Antagonistic pharmacodynamic effect

Two patients stabilized on a phenytoin regimen suffered a loss of seizure control after taking shankhapushpi, an Ayurvedic antiepileptic medicine, three times a day. There was also a significant decrease in serum phenytoin concentration from 9.6 to 5.1mg/L. To investigate the possible mechanisms, multiple doses of shankhapushpi were administered to rats and resulted in decreased plasma phenytoin concentrations, whereas single-dose administration was reported to interfere with the antiplatelet effect of phenytoin, thereby implying both a pharmacokinetic and pharmacodynamic basis for the interaction (73). 

There are several botanicals that have purported immunostimulating effects. These include Panax ginseng and Echinacea purpurea (74), which have both been used as an immune stimulant. Any potential adverse effect on the pharmacological activity of immunosuppressants has not been reported in patients or evaluated in clinical studies. Given the lack of data, it would be prudent to advise against concurrent intake of these botanicals, and closely monitor changes in efficacy in patients who self-administer these botanicals. 

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Pharmacodynamic drug interactions include the cases where drugs show additive or antagonistic pharmacodynamic effects. 

Algorithm for identification of pharmacodynamic drag interactions is based on comparison of biological activity spectra of the compounds (in the block diagram they are labeled as compound 1 and compound 2), predicted by PASS, together with information from the PharmaExpert knowledge base ( activity-activity relationships). Antagonistic pharmacodynamic effects are determined by ... 

Alosetron is a 5-HT3 antagonist that has been approved for the treatment of patients with severe IBS with diarrhea (Figure 62-5). Four other 5-HT3 antagonists (ondansetron, granisetron, dolasetron, and palonosetron) have been approved for the prevention and treatment of nausea and vomiting (see Antiemetics) however, their efficacy in the treatment of IBS has not been determined. The differences between these 5-HT3 antagonists that determine their pharmacodynamic effects have not been well studied. 

Antagonistic pharmacodynamic interactions, for example reversal of nondepolarizing muscle relaxants, or reversal of the toxic effects of opioids or of BDZs, are sometimes of value in critical situations. 

Guyader, D., Patat, A., Ellis-Grosse, E.J., Orczyk, G.P. Pharmacodynamic effects of a nonpeptide antidiuretic hormone V2 antagonist in cirrhotic patients with ascites. Hepatology 2002 36 1197-1203... 

Chaikin P, Gillen MS, Malik M, Pentikis H, Rhodes GR, Roberts DJ. Co-administration of ketoconazole with HI antagonists ebastine and loratadine in healthy sulgects pharmacokinetic and pharmacodynamic effects. Br J Clin Pharmacol (2005) 59, 346-54. 

Pharmacodynamic interactions generally involve additive, synergistic or antagonistic effects of drugs acting on the same receptors or physiological systems. These interactions are more difficult to classify than those with a pharmacokinetic basis. They are fairly common but may not always be recognised. 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorized as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic (additive or antagonistic effects), or combined interactions. The general principles of pharmacokinetics are discussed in Chapters 3 and 4 the general principles of pharmacodynamics in Chapter... 

The trials described so far have commonly shown a lack of usefulness of NKi receptor antagonists in the treatment of pain. But we do not know whether the failure of the selected compounds is a matter of pharmacodynamics (e.g. poor penetration of the blood brain barrier) or a genuine discrepancy between animal and human pain pathophysiology (Urban and Fox, 2000). Hence, animal tests should carefully be chosen whether they are predictive or not, and it would be helpful if a wider range of conditions could be examined (Hill, 2000a). Therefore, new preclinical analysis methods should be developed for a more effective judgement of likely clinical outcomes. 

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