Term
| what are the 2 kinds of CHF? |
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Definition
| forward and backward failure |
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Term
| what is forward failure CHF? what drugs are used in this situation? |
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Definition
| systolic dysfunction, inability to pump forward to maintain CO, decreased BP is the main consequence. BP = CO x PR. *this is really where cardiotonic drugs are used* - used mainly in acute livesaving situations, where the person is going to die (if the person is on these for a long period of time you can get cardiac remodeling where the ventricles are hypertrophic and stiff, can't fill with blood) |
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Term
| what is backward failure CHF? |
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Definition
| diastolic dysfunction due to inadequate relaxation to permit filling - causes cardiac/pulm congestion/fluid accumulation - ability to pump forward may increase when filling pressure is increased (when there is cardiac congestion) |
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Term
| increasing preload increases what? how does this affect CHF? |
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Definition
| HR, SV, and CO. increase of preload will worsen congestion/edema in CHF - in these situations, a decrease in preload is desired. |
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Term
| how can a decrease in preload be accomplished in CHF? |
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Definition
| with venodilators (nitrates) and diuretics (thiazides and loop diuretics) |
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Term
| how does increasing afterload affect pts with CHF? |
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Definition
| increasing afterload will decrease CO, the heart has to work harder to overcome increased peripheral resistance before ventricular ejection will occur |
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Term
| how does decreasing afterload affect pts with CHF? |
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Definition
| decreasing afterload in pts with CHF with arterial vasodilators (ACE inhibitors) will increase CO, because the heart doesnt have to work as hard to eject blood from the L ventricle |
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Term
| what is an example of neurohormonal activation in CHF? |
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Definition
| RASS (renin-angiotensin-aldosterone system) activation which initially will compensate for decreased CO along with the sympathetics, but if prolonged - this activation is deleterious and leads to cardiac remodeling/disease progression |
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Term
| what is the effect of reduced CO on the kidneys? |
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Definition
| reduced CO leads to reduced renal blood flow, which causes the kidneys to increase renin, which is an enzyme that converts angiontensinogen into angiotensin I, which is then converted by AC enzymes to angiotensin II - which is a very potent vasodilator that also causes the release of aldosterone from the adrenal glands (causes an increase in water reabsorption in the kidney) |
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Term
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Definition
| angiotension converting enzyme (angiotensin I -> angiotensin II) inhibitors |
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Term
| what are the short/long term effects of angiotension II? |
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Definition
short: increased vasoconstriction, increased preload/afterload, increased sympathetic firing (mainly due to decrease carotid sinus firing and subsequent baroreceptor reflex - kicks up HR/BP)
long: remodeling |
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Term
| what is the vicious CHF cycle? |
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Definition
| decreased CO, causing the body's continual release of sympathetics that ultimately increase afterload, which then decrease CO again, and etc |
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Term
| what are the 3 drugs we need to know for CHF? what is their intended effect? |
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Definition
| inotropic drugs consisting of digitalis glycosides (digoxin), sympathomimetics (dobutamine), and phosphodiesterase inhibitors (milrinone AND inamrinone) -> all intended to increase contractility via increase in intracellular Ca++ in the myocytes |
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Term
| what is the M/A for digoxin? |
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Definition
| it inhibits the Na+/Ka+ ATPase (moves Na+ out, K+ in), which is responsible for moving Na+ out of the cell. the main intended consequence of this is on the Na+/Ca+ exchange enzyme (also on the membrane), which usually brings Na+ back in - but since most of it never moved out due to digoxin blockade of the Na+/Ka+ ATPase - there is less Na+ to move out, and Ca+ stays put in the cell as a result - higher level of muscular activity |
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Term
| what is the danger with digoxin? |
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Definition
| it can induce preventricular contractions due to higher levels of Ca++ in the myocytes |
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Term
| what is the intracellular Ca++ called? |
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Definition
| "trigger Ca++" - activates release of more Ca++ from the sarcoplasmic reticulum |
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Term
| how does Ca+ stimulate the myocytes? |
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Definition
| Ca++ binds to troponin which allows the interaction of actin and myosin = heart contractility |
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Term
| what is the chemical structure of digoxin? |
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Definition
| a steroid nucleus with a lactone ring as well as sugar residues - it is lipid soluble -> will penetrate CNS |
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Term
| what are the 2 main effects of digoxin? |
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Definition
positive inotropic (heart contraction) effect: inhibition of Na/K ATPase which promotes increased intracellular Ca
negative chronotropic (heart rate) effect: dig stimulates the vagus nerve, which slows the HR down - PR interval increases (OD can cause bradycardia & heart block 1/2/3 degree) |
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Term
| what are the EKG effects of digoxin? |
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Definition
| the AP is shortened in phases 1-3, appearing on the EKG as a shortened Q-T interval w/S-T segment depression - ***phase 4 is automatically increased (due to increased automaticity which can promote the development of afteroptentials, leading to ectopic beats - PVCs, is b/c the less negative you are, the easier it is to generate another AP) |
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Term
| how does digoxin affect the SA & AV nodes? |
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Definition
| digoxins vagal effects decrease HR and AV conductions, increasing the PR interval and decreasing automaticity of the SA & AV nodes |
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Term
| can digoxin activate latent ventricular pacemaker activity, resulting in ectopic beats? |
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Definition
| yes, PVCs are a risk for digoxin |
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Term
| what is the therapeutic index for digoxin like? half life? |
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Definition
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Term
| what are the clinical uses for digoxin? |
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Definition
CHF: inotropic agent for systolic dysfunction
antiarrythmia: slow AV conduction (induce 1st degree heart block in order to slow ventricular rate/allow greater filling - but an OD can cause almost every type of arrhythmia including v-fib) |
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Term
| is digoxin subject to electrolyte/drug interactions? |
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Definition
| yes. hypokalemia often due to K-losing diuretics increasing dig toxicity (competes with Na/K ATPase, keeps dig around longer) and hyperkalemia due to ACEIs/K-sparing diuretics (spironolactone) reduce dig toxicity. hypercalcemia/increased intracellular Ca increases dig effects/toxicity, hypermagnesium reduces dig activity and quinidine increases dig toxicity |
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Term
| how do beta 1 agonists (such as dobutamine) work in comparison to digoxin? |
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Definition
| beta 1 agonists will stimulate the beta 1 receptor, which disassociates the gs protein, from which the alpha subunit then dissociates and stimulates adenyl cyclase to bump up cAMP, which is a 2nd messenger that phosphorylates protein kinase C, which gives PKA which phosphorylates the Ca++ channel -> allowing it to come down its concentration gradient |
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Term
| how do phosphodiesterase inhibitors such as milrinone work in comparison to digoxin and beta 1 agonists? |
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Definition
| milrinone inhibits phosphodiesterase, keeping cAMP from being degraded to AMP and allows it to continue stimulating PKA which phosphorylates the Ca++ channel -> allowing it to come down its concentration gradient |
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Term
| what is the effect of dobutamine? when is it used? |
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Definition
| increased CO, SV w/out marked increase in HR. it is used in acute congestive heart failure |
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Term
| what is the intended effect of the phosphodiesterase inhibitors and when are they used? |
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Definition
| milrinone and inamrinone are used for acute CHF and increase CO. they can also vasodilate |
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Term
| how do ACEIs/beta *blockers* help with CHF? |
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Definition
| ACEIs arteriodilate/venodilate, which reduces preload/afterload and thus pulm edema/congestion and PR. they block the RAA and SNS, slowing the progression of CHF and prevent deleterious cardiac remodeling |
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Term
| can successful tx of heart failure reduce HR? |
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Definition
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Term
| can atropine negate the PR interval lengthening effect of digoxin? |
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Definition
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