Vascular system drug effects

In reviewing intraarterial infusion of microencapsulated anticancer agents and its clinical applications, Nemoto (124) concluded that this mode of treatment can be used for a wide variety of tumors, providing remarkable therapeutic effects with minimal systemic toxicity. However, 25% of the treated tumors failed to respond, which was thought to be attributable to either inadequate catheterization, inadequate dose relative to tumor size, insufficient tumor vascularity, low drug sensitivity, or a combination of these factors. More carefully designed studies will be necessary before this technique is likely to meet with widespread acceptance. 

Diuretics increase the formation and excretion of urine. These drugs are used as antihypertensive agents because of their ability to increase the renal excretion of water and sodium, thus decreasing the volume of fluid within the vascular system. This situation is somewhat analogous to the decrease in pressure that would occur inside a balloon if some of the air inside were allowed to leak out. Consequently, diuretics appear to have a rather direct effect on blood pressure... 

The use of ACE inhibitors in treating heart failure has therefore increased dramatically over the last several years.53 There is evidence that these drugs should be used even more extensively and in higher doses, especially in the early stages of this disease.32,48 By reducing the detrimental effects of angiotensin II on the vascular system, early use of ACE inhibitors may prevent or delay the progression of this disease (see the next section, Effects and Mechanism of Action of ACE Inhibitors ). 

Diuretics work by inhibiting the reabsorption of sodium from the nephron, which, in turn, decreases the amount of water that is normally reabsorbed with sodium, thus increasing water excretion. This effect reduces congestion caused by fluids retained in the body and decreases cardiac preload by excreting excess fluid in the vascular system. Chapter 21 provides a more detailed discussion on the mechanism of action of diuretic drugs. 

Nitroprusside [nye troe PRUSS ide] is administered intravenously, and causes prompt vasodilation, with reflex tachycardia. It is capable of reducing blood pressure in all patients, regardless of the cause of hypertension. The drug has little effect outside the vascular system, acting equally on arterial and venous smooth muscle. [Note Because nitroprusside also acts on the veins, it can reduce cardiac preload.] Nitroprusside is metabolized rapidly (t1/2 of minutes) and requires continuous infusion to maintain its hypotensive action. Sodium nitroprusside exerts few adverse effects except for those of hypotension caused by overdose. Nitroprusside metabolism results in cyanide ion production, although cyanide toxicity is rare and can be effectively treated with an infusion of sodium thiosulfate to produce thiocyanate, which is less toxic and is eliminated by the kidneys (Figure 19.14). [Note Nitroprusside is poisonous if given orally because of its hydrolysis to cyanide.]... 

Acute drug effects on blood pressure are the result of changes in peripheral vascular resistance, cardiac output, or both. Recent unpublished results in the authors laboratory, using the pressure-volume conductance system (Pacher et al. 2003 and 2004 Fig, 2) in pentobarbital-anesthetized mice in vivo, indicate that the hypotensive effect of (-)-ll-OH-A -THC dimethylheptyl (HU-210) results primarily from a decrease in cardiac contractility (Fig. 2). In contrast, anandamide reduces both... 

---