By R. Kayor. Providence College. 2017.

The secretory capacity of both the or- This results in a lower concentration of drug in the ganic anion and organic cation secretory systems can be blood coming to the kidneys per unit of time and hence saturated at high drug concentrations order beconase aq 200MDI visa. Peritubular side Luminal side (plasma) (ultrafiltrate) Passive Diffusion An important determinant of the urinary excretion of Organic OA pool OA drugs (i. In general, the movement of drugs is favored from the tubular lumen to blood, partly because of the reabsorption of water that occurs throughout most portions of the nephron, which results in an increased concentration of drug in the luminal Active transport fluid. The concentration gradient thus established will Passive transport facilitate movement of the drug out of the tubular lu- men, given that the lipid solubility and ionization of the FIGURE 4. Hence, a reduction in se- lar secretion may be metabolized to compounds that cretory activity does not reduce the excretory process to are. This is often true for metabolites that are formed as zero but rather to a level that approximates the a result of conjugative reactions. Some substances filtered at the glomerulus are reab- These active secretory systems are important in sorbed by active transport systems found primarily in drug excretion because charged anions and cations are the proximal tubules. Active reabsorption is particularly often strongly bound to plasma proteins and therefore important for endogenous substances, such as ions, are not readily available for excretion by filtration. The the active secretory systems can rapidly and efficiently probable location of the active transport system is on remove many protein-bound drugs from the blood and the luminal side of the proximal cell membrane. Bidirectional active transport across the proximal Any drug known to be largely excreted by the kid- tubule also occurs for some compounds; that is, a drug ney that has a body half-life of less than 2 hours is prob- may be both actively reabsorbed and secreted. Several pharmacologically active urate is probably reabsorbed, whereas that eventually drugs, both anions and cations, known to be secreted are found in the urine is mostly derived from active tubular listed in Table 4. It is important to appreciate that these tubular Most drugs act by reducing active transport rather transport mechanisms are not as well developed in the than by enhancing it. In addition, their functional ca- loss (uricosuric agents, such as probenecid and sulfin- pacity may be diminished in the elderly. Thus, com- pyrazone) probably inhibit active urate reabsorption, pounds normally eliminated by tubular secretion will be while pyrazinamide, which reduces urate excretion, may excreted more slowly in the very young and in the older block the active tubular secretion of uric acid. This age dependence of the rate of renal drug se- plicating observation is that a drug may primarily in- cretion may have important therapeutic implications hibit active reabsorption at one dose and active secre- and must be considered by the physician who prescribes tion at another, frequently lower, dose.

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Epinephrine Norepinephrine A small dose of epinephrine causes a fall in mean Norepinephrine purchase 200MDI beconase aq with mastercard, administered to a normotensive and diastolic pressure with little or no effect on systolic adult either subcutaneously or by slow intravenous in- pressure. The baroreceptor may decrease, remain unchanged, or increase slightly, reflexes are discussed in detail in Chapter 9. The cardiac effects of epinephrine are due to its ac- (2) The reflex initiated is inhibitory, that is, opposite to tion on -adrenoceptors in the heart. Since epinephrine causes little change in the 102 II DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM Norepinephrine Epinephrine Isoproterenol Dopamine 100 50 180 150 120 90 60 10 g/min 0. Heart rate is given in beats per minute, blood pressure in millimeters of mercury, and peripheral resistance in arterial blood pressure. The endothelium can modulate Slow intravenous infusion of therapeutic doses of both vasodilation and vasoconstriction through its ability isoproterenol in humans produces a marked decrease in to locally synthesize and release vasodilators such as nitric total peripheral resistance, owing to the predominance oxide, endothelium-derived hyperpolarizing factor, and of vasodilation in skeletal muscle vascular beds. As a PGI2, and vasoconstrictors such as endothelin, which in consequence, diastolic and mean blood pressures fall turn directly affect vascular smooth muscle activity. The depressor action of isoproterenol is more Stimulation of 2-adrenoceptors located on the endothe- pronounced than that of epinephrine because isopro- lial cells in certain vascular beds (such as the coronary ar- terenol causes no vasoconstriction, whereas epinephrine tery) results in the release of nitric oxide and vasodilation. Systolic blood pressure may In any blood vessel, the final integrated response to remain unchanged or may increase. When an increase in either neuronally released norepinephrine or to circu- systolic blood pressure is seen, it is due to the marked in- lating epinephrine probably depends on the relative crease in cardiac output produced by isoproterenol. This is ate constriction of vascular smooth muscle, while pre- partly due to its ability to decrease mean blood pres- junctional and endothelial 2-adrenoceptors mediate sure, which then reflexively diminishes vagal activity, vasodilation. Effects on Vascular Smooth Muscle Postjunctional 1-adrenoceptors are always found in Effects on Nonvascular Smooth Muscle veins, arteries, and arterioles. Activation of these recep- tors results in the entry of extracellular calcium through In general, the responses to administered catechol- receptor-operated channels and in the release of intra- amines are similar to those seen after sympathetic nerve cellularly stored calcium; this is brought about through stimulation and depend on the type of adrenoceptor in the participation of the inositol triphosphate second- the muscle. Most of these are mediated through an and isoproterenol through their interaction with 2- interaction with -adrenoceptors.