Heart Failure Drugs
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| Determinants of oxygen demand by heart (4): | Diastolic filling pressure, affected by blood volume and venous tone.
Resistance to ejection of stroke volume during systole, which depends on BP and arterial tone.
Heart Rate.
Contractility
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| Types and examples of groups of drugs that decreases oxygen demand by lowering determinants (3): | Beta blockers: eg. proponolol, atenolol and labetalol.
Calcium channel blockers: eg. verapamil, nifedipine
Nitrates: eg. nitroglycerin.
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| Beta blockers: mode of action on heart | Affected largely by B2 recept. activated B2 receptors release cAMP -> influx of Ca into cells -> ^ contractility. Also ^ HR by stimulating SA&AV node. B blockers antagonise these effects and also help w/ hypertension by reducing renin pdtn by kidney.
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| Beta blockers: mode of action on lungs and smooth muscle | Affected predominantly by B1 receptors, therefore should not use non-selective on asthmatic patients, as it may precipitate asthma attacks due to bronchoconstriction.
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| Beta blockers: uses | CHIG:
Cardiac arrythmias (since catecholamines ^ HR), Hypertension (v renin pdtn and contractility), Ischaemic heart disease (decreasing oxygen demand from heart) and Glaucoma (reduces intraocular pressure by reducing aqueous humour production)
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| Beta blockers: toxicity and contraindications | WEBS: Withdrawal symptoms (drug dose must be tapered off), Erectile dysfunction, Bradycardia (presents as coolness of extremities) and Sedation (since catecholamines increases anxiety)
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| Calcium channel blockers: summary (refer to anti-hypertensives for more detailed questions) | Eg. Verapamil and Nifedipine. Blocks Ca channels, decreases Ca influx into cells -> relaxes smooth muscle. Vascular muscle particularly affected, esp arterioles, and so does not cause orthostatic hypotension. reduce contractility and SA AV node conduction
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| Nitrates: Mode of action & example | Nitroglycerin. Taken up into smooth muscle cells and de-nitrated. Nitrite ion is then released and converted into NO, which relaxes all types of smooth muscle
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| Nitrates: Uses | Relaxes all vascular smooth muscle, which ^ venous capacitance and v ventricular preload -> reduces oxygen demand of heart and CO. Increases coronary blood flow as epicardial coronary arteries affected. Decreased preload and afterload good for angina.
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| Nitrates: toxicity | Major vasodilation -> hypotension -> baroreceptors activated -> tachycardia. Also increases tolerance
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| Signs & symptoms of heart failure | Tachycardia, dyspnoea, orthopnoea, nocturnal paroxysmal dyspnea, pulmonary edema, peripheral edema, cardiomegaly, decreased exercise tolerance.
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| Drug used in heart failure: | Cardiac glycosides/ Digitalis
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| Cardiac glycosides: mode of action | Inhibits Na/K ATPase, increasing intracellular [Na] -> less Ca efflux (^ free Ca in sarcomere during systole) -> stronger systolic contractions. Affects both normal and failing heart.
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| Cardiac glycosides: effects | on heart: digoxin -> ^ contractility -> ^CO -> ^carotid sinus receptor & renal blood flow -> decreased sympathetic activity & deactivation of RAAS -> decreased preload & afterload. There is a decrease in QT & ST interval, inversion of T.
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| Cardiac glycosides: uses | Heart failure and atrial fibrillation, back up choice after ACEI and diuretics.
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| Cardiac glycosides: toxicity | Cardiac problems eg. a&v fib, premature ventricular depolarisation. GIT (nausea, vomiting, anorexia), Headache, confusion, fatigue, blurred vision. Rarely, gynecomastia.
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| Cardiac glycosides: treatment of toxicity | Reduce or stop treatment if side effects include vision & GIT. Correct K or Mg deficiency and anti-arrythmatic drugs to prevent cardiac arrest.
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| Cardiac glycosides: drug interactions | K+ & digitalis inhibit each other's binding to Na/K ATPase, therefore hypokalemia will increase effect of digitalis. HyperCa might worsen action as ^ Intracellular Ca. Mg has opposite effect of Ca. Verapamil ^ [digoxin]. Interaction w corticosteroids.
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