Heart failure
What is Heart Failure?A symptom complex due to the inability of the heart to function efficiently as a pump - there is a disproportion between the hemodynamic demand and the capacity of the heart to handle the demand ( Supply ≠ Demand)
Heart Failure
Heart failure occurs when cardiac output is inadequate to provide the oxygen needed by the body. It is a highly lethal condition, with a 5-year mortality rate conventionally said to be about 50%. The most common cause of heart failure is coronary artery disease.If Heart does not contract well (systolic HF) traffic (blood) piles up before the heart (lungs and periphery).
Role of physiologic compensatory mechanisms in the progression of HF
Chronic activation of the sympathetic nervous system and the renin-angiotensin-aldosterone axis is associated with remodeling of cardiac tissue, characterized by: loss of myocytes. Hypertrophy. fibrosis.Sequelae of Heart Failure
Right Heart Failure Systemic venous congestion: distended neck veins. enlarged liver. peripheral edema. ascites.Left Heart Failure Pulmonary edema (Dyspnea)
Symptoms of Heart Failure
Compensated (Asymptomatic) Uncompensated (Symptomatic) Fatigue Dyspnea Orthopnea (shortness of breath (dyspnea) which occurs when lying flat) Paroxysmal Nocturnal Dyspnea Ankle Edema Weight GainAdaptive mechanisms in heart failure Compensated
Goals of pharmacologic intervention in HFTo alleviate symptoms. Slow disease progression. Improve survival.
Summary of drugs used to treat heart failure.
ACE inhibitors (ACEI) - (Oral Meds)The ACE inhibitor are the agents of choice in HFBenazepril - Lotensin Captopril - Capoten Enalapril - Vasotec Fosinopril - Monopril Lisinopril – Prinivil
Angiotensin - converting enzyme inhibitors
Mechansim of action:Angiotensin - converting enzyme inhibitors
Actions on the heart: ACE inhibitors decrease: Vascular resistance. Venous tone. Blood pressure.preload andafterload
ACE inhibitors also blunt the usual angiotensin II mediated increase in epinephrine and aldosterone seen in HF.
Angiotensin - converting enzyme inhibitors,
Indications: Single-agent therapy in patients who present with mild dyspnea on exertion and do not show signs or symptoms of volume overload. In asymptomatic patients with an ejection fraction of less than 35 % (left ventricular dysfunction). (The term "ejection fraction" refers to the percentage of blood that's pumped out of a filled ventricle with each heartbeat.) Recent myocardial infarction also benefit from long-term ACE inhibitor therapy. In patients with all stages of left ventricular failure, with and without symptoms, and therapy should be initiated immediately after myocardial infarction.
ACE inhibitors improve clinical signs and symptoms in patients also receiving thiazide or loop diuretics and/or digoxin. The use of ACE inhibitors in the treatment of HF has significantly decreased both morbidity and mortality.
Angiotensin - converting enzyme inhibitors,
Angiotensin - converting enzyme inhibitors,Adverse effects: postural hypotension, renal insufficiency, hyperkalemia, Angioedema. persistent dry cough. ACE inhibitors should not be used in pregnant women, because they are fetotoxic
Angiotensin receptor blockers, & related agents
losartan (AT1 receptor-blockers) appear to have similar but more limited beneficial effects. Angiotensin receptor blockers should be considered in patients intolerant of ACE inhibitors.Angiotensin receptor blockers, & related agents (ARBs)
extremely potent competitive antagonists of the angiotensin type 1 (AT1)receptor. ARBs have the advantage of more complete blockade of angiotensin action, because ACE inhibitors inhibit only one enzyme responsible for the production of angiotensin II. ARBs do not affect bradykinin levels.Angiotensin receptor blockers, & related agents (ARBs)
All the ARBs are approved for treatment of hypertension based on their clinical efficacy in lowering blood pressure and reducing the morbidity and mortality associated with hypertension. Their use in HF is as a substitute for ACE inhibitors in those patients with severe cough or angioedema.Angiotensin receptor blockers, & related agents (ARBs)
Pharmacokinetics: orally active. require only once-a-day dosing. Losartan, the first approved member of the class, differs from the others in that it undergoes extensive first-pass hepatic metabolism, including conversion to its active metabolite. The other drugs have inactive metabolites. Elimination in the urine and feces All are highly plasma protein bound (greater than 90 percent)
Angiotensin receptor blockers, & related agents (ARBs)
Adverse effects: ARBs have an adverse effect profile similar to that of ACE inhibitors. However, ARBs do not produce cough. ARBs are contraindicated in pregnancy.β -adrenoceptor blockers Most patients with chronic heart failure respond favorably to certain β blockers in spite of the fact that these drugs can precipitate acute decompensation of cardiac function. Studies with bisoprolol, carvedilol, and metoprolol showed a reduction in mortality in patients with stable severe heart failure.Suggested mechanisms include attenuation of the adverse effects of high concentrations of catecholamines.
β -adrenoceptor blockers Most patients with chronic heart failure respond favorably to certain β blockers in spite of the fact that these drugs can precipitate acute decompensation of cardiac function. Studies with bisoprolol, carvedilol, and metoprolol showed a reduction in mortality in patients with stable severe heart failure.Suggested mechanisms include attenuation of the adverse effects of high concentrations of catecholamines.
Diuretics
Common thiazide diuretics Chlorothiazide (Diuril) Indapamide (Lozol) Metolazone (Zaroxolyn) Common loop diuretics Bumetanide (Bumex) Ethacrynic acid (Edecrin) Furosemide (Lasix) Common potassium-sparing diuretics Amiloride (Midamor) Eplerenone (Inspra) Spironolactone (AldactoneDiuretics
Their major mechanism of action in heart failure is to reduce venous pressure and ventricular preload. This results in reduction of edema and its symptoms, and reduction of cardiac size, which leads to improved pump efficiency. Loop diuretics, such as furosemide (Lasix), block the Na+- K+ - 2Cl_ in the ascending limb of the loop of Henle. loop diuretics are still part of the mainstay of therapy for CHF despite these potential problems Spironolactone and eplerenone, the aldosterone antagonist diuretics have the additional benefit of decreasing morbidity and mortality in patients with severe heart failure.Vasodilators
The vasodilators are effective in acute heart failure because they provide a reduction in preload (through venodilation), or reduction in afterload (through arteriolar dilation), or both. Some evidence suggests that long-term use of hydralazine and isosorbide dinitrate can also reduce damaging remodeling of the heart.Drug Therapy - Digitalis Glycosides
Action: Increases the force and velocity of myocardial contraction Digoxin (Lanoxin) Digitoxin (Crystodigin)Purple foxglove - digitalis
Drug Considerations - Digitalis Glycosides
Vasoconstrictor Interaction: concurrent use may increase the risk of cardiac arrhythmias – avoid if possible Oral Manifestations: increased gag reflex, nausea/vomitingOther Considerations: macrolide antibiotics (erythromycin) can increase bioavailability of DG resulting in toxicity; avoid these drugs watch for DG toxicity (tachycardia, N/V, hypersalivation, vision changes, fatigue, HA)DIGITALIS
Introduction Digitalis is the genus name for the family of plants that provide most of the medically useful cardiac glycosides, eg, digoxin.Inotropic Definition
Force of myocardial contraction Positive inotropic drug: increases force of contractions Negative inotropic drug: decreases force of contractionDigitalis Glycosides
Increase force of myocardial contraction. Increase myocardial contractility causing more complete emptying.Causes improved heart’s pumping abilityPharmacokinetics
Absorption: 65-80% absorbed after oral administration. Distribution: widely distributed to tissues, including the central nervous system. Metabolism: Small amount in liver & GI flora. Excretion: Unchanged drug from kidneysPharmacodynamics
At the molecular level, all therapeutically useful cardiac glycosides inhibit Na+/K+ ATPase, the membrane-bound transporter often called the sodium pump.Pharmacodynamics
Cardiac glycosides increase contraction of the cardiac sarcomere , by increasing the free calcium concentration in the vicinity of the contractile proteins during systole. An increase of intracellular sodium concentration because of Na+/K+ ATPase inhibition. Relative reduction of calcium expulsion from the cell by the sodium-calcium exchanger caused by the increase in intracellular sodium, ( contractile force, increases).
Clinical Use
Congestive heart failure: Cardiac arrhythmias: ( atrial fibrillation )Toxicity
Gastrointestinal Salivation Anorexia Nausea Vomiting Diarrhea CNS Headache Visual disturbances characteristic (green yellow halos around bright objects). Fatigue DrowsinessDigitalis is a fat-soluble steroid that crosses the blood-brain barrier and enhances vagal tone This action involves: sensitization of the baroreceptors. central vagal stimulation.
Toxicity
Cardiac Atrioventricular (AV) block. Excessive slowing of the heart supraventricular and ventricular tachycardia.Miscellaneous Excessive urination
Because cholinergic innervation is much richer in the atria. Enhanced vagal nerve activity causes a decrease in sinoatrial beating rate and velocity of atrioventricular conduction. facilitation of muscarinic transmission at the cardiac muscle cellTreatment for digitalis toxicity:
Mild cases that respond to simply stopping the drug temporarily. In severe cases the use of antidigoxin drug, antidote is given intravenously and inactivates digoxin in life-threatening situations.Other positive inotropic drugs
Dobutamine.
The selective β1 agonist that has been most widely used in patients with heart failure. Tachycardia and an increase in myocardial oxygen consumption have been reported. Therefore, the potential for producing angina or arrhythmias in patients with coronary artery disease must be considered.Dopamine has also been used in acute heart failure and may be particularly helpful if there is a need to raise blood pressure.Drugs without positive inotropic effects
Paradoxically, these agents-not positive inotropic drugs-are the first-line therapies for chronic heart failure. In acute failure, diuretics and vasodilators play important roles.Beneficial effects of pharmacologic intervention in HF
Reduction of the load on the myocardium. Decreased extracellular fluid volume. Improved cardiac contractility. Slowing of the rate of cardiac remodeling.IMPLICATIONS FOR DENTISTRY
Stress Factors-Eliminate needless stress for cardiac patients, especially anxiety or pain associated with dental procedures. Patients being treated for heart failure possess limited cardiac function. -These patients are at special risk in stressful situations because stress puts a greater workload on the heart and stimulates the release of endogenous catecholamines. -catecholamines increase the risk of digoxin-induced arrhythmias. -Fear and apprehension may also increase the likelihood of adverse CNS reactions to digoxin. -One practical conclusion is that antianxiety therapy or analgesics should be used preemptively if emotional stress or pain is likely.
Drug Interactions
The use of catecholamines in local anesthetic injections for patients taking digoxin is not contraindicated but should be approached with special caution. Proper injection technique to avoid intravascular injection should be followed. Many factors influence the decision to use vasoconstrictors in local anesthetic solutions, including the ability to achieve adequate anesthesia without vasoconstrictors and the volume of anesthetic solution required. The chief danger of sympathomimetic vasoconstrictors for patients taking digoxin is that the combination of drugs increases the risk of cardiac arrhythmias if significant amounts of vasoconstrictor enter the vascular space- The use of gingival retraction cords impregnated with epinephrine is not recommended in patients taking digoxin. Cardiac disease in general is a contraindication for their use. Considerable amounts of vasoconstrictor may be absorbed systemically from these retraction cords, and the possibility of cardiac arrhythmias developing is significant. If hemostatic retraction cords are to be used in patients who are on digoxin, the cords should be impregnated with an astringent in place of a vasoconstrictor.
Antisialagogues such as atropine and methantheline should not be used in patients taking digoxin because they tend to reduce the effects of digoxin. Muscarinic receptor agonists such as pilocarpine enhance the effect of digoxin on the SA node, the atria, and the AV node. Excessive salivation may be a sign of toxicity owing to digoxin.
Antibiotic therapy may alter the intestinal flora and, in so doing, increase the absorption of digoxin in patients whose gastrointestinal flora metabolizes digoxin. Erythromycin, and presumably other macrolides, has been shown to have this effect. Tetracyclines also seem to interact through this mechanism.