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In addition, diltiazem and verapamil are used in the treatment of atrial fibrillation. Pharmacokinetics Most of these agents have short half-lives (3 to 8 hours) following an oral dose. Amlodipine has a very long half-life and does not require a sustained-release formulation. Adverse effects First-degree atrioventricular block and constipation are common dose-dependent side effects of verapamil. Verapamil and diltiazem should be avoided in patients with heart failure or with atrioventricular block due to their negative inotropic (force of cardiac muscle contraction) and dromotropic (velocity of conduction) effects. Dizziness, headache, and a feeling of fatigue caused by a decrease in blood pressure are more frequent with dihydropyridines (ure 16. They1 decrease peripheral vascular resistance and lower arterial blood pressure by causing relaxation of both arterial and venous smooth muscle. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Therefore, long-term tachycardia does not occur, but salt and water retention does. Reflex tachycardia and postural hypotension often occur at the onset of treatment and with dose increases, requiring slow titration of the drug in divided doses. Due to weaker outcome data and their side effect profile, α-blockers are no longer recommended as initial treatment for hypertension but may be used for refractory cases. Other α -blockers with1 greater selectivity for the prostate are used in the treatment of benign prostatic hyperplasia (see Chapter 41). It has been shown to reduce morbidity and mortality associated with heart failure. Labetalol is used in the management of gestational hypertension and hypertensive emergencies. Clonidine is used primarily for the treatment of hypertension that has not responded adequately to treatment with two or more drugs.

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Treatment of the metabolic acidosis of renal dysfunction depends on the clinical manifestations and the severity of the acidosis. Most individuals with acute kidney injury can be managed with dialysis or using the guidelines for alkali administration listed previously. There is some recent data suggesting that alkali therapy can slow down the rate of decline in chronic kidney disease and reduce mortality in this setting [10]. While correction of volume depletion is an essential part of initial management of patients with diabetic ketoacidosis, the utility of intensive fluid administration may be limited after the intravascular volume has been restored because volume expansion then leads to the excretion of ketone anions in the urine. Consequently, fluid administration should be tempered after intravascular volume compromise has been corrected. As already discussed, the latter condition pertains to those who have sustained major urinary losses of ketones, rendering them depleted of potential bicarbonate substrate. Reversal of circulatory failure, hypoxemia, or sepsis reduces the rate of lactate production and enhances its removal. The potential benefits of alkali administration principally involve the maintenance of normal cardiovascular homeostasis through correction of acidosis. This potential advantage must be weighed against possible deleterious effects, such as volume overload, hypernatremia, and overshoot alkalosis, after restoration of tissue perfusion. As a result of these potential problems, no concrete recommendations can be made regarding alkali therapy in lactic acidosis. However, if the lactate level increases without a significant improvement in clinical status or blood pH, the benefit of continuing alkali administration should be questioned. It appears that correction of the underlying cause of lactic acidosis is the most important goal, because measures to raise the bicarbonate level without a fall in lactate have not been associated with a reduction in mortality. These findings are consistent with the hypothesis that the high mortality in lactic acidosis results from the underlying disorder causing the acidosis, but not from the acidemia per se. The treatment of toxins and ingestions is discussed in Section on Pharmacology, Overdoses, and Poisonings.

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