Physiologic antagonism

Marek GJ, Wright RA, Schoepp DD, et al (2000) Physiological antagonism between 5-hydroxytryptamine(2A) and group 11 metabotropic glutamate receptors in prefrontal cortex. J Pharmacol Exp Ther 292 76-87... 

Xanthines, primarily as the intramuscularly administered combination of caffeine and sodium benzoate, have been used in the treatment of CNS depressant overdosage. Black coffee has been used to physiologically antagonize alcohol intoxication, although many physicians believe that this ineffective therapy simply produces a wide-awake drunk. 

The effects of histamine on body tissues and organs can be diminished in four ways inhibition of histamine synthesis, inhibition of histamine release from storage granules, blockade of histamine receptors, and physiological antagonism of histamine s effects. Of these approaches, only the inhibition of histamine synthesis has not been employed clinically. The focus of this chapter is on Hi histamine receptor antagonists it provides a brief overview of the H2 blockers and the inhibitors of histamine release. More details can be found in Chapters 39 and 40. 

If an organ is innervated by both the sympathetic and parasympathetic divisions, a physiologic antagonism typically exists between these divisions. That is, if both divisions innervate the tissue, one division usually increases function, whereas the other decreases activity. For instance, the sympathetics increase heart rate and stimulate cardiac output, whereas the parasympathetics cause bradycardia. However, it is incorrect to state that the sympathetics are always excitatory in nature and that the parasympathetics are always inhibitory. In tissues such as the gastrointestinal tract, the parasympathetics tend to increase intestinal motility and secretion, whereas the sympathetics slow down intestinal motility. The effect of each division on any tissue must be considered according to the particular organ or gland. 

It may be useful at this point to acknowledge the fact that there are other types of antagonisms involving drug effects. Physiological antagonism involves those compensatory biological mechanisms that exist to maintain our homeostasis. For example,... 

By using a drug with opposite effects, e.g. histamine constricts bronchi, causes vasodilatation and increases capillary permeability. Adrenaline (epinephrine), by activating a and adrenoceptors, produces opposite effects — referred to as physiological antagonism. 

This is most effectively achieved by physiological antagonism of bronchial muscle contraction, namely by stimulation of adrenergic bronchodilator mechanisms. Pharmacological antagonism of specific bronchoconstrictors is less effective either because individual mediators are not on their own responsible for a large part of the bronchoconstriction (acetylcholine, adenosine, leukotrienes) or because the mediator is not even secreted during asthma attacks (histamine). 

Cause a nonparallel shift to the right Can be only partially reversed by T the dose of the agonist ° Appear to X the efficacy of the agonist Physiologic antagonism (different receptor)... 

Physiological Antagonism Two agonists, in unrelated reactions, cause opposite effects. The effects cancel one another. 

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