Cardiovascular 1 Flashcards
when does heart disease become heart failure?
Heart disease becomes heart failure when the heart is unable to meet the body’s oxygen (metabolic) requirements
what is congestive heart failure?
when the heart cannot compensate for reduced CO resulting in venous congestion and edema
What causes the heart to fail?
- Myocardial contractility failure
> Weakened heart and reduced contractility
=> Dilated cardiomyopathy (DCM)
=> Taurine deficiency
<><><><> - Systolic mechanical overload
> Pressure versus volume overload
=> Altered preload and/or afterload
=> Valvular disorders
<><><><> - Diastolic mechanical inhibition
> Feline hypertrophic cardiomyopathy (HCM)
> Pericardial disorders eg. pericarditis
<><><><> - Electrical disorders
> Dysrhythmias
preload
-work or stress the heart faces at the end of diastole
afterload
-resistance against which the heart must pump at systole
contractility
-the capacity of myocardium to contract
distensibility
-how easily the ventricles relax and fill
contraction synergy
-correlated/cooperative contraction of heart chambers
p What are the determinants of heart failure?
(1) preload
(2) afterload
(3) contractility
(4) distensibility
(5) heart rate
(6) contraction synergy
BP relationship to CO
CO x TPR
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CO = SV x HR
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- Reduced CO perceived as a decrease in mean arterial pressure (BP)
R-A-A-S activity - effects on the cardiovascular system
n increase Vasoconstriction
n increase Blood volume
SNS activity - effects on the cardiovascular system
n increase HR
n increase Contractility
n increase Vasoconstriction
n increase Renin
Congestive heart failure will manifest how?
clinical signs suggestive of poor cardiac performance:
- tachycardia
- decreased exercise tolerance
- peripheral and pulmonary edema
> dyspnea
- cardiac enlargement
- hypotension
Ideal approach to heart failure is to repair the primary abnormality
q Make the heart stronger if weak
q Make the heart fill better if indistensible
q Repair leaks if mitral or aortic valve insufficiency
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q Full attainment of these goals are currently not possible; approach management with two aims:
q Improve hemodynamic performance
q Modify vascular volume
Positive Inotrope drug types
- Na/K-ATPase Blockers
- Drugs that increase cAMP
- Caclium sensitizers
types of drugs that decrease preload
- diuretics
- venodilators and mixed vasodilators
drug classes that decrease afterload
- arteriodilators and mixed vasodilators
drug classes that treat reduced distensibility
- beta-adrenergic blockers
- Ca2+ channel blockers
mechanism of positive inotropes
increase contractility > increase CO
<><>
- decreased SNS activity > decrease HR and TPR (afterload)
- increase renal blood flow > decrease R-A-A-S
> decrease edema and decrease blood volume (decrease preload)
disadvantages and contraindications of positive inotropes
Disadvantages
- increased myocardial oxygen consumption
- Arrhythmogenic
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Contraindicated
- Valvular stenosis
- Cardiac tamponade
- HCM
Positive Inotropes
- i) Drugs that increase myocyte cAMP
beta-agonists (Sympathomimetics):
- Dobutamine
- Dopamine
b-agonists (Sympathomimetics) mechanism, drawback
increase cAMP > increase intracellular Ca2+
> interaction of actin and myosin
> increase contractility
> However progression of heart failure and mortality often increases
Dobutamine
- use
- admin
- receptors
- concerns
- Use is limited to acute treatment of severe heart failure due to systolic dysfunction
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Must be given by CRI in hospital setting - Onset of action is rapid (~2 min) as is offset due to short half-life (1-2 minutes)
<><> - Direct b1-receptor activation; some b2 and a1
- Tachycardia and arrhythmias are a concern
Dopamine
- use, preference
- effects based on dose
- Can also be used for short term tx in acute systolic heart failure— dobutamine preferred as less arrhythmogenic
<><> - medium dose > increase inotropy
- high dose > increase vasoconstriction
<><> - Used in the management of acute oliguric renal failure in the dog
> low dose > renal vasodilation
Na+/K+-ATPase Blockers
Digoxin
Digoxin
- type of drug
ii) Na+/K+-ATPase Blockers > cardiac glycoside
Digoxin mechanism
Inhibits Na+/K+-ATPase pumps on myocytes
- Results in an increase in intracellular Na+ that decreases expulsion of intracellular Ca2+ from the Na+/Ca2+-exchanger
- Intracellular calcium levels increase and are sequestered in the sarcoplasmic reticulum
- Action potential sees greater calcium released, enhanced actin- myosin interaction and an increase in inotropy ie contractility
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Beneficial effects of digoxin may also be due to increased vagal activity
Digoxin
- use, replacement
- elimination
Use in the dog for heart failure has been replaced by Pimobendan as first line drug !!
- Used occasionally for treatment of heart failure in the horse
- May be used for treatment of arrhythmias (see arrhythmia notes)
- Primary route of elimination is renal excretion
Digoxin toxicity and factors
- long half life, hard to get out of the body when toxicity occurs
- Narrow therapeutic range > monitor with TDM
- Drug interactions > diuretics and hypokalemia
- Arrhythmias: VPC’s, heart block, atrial & ventricular tachycardias
> Ventricular arrhythmia’s > lidocaine
Ca2+-sensitizers
Pimobendan
Pimobendan mechanism
- increase Ca2+-binding affinity of myocyte contractile proteins > increase inotropy without an increase in [Ca2+]IC
> Effects do not increase MVO2 ie. myocardial oxygen consumption
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Agents in this class also block PDE III enzymes - Produces balanced vasodilatory effects that can be beneficial in heart failure
- These agents aka “Inodilators”
Pimobendan seconday effects
- Cytokine modulation
- Positive lusitropy (rate of myocardial relaxation)
pimobendan use
Licensed in dogs; valvular insufficiency & DCM
> Works rapidly; no additional monitoring needed
pimobendan administration, safety, use with other drugs?
- Available as oral capsule
- Well tolerated and very good safety to date
- Often used with diuretics, ACEi’s etc
Drugs Used to Reduce Preload
- Diuretics
- Venodilators
Diuretics
- what they do, which ones are commonly used?
Reduce fluid overload, resolve pulmonary edema in congestive heart failure
- Furosemide, Hydrochlorothiazide, Spironolactone
Diuretics mechanism of action for heart failure
- dosing in combination?
- disadvantages?
- Reduce preload primarily by diuretic effect
- Furosemide venodilation aids acute relief of edema
- Reduce initial doses of diuretics when combing agents—-furosemide and hydrochlorothiazide
- Disadvantage is their activation of R-A-A-S
- Hypokalemia and digoxin toxicity
Venodilators
- ones we use
- Nitroglycerin
- Isosorbide
Nitroglycerin mechanism of action for heart failure
At therapeutic doses is considered a selective venodilator > increase venous capacitance
<><>
- via relaxation of smooth muscle
Nitroglycerin duration of action
- application
- Nitrates tend to have a high first pass effect
- Duration of action can be short (minutes)
> ointment > apply to inner pinna
> development of tolerance is possible with nitrates
when are nitrates indicated?
used with what?
adverse effect?
- Indicated in acute treatment of CHF
- Usually used in conjunction with furosemide
as nitroglycerin as monotherapy is limited - Hypotension can occur; headache in humans
