DRUG INDUCED CARDIOVASCULAR DISEASE:
HEART FAILURE (HF).
Coronary artery disease is the most common cause of heart failure (HF) Left ventricular ejection fraction (LVEF). Although drug-induced-heart-failure in patients without pre-existing left-ventricular-dysfunction is rare, and with pre-existing left-ventricular-dysfunction is more common. Other causes include (hypertension, myocarditis, and cardiac toxins, including drugs, which can exacerbate a stable pattern of HF. An identified precipitant of exacerbations of acute with heart-failure-reduced-ejection-fraction HFrEF was excessive salt intake (22%), antiarrhythmics, and calcium-channel blockers were all implicated. Interestingly, medications were not the primary cause of any exacerbations; rather, nonadherence to salt restrictions, followed by other noncardiac causes (URTI), common causes of excerbations.Many drugs can induce HF by reducing myocardial contractility (calcium-channel blockers, antiarrhythmic, anthracyclines, β-blockers), increasing preload (glitazones, NSAIDs, COX-2 inhibitors, corticosteroids), and increasing afterload (sympathomimetics, NSAIDs, and COX-2 inhibitors [vasodilatory-vasoconstrictive prostaglandins]).Mortality ratio with HF is very high, an annual mortality incidence of 5–10% in patients with mild disease and up to 30–40% in advanced disease. Mortality ratio in-hospital with HF is 3.5–15%.
CALCIUM-CHANNEL BLOCKERS are antagonism of L-type Calcium channels. They have negative inotropic effect, but their net effect on heart and symptoms depends on other hemodynamic effects in patient’s with cardiac dysfunction. Verapamil and diltiazem should be avoided in patients (HFrEF) because of strong negative ionotropic effects. Nifedipine also exacerbate HFrEF requiring hospitalization and should be avoided in patients with left-ventricular-dysfunction.Felodipine and amlodipine are effective for HF. Although other alternatives are available (long-acting nitrates, β-blockers, and ivabradine).
GLITAZONES appears hemodynamic effects in patients with HF. It increase plasma volume by 6–7%. Mechanism is unknown, may be increased by endothelial-cell-permeability. This Fluid retention is treated with loop diuretics but it’s reversible upon discontinuation of therapy. However, studies suggest that diuretics active in the distal collecting duct (hydrochlorothiazide and spironolactone) may be reduces fluid retention associated with glitazones.RISK: Tang et al. noted upon univariate analyses that females and insulin users were increased risk of fluid retention.
ANTIARRHYTHMIC AGENTS reduce myocardial contractility, the net effects on balancing hemodynamics. Disopyramide, flecainide, propafenone, and nondihyropyridine calcium-channel blockers have strongest negative inotropic effects, whereas amiodarone, ibutilide, and dofetilide have negligible negative inotropic effects. An investigators postulated that dronedaron directly or indirectly worsen HF in those with pre-existing poor systolic function, but mechanism still unknown.RISK: patients with HFrEF are risk for sudden cardiac death. Risk, benefit evaluation is extremely important because it further worsening HF symptoms.
ANTHRACYCLINES induced HF have not elucidated, oxidative damage may play a role. Formation of toxic metabolite, free radical generation, interference with intracellular calcium transport and myocardial β-adrenergic stimulation, reduced ADP–stimulated respiration, or release of excessive vasoactive compounds have suggested as possible mechanisms. Recovery from anthracycline-induced-heart-failure after doxorubicin-induced cardiac dysfunction. The risk of cardiac dysfunction is largely dose-dependent, cardiotoxicity occur with low doses in high-risk individuals.RISK: There is increased risk of development of doxorubicin-induced HF with increasing age. However, this drug incidence higher in children than in adults. All three of these risk factors (total dose, schedule of administration, and age) are independent predictors in multivariate analysis.
BIOLOGIC AGENTS: INfliximab binds with high affinity to TNFα, inhibiting binding with its receptor. Blocking the effect of TNFα, combined with other CV risk factors in patients with rheumatoid arthritis can cause HFrEF.RISK: Risk factors include older age, higher body-mass index, antihypertensive therapy, lower pretrastuzumab LVEF, cumulative anthracycline dose, rheumatoid arthritis, and history of coronary heart diseaseNSAIDs inhibits COX enzyme. In patients with HF, kidney homeostasis maintained by renal PGE2. Inhibition cause disrupts kidney homeostasis, leads to sodium and water retention (similar as NSAIDs) and exacerbates symptoms of HF. These drugs also antagonize the actions of ACE inhibitors and diuretics. Beta-BLOCKERS reduce myocardial contractility through competitive antagonism of β1-receptors.It initially exacerbate HF at high dose. However, during chronic therapy, carvedilol,metoprolol, and bisoprolol have improve LVEF and to reduce the incidence of HFrEF hospitalization. Differential diagnosis of drug-induced versus other causes of heart may be difficult to distinguish from other common precipitants, such as sodium and fluid excess, ischemia, poor adherence to medical therapy, uncontrolled hypertension, arrhythmias (especially atrial fibrillation), systemic infections, impairment in kidney function, anemia, thyrotoxicosis, ethanol ingestion, pulmonary embolism, and respiratory insufficiency
PREVENTION:These drugs (diltiazem, verapamil, disopyramide, flecainide, and propafenone) should be considered contraindicated in patients with HF or asymptomatic left-ventricular-dysfunction.Alternatives to glitazones for control blood sugar include insulin secretagogues (e.g., sulfonylureas, meglitinides), metformin, α glucosidase inhibitors, incretin agents, and insulin.Pharmacists can identify drug-induced causes of exacerbative symptoms of HF, guide treatment choices to avoid this condition, counsel patients with HF on the use of OTC medications, and ensure that patient receiving all efficacious therapies(ACE inhibitors, β-blockers, spironolactone, digoxin) at targeted doses.
