refer to antihypertensives)

3. Newer drugs to treat angina a. Metabolic modulators (pFOX inhibitors) Partially inhibit fatty acid oxidation because metabolism shifts to oxidation of fatty acids in ischemic myocardium that leads to greater oxygen requirement per unit of ATP. i. Angimax - trimetazidine ii. Vestar - trimetazidine iii. Vastarel - trimetazidine b. Potassium channel activators i. Aprior nicorandil ii. Nikoran - nicorandil c. Others i. Coralan ivabradine

Antiarrythmic
Ultimate goal is to restore normal rhythm and conduction Biggest problem : can cause arrhythmia (i.e. treatment of non-life threatening tachychardia may cause fatal ventricular arrhythmia)

Types of Antiarrythmic Drugs:

1. Class I Sodium channel blocker Bind and block fast Na channels that are responsible for rapid depolarization (phase 0) or fast response cardiac action potentials. Sodium channel blockade (1C>1A>1B) Increasing effective refractory period (1A> 1C > 1B) a. Class 1A i. Quinidine ii. Procainamide iii. disopyramide b. Class 1B i. Lidocaine >xylocaine >dolocaine >nobucaine ii. Tocainide iii. Mexiletine c. Class 1C i. Tambocor flecainide

ii. Propafenon iii. moricizine 2. Class II Beta adrenergic blockers (refer to antihypertensives) 3. Class III Potassium channel blocker Delay in repolarization and prolonged refractory period i. Anoion amiodarone ii. Cordarone amiodarone iii. Multaq drodenarone HCL 4. Class IV Calcium channel blocker (refer to hypertensives) 5. Others *direct nodal inhibition i. Cardiovert adenosine ii. Digoxin lanoxin iii. Magnesium sulphate

Positive inotropic agents

Substance that increases the force of muscular contractions of the heart.

Types of positive inotropic agents:

1. Cardiac glycosides Drug derived from Digitalis purpurea Increase the force of cardiac muscle contraction by binding to and inhibiting the action of a membrane enzyme that extrudes sodium ions from cell interior which results to greater force of contraction. Digoxin lanoxin DIgitoxin - lanoxin 2. Sympathomimetic (Adrenergic agonist) 2.1 Direct- acting antagonist Bind and activate, , 2, 1, 2 receptors. i. Epinephrine (adrenaline) ii. Norepinephrine (noradrenaline) > Inotrop >Levophed >Norphed >Norepin iii. Dopamax dopamine iv. Dobuject dobutamine HCl

2.2 Adrenergic drugs with mixed action Act both directly with receptor sites and partly by release of endogeneous norepinephrine. Ephredine > principal alkaloid of Ma Huang 3. Phosphodiesterase inhibitors Cyclic AMP is broken down by enzyme called cAMP-dependent phosphodiesterase (PDE). Inhibition of this enzyme prevents cAMP breakdown and increases its intracellular concentration. This increases cardiac inotropy, chronotropy and chromotropy.

a. PDE3 inhibitors used for treating decompensated heart failure (HF) except cilostazol . i. milrinone ii. inamrinone (formerly amrinone) iii. cilostazol b. PDE5 inhibitors used for treating male erectile dysfunction. Can be for hypertension. i. sildenafil ii. tadalafil

Antihyperlipidemic
Background
Hyperlipidemia also called hyperlipoproteinemia major cause of coronary heart disease (CHD) means abnormally high levels of fats in the blood (included fats : cholesterol, triglycerides)

Lipoprotein Since blood and other body fluids are watery so fats need a special transport system to travel around the body. They are carried from one place to another mixing with protein peptides called lipoproteins. Types of lipoprotein:

1. Chylomicrons carry mostly triglycerides 2. Very low density lipoproteins (VLDL) carry mostly triglycerides 3. Low density lipoproteins (LDL) transport cholesterol, may form deposits on walls of arteries and blood vessels. 4. High density lipoproteins (HDL) transport cholesterol back to liver for removal. Good for healthy cholesterol. Hyperlipidemia low HDL, high LDL Types of Hyperlipidemia: 1. Type I Primary hyperlipoproteinaemia, familial hyperchylomicronemia - high chylomicrons due to lipoprotein lipase or altered apo lipoprotein C2 deficiency. 2. Type II most common form a. Type II a cause of xanthelesma b. Type IIb high VLDL levels 3. Type III broad beta disease - high chylomicrons, high IDL (intermediate density lipoprotein) 4. Type IV hypertriglyceridemia. High triglycerides 5. Type V glucose intolerance and hyperuricemia. High vldl and chylomicrons

Types of Antihyperlipidemic (dyslipidemic) drugs:

1. Statins 3-Hydroxyl-3-methylglutanyl coenzyme A (HMG-CoA) reductase inhibitor HMG-CoA reductase catalyzes conversion of HMG-CoA to mevalonate during cholesterol synthesis i. Avamax atorvastatin ii. Lipitor atorvastatin iii. Pravaz pravastatin iv. Vidastat simvastatin v. Zocor HP(Heart Pro) simvastatin vi. Crestor - rosuvastatin 2. Fibrates 2- phenoxy-2-methyl propanoic acid derivatives Does not stop cholesterol biosynthesis but stimulate beta-oxidation of fatty acids in peroxisomes and mitochondria to decrease plasma levels of fatty acid i. Lipway fenofibrate ii. Lipanthyl fenofibrate 3. Cholesterol absorption inhibitors Decrease absorption of cholesterol in small intestine

i.

Ezetrol ezetimibe

4. Niacin Lower cholesterol and lipids Frequent side effect : prostaglandin mediated skin flushing Laropripant reduces niacin-induced skin flushing i. Tredaptive nicotinic acid and laropripant 5. Combination of statins and cholesterol absorption inhibitors Vytorin ezetimibe and simvastatin

Other cardiovascular drugs

Neuqinon Ubidecarenone (coenzyme Q10)

Haemostatic
Antihemorrhagic agents (stops bleeding) Systemic drugs inhibit fibrinolysis or promoting coagulation Locally acting hemostatic agents work by causing vasoconstriction or promoting platelet aggregation

Types of haemostatic drugs:

Systemic 1. Antifibrinolytics i. Hemostan tranexamic acid ii. Aminocaproic acid 2. Vitamin K i. Konakion phytomenadione

Antithrombotics
Drug which reduces thrombus formation

Types of antithrombotic drugs:

1. Thrombolytics Dissolve clots after they are formed a. Tissue plasminogen activator (t-PA) Protein included in breakdown of clots

Enzyme that catalyzes conversion of plasminogen to plasmin, enzyme responsible for clot breakdown. Only for embolic or thrombotic stroke i. Actilyse - alteplase ii. Retavase - reteplase iii. TNKase tenecteplase

b. Streptokinase Protein secreted by several species of streptococci that can bind and activate plasminogen. i. Streptokin streptokinase ii. Britton streptokinase streptokinase 2. Antiplatelet Limit migration or aggregation of platelets a. Cyclooxygenase inhibitor (COX2- inhibitor) Targets COX2, an enzyme responsible for inflammation and pain Aspilets - aspirin b. ADP receptor inhibitors Inhibits all types of P2Y receptors(in coupling) i. Plogrel - clopidogrel ii. Plaxetan - clopidogrel iii. Plavix - clopidogrel iv. Timiflo clopidogrel v. Effient prasugrel vi. Vasopid - ticlodipine c. Phosphodiesterase inhibitor (refer to positive inotropic agents) d. Glycoprotein IIb/IIIa inhibitors Inhibit GpIIb/IIIa receptor on surface of platelets i. Aggrastat - tirofiban e. Adenosine reuptake inhibitors Acts as reuptake inhibitor for purine and adenosine by blocking action of ENTs (Equilibrative nucleoside transporters) i. Persantin dipyridamiole 3. Anticoagulant Substance that prevents coagulation of blood a. Vitamin K antagonist Warfarin - coumadin b. Synthetic pentasaccharide inhibitors for factor Xa Arixtra fondaparinux Na

c. Heparin Clexane enozaparin Na Innohep tinzaparin Na

Hemorrheologic agents
Hemorrheologic agents improve the flow properties of blood by decreasing its viscosity, in patients with chronic peripheral arterial disease Trental pentoxifylline

Hematopoietic growth factors

Background

The finite life span of most mature blood cells requires their continuous replacement, a process termed hematopoiesis. Red blood cell production can increase more than twentyfold in response to anemia or hypoxemia, white blood cell production increases dramatically in response to a systemic infection, and platelet production can increase ten- to twentyfold when platelet consumption results in thrombocytopenia. The regulation of blood cell production is complex. Hematopoietic stem cells are rare marrow cells that manifest self-renewal and lineage commitment, resulting in cells destined to differentiate into the nine distinct blood-cell lineages. The hematopoietic growth factors are glycoprotein hormones that regulate the proliferation and differentiation of hematopoietic progenitor cells in the bone marrow. The first growth factors to be identified were called colony stimulating factors because they could stimulate the growth of colonies of various bone marrow progenitor cells in vitro. Many of these growth factors have been purified and cloned, and their effects on hematopoiesis have been extensively studied. Quantities of these growth factors sufficient for clinical use are produced by recombinant DNA technology.

Types of Hematopoietic growth factors:

1. Erythropoietin

Stimulates proliferation and maturation of committed erythroid progenitors to increase red cell production. (for anemia)

a. Epoietin alpha >Eprex >Renogen b. Epoietin beta >Recormon c. Methoxy polyethylene glycol epoetin beta >Mircera

2. Granulocyte colony-stimulating factor (G-CSF) For neutropenia Neutropenia, is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell. Granulokin filgrastim Peglasta - pegfilgrastim Granocyte 34 lenograstim 3. Thrombopoietin The cloning and expression of recombinant thrombopoietin, a cytokine that predominantly stimulates megakaryopoiesis, is potentially another milestone in the development of hematopoietic growth factors as therapeutic agents (Lok et al., 1994; de Sauvage et al., 1994; Kaushansky et al., 1994) Two forms of recombinant thrombopoietin have been developed for clinical use. One is a truncated version of the native polypeptide, termed recombinant human megakaryocyte growth and development factor (rHuMGDF), which is produced in bacteria and then covalently modified with polyethylene glycol to increase the circulatory half-life. The second is the fulllength polypeptide termed recombinant human thrombopoietin (rHuTPO), which is produced in mammalian cells. In vitro, both drugs are equally potent in stimulating megakaryocyte growth. Tpiao recombinant human thrombopoietin