Slide 1

Vicky Yang 8/30/12

Slide 2

Can I possibly make this topic interesting???

Slide 3

Diuretic Positive Inotrope ACE inhibitor

Slide 4

Diuretics

Slide 5

Loop Diuretics Furosemide Torsemide

Slide 6

Furosemide Lasix/Salix Pharmacologic effects Inhibits Na + /K + /2Cl - co-transporter on ascending limb Drug exerts effect intraluminally (Na +, Cl -, K + ) Dose 1-8 mg/kg bolus IV or IM 1 mg/kg/hr CRI Peak effect 30 min after IV dose, 1-2 hrs after oral dose Short duration of action (4-5 hours) Side effects Hyponatremia, hypochloremia, hypokalemia Alkalosis Ototoxicity especially with aminoglycosides Azotemia

Slide 7

Torsemide Longer duration of action Can persist for 12 hrs Approximately 10 times potency than furosemide More potassium-sparing Use as an adjunct to furosemide treatment

Slide 8

Thiazide Diuretics With or without spironolactone Hydrochlorothiazide Aldactazide

Slide 9

Hydrochlorothiazide Pharmacologic effects Inhibits Na +, Cl - co-transporter at early distal nephron Longer duration of action (16-24 hrs in humans) Dose 2 mg/kg q12 hrs Aldactazide: dose according to spironolactone 25 mg/25 mg Side effects Hypokalemia, hyponatremia, hypochloremia Hypercalcemia: increase reabsorption at proximal tubule

Slide 10

Aldosterone Receptor Blockers Adverse effects of aldosterone Na+ retention by inhibiting Na + /K + exchanger Promotes cardiac fibrosis Nephron growth Promotes endothelial dysfunction Inhibits release of NO Spironolactone RALES: 30% reduction in mortality Epleronone EPHESUS: 15% reduction in mortality

Slide 11

Spironolactone Pharmacologic effects Aldosterone-receptor blocker at distal tubule Increase Na + excretion K + sparing Dose 1-2 mg/kg q12 hrs Use as adjunct treatment with furosemide Side effects Hyperkalemia, hyponatremia Facial dermatitis in cats

Slide 12

Slide 13

Aquaretics Arginine vasopressin (AVP) V2 receptor antogonists Vaptans Conivaptan Tolvaptan Lixivaptan

Slide 14

Diuretic Resistance Can occur even after 1 dose of diuretic Intravascular fluid contraction RAAS activation Aldosterone induced nephron growth Increase Na + reabsorption Excessive circulating catecholamine Poor renal perfusion

Slide 15

Pimobendan Pharmacologic effects Ca+ sensitizer PDE III inhibitor Dosing 0.25-0.3 mg/kg Side effects GI (rare) Pro-arrhythmic

Slide 16

ACE Inhibitors RAAS stimulation -adrenergic system Low BP Hyponatremia Hypovolemia Chymase Tissue specific ACE

Slide 17

Adverse Effects of RAAS Vasoconstriction AT-1 receptor 1 -receptor bradykinin breakdown Myocardial remodeling AT-1 receptor Endothelial dysfunction aldosterone Na + retention aldosterone

Slide 18

ACE Inhibitors: Benefits Vasodilation Aids in diuresis Myocardial remodeling Potential anti-arrhythmic effects

Slide 19

Enalapril Pharmacologic effects Converted to enalaprilat by liver (active form) Competes with angiotensin 1 for ACE Long duration of action (12 hrs) Renal clearance Dose 0.5 mg/kg q12 hrs Side effects Hypotension hyperkalemia

Slide 20

Other ACEi Benazepril Benazeprilat active metabolite Renal and hepatic clearance 0.25-0.5 mg/kg q12 hrs Lisinopril No conversion needed Renal excretion Long half life 0.5 mg/kg q24 hrs

Slide 21

Other Methods of RAAS Blockage Angiotensin II receptor blockage Losartan Candesartan Valsartan Renin inhibition Aliskiren Aldosterone blocker for ACE inhibition escape

Slide 22

And Then Things Get Exciting I used furosemide (lots!), pimobendan (overdose!), ACEi but. were still in the O 2 cage!!

Slide 23

Vasodilators Preload reducers Venodilators Diuretics Nitrates (nitroglycerin) Afterload reducers Decrease vascular resistance Hydralazine Calcium channel blockers Mixed agents Nitroprusside

Slide 24

Phomocologic effects NO donor cGMP Ca 2+ vasodilation Dose 0.5-10 g/kg/min Fast acting Side effects Metabolized to thiocyanate by liver, cleared by kidneys CNS signs Hypotension

Slide 25

Nitroglycerin Pharmocologic effects Exogenous source of NO Dose - 1 q6-12 hrs Side effects Hypotension Nitrate tolerance

Slide 26

Hydralazine Pharmacologic effects Potassium channel opener (Opie) Interferes with Ca 2+ movement in smooth muscles (Plumb) Arteriole vasodilation Dose 0.5-3 mg/kg PO q12 hrs Side effects Hypotension

Slide 27

Or Things Get Really Bad Poor cardiac output Cardiogenic shock!! Circulatory shock from cardiac causes Peripheral constriction (cold peripheries) Anuria or oliguria Low systolic BP (

Acute Inotropes Dobutamine ( 1 > 2 > ) at 2-20 g/kg/min Dopamine ( at high doses) at 1-10 g/kg/min Pimobendan Epinephrine ( 1 = 2 > ) at 0.01 mg/kg Norepinephrine ( 1 > > 2) Vasopressin (V1, V2 receptors) at 0.01-0.04 U/min Side effects Arrhythmias Tachycardia Hypertension

Slide 29

Slide 30

Slide 31

Class I Na + Channel Blockers IA Quinidine, disopyramide, procainamide Inhibits fast Na + channels Prolongs APD and QT interval IB Lidocaine, mexiletine, tocainide, phenytoin Inhibits fast Na + channels (inactivated channels) Shortens APD in non-diseased tissue (no QT prolongation) Acts selectively on diseased/ischemic tissue Use dependency

Slide 32

Class I Na + Channel Blockers IC Flecainide, propafenone, moricizine Inhibits fast Na + channels Variably prolongs APD Good for supraventricular tachyarrhythmias

Slide 33

Class II -Blockers I f (pacemaker current) L-type Ca-channel Non-selective Propranolol, sotalol Risk of bronchiol spasm 1-selective Atenolol, metoprolol, bisoprolol, esmolol 1, 2, -blockade Carvedilol Bradycardia

Slide 34

Class III K + Channel Blockers Amiodarone Class I, II ( and ), III, IV Slow onset, loading required (10 mg/kg q12 hrs) Side effects: Liver toxicity Sotalol Class II, III 1-2 mg/kg q12 hrs Reverse use dependence (greater effects at low HR) Ibutilide, dofetilide, bretylium QT prolongation

Slide 35

Class IV Ca + Channel Blockers Dihydropyridine (DHP) Amlodipine Greater effects on vessels Non-DHP Diltiazem (1 mg/kg q8 hrs, 1.5 mg/kg q12 hrs for ER) Verapamil (1-5 mg/kg q8 hrs) Greater effects on myocardium L-type channels T-type channels (SA and AV node) Negative ionotrope

Slide 36

Digoxin Pharmacologic effects Inhibits Na + /K + ATPase Parasympathetic activation Decrease renin release Dose 0.003 mg/kg q12 hrs Side effects Nausea, vomiting, anorexia (parasymapathomimetic effects)

Slide 37

Supraventricular Tachycardia Esmolol (II) Atenolol (II) Metoprolol (II) Carvedilol (II) Sotalol (III) Amiodarone (III) Verapamil (IV) Diltiazem (IV) Digoxin

Slide 38

Ventricular Tachycardia Quinidine (IA) Procainamide (IA) Lidocaine (IB) Mexiletine (IB) Sotalol (III) Amiodarone (III)

Slide 39

Slide 40

Thrombus Formation Subendothelial tissue factor exposed Coagulation factors activated Platelet adhesion, activation, aggregation Thrombus formation from fibrin cross- linking

Slide 41

Slide 42

Platelet Inhibitors Aspirin Irreversibly inhibits COX-1 TXA 2, no effect on PGI 2 ADP receptor antagonists Prevent platelet aggregation, promote disaggregation Clopidogrel Glycoprotein IIb/IIIa receptor antagonists Blocks platelet activation and fibrinogen cross-linking abciximab

Slide 43

Anticoagulants Unfractionated heparin Binds thrombin Low-molecular weight heparin Dalteparin (Fragmin) Enoxaparin (Lovenox) Factor Xa inhibitors Rivaroxaban (Xeralto) Fondaparinux (Arixstra) Vitamin K antagonists Warfarin

Slide 44

Thrombolytics Tissue plasminogen activator Tenecteplase Longer half-life of tPA Streptokinase

Slide 45

Thank goodness theres no coronary artery disease!