Transcript of Vicky Yang 8/30/12. Can I possibly make this topic interesting???
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- Vicky Yang 8/30/12
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- Can I possibly make this topic interesting???
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- Diuretic Positive Inotrope ACE inhibitor
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- Diuretics
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- Loop Diuretics Furosemide Torsemide
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- 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
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- 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
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- Thiazide Diuretics With or without spironolactone
Hydrochlorothiazide Aldactazide
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- 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
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- 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
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- 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
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- Aquaretics Arginine vasopressin (AVP) V2 receptor antogonists
Vaptans Conivaptan Tolvaptan Lixivaptan
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- 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
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- Pimobendan Pharmacologic effects Ca+ sensitizer PDE III
inhibitor Dosing 0.25-0.3 mg/kg Side effects GI (rare)
Pro-arrhythmic
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- ACE Inhibitors RAAS stimulation -adrenergic system Low BP
Hyponatremia Hypovolemia Chymase Tissue specific ACE
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- Adverse Effects of RAAS Vasoconstriction AT-1 receptor 1
-receptor bradykinin breakdown Myocardial remodeling AT-1 receptor
Endothelial dysfunction aldosterone Na + retention aldosterone
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- ACE Inhibitors: Benefits Vasodilation Aids in diuresis
Myocardial remodeling Potential anti-arrhythmic effects
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- 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
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- 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
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- Other Methods of RAAS Blockage Angiotensin II receptor blockage
Losartan Candesartan Valsartan Renin inhibition Aliskiren
Aldosterone blocker for ACE inhibition escape
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- And Then Things Get Exciting I used furosemide (lots!),
pimobendan (overdose!), ACEi but. were still in the O 2 cage!!
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- Vasodilators Preload reducers Venodilators Diuretics Nitrates
(nitroglycerin) Afterload reducers Decrease vascular resistance
Hydralazine Calcium channel blockers Mixed agents
Nitroprusside
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- 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
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- Nitroglycerin Pharmocologic effects Exogenous source of NO Dose
- 1 q6-12 hrs Side effects Hypotension Nitrate tolerance
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- 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
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- 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
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- 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
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- 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
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- Class I Na + Channel Blockers IC Flecainide, propafenone,
moricizine Inhibits fast Na + channels Variably prolongs APD Good
for supraventricular tachyarrhythmias
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- 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
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- 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
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- 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
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- 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)
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- Supraventricular Tachycardia Esmolol (II) Atenolol (II)
Metoprolol (II) Carvedilol (II) Sotalol (III) Amiodarone (III)
Verapamil (IV) Diltiazem (IV) Digoxin
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- Ventricular Tachycardia Quinidine (IA) Procainamide (IA)
Lidocaine (IB) Mexiletine (IB) Sotalol (III) Amiodarone (III)
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- Thrombus Formation Subendothelial tissue factor exposed
Coagulation factors activated Platelet adhesion, activation,
aggregation Thrombus formation from fibrin cross- linking
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- 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
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- Anticoagulants Unfractionated heparin Binds thrombin
Low-molecular weight heparin Dalteparin (Fragmin) Enoxaparin
(Lovenox) Factor Xa inhibitors Rivaroxaban (Xeralto) Fondaparinux
(Arixstra) Vitamin K antagonists Warfarin
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- Thrombolytics Tissue plasminogen activator Tenecteplase Longer
half-life of tPA Streptokinase
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- Thank goodness theres no coronary artery disease!