Pharmacology II Module 1: Cardiovascular, Renal and Hematologic Pharmacology PDF

Pharmacology II MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Lecture TOPIC OUTLINE ET IOLOGY I. Antihypertensive Agents a. Hypertension...

Pharmacology II MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Lecture TOPIC OUTLINE ET IOLOGY I. Antihypertensive Agents a. Hypertension  Essential/ Primary Hypertension i. Classification  Secondary Hypertension ii. Etiology iii. Contributing Factors CONT RIBUT ING FACT ORS b. Basic Pharmacology of Antihypertensive Agents  Genetic factors i. Diuretics ii. Centrally Acting  Psychological stress Sympathoplegic Drugs  Environmental & dietary factors iii. Adrenergic Neuron- Blocking Agents iv. Beta-Adrenoceptor- Blocking Agents v. Alpha I Blockers vi. Alpha Adrenoceptor- Blocking Agents vii. Vasodilators viii. Calcium Channel Blockers ix. ACE Inhibitors x. Angiotensin Receptor- Blocking Agents (ARB) ANTIHYPERTENSIVE AGENTS BASIC PHARMACOLOGY O F ANTIHYPERTENSIVE AGE NTS HYPERTENSION  Drugs that alters sodium and water balance  Systolic blood pressure of 140 or greater or o Diuretics diastolic blood pressure of 90 or greater.  Drugs that alter sympathetic nervous system  Risk factors: function o Smoking o Sympathoplegic agents o Metabolic syndrome  Direct Vasodilators o Manifestations of end organ damage o Agents that block production or action at the time of diagnosis of angiotensin o Family history DIURET ICS CLASSIFICATION  Lowers BP by depleting the body of sodium Table 11.1 (Katzung) Classification of stores and reducing blood volume or other hypertension on the basis of blood pressure. Category mechanisms. Systolic/ Diastolic  Increase urine excretion Pressure  Reduce the circulating fluid volume to treat Normal < 120/80 edema and hypertension. Prehypertension  Agents used 120-139/ 80-89 Hypertension o Thiazide ≥ 140/90 Stage 1 o Loop diuretics 140-159/ 90-99 o Potassium-Sparing diuretics Stage 2 ≥ 160/100 o Osmotic diuretics JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 1  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II THIAZIDES o To increase the diuretic and hypotensive effects and reduce the  For mild to moderate hypertension and normal dangers of hyperkalemia. renal and cardiac function  Side Effects o Hydrochlorothiazide o Hyperkalemia o Chlorthalidone o Fatigue, lethargy  Uses: o Hypotension o Hypertension o Gynecomastia o Edema o Prophylaxis of calculus formation OSMOT IC DIURET ICS  Side Effects: o Hypokalemia  Used to reduce intracranial pressure (ICP) or o Muscle weakness Intraocular pressure (IOP). o Postural hypotension  Used in emergency cases that involves cranial o Hyperglycemia or spinal trauma and used to reduce the risk of o Increase uric acid level nervous system damage from swelling. o Mannitol LOOP DIURET ICS  Side Effects: o Fluid and electrolyte imbalance  Acts directly on the loop of Henle in the kidney o CNS symptoms to inhibit sodium and chloride reabsorption o GI symptoms which in turn inhibits water reabsorption back o Tachycardia into the bloodstream leading to increase urine o Allergic reactions formation. o Pulmonary edema o Furosemide o Bumetanide CENT RALLY ACT ING SYMPAT HOPLEGIC  Uses: DRUGS o Edema o Pulmonary edema o Ascites MET HYLDOPA o Hypertension combined with  Used for the treatment of hypertension during antihypertension especially in patients pregnancy. with kidney disease.  Lowers BP by reducing peripheral vascular  Side Effects: resistance with a variable reduction in heart o Fluid and electrolyte imbalance rate and cardiac output. o Hypotension  Pharmacokinetics: o Hyperglycemia and increase uric acid o Half-life: 2 hours level o Bioavailability: 25% o Initial Dose: 1 g/day POT ASSIUM-SPARING DIURET ICS  Toxicity:  Prevent potassium depletion and enhance the o Sedation natriuretic effects of other diuretics. o Mental lassitude & impaired mental  Counteracts the increase of glucose and uric concentration o Nightmares acid levels. o Mental depression o Spironolactone o Vertigo o Triamterene o Extrapyramidal symptoms (EPS)  Uses o Used in combination with thiazide diuretics CLONIDINE  Used in the treatment of hypertension JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 2  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II  Lowers BP in the supine position and rarely  Inhibits the stimulation of renin production causes postural hypotension. catecholamine.  Pharmacokinetics:  Most effective in patients with high plasma o Half-life: 8-12 hours renin activity. o Bioavailability: 95%  Half-life: 3-5 hours o Initial Dose: 0.2mg.day  Bioavailability: 25%  Toxicity:  Initial dose: 80mg/day o Dry mouth o Sedation Nervousness METOPROLOL & AT ENOLOL o Tachycardia o Headache (H/A) METOPROLOL o Sweating  Less bronchial constriction than propranolol at ADRENERGIC NEURON-BLOCKING AGENT S doses that produce equal inhibition of B- adrenoceptor responses.  Metabolized by CYP2D6 with high first-pass GUANETHIDINE metabolism.  Inhibits the release of norepinephrine from the  Half-life: 4-6 hours sympathetic nerve endings.  It replaces norepinephrine and causes a ATENOLOL gradual depletion of norepinephrine stores in  Less effective than metoprolol in preventing the nerve endings, complications of hypertensions  It interferes with amine release.  Half-life: 6 hours  Half-life: 5 days  Patients with reduced renal functions should  Toxicity: receive lower doses. o Symptomatic postural hypotension o Delayed or retrograde ejaculation NADOLOL, CART EOLOL, BET AXOLOL, & o Diarrhea BISOPROLOL RESERPINE NADOLOL & CARTEOLOL  Blocks the ability of aminergic transmitter  Non selective B-receptor antagonist vesicle to take up and store biogenic amines  Not metabolized & excreted in the urine. by interfering with the vesicular membrane associated transporter (VMAT) BETAXOLOL & BISOPROLOL  Half-life: 24-48 hours  BI-selective blockers  Bioavailability: 50%  Primary metabolized in the liver.  Initial dose: 0.25mg/ day  Toxicity: o Sedation PINDOLOL, ACEBUTOLOL , & PENBUTOLOL o Lassitude  These drugs are partial agonist o Nightmares  Lower BP but they are rarely used in Home o Severe mental depression Parenteral Nutrition (HPN). BET A-ADRENOCEPT OR-BLOCKING AGENT S LABET ALOL, CARVEDILOL, NEBIVOLOL  Labetalol is useful in the treatment of PROPANOLOL hypertension of pheochromocytoma &  Decrease BP primarily as a result of a hypertensive emergencies. Formulated as a decrease in cardiac output. racemic mixture of 4 isomers. JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 3  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II  Carvedilol also administered as a racemic VASODILAT ORS mixture. With a half-life of 7-10 hours.  Nebivolol is a Bl-selective blocker and vasodilating property that are not mediated by HYDRALAZINE & MINOXIDIL alpha blockade, with a half-life of 10-12 hours.  Oral vasodilators for long-term therapy for HPN. ESMOLOL  A BI-selective blocker; rapidly metabolized via NIT ROPRUSSIDE & FENOLDOPAM hydrolysis by RBC esterases.  Parenteral vasodilators for hypertensive  Short half-life: 9-10 minutes emergencies  Administered through IV infusion CALCIUM CHANNEL BLOC KERS & ALPHA I BLOCKERS NIT RAT ES  Used in ischemic heart disease & hypertensive PRAZOSIN, T ERAZOSIN, & DOXAZOSIN emergencies.  Produces their antihypertensive effects by HYDRALAZINE selectively blocking alpha I receptors in arterioles & venules.  Useful in combination therapy in the treatment  Reduces arterial pressure by dilating both of severe HPN resistance & capacitance vessels.  Hydralazine in combination with nitrates is  More effective when used in combination B- effective in heart failure. blockers & a diuretic.  Dilates arterioles but not veins.  Uses:  Well- absorbed & well metabolized in the liver. o Prostatic hyperplasia  Availability: 25% o Bladder obstruction symptoms  Half-life: 1.5 to 3 hours o Hypertension  Dose: 40 to 200mg/ day o benign prostatic hyperplasia (BPH)  Toxicity:  Toxicity: o Headache o Dizziness o Anorexia o Palpitations o Palpitations o Headache o Sweating o Lassitude o Flushing o Peripheral neuropathy ALPHA ADRENOCEPT OR-BLOCKING o Drug fever AGENT S MINOXIDIL PHENT OLAMINE & PHENO XYBENZAMINE  The effect results from the opening of potassium channels in smooth muscle  Nonselective agents membranes by minoxidil sulfate (active  Used in diagnosis & treatment of metabolite). Pheochromocytoma and in other clinical  Increase potassium permeability stabilizes the situations. membrane as its resting potential and makes  Used in the treatment of clonidine withdrawal contraction less likely. syndrome in combination with B-blockers.  Dilates arterioles but not veins  Half=life: 4 hours  Bioavailability: 90%  Initial Dose: 5-10mg/ day  Used in combination with B-blocker and a loop diuretic. JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 4  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II  Toxicity:  Rapidly metabolized by conjugation o Tachycardia  Half-life: 10minutes o Palpitations  Toxicity: o Angina o Reflex tachycardia o Edema o Headache o Headache o Flushing o Sweating o Increase intraocular pressure o Hypertrichosis CALCIUM CHANNEL BLOC KERS SODIUM NITROPRUSSIDE  Uses  Hypertensive emergencies and for severe o Angina heart failures. o Anti-arrhythmic effects  Dilates both the arterioles and the venous o Reduces peripheral resistance and BP vessel.  Moa  The action of sodium nitroprusside results from o Inhibits calcium influx to arterial the activation of guanylyl cyclase, either via smooth muscle cells. the release of nitric oxide or by direct o Ex. Verapamil, Diltiazem, stimulation of the enzyme. Dihydropyridine family  Rapidly metabolized by uptake into the RBC  Nifedipine and other dihydropyridine- are with release of nitric oxide and cyanide. more selective as vasodilators and less  Lowers BP rapidly & its effect disappear 1 –to cardiac depressant effects than Verapamil and 10 minutes after discontinuation. Diltiazem.  Toxicity: o Excessive BP lowering ACE INHIB IT ORS o Accumulation of cyanide o metabolic acidosis o arrhythmias LISINOPRIL, ENALAPRIL, CAPTOPRIL o death  Inhibition of ACE lowers BP by decreasing vasoconstriction. DIAZOXIDE  First or second line agents in the treatment of  Long-acting potassium channel opener that HPN are excellent alone, but can also be used causes hyperpolarization in smooth muscle in combination with diuretics and calcium and pancreatic B-cells. channel blocker.  Dilates the arterioles  Side Effects  Used in the treatment of hypoglycemia in o Rash/ photosensitivity hyperinsulinism. o Severe hypotension  Half-life: Approx. 24 hours o Chronic dry cough or nasal congestion  Partially metabolized o Hyperkalemia  Toxicity: ENAPRIL o Excessive hypotension o Angina  Inhibit the converting enzymes peptidyl o Ischemia dipeptidase that hydrolyzes angiotensin I to o Cardiac Failure angiotensin II and inactivates bradykinin, a potent vasodilator that works at least in part by FENOLDOPAM stimulating release of nitric oxide and  A peripheral arteriolar dilator for hypertensive prostacyclin. emergencies and postoperative HPN.  Enalapril  Acts primarily as an agonist of dopamine DI o Prodrug receptors, resulting in dilation of peripheral o Good choice for patients with other arteries and natriuresis. serious conditions: JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 5  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II  Heart failure  Following myocardial infarction  When high coronary disease risk exists  Diabetes  Renal disease and cardiovascular disease o Useful in treating patients with chronic kidney disease because they diminish proteinuria and stabilize renal function. o Drug of choice  For hypertensive patients with nephropathy- they slow the progression of renal disease. ANGIOT ENSIN RECEPTOR-BLOCKING AGENT S (ARB) LOSART AN AND VALSART AN  The first marketed blockers of angiotensin II type I receptor.  They have no effect on bradykinin metabolism therefore more selective blockers of angiotensin effects than ACE inhibitors.  Commonly used in patients who have had adverse reactions to ACE inhibitors. REFERENCES Book: Katzung B.G. et al. Basic and Clinical Pharmacology, 14th edition Notes from the discussion of: Anna Liza D. JAMIAS, RPh. RN. Central Philippine University PowerPoint presentation: College of Pharmacy JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 6 PBS3107 VASODILATORS & THE TREATMENT OF ANGINA PECTORIS ANGINA  When a patient has brief episodes of pain, squeezing pressure or tightness in the chest. Temporary plasma, an interference of blood, Occurs with activity or emotional stress. oxygen or nutrients to the heart which can result into coronary ischemia (restriction in TREATMENT blood flow) CORONARY VASODILATORS ISCHEMIC HEART DISEASE  These drugs are used for the treatment and  The primary symptom of ischemic heart prophylactic management of angina disease is ANGINA PECTORIS which is the o Nitrates most common form of angina o Beta-blockers o Calcium channel blockers ANGINA PECTORIS PATHOPHYSIOLOGY OF ANGINA  Chest pain resulting from decreased blood Table 12-1. Hemodynamic determinants of myocardial supply to the heart. oxygen consumption  Caused by transient episodes of myocardial ischemia which are due to imbalance in the Wall stress myocardial oxygen supply  Intraventricular pressure  Ventricular radius (volume) CLASSIC/EFFORT ANGINA  Wall Thickness Heart rate  If there’s an inadequate blood flow in the Contractility presence of CAD.  Diagnosis is usually made on the basis of  The myocardial oxygen requirement increases history and stress testing when there is an increase in heart rate, contractility, arterial pressure, or ventricular VASOSPASTIC/VARIANT/PRINZMETAL AGINA volume.  Caused by spasm in the coronary arteries (at DRUGS FOR THE TREATMENT OF ANGINA rest)  Usually occurs in younger patient NITRATES  Diagnosis is made on the basis of history Used most commonly for the relief of acute angina pectoris of for long-term prophylactic UNSTABLE ANGINA management.  Episodes of angina occurs at rest  Ex. Nitroglycerin  Caused by episodes increased epicardial o Oral SR, buccal, SL, parenteral, coronary artery resistance or small platelet transdermal, patch, topical occurring in the vicinity of an atherosclerotic ointment. (Once the patient is plague unresponsive to nitroglycerin  Can happen without physical exertion maybe it’s a sign of myocardial infarction) STABLE ANGINA  Ex. Isosorbide o Oral, oral SR, SL  Occurs when heart is working harder than usual PBS3107 VASODILATORS & THE TREATMENT OF ANGINA PECTORIS Cyanide Poisoning – methemoglobin ion has a Nitroglycerin & Isosorbide Dinitrate very high affinity for cyanide ion, thus  Bioavailability: very low administration of NaNO2 soon after cyanide  SL route – avoids first pass effect, and exposure regenerates active cytochrome achieves a therapeutic blood level  Antidote – amyl nitrite, NaNO2, Na2S2O3, rapidly. (sodium thiosulfate) or with methylene  PETN (Pentaerythritol tetranitrate) – blue administered when a much longer  Antidote (new) – hydroxocobalamin duration of action is needed.  Amyl nitrite – highly rapid absorption & avoids hepatic first pass effect MAJOR ACUTE TOXICITIES Isosorbide Mononitrate Direct extension of therapeutic vasodilation  Bioavailability: 100%  Orthostatic hypotension Transdermal Patch  Tachycardia  Applied every 24 hours to clean, dry,  Throbbing Headache hairless areas of the upper arm or body  Should not be applied below the elbow TOLERANCE or knee Continuous exposure to high level of nitrates  The sites be rotated to avoid skin can occur in the chemical industry, especially irritation & raw scarred or callused where explosives are manufactures. areas should be avoided. Monday sickness MECHANISM OF ACTION CLINICAL USE OF NITRATES  Nitroglycerin activation requires enzymatic  Rapid onset of action: 1 to 3 minutes action  SL – most frequently used agent for the  Nitroglycerin can be denitrated by gluthathione immediate treatment of angina S-transferase in smooth muscle & other cells.  Duration of action: short, not exceeding 20 to  A mitochondrial enzyme, aldehyde 30 minutes dehydrogenase isoform 2 & possibly isoform 3,  Not suitable for maintenance therapy appears to be key in the activation & release of  IV Nitroglycerin – rapid onset of action nitric oxide from nitroglycerin & pentaerythritol  Clinical use is restricted to the treatment of tetranitrate (PETN). severe, recurrent rest angina OTHER EFFECTS OTHER NITRO-VASODILATORS NO2 (nitrogen dioxide) – reacts with Nicorandil haemoglobin to produce methemoglobin, which  Nicotinamide nitrate ester has a very low affinity for oxygen, that’s why large doses of nitrites can result in  With vasodilating properties pseudocyanosis, tissue hypoxia, & death. Used  Approved for use in the treatment of in chemical and pharmaceutical industries. angina in Europe & Japan but not in the NaNO2 (sodium nitrite) – used as curing agent US. for meats (corned beef), exposure to large Molsidomine amounts of nitrite ion can occur and may  A prodrug that is converted to a nitric produce serious toxicity. oxide releasing metabolite PBS3107 VASODILATORS & THE TREATMENT OF ANGINA PECTORIS CALCIUM CHANNEL BLOCKERS  Atrioventricular block  Cardiac arrest, and Orally active agents with high first pass effect,  Heart failure high plasma protein binding & extensive metabolism BETA-BLOCKERS  Uses:  Angina First line of choice in chronic effort angina.  Hypertension Beneficial effects of beta blockers are related to  Supraventricular tachyarrhythmia their hemodynamic effects: (SVT)  Decrease heart rate, blood pressure, and  Drugs: contractility which decreases myocardial  Verapamil oxygen requirement at rest and during  Nifedipine exercise. Contraindications to the use of beta-blockers VERAPAMIL  Asthma  Other bronchospastic conditions  The first clinically useful member  Severe bradycardia  Inhibits calcium ion influx through slow  AV blockade channels into myocardial cells & vascular  Bradycardia-tachycardia syndrome smooth muscle cells  Severe unstable left ventricular failure  The result of attempts to synthesize more active analogs of papaverine, a vascodilator alkaloid NEWER ANTIANGINAL DRUGS found in opium poppy RANOLAZINE VERAPAMIL & DILTIAZEM Act by reducing a late sodium current that  Uses: antidysrhythmics but are used for their facilitates calcium entry via the sodium calcium vasodilating properties when treating angina exchange  Decreases heart rate therefore decreases the Approved in the US for angina. heart’s work TRIMETAZIDINE NIFEDIPINE pFOX inhibitors, partially inhibit the fatty acid  The prototype of the dihydropyridine family of oxidation pathway in myocardium. calcium channel blockers  Can be used more safely than verapamil or PERHEXILINE diltiazem in the presence of atrioventricular conduction abnormalities. Used for the treatment of angina but with  Reduces arterial blood pressureinvolving hepatotoxicity and peripheral neuropathy. peripheral arterial vasodilatation and reduction Currently approved in few countries. in peripheral vascular resistance. IVABRADINE TOXICITY Bradycardic drug.  Direct extensions of their therapeutic actions. Appears to reduce angina attacks.  Excessive inhibitions of calcium influx can cause:  Serious cardiac depression  Bradycardia PBS3107 VASODILATORS & THE TREATMENT OF ANGINA PECTORIS FASUDIL An inhibitor of smooth muscle Rho kinase and reduces coronary vasospasm in experimental animals. ALLOPURINOL Inhibits xanthine oxidase, an enzyme that contributes to oxidative stress and endothelial dysfunction in addition to reducing uric acid synthesis. TREATMENT OF PERIPHERAL ARTERY DISEASE (PAD) AND INTERMITTENT CLAUDICATION ARTHEROSCLEROSIS  Build-up of fats, cholesterol, and other substances in and on the artery walls.  Can result in ischemia of peripheral muscles just as coronary disease causes cardiac ischemia.  Pain (Claudication) occurs in skeletal muscles, especially in legs during exercise and disappears with rest  PAD is associated with increased mortality, limits exercise tolerance and may be associated with chronic ischemic ulcers, susceptibility to infection and the need for amputation. TREATMENT  Medical treatment directed at reversal or control of atherosclerosis requires measurement and control of hyperlipidemia, hypertension, and obesity; cessation of smoking; control of diabetes if present.  Physical therapy and exercise training  Antiplatelet drugs:  Aspirin  Clopidogrel  Drugs used exclusively for PAD:  Cliastazol  Pentoxifylline  Naftidrofuryl  Pharmacology II MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Lecture TOPIC OUTLINE Table 13-1 Therapies used in heart failure. I. Drugs Used in Heart Failure a. Heart Failure Chronic Systolic Heart Acute Heart Failure i. Proteins Failure ii. Pathophysiology of Heart Diuretics Diuretics Failure iii. Primary Signs and Aldosterone receptor Vasodilation Symptoms of All Types of antagonists Heart Failure Angiotensin-converting Beta agonists iv. Primary Factors of Cardiac enzyme inhibitors Performance b. Treatment Angiotensin receptor Bipyridines i. Cardiac Glycosides blockers ii. Bipyridines Beta blockers Natriuretic peptide iii. Beta-Adrenoceptor Agonists Cardiac glycosides Left ventricular assist iv. Investigational Positive device Inotrophic Drugs Vasodilators, neprilysin v. Diuretics inhibitor vi. ACE Inhibitors, ARBs, And Other Related Agents Resynchronization and vii. Vasodilators cardioverter therapy viii. Beta Blockers PROT EINS c. Management of Chronic Heart Failure i. Sodium Removal ACT IN ii. ACE Inhibitors iii. ARBs  An important contributor to the contractile iv. Vasodilators property of muscle and other cells. v. Beta Blockers and Ion  A protein that produces small contractile Channel Blockers filaments within muscle cells. vi. Digitalis d. Management of Acute Heart Failure DRUGS USED IN MYOSIN  A protein that produces thick, contractile filaments within muscle cells. HEART FAILURE  A molecular motor & converts chemical energy released from ATP into mechanical energy, thus generating force and movement. HEART FAILURE When contractility of the heart decrease, lesser  Occurs when cardiac output is inadequate to blood pumped >> affecting blood circulation, provide the oxygen needed by the body. progressing into heart failure.  Common cause: o CAD o HPN  2 Major Types o Systolic Failure o Diastolic Failure JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 1  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II  Neurohumoral compensation: o Sympathetic nervous system o Renin-angiotensin-aldosterone hormonal response PAT HOPHYSIOLOGY OF HEART FAILURE PRIMARY FACTORS OF C ARDIAC  Coronary artery disease PERFORMANCE  Cardiac output below normal range.  Systolic dysfunction  Preload o With reduced cardiac output &  Afterload significantly reduced ejection function,  Contractility is typical of acute failure, especially  Heart Rate resulting from myocardial infarction.  Diastolic dysfunction TREATMENT o Often occurs as a result of hypertrophy and stiffening of the CARDIAC GLYCOSIDES myocardium. DIGOXIN PRIMARY SIGNS AND SYMPT OMS OF ALL TYPES OF HEART FAILU RE o Digitalis lanata o Other source:  Tachycardia  Oleander  Decreased exercise tolerance  Lily of the Valley  SOB  Milkweed  Cardiomegaly o 65-80% absorption  Peripheral edema o Half-life: 36-40 hours  Pulmonary edema JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 2  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II ISAT AROXIME  Increases contractility by inhibiting Na+/ K+ - ATPase but in addition, it appears to facilitate sequestration of Ca2+ by the SR LEVOSIMERDAN  A drug that sensitizes the troponin system to calcium, also appears to inhibit phosphodiesterase and to cause some o All therapeutically useful cardiac vasodilation in addition to its inotropic effects. glycosides  Inhibit Na+/K+- ATPase- the OMECAMT IV MECARBIL membrane bound transporter  Parenteral agent that activates cardiac myosin  Its inhibitory action is and prolongs systole without increasing responsible of the therapeutic oxygen consumption of the heart. effect (positive inotrophy) as well as its toxicity. DIURET ICS o Increases cardiac contractility (Positive inotrophy effect) FUROSEMIDE BIPYRIDINES  Drug of choice in heart failure  Reduces salt and water retention, edema, and MILRINONE symptoms  Have no effect on cardiac contractility.  A bipyridine compound that inhibits  It reduces venous pressure and ventricular phosphodiesterase isozyme e (PDE-3). preload.  Oral and parenteral use  Half-life: 3-6 hours  It increases myocardial contractility by SPIRONOLACT ONE & EPL ERENONE increasing inward calcium flux in the heart o The aldosterone antagonist diuretic during the action potential. with additional benefit of decreasing  Inhibition of phosphodiesterase results in an morbidity in patient with severe heart increase in cAMP and the increase in failure who are also receiving ACE contractility and vasodilation. inhibitors. BET A-ADRENOCEPT OR AGONIST S ACE INHIBIT ORS, ARB s, AND OT HER RELAT ED AGENT S DOBUT AMINE  Selective beta 1 agonist- widely used in patient CAPT OPRIL with heart failure.  Reduces peripheral resistance thereby  Parenteral drug which produces an increase in reduces afterload cardiac output together with a decrease in  Also reduces salt, and water retention and in ventricular filling pressure. that way reduces preload.  Also used in acute heart failure and helpful if  Also reduces long-term remodeling of the there is a need to raise blood pressure. heart and vessels, an effect that may be responsible for the observed reduction in INVEST IGAT IONAL POSIT IVE INOT ROPHIC mortality and morbidity. DRUGS JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 3  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II LOSART AN B I Symptoms ACEI/ARB, B  An angiotensin AT1 receptor which appears to with severe blocker, exercise diuretic have similar beneficial effects. C II/III Symptoms Add with aldosterone ALISKIREN marked antagonist, (class II) or digoxin; CRT,  A renin inhibitor approved for HPN, was found mild (class ARNI, to have no definitive benefit in clinical trials for III) exercise hydralazine/ heart failure. nitrate4 D IV Severe Transplant, VASODILAT ORS symptoms LVAD at rest  Effective for the treatment of heart failure because they provide a reduction in preload or MANAGEMENT OF CHRONIC HEART reduction in afterload or both. FAILURE  Treatment of patients at high risk (stages A NESIRIT IDE and B) should be focused on control of  A synthetic form of the endogenous peptide hypertension, arrhythmias, hyperlipidemia and brain natriuretic peptide (BNP) diabetes.  Approved for use in acute cardiac failure.  A recombinant product with increase cGMP in SODIUM REMOVAL smooth muscle cells and reduces venous and arteriolar tone in experimental preparations.  Dietary salt restriction  Short half-life: 18 minutes.  Diuretics o Thiazide diuretics BET A BLOCKERS o Loop diuretics o Spironolactone o Eplerenone BISOPROLOL, CARVEDIL OL, MET OPROLOL, NEBIVOLOL ACE INHIBIT ORS  Most patients with chronic heart failure  Drug of choice in patients with left ventricular responds to these drugs. dysfunction without edema.  They precipitate acute decompensation of  First-line therapy for chronic heart failure cardiac function.  By reducing preload and afterload in  Mechanisms includes attenuation of the asymptomatic patients, ACE inhibitors adverse effects of high concentrations of (enalapril) slow the progress of ventricular catecholamines (including apoptosis), up- dilation and thus slow the downward spiral of regulation of beta receptors, decreased heart the heart failure rate, and reduced remodeling through inhibition of the mitogenic activity of ARBs catecholamines.  Are used to patients who cannot tolerate ACE Table 13-3 Classification and treatment of inhibitors. chronic heart failure. VASODILAT ORS ACC/AH NYHA Descriptio Management A Stage1 Class2 n A Prefailur No Treat obesity, VENODILATORS e symptoms hypertension, but risk diabetes, ISOSORBIDE DINITRATE factors hyperlipidemi present3 a, etc. JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 4  MODULE 1: Cardiovascular, Renal and Hematologic Pharmacology Pharmacology II  For patients with high filling pressures with REFERENCES dyspnea, helpful in reducing filling pressure Book: and the symptoms of pulmonary congestion. Katzung B.G. et al. Basic and Clinical Pharmacology, 14th edition Notes from the discussion of: ART ERIOLAR DILATOR Anna Liza D. JAMIAS, RPh. RN. Central Philippine University PowerPoint HYDRALAZINE presentation: College of Pharmacy  Used in patients whom fatigue due to low left ventricular output is the primary symptoms, and helpful in increasing forward cardiac output. BET A BLOCKERS AND IO N CHANNEL BLOCKERS BISOPROLOL, CARVEDILO L, MET OPROLOL, NEBIVOLOL  Therapy using these drugs are based on the hypothesis that excessive tachycardia and adverse effects of high catecholamine levels on the heart contribute to the downward course of heart failure. DIGIT ALIS  Indicated for patients with heart failure and atrial fibrillation.  Given only when diuretics and ACE inhibitors failed to control the symptoms MANAGEMENT OF ACUTE H EART FAILURE  Occurs frequently in patients chronic failure associated with: o Increased exertion o Increased emotion o Excess salt intake o Nonadherence to therapy or o Increased metabolic demand occasioned by fever, anemia, etc.  Treatment- intravenous treatment of the following: o Diuretics o Dopamine or Dobutamine o Levosimendan o Vasodilators o Conivaptan JACOMILLE, J.R.L.│BS IN PHARMACY 3– CPU│1ST SEM Page 5