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What does the cardiovascular system play a major role in?
Maintenance of homeostasis
The 3 primary pathways by which the heart can increase its cardiac output in response to body needs are what?
- Intrinsic response to changes in muscle length
- Contractile response
What depends directly on heart rate, myocardial wall tension, and inotropic state?
Myocardial oxygen demand
During cardiac failure, the body attempts to compensate by what intrinsic homeostatic mechanisms?
- Activation of sympathetic system
- Renin-angiotensin-aldosterone system
- Myocardial hypertrophy
What happens when the compensatory mechanisms act long term?
- Increased myocardial demand
- Results in CHF
What is chronic failure of the cardiac pump, resulting in an inadequate cardiac output and insufficient delivery of oxygen to meet the tissue requirements?
What are clinical signs of CHF(5)?
- Exercise intolerance
- Labored breathing
- Edema in extremities
- Dry cough
Clinical signs of CHF are due to fluid accumulation in the lungs (pulmonary edema as what side heart failure?
What compounds are important cardiac glycosides and collectively referred to as digitalis (3)?
The therapeutic response to digitalis in CHF includes what (5)?
- Improved myocardial contractility
- Increased CO
- Diminution of edema
- controls cardiac arrhythmias
Cardiac glycosides increase contractile strength of the normal as well as failing heart by what?
Increasing calcium availability in the myocardial fiber
Digitalis exerts a positive inotropic action on the heart muscle, this is due to what?
Inhibition of Na/K ATPase enzyme in sarcolemmal membrane of cardiac tissue
The increase in intracellular Ca+ ion increases the amount of calcium available for contractile proteins, this induces what?
Increased myocardial contraction (positive inotropic action)
How does digitalis decrease heart rate?
- Decreasing the rate of discharge from the SA node
- (due to stimulation of vagal afferents)
The increase of intracellular Na+ ion with decrease in K+ ion induces partial depolarization of the cell, thus reduces diastolic potential to threshold level which leads to...
In CHF, the diuretic effect produced by digitalis is due to what?
Increased renal blood flow, and an associated decrease in aldosterone secretion
What is not a prominent feature of digitalis therapy, if edema does not accompany with CHF?
Digitalis does not induce diuresis if edema is not what?
Diuretic response to digitalis is secondary to what?
- Circulatory improvement
- (Not a direct effect on the kidney)
Digitalis induces vomiting in dogs, after intravenous injection of digoxin, due to stimulation of what?
Chemoreceptor trigger zone
Where is the chemoreceptor trigger zone located?
Floor of the 4th ventricle of the brain and connected by neural pathways to the emetic center in the lateral reticular formation of the medulla oblongata
Vomiting accompanied by protracted diarrhea in dogs undergoing therapy with oral digitalis preparations is suggestive of what?
How is higher bioavailability of digoxin achieved?
When administered in elixir form
Why are cardiac glycosides absorbed to a new low extent in ruminant species?
Because of metabolism by ruminal microorganisms
Since digoxin is not well distributed to fat, it is always baded on what?
- Lean body weight
- (to avoid overdose in obese animals)
What is mostly preferred to treat atrial fibrillation/ flutter?
What reduces ventricular rate by slowing AV conduction in atrial arrhythmias?
Digitalis is indicated to treat (2)?
What involved initial administration of a large amount of digitalis, in several divided doses over a relatively short period of time to achieve rapid desirable therapeutic effect?
What is the main aim of therapy with digitalis?
Determine the smallest amount of glycoside that will effectively maintain the patient in a state of cardiac compensation
In digoxin in dogs, steady state concentration will be attained on what days of maintence?
- 6 to 8 day of therapy
- (assessed P for response to Tx)
Since the renal and hepatic functions are considered to be important in digitalis elimination, dose levels should be reduced in what? Animals with kidney or liver disease
When is IV administration of digitalis indicated (3)?
- when animal does not retain oral medications
- Acute cardiac decompensation
- Respiratory distress
What administration route of digoxin is not preferred?
What is the therapeutic plasma concentration in digoxin?
0.6 to 2.4 ng/ml
What can digitalis toxicity evoke?
- Incomplete/Complete heart block with dropped beats
- (Ventricular bigeminal rhythm)
The antiarrhythmic activity of K+ in digitalis intoxication is due to what?
Inhibition of cardiac glycoside binding to Na, K-ATPase enzyme
Increased Ca++ ion may enhance the toxic effects of digitalis by what?
Increasing the intracellular calcium stores
What is an exchange esin that binds to glycoside within digestive tract, thus enterohepatic circulation of bound form of glycoside is hindered, thereby hastening elimination of digitalis glycosides?
Intermittent administration of a diuretic during maintenance therapy of digoxin induces diuresis, thus what?
Cardiac preload can be effectively reduced.
What is the preferred loop action diuretics?
What diuretic produces a higher K+ excretion in urine, it increases Ca++ binding proteins in distal renal tubule and enhances renal tubular reabsorption of Ca++?
What is the limitation of potassium sparing diuretics?
Slow onset of action
An oral combination preparation containing what produces diuresis without either delayed onset of action or excessive urinary excretion of potassium?
What is decreased volume of distribution of digoxin due to its displacement by quinidine from tissue binding sites?
What exerts a positive inotropic action on the failing heart without increasing the myocardial oxygen consumption, also decreases ventricular filling pressure (preload) and vascular resistance (afterload)?
What enzyme is responsible for the selective metabolism of CAMP, accumulation of intracellular CAMP leads to increased cardiac contractility and peripheral vasodilation?
Phosphodiesterase isoenzyme III
What produces positive inotropic effect and vasodilation; increases the binding efficiency of cardiac myofibril to the calcium ions without increasing oxygen demand?
What is a B1 agonist, produces myocardial contraction of heart, decreases ventricular filling pressure, and has weak positive chronotropic action?
What are 2 drawbacks in the use of dobutamine?
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