Antagonism between drugs

Drugs that enhance the effects of each other are called synergistic. Antagonism between drugs creates diminished drug effects. 

Lanier ER, Hazen R, Ross L, Freeman A, Harvey R (2005) Lack of antagonism between abacavir, lamivudine, and tenofovir against wild-type and drug-resistant HlV-1, J Acquir Immune Defic Syndr 39 519-522... 

Competition for receptors, hence receptor antagonism, is governed by the law of mass action that is, the interaction between drug and receptor depends on the concentration of drug in the vicinity of the receptor and the number of receptors present. Because agonist and antagonist have an affinity for the same receptors, the two substances compete for binding to the receptors. 

In vitro antagonism between nitrofurantoin and the quinolones has been shown, but a demonstration of clinical relevance warrants further study. Certain drugs used in treating gout, which inhibit tubular secretion, can affect UTI therapy by raising serum levels of nitrofurantoin with concomitant diminished urinary levels. 

Rawles JM. Antagonism between non-steroidal anti-inflammatory drugs and diuretics. Scott Med J 1982 27(l) 37-40. 

Tweeddale MG. Antagonism between antipyretic analgesic drugs and spironolactone in man. Clin Res 1974 22 727A. 

Richards CD, Hesketh TR (1975) Implications for theories of anaesthesia of antagonism between anaesthetic and non-anaesthetic steroids. Nature 256 179-182 Richter W, Messmer K, Hedin H, Ring J (1978) Adverse reactions to plasma substitutes incidence and pathogenesis. In Watkins J, Ward AM (eds) Adverse response to intravenous drugs. Academic Press, London, Grune Stratton, New York, pp 49-70 Rothman S, Orland FJ, Flesch P (1945) Group specificity of epidermal allergy to procaine in man. J Invest Dermatol 6 191-199... 

The effects of yohimbine on behaviour, which are characterised by the induction of anxiety in normal individuals and the activation of psychotic processes in schizophrenics [1061] are so marked that it has been suggested [1070] that yohimbine could be employed to provide a model anxiety state in animals for use in the screening of potential anti-anxiety drugs. Whether these central effects are in any way related to an antagonism between yohimbine and serotonin [1071-1077] is open to debate. Certainly the actual levels of serotonin in the brain are unaffected, although the content of noradrenaline is halved [1078, 1079]. 

Sinha, Y. K. and West, G. B., Antagonism between local anaesthetic drugs and 5-hydroxytryptamine, J. Pharmacie 5, 370 (1953). 

Antagonism between folic acid and the anticonvulsants used in the treatment of epilepsy is part of their mechanism of action about 2% of the population have (drug-controlled) epilepsy. Relatively large supplements of folic acid (in excess of 1000 Jg/day) may antagonize the beneficial effects of the anticonvulsants and lead to an increase in the frequency of epileptic attacks. If enrichment of a food such as bread with folate is to provide 400 Jlg/day to those who eat little bread, those who eat a relatively large amount may well have an intake in excess of 1000 Jg/day. 

These results clearly demonstrate that PCP-like drugs administered centrally produce stereotyped behavior that is mediated by PCP receptors. A causal relationship between binding to PCP receptors and induction of stereotyped behavior is also supported by the ability of metaphit, which specifically acylates PCP receptors in vivo, to antagonize induction of stereotyped behavior. The order of drug potency of PCP analogs and dexoxadrol to induce stereotyped behavior is similar to that seen in other studies on the binding of 3H-PCP (Hampton et al. 1982 Murray and Leid 1984) and... 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

---