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USMLE - Pharm
Kaplan Section 3 Chapter 4 CHF Drugs
Question | Answer |
---|---|
What is the main problem in heart failure? | defects in cardiac contractility --> inadequate CO |
Name some signs/symptoms of CHF | dec exercise tolerance, muscle fatigue, dec BP, myocardial hypertrophy |
Talk about reflex compensation for dec mean BP in HF pt | Inc SANS reflex --> 1. tachy, 2. inc arterial tone (inc afterload, dec CO, dec renal perfusion), 3. inc venous tone (inc preload, inc fiber stretch). Activation of renin-ANG system --> edema, dyspnea, pulmonary congestion (due to inc volume retention) |
To decrease preload in CHF, which drugs should you use? | Diuretics, ACEi's, AT-1 antagonists, and vasodilators (DAAVe) |
To decrease afterload in CHF, which drugs should you use? | ACEi's, AT-1 antagonists, and vasodilators (AAVe) |
To increase contractility in CHF, which drugs should you use? | Digitalis, B agonists, bipyridines (DoBBy) |
Why are ACEi's used prophylactically post-MI? | Opposes the "remodeling" in the heart that can lead to heart failure. |
What does bradykinin do? | Vasodilation |
What does ACE do to bradykinin? | ACE breaks down and inactivates bradykinin. ACEi spares bradykinin, promoting vasodilation via bradykinin. |
What are the primary drugs used for mangagement of heart failure? | ACEi's. |
What do cardiac glycosides do? Give example of a cardiac glycoside. | Digitalis. Block Na/K ATPase --> increase contractility |
What is the mechanism of digitalis? | Block Na/K ATPase (2 K in/3 Na out)-->dec 3 Na+ (in)/2 Ca2+ (out) exchange-->inc Ca2+ in cytoplasm-->inc Ca2+ into sarcoplasmic reticulum-->inc Ca2+ release-->Ca2+ bind to troponin--> tropomyosin moves-->actin & myosin interact-->inc contractility |
How is digitalis affected by potassium levels in the body? | Digitalis binds to and blocks the Na/K ATPase to eventually increase contractility in the heart. K+ inhibitis this binding. Therefore, hyperK+ decreases the effectiveness of digitalis, and hypoK+ increases its effects and can lead to toxicity. |
How do Mg and Ca affect digitalis? | toxicity of the drug is increased by hyPOMg and by hyPERCa. |
How does an increase in cardiac contractility benefit heart failure patients? | block Na/K ATPase (2 K in/3 Na out) --> inc contractility --> inc CO --> reverses the compensatory tachy, the inc in BP, & the inc in TPR. Better renal perfusion and diuresis. |
Talk about the direct actions of digitalis as they pertain to the AV node, the atria, and the ventricles | Direct: inhibition of the Na/K ATPase. Dec conduction velocity in AV node; dec AP duration and ERP in atria and ventricles; inc abnormal automaticity and arrhythmias in atria. |
Talk about the indirect actions of digitalis as they pertain to the AV node, the atria, and the ventricles | Ach-mimic --> vagal stimulation. Inc ERP and dec conduction velocity (possible AV block) in AV node. Dec SA nodal rate in atria. |
Talk about the B1-like actions of digitalis as they pertain to the AV node, the atria, and the ventricles | Positive chrono, dromo, and inotropy. Dec refractory period (possible AV nodal tachy) in AV node. Inc SA nodal rate in atria. Inc conduction velocity in both atria and ventricles. Inc phase 4 slope and inc abnl automaticity in ventricles. |
Half life of digoxin | 20-40 hrs |
What can digitalis be used for? | CHF, supraventricular tachy arrhythmias (e.g. aFib), slow inc in AV conduction by quinidine. |
Early toxicities of digitalis | Early anorexia, nausea, ECG changes (dec QT, T-wave inversion, premature ventricular contraction, bigeminy). |
Later toxicities of digitalis | CNS: disorientation, visual halos, hallucinations. |
Severe cardiac toxicities of digitalis | SVT's, Avnodal tachy's, AV block, ventricular tachy's, or vFib. |
In which patients should you absolutely avoid digitalis? | Wolf Parkinson White arrhythmias. |
Inamrinone | Bipyridine. Inc contractility in CHF. Inhibit phosphodiesterase --> inc cAMP --> inc inotropy (contractility) and vasodilation. |
Milrinone | Bipyridine. Inc contractility in CHF. Inhibit phosphodiesterase --> inc cAMP --> inc inotropy (contractility) and vasodilation. |
Amrinone | Bipyridine. Inc contractility in CHF. Inhibit phosphodiesterase --> inc cAMP --> inc inotropy (contractility) and vasodilation. |
Why wouldn't you want to use Milrinone? | Decreases survival in CHF! Milly kills people! |
Side effect of amrinone | thrombocytopenia (low blood platelets) |
What is chronotropy? | heart rate |
What is dromotropy? | conduction velocity |
What is inotropy? | contractility |
What is tachyphylaxis? | The rapidly decreasing response to a drug or physiologically active agent after administration of a few doses |
Which drugs are commonly used in chronic heart failure? | Diuretics. Inc elimination of Na and H2O --> less volume --> dec preload and afterload --> relieve sx's of heart failure. |
What is special about using spironolactone in conjunction with ACEi's for heart failure patients? | This combo reduces mortality. |
Nesiritide | recombinant human B-type natriuretic peptide. Activate the BNP receptor --> inc cGMP --> relax smooth muscles of veins and arteries. |
When should you use nesiritide? | In decompensated CHF patients who have dyspnea at rest with minimal activity. |
What are the big classes of drugs you can use for the treatment of CHF? | ACEi's (-oprils), AT-1 antagonists (-artans), cardiac glycosides (to inc contractility, digitalis), bipyridines (inhibit phosphodiesterase), sympathomimetics (dobutamine, dopamine), diuretics (thiazide, loop), B blockers (carvedilol), CaCB's (amlodipine), |