Exam 3- Cardiac Glycosides and Inodilators Flashcards
What breed of dogs is Endocardiosis associated with?
Cavalier King Charles Spaniels - Thickening of the mitral valves- depending on which is worse, you will have left or right sided heart failure
What breed is most commonly associated with Dilated Cardiomyopathy
Doberman
What is Class I of congestive heart failure
Only strenuous exercise is limited
What is Class II of congestive heart failure
Fatigue, shortness of breath, cough on exercise.
What is Class III of CHF
Comfortable at rest but exercise is minimal
What is class IV of CHF
no capacity for exercise, clinical signs at rest
What drugs can be used in CHF?
digoxin, pimobendan, ACE inhibitors (enalopril) and other inotropic drugs are used for Class, II, III, IV.
What are the difficulties of Digoxin
This is unpredictable from animal to animal because of the binding to different tissues and the protein binding. The theraputic index and the lesal dose are very closely associated. -Many preparations are given orally. The absorbption factor can be vaiable from one manufacturer
What is the relationship between Glycoside and Ca
Glycoside increase the intracellular calcium in the sarcoplasm, which allows for a raise of Ca to interact with the contractile proteins. which in turn increases the contractile forces and rate of contraction
What are the major actions of cardiac glycosides?
increased force and velocity of contraction
- Positive inotropic action- observed in a normal and failing heart.
- Slowing of the heart rate- negative chronotropic effect- due to a stimulation fo the vafus nerve and also improved baroreceptor sensitivity countering sympathetics
- Slowing of conduction at the AV node- negative dromotropic effect- can get AV block completely. This effect can be exploited in atrial arrythmia.
Where in the body is the main source of elimination for Digoxin in dogs and cats
Renal excretion. This means that you need to take extra care when the animal has kidney disease or renal issues.
What are some potential effects of digoxin on the heart rhythm and GI tract?
- Auricular arrhythmias/tachycardia
- Calcium levels increase too high
- AV block
- Ventricular arrhythmias/Extra-systole/pulsus bigemini/ventricular fibrillation
- DI distrubances- anorexia, vomiting, diarrhea
How do you treat a Digoxin toxicity?
- Remove the drug- withdraw digoxin and allow it to be cleared
- Ventricular arrhythmias- treated with lidocaine, phenytoin, propranolol
- IV fluids to maximize renal clerance-K if serum K low - toxicity of glycosides worse with low K - care diuretics
- Use K sparing diuretics
What is a common inodilator?
Pimobendan: Vetmedin
How do inodilators work?
Ca sensitizer and phosphodiesterase III inhibitor
- Troponin I inhibits actin and myosin combination until calcium binds to troponic C. Calcium sensitizer increases binding calcium to troponin c
- Phosphodiesterase III inhibitor prevents cAMP breakdown and increases PKA action and icnrease voltage-activated calcium currents.
What are the theraputic responses to glycosides and pimobendan
- increases in cardiac output
- Decreases in heart rate
- Decreases in venous pressure
- Reduced heart size
- Water loss and reduced body weight
What are examples of other positive inotropic drugs?
- Dopamine- D5 receptors on heart (increases cAMP)
- Dobutamine Beta-1 agonist - useful I/V with acute reversible heart failure
- Amrinone- phosphodiesterase III inhibitor useful I/V increases cAMP increases calcium influx
What is the mechanism of action for Class I antidysrhythmic drugs?
Block voltage-sensitive Na channels
These drugs bind to Na channels in a state-dependent manner
- Druge bind most strongly when Na channel open or in the refractory state hence effects use-dependent and class I drugs bind to channels in Depolarized/Damaged muscle
comment: blocks high frequency excitation, allows normal frequency
Explain the action of class Ib antidysrhythmic drugs
- These drugs associate and dissociate rapidly- within the time of a normal heart beat and also selectively binds to refractory channels during depolarized, ischemic muscle
Used for the control of ventricular dysrhythmias after myocardial infarciton
Example: Lidocaine
Explain the mechanism of action for Class Ic antidysrhythmic drug
- Class Ic drugs associate and dissociate more slowly, achieving a steady state block level that does not vary with the stage of the cycle
- used for a general reduction in excitation and have less effect against premature beats like Ib
will suppress re-entrant rhythms
Examples: flecainide
Explain the mechanism of the Clas Ia drugs
This is the oldest group of drugs.
Midway in their kinetics between class Ib (dissociates quickly) and Ic (dissociates slowly)
Examples: Procainamide and Quinidine
Explain the mechanism of Class II Antidysrhythmic drugs
Beta antagonists : Propranolol
Beta 1- receptors on the heart produce increase heart rate and excitability.
Therefore: Beta antagonists are used to reduce excitability if due to sympathetic over-activity and reduce the AV conduction in atrial tachycardias to slow ventricular rate
Cat- thyroid hyperplasia- can give raise to arrhythmias
Explain the mechanism of Class III antidysrhythmic drugs
Originally based on amiodarone but now others
- Special feature is that it prolongs the cardiac action potential and increase refractory period
- This produces ventricular and supra-ventricular antidysrhythmic effects. Complex mechanism including K channel block and calcium channel block
Explain the mechanism of Class IV antidysrhythmic drugs
Verapamila nd diltiazem are main examples
Block voltage-sensitive Ca channels
Shorten plateau phase of the action potential and reduce force of contraction.
The reduction of Ca inhibits transient inward current and thus suppressing premature ectopic beats and re-entrant rhythms.
Dilates coronary arteries as well
