0-Adrenergic antagonist

The general clinical applications of alpha and beta antagonists are presented below. Specific agents within each major group are also discussed. 

It will increase the concentration of transmitter in the synaptic cleft and, therefore, the postsynaptic stimulatory action. 

The postsynaptic cells will respond with a reduction of receptors exposed on the surface. This is one of the effects leading to a fairly rapid and noticeable decrease 

It will increase the pres niaptic negative feedback, reducing both the rate of transmitter release and (by regulation at the genetic level) the amount of S5mthetic en-z mies,e.g. of tyrosine hydroxylase. 

The intracellular pool of transmitter will be depleted. This will disinhibit tyrosine hydroxylase at the protein level, and therefore the actual turnover of S5mthesis will be increased, despite the reduced prevalence of S5mthet-ic enz5mies. 

there are various dmgs with different ranges and specificities. Cocaine has a particularly broad spectrum, affecting the reuptake of norepinephrine, dopamine, and serotonin alike. The effect of cocaine can be quantitatively studied in mice by observing their excitement in response to being placed into a new environment, which is measured simply as the distance travelled within their new home over time. In experiments with transgenic mice, the reuptake transporters for both dopamine and serotonin had to be deleted in order to abolish the increase in excitement induced by cocaine. 

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In order to improve the properties of the well-known adrenergic antagonist, two chemical modulations on classical drugs including NO-donor moiety have been described. On the one hand, chemical modifications on Prazosin, an a 1-adrenergic antagonist, including furoxanyl moieties have been reported [70,182,183]. hi this approach, the 2-furanylcarbonyl moiety of Pra-... 

Carvediol is a vasodilator with beta-adrenergic antagonist activity. It has cardioprotective activity in animal models. The antioxidant effect of carvediol was compared with five other beta blockers in iron-initiated lipid peroxidation, where it inhibited TBARs formation and protected membrane-bound tocopherol in rat brain homogenate (Yue et al., 1992a). The ortJ <)-substituted phenoxylethyl-amine is responsible for the improved antioxidant activity. 

Identify factors that guide selection of a particular a-adrenergic antagonist for an individual patient. 

Compare and contrast a-adrenergic antagonists versus 5a-reductase inhibitors in terms of mechanism of action, treatment outcomes, adverse effects, and interactions when used for management of benign prostatic hyperplasia. 

Among the a-adrenergic antagonists, alfuzosin is considered functionally uroselective because in usual therapeutic doses, it produces relaxation of the bladder neck and prostatic smooth... 

Stromal tissue is the primary locus of aradrenergic receptors in the prostate. It is estimated that 98% of the a-adrenergic receptors in the prostate are found in prostatic stromal tissue. Of the arreceptors found in the prostate, 70% of them are of the a1A-sub-type.5 This explains why a-adrenergic antagonists are effective for managing symptoms of BPH.6... 

For patients with moderate to severe symptoms, the patient is usually offered drug treatment first. a-Adrenergic antagonists are preferred over 5a-reductase inhibitors because the former have a faster onset of action (days to a few weeks) and improve symptoms independent of prostate size. 5a-reductase inhibitors have a delayed onset of action (i.e., peak effect may... 

TABLE 49-4. Comparison of a-Adrenergic Antagonists and 5a-Reductase Inhibitors for Treatment of Benign Prostatic Hyperplasia47... 

OC-Adrenergic antagonists are recommended as first-line treatment for moderate to severe BPH. The agents in this pharmacologic class can be classified by several characteristics (Table 49-6) ... 

TABLE 49-6. Comparison of Pharmacologic Properties of oc-Adrenergic Antagonists... 

Ejaculation disorders, including delayed and retrograde ejaculation, occur with all adrenergic antagonists and are an... 

In patients with BPH and hypertension, it is not recommended to use an a-adrenergic antagonist alone to treat both disorders. In the ALLHAT study, where doxazosin was compared to other agents for treatment of essential hypertension, doxazosin was associated with a higher incidence of congestive heart failure. Therefore, in patients with hypertension and BPH, it is recommended that an appropriate antihypertensive be added to an a-adrenergic antagonist.11... 

To streamline and reduce the cost of treatment regimens, it has been suggested that the a-adrenergic antagonist maybe discontinued after the first 6 to 12 months of combination therapy. However, long-term treatment is required to determine if such a regimen is as effective as continuous combination therapy.42,43... 

Drug treatment failures may result from a variety of factors. Initial failure to respond to a-adrenergic antagonists occurs in 20% to 70% of treated patients. It is likely in these patients that the static factor may predominate as the cause of symptoms in these patients. Initial failure to respond to 5a-reductase inhibitors occurs in 30% to 70% of treated patients. 

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