Receptor function in heart failure

Article Abstract:

The physiological responses of the body often change in response to chronic stimuli of some sort. These changes sometimes make it difficult to understand the processes going on, and also make it difficult to predict the future responses to drugs that are administered over a long period. Patients with heart failure have increased amounts of norepinephrine, a natural transmitter substance involved in regulating the heart rate and blood pressure, as well as many other functions. There are receptors called adrenoreceptors on the surface of many different cell types initiating the response of those cells to norepinephrine. However, when the norepinephrine is increased over a long period of time, some of these receptors decrease in number in a physiological attempt to balance stimulus and response. Such a decrease in a receptor as a physiological response is referred to as down-regulation. Heart muscle cells have adrenoreceptors of the beta-1 and beta-2 subtypes; the beta-1 subtype is down-regulated, while the beta-2 subtype is not. This observation may explain why drugs that work by stimulating the beta adrenoreceptors do not seem to be useful over long periods of time. Such drugs, called beta-adrenergic agonists, may work at first, but as the receptors become down-regulated, there are simply fewer receptors on which the drug can work, and hence the effectiveness of the drug is reduced. There are several ways that this problem might be circumvented. One would be to develop drugs that do not affect the receptors themselves, but rather affect some other step in the sequence of events, which begins with receptor stimulation. One method may actually be to inhibit the beta adrenoreceptors with beta blocker drugs. This seemingly paradoxical effect may work as follows: the inhibition of the beta adrenoreceptors would result in the reversal of the down-regulation. This up-regulation would increase the number of receptors and restore some of the lost responsiveness. Although some preliminary evidence suggests that this approach might improve heart function in some patients with heart failure, there is insufficient evidence yet to indicate that the treatment actually improves the survival of such patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Adrenergic beta agonists, Adrenergic beta-agonists, Beta adrenoceptors, Adrenergic beta receptors

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Cardiovascular pharmacology of adrenergic and dopaminergic receptors: therapeutic significance in congestive heart failure

Article Abstract:

Adrenoreceptors are cellular receptors that respond to adrenalin and related compounds. The understanding of the function of these receptors is critical in developing effective drugs for treating heart failure. However, these receptors exist in a variety of types, and both the function of these types and their anatomical distribution have unclear to researchers. There is no way to categorize receptors except for subtle differences in their pharmacologic action. All adrenoreceptors respond to adrenalin and related compounds, but some may respond proportionately more to one drug, and others proportionately more to another. The first classification of adrenoreceptors was into alpha and beta subgroups, which is now based on their response to the drug dichloroisoproterenol. The alpha and beta classes are now divided further alpha-1, alpha-2, beta-1, and beta-2 subtypes. As research continued, closely related receptors were identified on the basis of their response to dopamine, a compound closely related to adrenalin. Similarly, the dopamine adrenoreceptors, which are often abbreviated DA adrenoreceptors, may be divided into groups. DA-1 and DA-2 subtypes differ in their response to certain drugs. It is well established that drugs which stimulate adrenoreceptors can provide useful benefits for patients with heart failure. However, drugs which stimulate the dopamine adrenoreceptors may also prove to be of great value in treating heart failure. One such drug is ibopamine. Ibopamine stimulates a variety of receptors; the stimulation of the DA-1 receptors results in a relaxation of the peripheral blood vessels; this reduces the resistance against which the overloaded heart must work. Ibopamine also increases the excretion of sodium, resulting in improved kidney function. The stimulation of the DA-2 adrenoreceptor by ibopamine has similar effects that are of benefit to he patient with heart failure. Ibopamine also affects the alpha- and beta-adrenoreceptors, which results in a variety of effects, including a direct increase in the strength of the contracting heart muscle and a corresponding improvement in the pumping of the blood. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Clinical pharmacology of ibopamine

Article Abstract:

An understanding of the action of drugs in cases of heart failure requires an appreciation of the physiology of many systems, not just the heart. Many drugs are capable of increasing the strength of the heartbeat and causing the blood vessels to either constrict or dilate; the precise actions of individual drugs usually depend upon how it affects individual receptors. Receptors for the compound adrenaline were first classed as either alpha or beta on the basis of their responses to different drugs. Further pharmacologic study showed that each could be subdivided into two more categories, resulting in alpha-1, alpha-2, beta-1, and beta-2 adrenoreceptors. There are also two receptors that respond to the chemically similar compound dopamine (DA); these are classed DA-1 and DA-2. Very few drugs stimulate all six of these receptor types, but one such drug is epinine. The study of this drug is important, since it is one of the few drugs in this class of compounds that not only causes the peripheral blood vessels to relax, but also the blood vessels of the kidney to relax as well. In patients with heart failure, the relaxation of blood vessels is important to reduce the resistance against which the heart must work, and to improve the flow of blood through the organs. When given orally, the drug ibopamine is converted into epinine by the metabolism of the body. In patients with heart failure, ibopamine results in a small, temporary increase in blood pressure, an increase in the output of the heart, and a decrease in the resistance of the blood vessels to blood flow. There is an unexplained discrepancy between the concentration of the drug and its effects. The peak level of epinine occurs about 30 minutes after an oral dose of ibopamine. After that, the drug is rapidly eliminated. However, the output of the heart is still increased four to six hours after the administration of the drug, when the amount of epinine in the blood is virtually nil. No serious side effects have been associated with ibopamine, but about 10 percent of all patients experience some stomach upset. (Consumer Summary produced by Reliance Medical Information, Inc.)

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