Pharmacotherapy of cardiovascular diseases -MUDr. Alena Machalová, Ph.D., Department of Pharmacology Tato prezentace je autorským dílem vytvořeným zaměstnanci Masarykovy univerzity. Studenti předmětu ZLFA0722p mají právo pořídit si kopii prezentace pro potřeby vlastního studia M i' li I MED Cardiovascular diseases = diseases of heart and blood vessels! Are closely connected to other disorders (atherosclerosis, dyslipidaemia, obesity, hypertension...) Pharmacotherapy is usually complex and drugs from many classes are used in combinations Risk factors Given: age, gender, genetic disposition Changeable: atherosclerosis, hypertension, dyslipidaemia/hyperlipoproteinaemia, smoking, diabetes mellitus, obesity, bad eating habits, stress... Risky is ILDL-concentration, j, HDL- concentration It is important do pay attention to those factors, which can be changed M li li I MED COMPLEX THERAPY of CVS diseases Diagnoses morphin IHD Hypertension Related risk factors Dyslipidaemia -1-1 Hypertension i Risk of thrombosis Drugs Heart failure chronic, acute ANTIARRHYTMICS INOTROPICS ANTIHYPERTENSIVES HYPOLIPIDEMICS ANTITHROMBOTICS Pharmacotherapy is usually complex and drugs from many classes are used in combinations MED COMPLEX THERAPY of CVS diseases Diagnoses morphin I IHD isk factors Dyslipidaemia Risk of thrombosis Drugs Dysrrhytmia Heart failure chronic, acute Hypertesion ANTIARRHYTMICS INOTROPICS ANTIHYPERTENSIVES HYPOLIPIDEMICS ANTITHROMBOTICS Pharmacotherapy is usually complex and drugs from many classes are used in combinations It'll HI MED DYSLIPIDEMIA together with HYPERTENSION are the main factors in development of ATHEROSCLEROSIS Atherosclerotic plaque obstructs the vessel ■=> IHD If ruptured, consequenting thrombus may occlude the vessel ■=> AMI, stroke 5 M Ii II I MED RISK OF THROMBOSIS Anticoagulants Antiaggregants Fibrinolytics ANTITHROMBOTICS Thrombus prophylaxis (usually in venous vessels) heparin, nadroparin, dabigatran, apixaban warfarin Thrombus prophylaxis (usually in arteries) ASA, Clopidogrel Dissolution of formed thrombus (arteries and veins) alteplase, reteplase M Ii II I MED HYPOLIPIDEMICS PYSLIPIPEMIAS Some of the most often metabolic disorders CHOLESTEROL i Hypercholesterolemia s, Combined hyperlipoproteinemia hyperlipidemia NON-PHARMACOLOGICAL APPROACH ■ Diet regimen with restriction of animal fat ■ Healthy life-style (no smoking, regular exercise) TRIGLYCERIDES T Hypertriglyceridemia S Primary Geneticaly determined S Secondary Result of another disease HYPOLIPIDEMICS Decreasing plasma CHol (LDL) — Decrease of intestinal (re)absorption of bile acids/cholesterolu RESINS, EZETIMIB — Inhibition of CH and VLDL synthesis ([STATINS} — ^Increase density of membrane LDL receptors PCSK9 inhibitors Decrease of plasma TG — InfliJPQTP synthesis of VLDL and conversion of plasma lipoproteins CnBRATES)STATINS (INDIRECTLY) — Gene therapy 3 x 1012 genome copies of human lipoprotein lipase in a viral vector to treat hyperlipoproteinemia I Glybera 1st choice drugs in all types of dyslipidaemia are STATINS!! IUI 0 III STATINS 1st choice drugs in atherosclerosis Mo A - competitive inhibitors of HMG-CoA reductase (hydroxy methyl glutaryl Co A reductase) + significant antiinflammatory effect -> 1^ LDL clearence ■ pleiotropic (extralipid) statin effects: ■ antiinflammatory !!! ■ antiaggregant ■ positive effects in endothelial dysfunction AE: liver disorders: t activity of transaminases and kreatinkinase (monitoring is necessary!) ■ Myalgia, rhabdomyositis (0,5% of pacients) can lead to rhabdomyolysis and kidney failure (most often after combination with FIBRATES and CYP3A4 inhibitors) ■ interactions!! ■ simvastatin, atorvastatin ■ lovastatin, fluvastatin, pravastatin, rosuvastatin (long acting) M U íl I MED FIBRATES MoA: agonists of nuclear PPAR-a rec. (peroxisome proliferator-activated receptors)- inhibit liver production of VLDLand 1s catabolism of VLDL -> decrease export of TG to peripheral tissues I: isolated hyper TG-emia (when resistant to statin) AE: nausea, vomiting, risk of bile stones (ŤCH in bile), myalgia (dangerous is myositis or rhabdomyolysis) fenofibrate ciprofibrote, bezafibrate ANTIHYPERTENSIVES HYPERTENSION • repeatedly increased blood pressure (BP) 140/90 mm Hg at least at 2 out of 3 measurements taken at least at two separated visits at the doctor • prevalence in adult population 20-30 % WHY TREAT HYPERTENSION AS IT IS NOT PAINFUL? Vessels Heart Brain Kidneys Retinas 4 4 14 4 Endothelium AMI, HF Stroke Chronic KF Loss of dysfunction fuction M ii III MED Classification of arterial hypertension according to etiology • primary (esencial) - about 95 % of all patients with hypertension; multifactorial disease without identified cause • secondary - disease with identified cause - nephrogenic - most often, kidney diseases - renovascular - narrowing of renal artery - endocrine - adrenal or thyroid glands disease - drug-associated hypertension - chronic therapy by corticoids, NSAID, hormonal contraception - hypertension in pregnancy M y || i M E U Therapy of arterial hypertension Aim: BP under 140/90 mm Hg in patients with | CV risk DM under 130/85 mm Hg Non-pharmacological approach: • Lifestyle changes - smoking, alcohol, medications • Aerobic exercise, no isometric load • Increase amount of nonsaturated FA, Ca++, K+ • Body weight Pathophysiological causes ■ P=R.Q ■ Change in peripheral resistence (R) ■ Q - cardiac output ■ Increased circulating volume ■ Increased contractility ■ (Increased heart rate) Farmacotherapy of hypertension 1. ACE-inhibitors (ACE-I) 2. angiotensin II receptor blockers 3. Ca++ channel blockers 4. diuretics Some of these drug 5. betablockers classes are used also in therapy of renin inhibitors ■ IHD 6. ■ Arrytmias 7. drugs acting centrally ■ Chronic HF 8. alpha-blockers 9. drugs with direct vasodilatant mechanism ANTIHYPERTENSIVES • act on three effector locations (heart, vessels, kidney) influence medium and long-term mechanisms of BP regulation ||J| IJ [J { MED ACE-inhibitory (ACEi) 1st choice drugs MoA: 1) reversible ACE inhibition I/) 2) bradykinin degradation blockade (vasodilation) < ^ Captopril, Perindopril fci) I- Angiotensin II receptor blockers (sartans) MoA: Competitive antagonists on AT1 1st choice druSs valsartan, losartan Renin inhibitors (kirens) 2nd choice! MoA: bind to the active site of renin and inhibit the binding of renin to angiotensinogen, which is the rate-determining step of the RAAS cascade aliskiren IUI U N I MED Common pharmacodynamic effect of ACEi and sartans - decrease in peripheral vessels resistance - (via low AT1 stimulation or f bradykinin) - decrease intravascular volume - specific dilatation of vas efferens - positive glycometabolic effects - antiproliferative activity ACEi Kinetics: liver microsomal metabolisms (enalapril = prodrug) VARIABILE HALF-LIFE (Captopril vs Perindopril) AE: - hypotension, hyperkalemia - decrease degradation of several small neuropeptides (bradykinin) —► dry cough -angiooedema CI: - pregnancy, breast-feeding - primary hyperaldosteronism rill MED ACEi Indications: - hypertension - heart insufficiency -AMI —> Significant decrease in mortality rate in AMI, CVD 1st choice in: -state after AM I, CVA - remodelation of heart and vessels - LV hypertrophy, heart failure - DM Sartans Angiotensin II receptor blockers Kinetics: variable AE, indications, CI: the same as ACEi BUT NO cough!! Losartan, valsartan Renin inhibitors - kirens AE: Hypotension Diarrhoea Angiooedema 2nd choice! aliskiren We do not combine drugs acting on RAAS! (ACEi+sartans in patients with diabetic nephropathy) M ii III MED Calcium channel blockers Mo A: specifically block L-channel in heart and vessel muscle cells Smooth musscle cells (vessels, bronchi, GIT, uterus) ■=> decrease in peripheral resistence Electrical conduction system of the heart (SA, AV node) ■=> negative chronotropic, dromotropic and inotropic effect affect mostly vessel smooth muscle (= are vasoselective) ■=> do not influence myocard, decrease blood pressure Antihypertensives (monotherapy as well as in combinations) Calcium channel blockers Mo A: specifically block L-channel in heart and vessel muscle cells Smooth musscle cells (vessels, bronchi, GIT, uterus) ■=> decrease in peripheral resistence Electrical conduction system of the heart (SA, AV node) ■=> negative chronotropic and inotropic effect strong effect also on electric activity of heart incl coronary vessels Antiarrhytmics Angina pectoris (I H D) MED Calcium channel blockers Dihydropyridines - affect mostly vessel smooth muscle 1. generation - lower vasoselectivity, shorter effect nifedipin 2. generation - higher vasoselectivity, longer effect nitrendipin (fast onset), felodipin, isradipin, nisoldipin, nilvadipin, nimodipin 3. generation - antiatherogenic effects, long effect amlodipin a CAVE - CCB have negative inotropic effect! # > not in decreased function of LV > not to be combined with other negatively inotropic drugs (BB) Non-dihydropyridines - strong effect also on electric activity of heart diltiazem .... „ T verapamil IUI * mA MED Calcium channel blockers PK: variable bioavailability variable half-life (e.g. nifedipin vs. amlodipin - 2 vs. 40 h) CYP metabolisation AE: gum hyperplasia oedema, hypotension, headache bradykardia (Non-DHP), reflexive tachycardia (DH pyridines) negative inotropic effects constipation I: hypertension angina pectoris local vasodilation in interventions (i.a. application) tachyarytmia (non-dihydropyridines) CI: AV block, heart failure (verapamil, diltiazem) tachykardia (DH pyridines) Diuretics and aldosterone antagonists - drugs increasing excresion of water and Na+ - act in tubular system of kidneys acetazolamide Thiazide diuretics/distal hydrochlorothiazide, indapamid Loop diuretics furosemide Potassium-sparing diuretics amiloride Aldosterone antagonists spironolaktone, eplerenone mannitol MED Thiazides Inhibit resorption of Na and CI in distal tubulus. ■=> inhibition of water resorption ■=> increased diuresis, (up to 12 h) + vasodilation Hypotensive effects with delay 3-4 days, full clinical effect (in 3-4 w). The most often prescribed diuretics (HT, HF). hydrochlorothiazide, indapamide Insufficient efficacy when impaired kidney function ■=> loop diuretics are indicated Loop diuretics Inhibit co-transport of Na/K/2CI in thick ascending loop of Henle —► decrease interstitial osmolarity —► decrease water reabsoption from lumen —> increased diuresis The strongest, short effect + vasodilatant efficacy Lots of AE: loss of ions (Na, CI, K, Ca, Mg), possibly hepato-, nephro-, ototoxic I: HT, lung oedema, congestive heart failure, hypercalcemia, chronic renal failure furosemide ARE VERY EFFECTIVE (even in kidney insufficiency), BUT BIG LOSS OF IONS Risk of activation of RAAS M ii li 1 Potassium-sparing diuretics Aldosterone antagonists Inhibit resorption of Na in collecting ducts weaker effects, lower loss of K+, suitable for combinations I: Rezistant hypertension and hyper-aldosteronismus amiloride Potassium-sparing diuretic Aldosterone antagonist spironolakton Increased diuresis ■ Na+ goes out ■ K+ stays in positive effects on remodelation —► in heart failure also in monotherapy AE: gynekomastia, menstruation problems eplerenon (selective for mineralocorticoid rec) M ii Ii I MED Carboanhydrase inhibitors / proximal diuretics Act in proximal tubule Mo A: Inhibit carboanhydrase ■=> Increase excretion of Na+ and water ■=> Urine is more alcalic ■=> Metabolic acidosis INDICATIONS: • glaucoma • altitude sickness • metabolic alkalosis • epilepsy acetazolamide Osmotic diuretic Act in the whole nephron Mo A: cannot be reabsorbed and cause leads to hyperosmolarity of filtrate INDICATIONS: ■ Forced diuresis ■ Increased intraocular presuure, ■ Acute renal failure mannitol 31 Not used in therapy of HT M Ii II I MED Diuretics General characteristic: Advantages: usually possible combination with others AHT potentiation of other AHT effects no influence on CNS cheap Disadvantages: metabolic effects low tolerance (in elderly people) Diuretics General characteristic: AE: potassium depletion (except K+ sparing) hyperurikemia (thiazides, loop diuretics) weakness, nausea dysbalance in glycid and lipid metabolism (thiazides) hypovolemia, hypotension (furosemid) hyperkalemia, hypomagnezemia (amilorid, spironolakton) CI: gout (thiazides) renal failure, hyperkalemia (K+ sparing) Relative: pregnancy, metabolic syndrome Diuretics General characteristic: potassium de All AE are strongly dose-dependent hyperurikemi; ^ If possible, the lowest effective doses are weakness, ric preffered dysbalance ir ^ Usually combined with other AHT hypovolemia, hypotension (furosemid) hyperkalemia, hypomagnezemia (amilorid, spironolakton) CI: gout (thiazides) renal failure, hyperkalemia (K+ sparing) Relative: pregnancy, metabolic syndrome Diuretics-INDICATIONS 1. HYPERTENSION ■ combined therapy (thiazides, potassium-sparing) ■ kidney failure (loop diuretics) ■ in resistant hypertension (Aldosterone antag.) 2. HEART FAILURE ■ Chronic HF (thiazides, potassium sparing, loop d.) 3. FORCED DIURESIS (loop, osmotic) 4. OEDEMAS (loop, osmotic) 5. HYPERKALEMIA (loop) 35 MUNI MED Betablockers MoA: block adrenergic reactions provided by activation of p receptors (CV effect mostly by PJ. Act as competitive antagonists of noradrenaline, dopamine and adrenaline. Antihypertensive effects: ■ targeting RAAS (inhibitit release of renin) ■=> decrease of volume ■ decrease of HR and cardiac output "1 antiischemic effects ■ decrease of 02 consumption J Final BP levels are reached in 14 days of therapy!! They have most AE of all 1st choice drugs (especially in young patients) M ii li 1 MED Betablockers ■ Lipofility /hydrof ility ■ Selectivity ■ Parcial agonistic activity ■ Other effects ( eg. a -rec blockade, direct vasodilatant eff...) Bradines (ivabradine) Alternative to betablockers Mo A: Inhibit Na/K chanell (lf current) in SA node. Negative chronotropic effect Classification by selectivity NON-SELECTIVE ß, + ß2 rec W/0 ISA Sotalol (antiarrytmic) timolol antiglaucomatic WITH ISA Carteolol antiglaucomatic Not used in CV therapy CARDIOSELECTIVE ß1 rec w/o ISA metoprolol atenolol esmolol t1/2 = 2-10 min. WITH ISA acebutolol nebivolol t1/2= 30-50 hod + mild vasodilatant 1 Celiprolol = ß-,, a1, a2, vasodilatation (ß2 ISA) labetalol, Carvedilol = ß2, a1 Beta blockers with combined effects Apart from ßi and ß2 act on ■ a,- rec, Ca2+ channels ■ antioxidant eff. Carvedilol I: hypertension, IHD, HF labetalol I: severe hypertension (i.v.) in pregnancy (from the i. trimester) Beta-blockers I: HT AP arytmia chronic heart failure (cave!) glaucoma, tremor CI: asthma AV block CHOPD (relat.) bradycardia DM (relat.) difficult erection (some) Abused by athletes! AE: Negative influence on lipid and glycid metabolism ■ bronchospasm (non-selective) ■ disrupted peripheral circulation (non-selective) ■ bradyarrhytmia (BB without ISA) ■ insomnia, sedation, depression (lipofilic BB) rebound phenomenon fj| |J [j j M E 8 <■ Beta-blockers Individual choice of drug: Older patient Younger patient IHD, AMI IHD, AP DM II. pregnancy bradycardia under 50 heart failure IDLE hyperliproteinemia HT during surgery (31 or with ISA NS not with strong ISA BB generally suitable more than others low doses P-,, with ISA p1? alpha+beta withdraw BB (or with ISA) carve,bisopr,metopr p1? with ISA, vasodil. with ISA esmolol MUNI MED Farmacotherapy of hypertension 1. 2. angiotensin II receptor blockers 3. Ca++channel blockers Some of these drug classes are used also 6. renin inhibitors 7. drugs acting centrally in therapy of ■ IHD ■ Arrytmias ■ Chronic HF 8. alpha-blockers 9. drugs with direct vasodilatant mechanism ANTIHYPERTENSIVES • act on three effector locations (heart vessels, kidney) influence medium and long-term mechanisms of BP regulation ||J| IJ [J { MED Centrally acting antihypertensives Imidazoline receptor agonists imidazoline I., receptor in medulla oblongata I.,- in CNS and kidney l2- pain modulation, neuroprotection l3 - insulin secretion Unlike central cu-agonists ■ DO NOT CAUSE sedation ■ rebound fenomenon I heart + vessels + kidney stimulation by sympathetic NS I renin and vasopressin secretion great positive effect on glycaemia and insulin resistance moxonidine rilmenidine M K Ii I MED Centrally acting antihypertensives Central a2 agonists a -metyldopa - false precursor of NA + a2 stimulation Indicated in pregnancy Clonidine - 012 stimulation, sedation, strong rebound phenomenon Indicated in hypertension crisis (ICU) Central a2 agonist + peripheral ai antagonist Urapidil - very strong anti HT Alpha blockers - selective reversible a,-lytics - no effect on a2rcp. - do not increase NA - advantageous effects in prostate hyperplasia AE: postural hypotension especially after 1st dose (prazosin) —► start with lower dose given in the evening before sleep I: monotherapy in BHP combination in hypertension prazosin doxazosin terazosin Urapidil Direct vasodilatators Calcium channel blockers were Nitrates discussed earlier 1st choice in angina pectoris, J, chronic efficacy Using free SH- groups (from glutathion) they cause release of NO in endothelium (EDRF) —► vasodilation —► antithrombotic action AE: Tachyphylaxis!, headaches, orthostatic hypotension nitroglycerine - for acute attacks natrium nitroprusside - for acute attacks isosorbid dinitrate (ISDN) - infusion in HT crisis, prophylaxis isosorbid 5-mononitrate (ISMN) - active metabolite, chronic AP molsidomin - different structure, fibrinonolytic minoxidil - vasodilatatory and prevention of hair loss M Ii II I MED ANTIARRHYTM ICS COMPLEX THERAPY of CVS diseases Diagnoses morphin IHD I Hypertension Dysrrhytmia Risk factors Dyslipidaemia Risk of thrombosis Drugs Hypertesion Heart failure chronic, acute ANTIARRHYTMICS INOTROPICS ANTIHYPERTENSIVE? HYPOLIPIDEMICS ANTITHROMBOTICS Pharmacc oerapy is usually complfiK and drup from many classes are used in combinations 1-1 U II I MED ANTIARRHYTMICS 1. Classification by Vaughan Williams Classes I. (A,B,C) II, III, 2. Others AA Catecholamines, digoxin, atropine,...... Drugs, which DIRECTLY or UN DIRECTLY affect electrophysiological processes on membranes, thus influecing generation and lenght of action potential. Ail 48 MED ANTIARRHYTHMIC DRUG CtASS DRUG PRIMARY MECHANISM OF ACTION* Class IA Quinidine, procainamide, disopyramide Na+ channel blocker, prolongs action potential duration (APD) Class IB Lidocaine, mexiletine Na+ channel blocker, rapid dissociation Class IC Flecainide, propafenone Na1 channel blocker, slow dissociation Class II Propranolol, Sotalol, esmolol (3 Adrenergic blocker Class III 1 Amiodaroneiotaiol, ibutilide, dofetilider dronedarone Prolongs APD (primarily by K' channel blockade) Class IV Verapamil, diltiazem Ca;+ channel blocker (nondihydropyridine) Miscellaneous Adenosine Adenosine receptor agonist Miscellaneous ^^^^ Na\ K'-ATPase inhibitor M Ii Ii I MED Class I 5 (weak); lidocatoe, meKiietine \c (strong): ttecainldeH propafenone Class W Calcium-channel blocker Verapamil Dilliszen ClaK III Potassium-channel blacker Amiodaron e Sotafel Beta-blocker Propranolol Metoprolol MUNI MED Amiodarone - Mo A: K+ ion channels block ADVERSE EFFECTS Dose-depentent frequency 1. MoA ■ Imparied trasmission of signal ■ negative inotropic eff. 2. Specific AE ■ fotosenzitisation (10%) ■ irreversible lung fibrosis 3. Effects on thyroid ■ HYPOTHYREOSIS (10%) ■ THYREOTOXIKOSIS (rare) INDICATION ■ Prophylaxis of fibrilation or flutter of atrium (in CHF) ■ Pharmacological cardioversion of fibrilation or flutter of atrium Highly lipofilic ■=> accumulates in liver and body fat Very long half-life Lots of interactions (P-g/p., CYP) IUI ■> il I MEG DigOXin - Heart glycoside kardiotonic + antiarrhytmic drug ■ Activates parasympaticus via nervus vagus ■=> antiarrhytmic effects ■=> negative chronotropic eff ■ Inotropic effect is caused by inhibition of Na/K ATP-ase pump ■=> positive inotropic eff INDICATION; ■ CHF (positive inotropic eff) ■ Arrhytmia (atrial fibrillation with fast response) Narrow therapeutic window (TDM) Large volume of distribution Renal elimination Lots of interactions (P-glp.) AE: inhibiction of Na/K pump in myocardium, CNS and GIT AV blockades, sinus bradycardia, excitability Weakness, depression, halucinations, yellow color perception Nauzea, vomiting, diarrhoea, sweating Digitalis intoxication yum ME J COMPLEX THERAPY of CVS diseases Diagnoses morphin IHD I Hypertension Dysrrhytmia Risk factors Dyslipidaemia Risk of thrombosis Drugs Heart failure chronic, acute Hypertesion ANTIHYPERTENSIVES HYPOLIPIDEMICS ANTITHROMBOTICS Pharmacotherapy \r usually compJex and drugs from rrr mbinations INOTROPICS HI U M I MED DRUGS WITH POSITIVE INOTROPIC EFFECT Heart glycosides (cardiotonics) DO NOT INCREASE FREQUENCY Chronic HF Catecholamines Inhibitors of PDE-3 Calcium sensitisers INCREASE FREQUENCY, EXCITABILITY AND CONDUCTION Acute HF INOTROPICS Heart glycosides (cardiotonics) digoxin Catecholamines adrenaline, dobutamine, noradrenaline, dopamine Inhibitors of PDE-3 milrinone Calcium sensitisers levosimendan DRUGS WITH POSITIVE INOTROPIC EFFECT MoA: inhibition of Na/K ATP-ase pump "=> influx of Ca2+ into sarcoplasma MoA: stimulation of p rep. ■=> indirect effect on Ca2+ influx MoA: specific blockade of phosphodiesterase -3 in myocardium O bloc degradation of cAMP O cardiostimulation MoA: strogner binding of myofilaments to troponin C o increased contractility M11 li I MED Conclusions MUNI MED Pharmacotherapy of hypertension 1. Non-pharmacological approach 2. Hypertension is often accompanied by other CV diagnoses (combined therapy) 3. Antihypertensives of the 1st choice, alone, or in combinations O RAAS Inhibitors ■=> Ca channels blockers ■=> Diuretics, betablockers.... M ■> ii I MED Pharmacotherapy of IHD (dyslipidemia, hypertension, obesity, DM2, thrombosis prevention) «=> NITRATES and NO donors ■=> Dihydropyridines (in case of present hypertension) Decreasing metabolic demands of the heart ■ decrease of workload (negative chronotropic, dromotropic ef) ■ prolong oxygen delivery to myocardium (longer diastole) ■—1\ slower frequency O BETABLOCKERS * and conduction ^> Non-dihydropyridines Pharmacotherapy of chronic HF 1. Decrease water retention Inhibition of RAAS DIURETICS ACEi, sartans 2. Decrease myocardium remodelation 3. Increase myocadrium contractility ■=> digoxin 4. Decrease peripheral resistence ■=> Vasodilatants 5. Optimalisation of frequency and sympathetic activity ■=> 6. Therapy of arrhytmias Beta blockers digoxin, amiodarone Pharmacotherapy of acute HF 1. Acute oedemasO DIURETICS - furosemide i.v. 2. Hypertension crisis ■=> Vasodilatants - nitroglycerin i.v., ISDN 3. Severe systemic HYPOTENSION ■=> noradrenaline i.v. 4. Increasing CONTRACTILITY of MYOCARDIUM «=> 5. ARRHYTMIAS ■=> Positively inotropic drugs levosimendan, dopamine, dobutamine Choose of AA according to the type of dysrrhytmia Often are surgical solutions of acute dysrrhytmias. Important is prevention. Thank you for your attention