BMS3-25 Antihypertansives, Antianginal drugs, drugs used to treat heart failure, anticoagulants, drugs used to treat hyperlipidemia, peripheral vasodilators-Assoc. Prof. Ahmet Özer ŞEHİR.pdf

DRUG AFFECTING THE CARDIOVASCULAR SYSTEM Doç. Dr. Ahmet Özer Şehirli LEARNİNG OBJECTIVES Describes of; Antihypertensive Drugs Antianginal Drugs Antiaritmic Drugs Congestive Heart Failure The Heart Introduction Hypertension > 140 mmHg > 90 mmHg *********************************************...

DRUG AFFECTING THE CARDIOVASCULAR SYSTEM Doç. Dr. Ahmet Özer Şehirli LEARNİNG OBJECTIVES Describes of; Antihypertensive Drugs Antianginal Drugs Antiaritmic Drugs Congestive Heart Failure The Heart Introduction Hypertension > 140 mmHg > 90 mmHg **************************************************** Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP) Types of Hypertension Essential Secondary A disorder of unknown origin affecting the Blood Pressure regulating mechanisms Secondary to other disease processes **************************************************** Environmental Factors Stress Na+ Intake Obesity Smoking Normal Blood Pressure Regulation • Hydraulic equation: Blood Pressure = Cardiac output (CO) X Resistance to passage of blood through precapillary arterioles (PVR) • Physiologically CO and PVR is maintained minute to minute by – arterioles (1) postcapillary venules (2) and Heart (3) • Kidney is the fourth site – volume of intravascular fluid • Baroreflex, humoral mechanism and renin-angiotensinaldosterone system regulates the above 4 sites Baroreceptor reflex arc • Postural baroreflex: The Renal response • Long-term blood pressure control – by controlling blood volume • Reduction in renal pressure - intrarenal redistribution of pressure and increased absorption of salt and water • Decreased pressure in renal arterioles and sympathetic activity – renin production – angiotensin II production • Angiotensin II: – Causes direct constriction of renal arterioles – Stimulation of aldosterone synthesis – sodium absorption and increase in intravascular blood volume HYPERTANSION VE ANTIHYPERTANSIVE DRUGS 1. Diuretics 2. Sympatholytics a) Centrally acting sympatholytic drugs b) Adrenergic neuron blockers c) Adrenergic receptor blockers C1)Alpha receptor blockers C2) Beta receptor blockers 3) Vazodilators a) Direct acting vasodilators b) Ca channel blocker 4) Angiotensin inhibitors a) Angiotensin Converting Inhibitors b) Angiotensin receptor blockers Antihypertensive Drugs • Diuretics: – Thiazides: Dichlotiazide, Hydrochlorothiazide, chlorthalidone – High ceiling: Furosemide – K+ sparing: Spironolactone, triamterene and amiloride MOA: Acts on Kidneys to increase excretion of Na and H2O – decrease in blood volume – decreased BP • Angiotensin-converting Enzyme (ACE) inhibitors: – Captopril, lisinopril., enalapril, ramipril and fosinopril MOA: Inhibit synthesis of Angiotensin II – decrease in peripheral resistance and blood volume • Angiotensin (AT1) blockers: – Losartan, candesartan, valsartan and telmisartan MOA: Blocks binding of Angiotensin II to its receptors Antihypertensive Drugs • Centrally acting: – Clonidine, methyldopa MOA: Act on central α2A receptors to decrease sympathetic outflow – fall in BP • ß-adrenergic blockers as the same time renin synthesis inhibitor: – Non selective: Propranolol (others: nadolol, timolol, pindolol, labetolol) – Cardioselective: Metoprolol (others: atenolol, esmolol, betaxolol) MOA: Bind to beta adrenergic receptors and blocks the activity • ß and α – adrenergic blockers: – Labetolol and carvedilol • α – adrenergic blockers: – Prazosin, terazosin, doxazosin, phenoxybenzamine and phentolamine MOA: Blocking of alpha adrenergic receptors in smooth muscles vasodilatation Antihypertensive Drugs (VASODILATORS)– • Calcium Channel Blockers (CCB): – Verapamil (Shouldn’t use congestive heart failure), diltiazem, nifedipine, felodipine, amlodipine, nimodipine etc. MOA: Blocks influx of Ca++ in smooth muscle cells – relaxation of SMCs – decrease BP • K+ Channel activators: – Diazoxide, minoxidil, pinacidil and nicorandil MOA: Leaking of K+ due to opening – hyper polarization of SMCs – relaxation of SMCs • Direct Effect Vasodilators: – Arteriolar – Hydralazine (also CCBs and K+ channel activators) Diuretics • The first option is used in conjunction with ACE inhibitors to treat hypertension. • Drugs causing net loss of Na+ and water in urine • Mechanism of antihypertensive action: – Initially: diuresis – depletion of Na+ and body fluid volume – decrease in cardiac output – Q: Why? Answer: reduction in total peripheral resistance (TPR) due to deficit of little amount of Na+ and water (Na+ causes vascular stiffness) Diuretics – adverse effects • Adverse Effects: – Hypercalcemia – – Hyperglycemia: Inhibition of insulin release due to K+ depletion (proinsulin to insulin) – precipitation of diabetes – Hyperlipidemia: rise in total LDL level – risk of stroke – Hyperurecaemia: inhibition of urate excretion – Hypovolemia – Hypokalemia – Hypomagnesemia – Hyponatremia Angiotensin Converting Enzyme (ACE) Inhibitors What is Renin - Angiotensin? (Physiological Background) RAS - Introduction • Renin is a proteolytic enzyme and also called angiotensinogenase • It is produced by juxtaglomerular cells of kidney • It is secreted in response to: – Decrease in arterial blood pressure – Decrease Na+ in macula densa – Increased sympathetic nervous activity • Renin acts on a plasma protein – Angiotensinogen (a glycoprotein synthesized and secreted into the bloodstream by the liver) and cleaves to produce a decapeptide Angiotensin-I • Angiotensin-I is rapidly converted to Angiotensin-II (octapeptide) by ACE (present in luminal surface of vascular endothelium) • Furthermore degradation of Angiotensin-II by peptidases produce Angiotensin-III • Both Angiotensin-II and Angiotensin-III stimulates Aldosterone secretion from Adrenal Cortex (equipotent) • AT-II has very short half life – 1 min RAS - Physiology Increased Blood Vol. Rise in BP Vasoconstriction Na+ & water retention Kidney (Adrenal cortex) RAS – actions of Angiotensin-II. 1. Powerful vasoconstrictor particularly arteriolar – direct action and release of Adr/NA release – Promotes movement of fluid from vascular to extravascular – More potent vasopressor agent than NA – promotes Na+ and water reabsorption – It increases myocardial force of contraction (CA++ influx promotion) and increases heart rate by sympathetic activity, but reflex bradycardia occurs – Cardiac output is reduced and cardiac work increases 2. Aldosterone secretion stimulation – retention of Na++ in body 3. Vasoconstriction of renal arterioles – rise in IGP – glomerular damage 5. Decreases NO release 6. Decreases Fibrinolysis in blood 7. Induces drinking behaviour and ADH release by acting in CNS – increase thirst 8. Mitogenic effect – cell proliferation Angiotensin-II • What are the ill effects on chronic ? – Volume overload and increased t.p.r • Cardiac hypertrophy and remodeling • Coronary vascular damage and remodeling – Hypertension – long standing will cause ventricular hypertrophy – Myocardial infarction – hypertrophy of non-infarcted area of ventricles – Renal damage – Risk of increased CVS related morbidity and mortality • ACE inhibitors reverse cardiac and vascular hypertrophy and remodeling ACE inhibitors • Captopril, lisinopril., enalapril, ramipril and fosinopril etc. Adverse effects • Cough – persistent brassy cough in 20% cases – inhibition of bradykinin and substanceP breakdown in lungs • Hyperkalemia in renal failure patients with K+ sparing diuretics, NSAID and beta blockers (routine check of K+ level) • Angioedema: swelling of lips, mouth, nose etc. • Rashes, urticaria etc • Contraindications: Pregnancy, bilateral renal artery stenosis, hypersensitivity and hyperkalaemia ACE inhibitors – other uses • • • • • Hypertension Congestive Heart Failure Myocardial Infarction Prophylaxis of high CVS risk subjects Diabetic Nephropathy Angiotensin Receptor Blockers (ARBs) Angiotensin Receptors: • Specific angiotensin receptors have been discovered, grouped and abbreviated as – AT1 and AT2 • They are present on the surface of the target cells • Most of the physiological actions of angiotensin are mediated via AT1 receptor • Transducer mechanisms of AT1 inhibitors: In different tissues show different mechanisms. – Losartan is the specific AT1 blocker Angiotensin Receptor Blockers (ARBs) • Competitive antagonist and inverse agonist of AT1 receptor • Does not interfere with other receptors except TXA2 • Blocks all the actions of A-II - vasoconstriction, sympathetic stimulation, aldosterone release and renal actions of salt and water reabsorption • No inhibition of ACE Angiotensin Receptor Blocker • Adverse effects: –Foetopathic like ACEIs – not to be administered in pregnancy –Rare 1st dose effect hypotension –Lower incidence of angioedema Beta-adrenergic blockers • Non selective: Propranolol (others: nadolol, timolol, pindolol, labetolol) • Cardioselective: Metoprolol (others: atenolol, esmolol, betaxolol) • All beta-blockers similar antihypertensive effects – irrespective of additional properties – Reduction in CO but no change in BP initially but slowly – Adaptation by resistance vessels to chronically reduced CO – antihypertensive action – Other mechanisms – decreased renin release from kidney (beta-1 mediated) – Reduced NA release and central sympathetic outflow reduction – Non-selective ones – reduction in g.f.r but not with selective ones – Drugs with intrinsic sympathomimetic activity may cause less reduction in HR and CO Beta-adrenergic blockers • Advantages: – No postural hypotension – No salt and water retention – Low incidence of side effects – Low cost – Once a day regime – Preferred in young non-obese patients, prevention of sudden cardiac death in post infarction patients and progression of CHF • Drawbacks (side effects): – Fatigue, lethargy (low CO?) – decreased work capacity – Loss of libido – impotence – Cognitive defects – forgetfulness – Difficult to stop suddenly – Therefore cardio-selective drugs are preferred now Beta-adrenergic blockers • Advantages of cardio-selective over non-selective: –In asthma –In diabetes mellitus –In peripheral vascular disease Αlpha-adrenergic blockers • Non selective alpha blockers are not used in chronic essential hypertension (phenoxybenzamine, phentolamine), only used sometimes as in phaechromocytoma • Specific alpha-1 blockers like prazosin, terazosin and doxazosine are used • PRAZOSIN is the prototype of the alpha-blockers • Reduction in t.p.r and mean BP – also reduction in venomotor tone and pooling of blood – reduction in CO Αlpha-adrenergic blockers. • Adverse effects: – Prazosin causes postural hypotension – start 0.5 mg at bed time with increasing dose and upto 10 mg daily – Fluid retention in monotherapy – Headache, dry mouth, weakness, dry mouth, blurred vision, rash, drowsiness and failure of ejaculation in males • Current status: – Several advantages – improvement of carbohydrate metabolism – diabetics, lowers LDL and increases HDL, symptomatic improvement in BHP – But not used as first line agent, used in addition with other conventional drugs which are failing – diuretic or beta blocker • Doses: Available as 0.5 mg, 1 mg, 2.5 mg, 5 mg etc. dose:14 mg thrice daily (Minipress/Prazopress) Calcium Channel Blockers Classification Calcium Channel Blockers – Mechanism of action • Three types Ca+ channels in smooth muscles – Voltage sensitive, receptor operated and leak channel • Voltage sensitive are again 3 types – L-Type, T-Type and N-Type • Normally, L-Type of channels admit Ca+ and causes depolarization – excitation-contraction coupling through phosphorylation of myosin light chain – contraction of vascular smooth muscle – elevation of BP • CCBs block L-Type channel: – Smooth Muscle relaxation – Negative chronotropic, ionotropic and chronotropic effects in heart • DHPs have highest smooth muscle relaxation and vasodilator action followed by verapamil and diltiazem • Other actions: DHPs have diuretic action Calcium Channel Blockers • Contraindications: –Unstable angina –Heart failure –Hypotension –Post infarct cases –Severe aortic stenosis Vasodilators - Hydralazine • Directly acting vasodilator • MOA: hydralazine molecules combine with receptors in the endothelium of arterioles – NO release – relaxation of vascular smooth muscle – fall in BP Vasodilators - Minoxidil • Powerful vasodilator, mainly 2 major uses – antihypertensive and alopecia • Rarely indicated in hypertension especially in life threatening ones • More often in alopecia to promote hair growth • Orally not used any more • MOA of hair growth: – Enhanced microcirculation around hair follicles and also by direct stimulation of follicles – Alteration of androgen effect of hair follicles Sodium Nitroprusside • Rapidly and consistently acting vasodilator • Relaxes both resistance and capacitance vessels and reduces t.p.r and CO (decrease in venous return) • Uses: Hypertensive Emergencies, 50 mg is added to 500 ml of saline/glucose and infused slowly with 0.02 mg/min initially and later on titrated with response (wrap with black paper) • Adverse effects: All are due release of cyanides (thiocyanate) – palpitation, pain abdomen, disorientation, psychosis, weakness and lactic acidosis. Centrally acting Drugs • Alpha-Methyldopa: a prodrug – Precursor of Dopamine and NA – MOA: Converted to alpha methyl noradrenaline which acts on alpha-2 receptors in brain and causes inhibition of adrenergic discharge in medulla – fall in PVR and fall in BP – Various adverse effects – cognitive impairement, postural hypotension, positive coomb`s test etc. – Not used therapeutically now except in Hypertension during pregnancy • Clonidine: Imidazoline derivative, partial agonist of central alpha-2 receptor – Not frequently used now because of tolerance and withdrawal hypertension – Read it yourself Treatment of hypertension Treatment of Hypertension: 7 classification Categories BP Systolic Diastolic Normal >120 <80 Prehypertension 120-139 80-89 Stage1 149-159 90-99 Stage2 >160 >100 Risk factors 1. Age above 55 and 65 in Men and Woman respectively 2. Family History 3. Smoking 4. DM and Dyslipidemia 5. Hypertension 6. Obesity 7. Microalbuminuria Treatment of Hypertension Angina pectoris • Sudden,severe,pressing chest pain starting substernal &radiate to left arm. • Due to imbalance between myocardium oxygen requirement and oxygen supply. • Risk factors : Age,sex,obesity.smoking,diabetes. ANGINA PECTORIS Severe constricting chest pain, often radiating from the precordium to the left shoulder and down the arm, due to insufficient blood supply to the heart that is usually caused by coronary disease Classification of angina 1. Exertional angina, Stable,Atherosclerotic,Classic, Due to obstruction of coronaries by atheroma. 2. Variant, Vasospastic angina due to Spasm of coronaries. 3- Unstable angina. Nitrates & Nitrites • Preparations : • 1- Short acting: • Start within few minutes and total duration of action 15-30 minutes. • A) Nitroglycerine (Glyceryl trinitrate) • Used as sublingual tablets. • B) Isosorbide dinitrate • As sublingual spray. • C) Amyl nitrite –Inhalation 2- Long acting • Nitroglycerine, Isosorbide dinitrate, • Isosorbide mononitrate,Erythrityl – • Tetranitrate. – Action of all start withen hours and continue for hours . • They are given : Orally,Ointment,Buccal,Transdermal patch,Parenteral. Pharmacological actions • Nitrates relax all types of smooth muscles vascular or non vascular . • Relax both arteries and veins but more effective on veins. • They have no direct effect on cardiac or skeletal muscles. • NO released stimulate guanylyl cyclase • In platelets causing increase cGMP that decrease platelet aggregation. • Decrease myocardial oxygen requirement and platelet aggregation. Adverse effects • • • • • • • • Orthostatic hypotension Throbbing headache Tachycardia Facial or cutaneous flushing Tolerance (Tachyphylaxis) Salt and water retention Carcinogenicity Methaemoglobinemia only with nitrities Contraindication • Nitrates are contraindicated in increase intracranial pressure. • Nitrates can be used safely in increase of intraocular pressure (Glucoma). Calcium channel blockers • 1- They block calcium entry in myocardium causing ; –A) decrease myocardium contractility & myocardium oxygen requirement. • B) decrease heart rate causing decrease in myocardium oxygen requirement. • 2-Block calcium entry in vascular smooth muscles (arterioles) causing • a)decrease in peripheral resistance( after load)------ decrease in oxygen requirement. • b)Relief of coronary spasm. Clinical uses • In all types of angina but very effective in variant angina . • Used mainly in prophylactic therapy. β-Adrenoceptor blocking drugs • They are not vasodilators • They are used in treatment of angina : • They decrease both heart rate & myocardial contractility that decrease in myocardial oxygen requirement at rest & in exercise so improve exercise tolerance. Clinical uses They are effective in the prophylactic treatment of classic & unstable angina. • They are not used in variant angina. • They are effective in treatment of silent or ambulatory angina (no pain ). • Decrease mortality of patients with recent myocardial infarction. • Potassium channel openers (Nicorandil ) –Activation of potassium channels. • • • • Nitric oxide release. Arterio & venodilators. Used as prophylactic therapy . May cause : Headache,flushing,dizziness. Drug treatment of angina • • • • • • • 1- Acute attack : Short acting nitrates or nitritis. 2- Prophylactic therapy ; Long –acting nitrates. Calcium channel blockers. β- adrenoceptors blockers. Potassium channel openers. Combination therapy • Nitrates and β-adrenoceptors blockers. • Calcium channel blockers and β-adrenoceptor blockers .? ? • Calcium channel blockers and nitrates. • Calcium channel blockers, β-adrenoceptor blockers, nitrates. Antiarrhythmic Drugs Or Doing Drugs for Your Heartbeat Arrhythmia • Heart condition where disturbances in – Pacemaker impulse formation – Contraction impulse conduction – Combination of the two Results in rate and/or timing of contraction of heart muscle that is insufficient to maintain normal cardiac output (CO) To understand how antiarrhythmic drugs work, need to understand electrophysiology of normal contraction of heart Antiarrhythmic drugs • Biggest problem – antiarrhythmics can cause arrhythmia! – Example: Treatment of a non-life threatening tachycardia may cause fatal ventricular arrhythmia – Must be vigilant in determining dosing, blood levels, and in follow-up when prescribing antiarrhythmics Therapeutic overview • • • • Na+ channel blockade β-adrenergic receptor blockade Prolong repolarization Ca2+ channel blockade • Adenosine • Digitalis glycosides Classification of antiarrhythmics (based on mechanisms of action) • Class I – blocker’s of fast Na+ channels – Subclass IA • • • • Cause moderate Phase 0 depression Prolong repolarization Increased duration of action potential Includes – Quinidine – 1st antiarrhythmic used, treat both atrial and ventricular arrhythmias, increases refractory period (antimalarial drug) – Procainamide - increases refractory period but side effects – Disopyramide – extended duration of action, used only for treating ventricular arrthymias Classification of antiarrhythmics (based on mechanisms of action) – Subclass IB • • • • Weak Phase 0 depression Shortened depolarization Decreased action potential duration Includes – Lidocaine (also acts as local anesthetic) – blocks Na+ channels mostly in ventricular cells, also good for digitalis-associated arrhythmias (Local anesthetic drug) – Mexiletine - oral lidocaine derivative, similar activity – Phenytoin – anticonvulsant that also works as antiarrhythmic similar to lidocane (antiepileptic drug) Classification of antiarrhythmics (based on mechanisms of action) – Subclass IC • Strong Phase 0 depression • No effect of depolarization • No effect on action potential duration • Includes – Flecainide (initially developed as a local anesthetic) » Slows conduction in all parts of heart, » Also inhibits abnormal automaticity – Propafenone » Also slows conduction » Weak β – blocker » Also some Ca2+ channel blockade Classification of antiarrhythmics (based on mechanisms of action) • Class II – β–adrenergic blockers – Based on two major actions 1) blockade of myocardial β–adrenergic receptors 2) Direct membrane-stabilizing effects related to Na+ channel blockade – Includes • Propranolol – causes both myocardial β–adrenergic blockade and membrane-stabilizing effects – Slows SA node and ectopic pacemaking – Can block arrhythmias induced by exercise or apprehension – Other β–adrenergic blockers have similar therapeutic effect • • • • • • • • Metoprolol Nadolol Atenolol Acebutolol Pindolol Stalol Timolol Esmolol Classification of antiarrhythmics (based on mechanisms of action) • Class III – K+ channel blockers – Developed because some patients negatively sensitive to Na channel blockers (they died!) – Cause delay in repolarization and prolonged refractory period – Includes • Amiodarone – prolongs action potential by delaying K+ efflux but many other effects characteristic of other classes • Ibutilide – slows inward movement of Na+ in addition to delaying K + influx. • Bretylium – first developed to treat hypertension but found to also suppress ventricular fibrillation associated with myocardial infarction • Dofetilide - prolongs action potential by delaying K+ efflux with no other effects Classification of antiarrhythmics (based on mechanisms of action) • Class IV – Ca2+ channel blockers – slow rate of AV-conduction in patients with atrial fibrillation – Includes • Verapamil – blocks Na+ channels in addition to Ca2+; also slows SA node in tachycardia • Diltiazem • Those used in the treatment of bradyarrhythmias (atropine, adrenaline, isoprenaline, oksprenal, ephedrine) Used in the treatment of bradycardia. Drugs used in Heart Failure But, first, some muscle review! Regulation of cardiac myocyte Ca2+ flux Regulation of cardiac contractility by β-adrenerg receptors Cellular Mechanisms of Contractile Pathophysiology Drugs used in Heart Failure • Heart failure: insufficient cardiac output to adequately perfuse the tissues, despite normal filling of the heart. • Congestive heart failure: combined right and left heart failure to produce pulmonary congestion and peripheral edema. • Causes: hypertension, valvular disease, cardiomyopathy, and most commonly, coronary artery disease. Drugs used in Heart Failure • Low cardiac output increae SNS activity  stimulates the rate and force of the heart beat and maintains bp by incr vascular resistance. • In the failing heart, this afterload further decrease cardiac output. • The resultant decrease renal blood flow renin secretion and increase plasma and angiotensin and aldosterone levels  • Na+ and H2O retention increase the blood volume and bpincrease Pressure (edema). • Lead to abnormal ventricular dilation that increase morbidity and mortality. • • • • • • Inotropic Drugs (Strophantin K, Digoxin, Digitoxin) Digoxin – a cardiac glycoside extracted from foxglove leaves (Digitalis sp) is the most important inotrope. Increase the contractile force. Particularly indicated in patients with atrial fibrillation. Inhibits the Na+/K+-ATPase, which is responsible for Na+/K+ exchange across the muscle cell membrane increase [Na+]inincrease [Ca2+]inincrease force of myocardial contraction. Digoxin and K+ ions compete for a “receptor” (Na+/K+ATPase) on the ext membrane. So, the effects of digoxin may be dengerously increase by hypokalemia, produced, for example, by diuretics. Positive Inotropic Mechanism of Digoxin Inotropic Drugs • Indirect Effects: – Digoxin increase vagal activity and faciliates muscarinic transmission to the heart. This… i. Slow HR ii. Slows atrioventricular conductance. iii. Prolongs the refractory period of the atrioventrivular node. Effects on Other Organs: Digoxin may cause anorexia, nausea, vomiting or diarrhea by affecting the smooth muscle of the gut. Inotropic Drugs • Toxicity: -Digoxin toxicity is quite common because arrhythmias can occur at concentrations that are only 2-3 x that of the optimal therapeutic dose. - Treatment may entail K supplements, antiarrhythmic drugs (lidocaine or phenytoin) or even digoxin-specific Ab fragments (Fab). Sympathomimetic Agents • Activate cardiac β-receptors  AC cAMPphosphorylation of L-type Ca2+ channels (opens) increase [Ca2+]influx and the force of myocardial contraction. • Dobutamine used in acute severe HF. • Dopamine incr renal perfusion by stimulates dopamine receptors in the renal vasculature. Drugs used in Heart Failure (cont’d) • Treatment of mild HF usually starts with an angiotensin converting enzyme (ACE) inhibitor. - decrease load on the heart. - decrease symptoms. - slow disease progression. - prolong life. The other drug is Amrinone (phosphodiesterase enzyme inhibitör) β-Receptor Antagonists (β Blockers) • Acutely, β-blockers can decrease myocardial contractility and worsen HF. • Long-term, however, administration has been shown to improve the survival of stable patients with HF (blocking the damaging effects of overactive sympathetic activity). • Start with a low dose and gradually incr over wks.. • Carvedilol, bisoprolol, and metaprolol, given with an ACE inhibitor and diuretic for ~1 yr has been shown to reduce mortality from 11-17% to 712%. DRUGS USED IN TREATMENT HYPERLIPIDEMIA • Coronary heart disease is the formation of the height of the biggest factors in cholesterol levels. The reduction of elevated plasma cholesterol level decreases the rate of progression of atherosclerotic disease in the long term and acute coronary events (angina pectoris, acute MI) also reduces the development. DRUGS USED IN TREATMENT HYPERLIPIDEMIA • Lipid-lowering drugs HMG CoA reductase inhibitors are atorvastatin, fluvastatin, lovastatin, simvastatin. These drugs are involved in the synthesis of cholesterol in liver β-hydroxy-β-methylglutaryl coenzyme A reductase and inhibit cholesterol synthesis by blocking the enzyme. They also provide clearance of LDL particles from circulation by increasing the number of LDL receptors. Side Effects: Myopathy DRUGS USED IN TREATMENT HYPERLIPIDEMIA – Bile acid binding resins: fenofibrate, gemfibrosil, colestipol, cholestyramine. After oral ingestion of these drugs are not connecting the absorption of bile acids from the liver by blocking the entrance to their enterohepatic cycles provide the faeces disposal. Thus, the liver converts cholesterol into bile acids to improve the reduced bile concentration. Side Effects: Constipation, bloating sensation, heartburn and diarrhea ANTICOAGULANT DRUGS • Heparin: Inhibits the clotting factors. Used in the prevention of deep vein thrombosis and pulmonary embolism. Only parenteral use. Venous thrombosis prophylaxis is used in open heart surgery and during hemodialysis. I.v. infusion (40,000 units heparin in 500 ml of 5% glucose solution), iv injection (10,000 units every 6 hours) or sc (2x500 unit) applicable ways. Prophylactic continuous i.v. infusion i.v. Injections can be made. HEPARIN Before the surgery, the s.c lines given in low doses. Don’t used as a im. Excessive bleeding as a side effect, osteoporosis (loss of bone tissue Ca ++) make a temporary hair loss. In allergic people, head trauma undergoing active tuberculosis and used in a new operation. When bleeding occurs, the drug cut to 1-1.5 mg of protamine sulfate and 100 units of heparin (protamine: heparin antagonist) IV slowly Injections can be . ORAL ANTİCOAGULANTS Only used orally. After 2-3 days after starting the drug began to be given effect; It continues until a few days after discontinuation of the drug. They prevent the biosynthesis of certain clotting factors, vitamin K formed through the body. Only has an effect in vivo. There is no in vitro activity. It increases sensitivity to these drugs in the following cases: Vitamin K deficiency, Hyperthyroidism Congestive heart failure, Elderly patients Alcoholics and those with liver disease. Antithrombotic Drugs • Aspirin: Prevents platelet aggregation. Side Effects: GI ulceration, bleeding, hemorrhage • Dipyridamole: prevents platelets aggregation. Side Effects: GI disorders, dizziness, headache • PGI2: incidence of thrombus formation decreases. Angina, pulmonary hypertension used. Side Effects: GI disturbances, headache, dizziness Thrombolytic Drugs • Streptrokinase, urokinase, Anistrepiase, TPA (tissue plasminogen activator): Fibrin and fibrinogen stimulates the degradation of those. After infarction, ischemia, coronary artery thrombosis in the pulmonary embolism, deep vein thrombosis used. • Side Effects: Bleeding, rarely anaphylactic reactions Peripheral vasodilators Peripheral vasodilators, peripheral arteries and arterioles are connected to the narrowing and blockages used in the treatment of local circulatory failure. This circulation failure are; Vasospastic diseases; The resulting increase in sympathetic tone due to local spasms of the vessels develop local ischemia. For example, Raynaud's syndrome Developing organic lesions as a result of the blockage in the artery wall; Lipid accumulation in the artery wall, intimal thickening, plaque formation and thrombus development in the injured endothelial vessel lumen narrows and clogs. Nylidrin Skeletal muscle activates beta-adrenergic receptors in blood vessels. Progressive angina pectoris heart also warned that should not be used in acute myocardial infarction and paroxysmal tachycardia. Papaverine It is an alkaloid found in opium poppy. Large vessels are relaxed, not addictive. It decreases the total peripheral vascular resistance. I.v. When used with quinidine-like effects can lead to death. Dipyridamole Vasodilator effects and are smooth muscle relaxants. References – Prof. Dr. S. Oğuz Kayaalp, Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 10. Baskı, Hacettepe Taş, 2002. – Bertram G. Katzung, Basic&Clinical Pharmacology, 7th edition, Appleton&Lange, 1998. • Roger L. Royster, MD • John F. Butterworth IV, MD • Leanne Groban, MD • Thomas F. Slaughter, MD • David A. Zvara, MD. Cardiovascular Pharmacology • https://www.slideshare.net/rezahei/cardiovascular-pharmacology76647530 • https://www.slideshare.net/crisbertc/cardiovascular-drugs