Exam 1: Lecture 9: Heart Failure 2 Flashcards
What % of CO should kidney get?
about 25%
3 Categories of drugs used in HF
Positive Inotropic drugs
Vasodilators
Misc drugs for chronic failure
Ways in increase isotropy?
Sympathetic Activation
Circulating Catecholamines
Heart Rate (Bowditch effect)
Afterload (Anrept effect)
Parasympathetic (Vagal) Inhibition
Positive Bowditch effect “staircase effect or Treppe effect”
Described by Henry Pickering Bowditch in 1871
Summarized: Tension of heart muscle will increase as HR increases.
leads to increase in CO, due to increased in Ca in SR…not enough time/efficiency in mechanisms that remove Ca between heart beat.
Main player = NCX (Sodium/Calcium exchanger)
Woodworth effect
higher than normal systolic peak following Bowditch effect
Negative Bowditch effect
Can be caused by some drugs
Increase in HR = decrease in tension
can be due to mutations or negative regulation of SERCA2a or phospholamban
Anrep effect
myocardial tension increases with afterload
consistent with Frank-starling law.
Digoxin (Lanoxin)
Cardiac glycoside, only one that’s currently clinically important
Comes from foxglove
Indicated: A.fib, HF and abortion
Mech: Positive inotrope, inhibit myocardial Na/K ATPase
No longer a 1st line heart failure
Side effects: Narrow TI, Atrial arrhythmia, A-V conduction block, Gynecomastia (feminization)
OD treated with anti-digoxin antibody
Digoxin Mechanism of action
Inhibit Na/K-ATPase = Block Na leaving cell leaving it more depolarized, changing efficacy of NCX and increases Ca conc in cell, increases Ca release from SR and stimulates contractile machinery
Oubain
Used to be used therapeutically but no more. Used experimentally
Positively inotropic, making Ca conc go way up = increase contraction.
Has very low TI
after period of time/inc conc it can cause secondary sub threshold AP = bad
Dobutamine
B-receptor agonists
** B1-receptor specific agonist racemate **, considered B1-specific
usually IV
Positive inotrope that increases CO, little effect on HR
Indicated: cariogenic shock, septic shock and acute or potentially reversible HF
side effect: Hypertension, angina, tachyarrhythmia
(+) isomer of Dobutamine effects on…
B1-agonist, a1-antagonist and a weak-agonist at B2 (vasodilator)
(-) isomer of Dobutamine effects on…
B1-agonist and a1-agonist
Phosphodiesterase inhibitors (PDEi)
Focus on Type3 (PDE), leading to accumulation of more cAMP by preventing it from being turned into AMP
Cardiovascular actions of PDEi
increase systemic circulation via vasodilation
increase organ perfusion, decrease systemic vascular resistance and arterial pressure
Cardiopulmonary actions of PDEi
increase contractility and HR (+ inotropic/chronotropic)
increase stroke volume and ejection fraction
decrease ventricular preload (2ndary to increased output)
Milrinone
PDE3 inhibitor
a bipyridine available as Primacor
Indicated: HF or pulmonary arterial hypertension (RV into Lung) and also used in acute severe asthma
Side effect: Ventricular arrhythmia, hypotension, headache and dizziness
Aldosterone Antagonists
“K+ sparing diuretics”
inhibit mineralocorticoid receptor upregulation, decreasing ENaC and Na/K+ ATPase in DCT, increasing Na/H20 excretion and K+ retention
Spironolactone has off target effects, Eplerenone is more specific but has lower Emax
Spironolactone
“K+ sparing diuretic”
Competitive inhibitor of aldosterone receptor, also blocks effects of testosterone and other hormones
Indicated: HF, edema, primary hypertension. issues with androgens such as hirsutism and PCO
Indicated in HF where EJ < 35%
side effects: increased urination, hyponatremia, hypotension, Ataxia, Feminization
Eplerenone
“K+ sparing diuretic”
More selective for receptor than spironolactone, but 50% Emax
Indicated: Chronic HF, primary hypertension
side effects: Increased urination, Hyponatremia, hypotension
Atrial natriuretic peptide (ANP)
is release by cardiac atria when the muscle is stretched in response to expanded blood volume….promotes physiology that decreases BV
Physiology that decreases Blood volume?
increase vasodilation, decrease production of aldosterone, increase natriuresis, diuresis, EJ and decrease BP
3 major naturetic peptides
A,B and C naturetic peptides.
BNP secreted by heart ventricles
How do naturetic peptides have effect?
Receptors are located on tissues throughout the body
A-type naturetic receptor
Selective for ANP and BNP
Nesiritide
Synthetic BNP, administered as IV
developed for acute decompensating HF
Overall, found it doesn’t really work more than placebo
Side effects: Hypotension, Headache, Bradycardia and Kidney failure
Positive inotropic drugs?
Cardiac glycosides
Beta agonists
PDE inhibitors
Vasodilators
PDE inhibitors
Nitrates, nitroprusside, hydralazine
Loop diuretics
