Toxic interactions

Murphy SD. 1980. Toxic interactions with dermal exposure to organophosphate insecticides [Abstract]. Toxicol Lett 5(Supplement 1) 34. 

Broadly speaking, toxic interactions between chemicals and cellular sites of action are of two kinds ... 

Non-selective NSAIDs [those that inhibit both cyclooxygenase-1 and -2 (COX-1 and COX-2)] cause gastric mucosal damage by two primary mechanisms (1) a direct toxic interaction and (2) systemic pharmacologic actions. 

Maintaining the stability of a biological treatment of wastewaters containing formaldehyde and urea is complicated because some compounds exert a toxic effect on the processes involved. Figure 19.5 shows the possible toxic interactions between the different compounds and processes. 

Thawley DG, Willoughby RA, McSherry BJ. et al. 1977. Toxic interaction among lead, zinc, and cadmium with varying levels of dietary calcium and vitamin D. Environ Res 14 463-475. 

Khangarot, B.S. and PK. Ray. 1990. Acute toxicity and toxic interaction of chromium and nickel to common guppy Poecilia reticulata (Peters). Bull. Environ. Contamin. Toxicol. 44 832-839. 

Chlordane-induced mortality of the long-billed curlew (Numenius americanus) has been documented at least four times since 1978, despite restriction of technical chlordane use since 1980 to subterranean applications for termite control (Blus et al. 1985). Death of these curlews was probably due to over-winter accumulations of oxychlordane of 1.5 to 5.0 mg/kg brain FW and of heptachlor epoxide at 3.4 to 8.3 mg/kg — joint lethal ranges for oxychlordane and heptachlor epoxide in experimental birds — compared to 6 mg/kg brain for oxychlordane alone and 9 mg/kg for heptachlor epoxide alone (Blus et al. 1985). Additional research is needed on toxic interactions of chlordane components with each other and with other chemicals in the same environment. 

Birnbaum, L.S., H. Weber, M.W. Harris, J.C. Lamb IV, and J.D. McKinney. 1985. Toxic interaction of specific polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin increased incidence of cleft palate in mice. Toxicol. Appl. Pharmacol. 77 292-302. 

Membranes separate cells from their external environment, and the internal components of cells from each other. Many biochemical processes taking place within cells occur on a framework of membranes. Toxicant interactions with membranes figure prominently in many types of toxic effect. 

Laurie RD, Bercz JP, Wessendarp TK, et al. 1986. Studies of the toxic interactions of disinfection by-products. Environ Health Perspect 69 203-207. 

Ethyiene dibromide Do not expose patients to ethylene dibromide or its vapors. This precaution is based on preliminary results of animal research which suggest a toxic interaction between inhaled ethylene dibromide and ingested disulfiram results in a higher incidence of tumors and mortality in rats. 

Lamb RG, Borzelleca JF, Condie LW, et al. 1989. Toxic interactions between carbon tetrachloride and chloroform in cultured rat hepatocytes. Toxicol AppI Pharmacol 101 106-113. 

Co-administration with MAOIs can lead to a dangerous toxic interaction (see page 163). Though in the past such a combination might have been used for very treatment-resistant patients it would be very rare to consider it now. 

Subclass Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities, Interactions... 

Pilocarpine Like bethanechol, partial agonist Like bethanechol Glaucoma Sjogren s syndrome Oral lozenge and topical Toxicity interactions Like bethanechol... 

Verapamil Calcium channel (ICa-i type) blockade Slows SA node automaticity and AV nodal conduction velocity decreases cardiac contractility t reduces blood pressure Supraventricular tachycardias Oral, IV hepatic metabolism caution in patients with hepatic dysfunction Toxicity Interactions See Chapter 12... 

Combined arteriolar and venodilator Releases NO spontaneously activates guanylyl cyclase Marked vasodilation reduces preload and afterload Acute cardiac decompensation hypertensive emergencies (malignant hypertension) IV only duration 1-2 min. Toxicity Excessive hypotension, thiocyanate and cyanide toxicity Interactions Additive with other vasodilators... 

Neither selegiline nor rasagiline should be taken by patients receiving meperidine. They should be used with care in patients receiving tricyclic antidepressants or serotonin reuptake inhibitors because of the theoretical risk of acute toxic interactions of the serotonin syndrome type (see Chapter 16), but this is rarely encountered in practice. The adverse effects of levodopa may be increased by these drugs. 

Rasagiline Inhibits MAO-B selectively, higher doses also inhibit MAO-A Increases dopamine stores in neurons may have neuroprotective effects Parkinson s disease adjunctive to levodopa smooths levodopa response Oral Toxicity interactions may cause serotonin syndrome with meperidine, and theoretically also with selective serotonin reuptake inhibitors, tricyclic antidepressants... 

---