CHF PHARM- Duan Flashcards
What are the categories of positive inotropic drugs used to treat CHF?
- Cardiac glycosides
- Bipyridines
- sympathomimetics
Name the cardiac glycosides.
- Digoxin (Lanoxin)
2. Digitoxin
What are the types of diuretics used to treat CHF?
- Loop diuretics
2. Aldosterone antagonist diuretics
What are the loop diuretics?
- Furosemide or Lasix
2. Bumentanide or Bumex
What are the aldosterone antagonist diuretics?
- spironolactone or Aldactone
What are the types of ACE inhibitors and Angiotensin blockers used to treat CHF?
- ACE inhibitors - Captopril or Capoten and Lisinopril or Prinivil
- Angiotensin receptor blockers - Losartan or Cozaar and Candesartan or Atacand
What are the types of Vasodilators used to treat CHF?
- organic nitrates and NO donors
- Hydralazine
- B-adrenergic blockers
Name the organic nitrates.
- Nitroglycerin
2. Nitroprusside or Nitropress
Name the B-adrenergic blockers.
- Metroprolol or Lopressor
- Bisoprolo or Zebeta
- Carvedilol or Coreg
Describe heart failure.
a complex clinical syndrome that can result from any structural or functional cardiac disorder or damage that impairs the ability of the ventricle to fill with or eject blood and is recognized by a characteristic pattern of hemodynamic, renal, neural, and hormonal responses
What are the primary symptoms of all types of CHF?
- Cardiomegaly - find via (echocardiograph, x-ray)
- Tachycardia - find via (ECG)
- Decreased exercise tolerance
- Shortness of breath (SOB) and other respiratory symptoms
- Peripheral edema and pulmonary edema
- Cachexia (wasting of adipose tissue and skeletal muscle) and malnutrition
- Cyanosis
Why do people with CHF have issues with malnutrition?
The GI tract is congested so it doesn’t work very well and it makes a person feel full and decreases appetite.
Why do people with CHF have decreases tolerance to exercise?
The decrease in oxygen due to decrease in cardiac output.
What are the stages of progression of CHF?
- normal but may be at high risk for developing CHF
- asymptomatic even with exercise but with abnormal left ventricular function
- compensated CHF - usually no symptoms but decreased exercise tolerance and abnormal left ventricular function
- Decompensated CHF - extreme exercise intolerance and abnormal left ventricular function
- refractory CHF - symptoms cannot be controlled even with treatment
What is one function that is affected in CHF?
Regulation of Cardiac output. Normally the heart can make small changes in the heart rate and contractile force to increase the cardiac output.
What is the main issue with heart failure?
The weakened contractile force and decreased cardiac output. Cardiac output is determined by heart rate and contractile force.
What happens in CHF when there is inadequate contractility?
There is a rise in venous blood pressures leading to impaired fluid drainage from the tissues. This causes many serious clinical effects.
What are some effects of right sided CHF?
- lower limb edema
- intravascular clotting
- thromboembolism
What are some effects of left sided CHF?
- pulmonary edema
- respiratory distress
- can lead to right sided heart failure
What is the most important intrinsic compensatory mechanism of the body in CHF?
Myocardial hypertrophy:
- during increased pressure and volume overload an increase in myocardial mass helps maintain cardiac performance
- with thickened heart muscle metabolic demands increase
- eventually ischemic changes, impairment of diastolic filling and remodeling due to the increased myocytes will lead to these myocytes dying at an accelerated rate and remaining myocardium is subject to even greater overload
What are some major causes of left sided CHF?
- CAD
- MI
- Hypertension
- Valvular lesions and insufficiency
- Drugs - such as alcohol, cocaine and meth
- idiopathic dilated cardiomyopathy
- restrictive cardiomyopathy
What are some major causes of right sided CHF?
- secondary to left sided HF and its causes
- pulmonary emphysema
- pulmonary valve lesions
- tricuspid valve stenosis or insufficiency
What is another compensatory mechanism in CHF?
The neuro-hormonal reflex:
- decreased cardiac output is sensed at the carotid baroreceptors leading to increased sympathetic outflow
- increased sympathetic response causes an increase in the force of contraction, heart rate and preload of the heart
- the juxtaglomerular apparatus in the kidneys also sense decreased blood flow when cardiac output decreases
- renin is released which will activate angiotensin which leads to blood vessel constriction and to an increase in sodium and water to increase blood volume
The compensatory mechanisms of the heart in response to CHF do what?
Increase the work of the heart and lead to a further decline in cardiac function.
What are some potential biochemical mechanisms that explain impaired contractility in CHF?
- decreased rate of calcium binding by sarcoplasmic reticulum
- decreased intracellular levels of cyclic AMP
- decreased β-receptor density or coupling
- decreased Na/Ca exchange
- decreased content of myofibibrillar protein
- decreased activity of actomyosin and/or myosin ATPase
Treatment of CHF focuses on what?
Correcting the underlying causes of pathophysiology.
The compensatory mechanisms of the heart in response to CHF can be described by what pneumonic?
Heart - SAVER
S - sympathetic outflow increased A - atrial natriuretic peptide released V - vasopressors released E - endogenous digitalis like factor released R - renin-angiotensin system activated
Cardiac glycosides are what?
Inotropic agents
What is the main cardiac glycoside in use?
Digitalis - Digoxin (the prototype drug) and Digitoxin.
Digitalis is the genus name for a family of plants containing cardiac glycosides. Name one of these plants.
Foxglove.
What structural components of digoxin are necessary to have an effect on the heart?
It’s steroidal nucleus and lactone ring.
Digoxin molecules also contain sugar moieties. Why are these important?
They affect the pharmacokinetics of the different cardiac glycosides.
Which of the two main cardiac glycosides in use (digoxin and digitoxin) has the quickest onset of action?
Digoxin - 10-30 minutes. The onset of action of Digitoxin is 30 min - 2 hours.
Which of the two main cardiac glycosides in use (digoxin and digitoxin) has the longest duration of action in which there is maximal effect?
Digitoxin - about 4-12 hours and stays in the system for 2-3 weeks. Digoxin has a duration of maximal effect of 1-5 hours and stays in the system for about 2-6 days.
Describe the mechanical effects of cardiac glycosides.
- increases the force of contraction by increasing both the velocity of myocardial contraction and maximum force
- increased contractility leads to:
increased cardiac output, decreased end diastolic volume, and increased ejection fraction - improvement in circulation leads to decreased sympathetic activity, decreased peripheral resistance and increased renal blood flow
- Heart rate will decrease due to increased Vagal tone
- overall - oxygen demand is decreased
Cardiac glycosides reduce symptoms of what?
They reduce symptoms resulting from pulmonary vascular congestion and elevated systemic venous pressure.
In the setting of CHF, cardiac glycosides do not have much affect on blood pressure but in the absence of CHF what happens?
There will be a direct increase in peripheral vascular resistance due to vasoconstriction.
What are the main electrical effects of cardiac glycosides on the heart?
- decreased conduction through the AV node
- increased automaticity
- decreased heart rate due to increased vagal tone and improved hemodynamics
What is the mechanism of action of the cardiac glycosides?
- inhibit sodium potassium ATPase resulting in increased intracellular sodium
- increased intracellular sodium increases intracellular calcium via the sodium calcium exchange pump
- increased myocardial uptake of calcium augments calcium release to myofilaments during excitation leading to a positive inotropic response
What are the therapeutic uses of cardiac glycosides?
- positive inotropic effect on the heart so used to treat severe left ventricular systolic failure after initiation of diuretics and ACE inhibitors.
- if CHF is accompanied by A-Fib then cardiac glycosides are the first choice of meds because of the vagal effect on the AV node (slows ventricular rate, does NOT revert the A-fib to normal sinus rhythm)
- can also be used in atrial flutter and paroxysmal atrial tachycardia due to its Vagal effects - these are supra ventricular arrhythmias
Digitalis is often prescribed for long-term use and has a low margin of safety. What is the safest method for prescription?
Slow digitalization via maintenance doses. Can be given IV if rapid effect is needed but this can be dangerous so the loading does is divided into 3-4 doses given over 24 hours.
What are the contraindications of cardiac glycosides?
- cardiac tamponade
- constrictive pericarditis
- hypertrophic obstructive cardiac myopathy
- Wolf-Parkinson-White syndrome
- When CHF symptoms are caused by the body’s extreme need for blood - like in chronic severe anemia, Paget’s disease, some forms of severe hepatic or renal disorders and in septic shock
Digitalis has a very narrow therapeutic index. What are the early signs of digoxin toxicity?
Distaste for food, nausea, vomiting, diarrhea, disturbance of vision (Vision change also called chromatopia). The nausea and vomiting are due to a central effect and may be the only earliest signs of digitalis intoxication.
What are some later signs of digoxin toxicity?
A complete spectrum of cardiac arrhythmias may result including
A-V block, ventricular extrasystoles and ventricular fibrillation.
What are the symptoms of chronic digitalis toxicity?
Exacerbations of heart failure, weight loss, cachexia, neuralgias, gynecomastia, yellow or green vision, delirium
Often Digoxin is used in conjunction with diuretics. What may be a problem here?
The cardiac toxicities that may be caused by digoxin are enhanced by hypokalemia and loss of potassium may be a problem with diuretic use.
How is digitalis intoxication treated?
1) withdrawal of the drug
2) KCl orally or slow IV
3) treatment of arrhythmias with b-blocker or lidocaine; 4) Severe glycoside toxicity usually treated by cardiac pacemaker catheritization, 5) administration of digitalis antibodies, digoxin immune fab (digibind®, digifab®).
Cardiac inotropic agents such as Bipyradines may be used to treat CHF. How do they work?
They are selective inhibitors of phosphodiesterase 3. Blocking leads to increased cAMP which in turn increases calcium entry during an action potential.
What are the two types of Bypyrdines used?
- Inamrinone or Inocor
- Milrinone or Primacor or Corotrope
- these are given IV for acute heart failure
- toxicity to liver and cardiac arrhythmia formation prevents long term use
What are the Beta agonists used to treat CHF?
- dobutamine - increases contraction force without a large increase in rate and without prominent vascular effects
- dopamine - similar to dobutamine
- given IV and may induce tolerance
What is the major diuretic given in CHF and why?
Spironolactone. It is an aldosterone antagonist so it stops the increased sodium and water retention triggered by the renin-angiotensin-aldosterone system.
Why are ACE inhibitors and angiotensin blockers used in treatment of CHF?
They counter the increased sodium and water retention.
How do the ACE inhibitors work?
- Captopril and Lisinopril often given
- They suppress Ang II and aldosterone production, decrease sympathetic nervous system activity, and potentiate the effects of diuretics.
- they are potent arterial dilators that reduce afterload on the heart which increases cardiac output
- contraindicated in CHF patients with reduced renal blood flow since they will limit the kidney’s ability to regulate glomerular perfusion - instead use an angiotensin blocker
Why are ACE inhibitors useful following acute MI?
- they can reduce ventricular dysfunction and mortality
2. they can prevent adverse ventricular remodeling
What are the common side effects of the ACE inhibitors?
a dry, persistent cough, abdominal pain, constipation, diarrhea, rash, dizziness, fatigue, headache, loss of taste, loss of appetite, nausea, vomiting, numbness in the hands or feet, kidney failure and increased levels of potassium in the blood.
Which vasodilators may be used in treatment of CHF?
Nitrates such as:
- nitorglycerin
- Nitroprusside
- Isosorbide dinitrate
- Hydralazine or Apresoline
How does Hydralazine work?
Causes direct relaxation of arterial smooth muscle and reduces right & left ventricular afterload by reducing pulmonary and systemic vascular resistance. May be effective in CHF patients with renal dysfunction who can not tolerate ACE inhibitors. May be most effective when combined with vesodilating agents (eg. organic nitrates).
Beta blockers are used in treatment of CHF for what?
They decrease heart rate. In CHF, the decreased contractility leads to a compensatory increased heart rate via activation of B1 receptors. Beta blockers counteract this.
Which Beta blockers are used in treatment of CHF?
- metoprolol or Lopressor- selective for B1
- Bisoprolo or Zebeta - selective for B1
- Carvedilol or Coreg - non-selective Beta blocker and alpha 1 receptor antagonist
How does CHF increase preload on the heart?
The dysfunction of the heart causes increased blood volume and increased venous tone leading to increased atrial filling pressures.
What therapeutic strategies treat increased preload?
- salt restriction
- diuretic therapy
- venodilator drugs
How does CHF increase afterload on the heart?
Heart dysfunction leads to increased sympathetic stimulation and activation of the renin-angiotensin system leading to increased vascular resistance and increased blood pressure.
What therapeutic strategies treat increased afterload?
- arteriolar vasodilators
2. decrease angiotensin II via ACE inhibitors
Decreased myocardial contractility leads to what in CHF?
Decreased cardiac output leading to damaging compensatory mechanisms.
What therapeutic strategies treat decreased contractility?
Inotropic drugs such as cardiac glycosides, Bipyradines and beta agonists.
