1. Commonly Used Veterinary Cardiac Drugs
Vicky Yang
8/30/12

2. Can I possibly make this topic interesting???

3. CHF – What to Give?
Diuretic
Positive Inotrope
ACE inhibitor

4. Diuretics

5. Loop Diuretics
Furosemide
Torsemide

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

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

8. Thiazide Diuretics With or without spironolactone Hydrochlorothiazide
Aldactazide

9. Hydrochlorothiazide Pharmacologic effects Dose Side 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

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

11. Spironolactone Pharmacologic effects Dose Side 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

13. Aquaretics Arginine vasopressin (AVP) V2 receptor antogonists
“Vaptans”
Conivaptan
Tolvaptan
Lixivaptan

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

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

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

17. Adverse Effects of RAAS
Vasoconstriction
AT-1 receptor
a1-receptor
bradykinin breakdown
Myocardial remodeling
Endothelial dysfunction
aldosterone
Na+ retention

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

19. Enalapril Pharmacologic effects Dose Side 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

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

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

22. And Then Things Get Exciting…
I used furosemide (lots!), pimobendan (overdose!), ACEi
but….
we‘re still in the O2 cage!!

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

24. Nitroprusside Phomocologic effects Dose Side effects
NO donor  cGMP  Ca2+  vasodilation
Dose
mg/kg/min
Fast acting
Side effects
Metabolized to thiocyanate by liver, cleared by kidneys
CNS signs
Hypotension

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

26. Hydralazine Pharmacologic effects Dose Side effects
Potassium channel opener (Opie)
Interferes with Ca2+ movement in smooth muscles (Plumb)
Arteriole vasodilation
Dose
0.5-3 mg/kg PO q12 hrs
Side effects
Hypotension

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 (<90 mmHg)
Treatment goal
Reduce cardiac load (preload reduction)
Preserve cardiac function (positive inotropes)
Maintain BP

28. Acute Inotropes Dobutamine (b1 > b2 > a) at 2-20 mg/kg/min
Dopamine (a at high doses) at 1-10 mg/kg/min
Pimobendan
Epinephrine (b1 = b2 > a) at 0.01 mg/kg
Norepinephrine (b1 > a > b2)
Vasopressin (V1, V2 receptors) at U/min
Side effects
Arrhythmias
Tachycardia
Hypertension

29. The Dreaded Arrhythmias

31. Class I – Na+ Channel BlockersIA
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

32. Class I – Na+ Channel BlockersIC
Flecainide, propafenone, moricizine
Inhibits fast Na+ channels
Variably prolongs APD
Good for supraventricular tachyarrhythmias

33. Class II – b-Blockers If (pacemaker current) L-type Ca-channel
Non-selective
Propranolol, sotalol
Risk of bronchiol spasm
b1-selective
Atenolol, metoprolol, bisoprolol, esmolol
b1, b2, a-blockade
Carvedilol
Bradycardia

34. Class III – K+ Channel Blockers
Amiodarone
Class I, II (a and b), 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

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

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

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

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

39. Anti-Thrombotics

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

42. Platelet Inhibitors Aspirin ADP receptor antagonists
Irreversibly inhibits COX-1
↓TXA2, no effect on PGI2
ADP receptor antagonists
Prevent platelet aggregation, promote disaggregation
Clopidogrel
Glycoprotein IIb/IIIa receptor antagonists
Blocks platelet activation and fibrinogen cross-linking
abciximab

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

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

45. Thank goodness there’s no coronary artery disease!