Agonists adverse effects

Several steroidal and non-steroidal glucocorticoid receptor selective dissociated agonists are in development by many pharmaceutical companies and some are now in clinical development. This suggests that the development of dissociated glucocorticoids with a greater margin of safety is possible and may even lead to the development of oral compounds that do not have significant adverse effects. 

Vigabatrin has an unacceptable adverse effect profile, but consistent findings in animal studies suggest that GABA agonists deserve further study. a-AMPA antagonism, or antikindling action, may also be important for some anticonvulsants. 

Adverse effects of the inhaled P2-agonists include tachycardia, tremor, and hypokalemia, which are usually not problematic. Because of increased adverse effects, oral (i2-agonists should be avoided in patients who are able to use inhaled medications. 

In patients hospitalized because of asthma, patient-initiated (on-demand) therapy may result in decreased nebulized doses, decreased adverse effects, and shorter hospital stays than ther-apy given regularly at 4-hour intervals.20 In patients admitted to the intensive care unit and placed on mechanical ventilation, P2-agonists can be delivered via an MDI or nebulization through the ventilatory circuit. 

P2-Agonists cause airway smooth muscle relaxation by stimulating adenyl cyclase to increase the formation of cyclic adenosine monophosphate (cAMP). Other non-bronchodilator effects have been observed, such as improvement in mucociliary transport, but their significance is uncertain.11 P2-Agonists are available in inhalation, oral, and parenteral dosage forms the inhalation route is preferred because of fewer adverse effects. 

Adverse effects of P2-agonists are dose-related and include palpitations, tachycardia, and tremor. Sleep disturbance may also occur and appears to be worse with higher doses of inhaled long-acting P2-agonists. Increasing doses beyond those clinically recommended is without benefit and could be associated with increased adverse effects. 

Tegaserod maleate (Zelnorm) is a partial serotonin (5-HT4) receptor agonist that causes an increase in peristaltic activity and intestinal secretion and moderation of visceral sensitivity. It increases the frequency of bowel movements and reduces abdominal discomfort, bloating, and straining. It is indicated for the treatment of patients younger than 65 years of age who experience chronic idiopathic constipation. The most common adverse effects include headache, abdominal pain, diarrhea, and nausea. 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Develop a formal plan to assess response and adverse effects of dopamine agonists. When appropriate, be sure to make dose adjustments. 

Several randomized trials have demonstrated that leuprolide and goserelin are effective agents when used alone in patients with advanced prostate cancer.19 Response rates around 80% have been reported, with a lower incidence of adverse effects compared with estrogens.19 There are no direct comparative trials of the currently available LHRH agonists or the dosage formulations, but a recent meta-analysis reported that there is no difference in efficacy or toxicity between leuprolide and goserelin. Therefore, the choice between the two usually is made based on cost and patient and physician preference for a dosing schedule. 

The most common adverse effects reported with LHRH agonist therapy include a disease flare-up during the first week of therapy, hot flashes, erectile impotence, decreased libido, and injection-site reactions.19 The disease flare-up is thought to be caused by initial induction of LH and FSH by the LHRH agonist and manifests clinically as either increased bone pain or increased urinary symptoms.19 This flare reaction usually resolves after 2 weeks and has a similar onset and duration pattern for the depot LHRH products.33,34... 

The most common adverse effects of LHRH agonists are disease flare-up during the first week of therapy (e.g., increased bone pain, urinary symptoms), hot flashes, erectile impotence, decreased libido, and injection-site reactions. 

N-methylscopolamine (Costa et al. 1982b Schwab et al. 1983). Animals made tolerant to disulfoton were resistant to the lethal or adverse effects of cholinergic agonists, such as carbachol (Brodeur and DuBois 1964 Costa et al. 1981 Schwab and Murphy 1981) and oxotremorine (Costa et al. 1982b McPhillips 1969a), which are not hydrolyzed by acetylcholinesterase. Tissues from animals tolerant to disulfoton such as the ilea (Foley and McPhillips 1973 McPhillips 1969b McPhillips and Dar 1967) and the atria (Perrine and McPhillips 1970 Schwab et al. 1983), were resistant to the effects of carbachol and/or oxotremorine. Because the uterus and vas deferens have a relatively sparse parasympathetic innervation compared to the ileum and do not receive a steady flow of impulses via this system, these tissues were not as subsensitive to carbachol as the ileum (Foley and McPhillips 1973). Thus, acetylcholine accumulation may be a prerequisite for tolerance development. 

---