CHF Drugs Flashcards
Heart failure general stats
4-5million current cases
Kills 300,000 a year
Most common causes are due to MI, chronic untreated HTN, CAD and chronic dysrhythmias
Characterized as a reduction in stroke volume and cardiac output at any given EDV measurement compared to an unaffected heart
Frank starling relationship summary
Generally speaking, the EDV and ventricular tension are directly proportional to a point
- as EDV/preload increases, the natural ventricular tension increases (contractility)
- this occurs until a max curve point is reached (signifies the myofibrils are too stretched out and cant connect with each other)*
Positive/negative inotropic agents directly affect the tension/contractile force (not the EDV)
- indirectly increases the EDV
- up and to the left increase for positive, down and to the right for negative
Vasodilators indirectly affect contractility and directly affect EDV( increasing EDV and contractility)
- shift up and to the left
Morphological changes in myocardium curing heart failure
1) atrial naturetic peptides are reduced in quantity released (can cause edema or worsen it)
2) down regulation of B1 and B2 receptors and some mild down regulation of A1 receptors (all decreases max contractility)
* these both cause increases in ESV with each heart beat, eventually leading to a state of low output congestive heart failure if not treated*
What are the 3 cardinal physiological symptoms of CHF?
Ventricular hypertrophy (cardiomegaly)
Edema (in either pulmonary or cardiac or both)
Weak/rapid pulses (causes baroreflex activation)
the goal of treatment is not to cure, but rather reverse/prevent these symptoms from worsening
Is heart failure ever cured?
No, it is just maintained and preventing further myocardium death
- only way to completely cure is heart transplant
What are the pharmacological and nonpharmacological treatments of CHF?
Non-pharm:
1) diet and Na+ reduction
2) exercise (30-45 min)
Pharm:
1) Vasodilators (decrease afterload)
2) diuretics
3) ACEIs/ARBs
4) Positive inotropic agents (increase contractility)
What are the broad effects of cardiac glycosides?
Increased rate and peak of phase 0 in ventricular tissues
Shortens phase 2 in ventricular tissues
Effects phase 3 and 4 (shortening both) causing shorter refractory periods and action potential durations
Causes decreases pulmonary systemic pressures, renal artery resistance and both preload/afterload
Causes increases in glomerular filtration rate, renal blood flow and urinary output
have great lipid solubility
ECG effects of digoxin
1) Increases PR interval (decreases heart rate and AV nodal conduction)
2) increases RR interval
3) shortens QT interval
4) depresses ST segment
* hockey stick formation*
Mechanism of action of digoxin and other cardiac glycosides
Inhibits the Na/K-ATPase pump
- leads to increased intracellular sodium and calcium
This allows for more calcium to be present inside cells for contractile phases, leading to more calcium
- the sodium/calcium exchanger cant work since the sodium/potassium channel doesn’t work
Adverse side effects of digoxin and cardiac glycosides
- note this is not a 1st line agent and usually used last resort due to low margin of safety*
- prodysrhythmic (due to potassium and sodium being excreted at higher rates)
- visual/neurologic disturbances
- GI effects
- anorexia and vomiting
note taking this with diuretics actually enhances morbidity w/ poor monitoring since potassium is excreted even faster causing hypokalemia
How is digoxin poisoning/overdose treated?
Cholestyramine (binds digoxin and allows excretion)
digoxin immune Fab antibody (binds digoxin and allows secretion but is better
- administered IV w/ immediate onset of action
- taking this will also cause CHF symptoms to show back up
Drug-drug interactions and biological issues to monitor for digoxin and other cardiac glycosides
1) Must monitor electrolytes:
- specifically plasma K+ and Ca2+ levels (can lead to dysrhythmia if not monitored)
2) diuretics (changes electrolytes (specifically potassium) even more dramatically since both digoxin and diuretics promote rapid urination, must monitor even closer)
3) altering glycosides metabolism such as thyroid hormone/barbiturates class 1a and CBBs (can lower metabolism of the drug)
4) altering glycoside absorption such as antacids, bile salt blockers, anti cholinergic and tetracyclines (causes increased apparent dose)
What are the main reasons why cardiac glycosides and digoxin are prescribed?
CHF
Post-MI damage
Atrial fibrilation
note it is NEVER a first line
Isoproterenol
MOA: B1 receptor mediated increases in intracellular cAMP levels by increasing calcium gradient into the cell and promotes calcium release from the sarcoplasmic reticulum
- results in elevated intracellular calcium and membrane excitation/contraction
- will increase BOTH contractility and HR
- used acutely only
Dopamine
MOA:
Neurotransmitter that possess intrinsic activity and serves as a metabolic precursor of NE and epinephrine. Binds to D1 and D2 receptors.
has varying effects based on doses
1) low doses: acts on renal/mesenteric/coronary and intracerebral vasculature
- generates vasodilation, increased renal blood flow and treats edema
2) moderate doses: acts on B1 adrenergic receptors resulting in increased CO w/ vasodilation and cardiac contractility as well as heart rate
- this is the treatment dosage for CHF !!
3) high douses: acts on a1 Adrenergic receptors which increases SVR and renal vasoconstriction
- dont use this unless specifically indicated
Dobutamine
MOA:
Similar to dopamine except is specific for increasing contractility B1 receptor stimulation and less heart rate B1 receptor and a1 receptor activation
- causes increased contractility and stroke volume without causing an increase in heart rate.
- increases cardiac output and preload with decreases in SVR
- There is NO release of NE in response to this drug (compared to dopamine where there is
very indicated for short-term management of acute heart failure especially following an MI (however you cant keep this on people, only for 48hrs, must switch to cardiac glycoside)
PK: infused IV and is hepatic metabolism
How does cardiac glycosides fix hypertrophy?
By Increasing coronary flow to the heart
Phosphodiesterase Inhibtors (Inamrinone and milrinone)
MOA: inhibits cAMP phosphodiesterases that are designed for breaking down cAMP. This therefore increases intracellular calcium. Produce similar effect to positive inotropic agents and often are coadministered with positive inotropic agents
- referred to as “inodilators” since they are IV drugs that also produce vasodilator effects on top of positive inotropic effects
- produce minimal chronotropic effects and also decreases SVR
often used with digoxin
Why are CBBs not used as an adjunct in CHF therapies?
While they can be used, they do produce an overall cardiodepressant action and produce reflex tachycardia
- verapamil is the only one used, especially if prominent LVH is present, and it has to be monitored when first started.
