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Dosing requires adjust- dofetilide generic confido 60caps free shipping, which may limit its efficacy when local hy- ment in patients with renal insufficiency cheap confido 60caps line. Dofetilide demonstrates reverse use dependence, that Oral bioavailability >90% is, less influence on the action potential at faster heart Onset of action 0. Because of the lack of significant His-Purkinje System and Ventricular Muscle hemodynamic effects, dofetilide may be useful in pa- Ibutilide increases the ERP of ventricular myocytes tients with CHF who are in need of therapy for and Purkinje fibers but has no clinically significant ef- supraventricular tachyarrhythmias. Electrocardiographic Changes Adverse Effects There are no changes in the PR or QRS intervals, which The incidence of noncardiac adverse events is not dif- reflects a lack of effect on the conduction velocity. Although there is no relationship between the plasma The principal cardiac adverse effect is the risk of tor- concentration of ibutilide and its antiarrhythmic effect, sades de pointes due to QT prolongation. Hemodynamic Effects Contraindications Ibutilide has no significant effects on cardiac output, Contraindications include baseline prolongation of mean pulmonary arterial pressure, or pulmonary capil- the QT interval, use of other QT-prolonging drugs; lary wedge pressure in patients with or without com- history of torsades de pointes; a creatinine clearance of promised ventricular function. Because of extensive first-pass Verapamil increases serum dofetilide levels, as do drugs metabolism, ibutilide is not suitable for oral administra- that inhibit cationic renal secretion, such as ketocona- tion. Oral bioavailability >90% Ibutilide Fumarate Onset of action Minutes Ibutilide (Corvert) is a structural analog of sotalol and Peak response Minutes produces cardiac electrophysiological effects similar to Plasma half-life 3–4 hours (range those of the antiarrhythmic agents in class III. Thus, ibutilide acts by Ibutilide is approved for the chemical cardioversion of blocking the rapid component of the delayed rectifier recent-onset atrial fibrillation and atrial flutter. Ibutilide current (IKr) as well as by activation of a slow inward appears to be more effective in terminating atrial flutter current carried predominantly by sodium. It can also lower the defibrilla- 16 Antiarrhythmic Drugs 191 tion threshold for atrial fibrillation resistant to chemical plasma concentrations that show no effect on the His- cardioversion. Adverse Effects His-Purkinje System and Ventricular Muscle The most important electrocardiographic change The major adverse effect associated with the use of ibu- produced by verapamil is prolongation of the PR inter- tilide is the risk of torsades de pointes due to QT pro- val, a response consistent with the known effects of the longation. Verapamil has no ef- events (all 2%) include hypotension and hyperten- fect on intraatrial and intraventricular conduction. The sion, bradycardia and tachycardia, and varying degrees predominant electrophysiological effect is on A-V con- of A-V block. Hemodynamic Effects Contraindications Usual IV doses of verapamil are not associated with marked alterations in arterial blood pressure, periph- Contraindications to the use of ibutilide include base- eral vascular resistance, heart rate, left ventricular end- line prolongation of the QT interval, use of other QT- diastolic pressure, or contractility. Pharmacokinetics The pharmacokinetic characteristics of verapamil: Drug Interactions Ibutilide has significant drug interactions. Oral bioavailability 20–35% Onset of action 1–2 hours Peak response 1–2 hours CLASS IV Duration of action 8–10 hours Plasma half-life 2.
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Reflex-m ediated cardiac stim ulation elim ination contributes to the cum ulative and pro- is a com m on feature of vasodilator treatm ent and longed effects of the drug confido 60caps amex. G uanethidine reduces blood pressure by its ability A -blocker will reduce the cardiac stim ulation and thus to dim inish vascular tone; both the arterial and venous preserve the effectiveness of the vasodilator buy confido 60caps low price. The result- the vasodilator will prevent the increase in peripheral ing venous pooling contributes to orthostatic hypoten- vascular resistance that occurs on initiation of treatm ent sion, a prom inent feature of guanethidine treatm ent. Furtherm ore, vasodilator treatm ent The reduction in blood pressure is m ore prom inent initiates reflexes that lead to an increase in plasm a renin when the patient is standing than recum bent. This event re- creased venous return and the inability of sym pathetic quires two successive steps: (1) transfer of norepineph- nerve im pulses to release enough transm itters to stim u- rine across the neuronal m em brane into the cytosol by late the heart occur during the early stages of guanethi- an energy-dependent carrier-m ediated active process, dine therapy. A s a consequence of this inhibition of effects that are due prim arily to the im balance between vesicular uptake, norepinephrine cannot be stored in- sym pathetic and parasym pathetic function it produces, traneuronally, and m uch of the cytosolic am ine is m e- it is generally reserved for the treatm ent of severe hy- tabolized by M A O. In addition to im pairing norepinephrine storage and A com m on and troublesom e side effect is postural thereby enhancing its catabolism, reserpine im pairs the hypotension. Sexual im potence does occur, and m ale vesicular uptake of dopam ine, the im m ediate precursor patients m ay have difficulty ejaculating. Since dopam ine m ust be taken up unopposed parasym pathetic activity include such gas- into the adrenergic vesicles to undergo hydroxylation trointestinal disturbances as diarrhea and increased gas- and form norepinephrine, reserpine adm inistration im - tric secretion. The com bined effects of G uanethidine m ay aggravate congestive heart fail- the blockade of dopam ine and norepinephrine vesicular ure or actually precipitate failure in patients with m ar- uptake lead to transm itter depletion. This central pheochrom ocytom a because the drug m ay release cate- transm itter depletion is responsible for the sedation and cholam ines from the tum or. The concom itant use of other CNS side effects associated with reserpine ther- m onoam ine oxidase (M AO ) inhibitors and guanethi- apy. The depletion of brain am ines also m ay contribute dine is also to be avoided, since this com bined drug to the antihypertensive effects of reserpine. A s with other sym pathetic certain other adrenom im etic drugs, that is, biotransfor- depressant drugs, tolerance to the antihypertensive ef- m ation and neuronal uptake. D angerously high concen- fects of reserpine can occur, owing to a com pensatory trations of catecholam ines at receptor sites are possible. Reserpine, am itriptyline) and som e phenothiazines block the sym - therefore, should be used in conjunction with a diuretic.
