Minimal effective dose , combination

Neurotoxic reactions have been periodically reported with lithium alone or in combination with antipsychotics, CBZ, verapamil, or methyidopa, with the elderly probably at much greater risk for such events (Table 10-21). Although such drug combinations are often necessary and usually well tolerated, common clinical sense dictates that only the minimally effective doses be prescribed. It is also advised that patients carry or wear some form of identification indicating that they are receiving... 

Intracavernosal injection or urethral suppository therapy with alprostadil (PGE1) is a second-line treatment for erectile dysfunction. Doses of 2.5-25 meg are used. Penile pain is a frequent side effect, which may be related to the algesic effects of PGE derivatives however, only a few patients discontinue the use because of pain. Prolonged erection and priapism are side effects that occur in less than 4% of patients and are minimized by careful titration to the minimal effective dose. When given by injection, alprostadil may be used as monotherapy or in combination with either papaverine or phentolamine. 

An example of sequential blocking is the use of a sulfadiazine with pyrimethamine 9.31) in toxoplasmosis, a protozoal disease (Wettingfeld, Rowe and Eyles, 1956). In this sequence, the sulfonamide blocks the incorporation of / -aminobenzoic acid into dihydrofolic acid, and the pyrimethamine prevents the reduction of this pteridine to tetrahydrofolic acid (Sections 9.3.2 and 9.3.3). In malaria, as early as 1959, Hurly made the observation that pyrimethamine and sulfadiazine potentiated one another to such a degree that the combination could actually cure Pl.falciparum infections. Thus, less than 0.1 m.e.d. (minimal effective dose) of pyrimethamine and 0.25 m.e.d. of sulfadiazine were, together, as effective as 1.0 m.e.d. of either drug separately. In current tropical medicine, Maloprim , a combination of pyrimethamine and dapsone 9.17) (the latter chosen because of its slow rate of excretion which matches that of pyrimethamine), forms an excellent replacement for chloroquine in cases of Pl.falciparum... 

This was the first documented study of exposure of a military volunteer to a threshold dose of both i.m. BZ and oral LSD, given together. It included a careful baseline for each measurement used. Clinical observations were scheduled at 1, 2, 3, 4, 5, 6, 10, 24, 48 and 72 hours after administration of drug. Vital signs and neurological status were recorded at approximately the same intervals. The examining physician frequently documented mental status. These data were less than optimal due to the relative infrequency of observations and the sparseness of behavioral descriptions. Even in combination, the doses used were too small to cause more than minimal effects. 

Fig. 24. EA 3443 Effect of combined percutaneous doses on NF performance. The horizontal blue line represents minimal (25%) performance impairment.

A study on the photoprotective effect of the topical application of 2% vitamin E and 5% vitamin C in humans showed no effect with the application of each substance alone, but an enhanced photo-protective effect after applying vitamins E and C combined, which was attributed to the regeneration of vitamin E by vitamin C.20 This enhanced effect has also been shown with the topical application of a combination of 15% ascorbic acid and 1% a-tocopherol to porcine skin.21 The combined systemic supplementation of vitamins C and E was similarly able to reduce sunburn reactions22 and to increase the minimal erythema dose (MED), a measure for individual photosensitivity, more than supplementation with either vitamin E or vitamin C alone.23,24 An oral supplementation with an anti-oxidative combination of carotenoids (P-carotene and lycopene), vitamin C, vitamin E, selenium, and proanthocyanidins (Seresis , Pharmaton SA, Lugano, Switzerland) also reduced the development and grade of UVB-induced erythema 25... 

Oral steroid is most frequently used for maintenance treatment (prednisolone 5 to 15 mg/day or equivalent). " Alternate-day regimens, although not evaluated, are often used in children to minimize growth retardation. Monthly pulse IV steroids in conjunction with cyclophosphamide resulted in more sustained remission, fewer relapses, and no significant increase in side effects. This combination has also been shown by meta-analysis to be more beneficial than steroid or cyclophosphamide alone. Cyclophosphamide, because of its bladder and gonadal toxicity, has been given as monthly and then bimonthly intravenous injection, instead of daily administration, for up to 2 or more years. However, toxicity is still a concern. A recent trial in Emope showed that after initial lower pulse doses of IV cyclophosphamide, oral azathioprine was able to attain remission rates similar to those of higher initial pulse doses of cyclophosphamide with quarterly foUow-up doses. ... 

Today, L-dopa is used almost exclusively as a combination product with decarboxylase inhibitors. Starting L-dopa doses of 200-300 mg/day often are adequate for relief of disability. Some patients require larger amounts on a daily basis however, the usual maximal dose of L-dopa needed by patients even with severe parkinsonism is 800 mg/day. Slow buildup of dose (e.g., increments of 100 mg L-dopa per week) can help to assess the lowest effective dose and minimizes the risk for adverse effects, such as postural hypotension, nausea, vomiting, sedation, and vivid dreams. 

A study in 12 healthy subjects showed that, in contrast to lorazepam, bus-pirone 10 or 20 mg did not appear to interact with alcohol (i.e. worsen the performance of certain psychomotor tests), but it did make the subjects feel drowsy and weak. - Similarly, another study in 13 healthy subjects found that combining buspirone (15 and 30 mg/70 kg) and alcohol caused sedation, but very little impairment of performance. In this study, the sedative effects were broadly similar to those seen with alprazolam plus alcohol, but alprazolam plus alcohol clearly impaired performance. Similar findings were reported in another earlier comparison with diazepam. A further study reported that single 5 to 15-mg doses of buspirone had a minimal effect on performance in both light and moderate female social drinkers. ... 

The approval of buprenorphine for the office-based treatment of opioid dependence represents a major departure from the earlier methadone clinic system. Physicians with addiction specialist credentials or those who have completed 8 hours of approved training can become qualified to treat up to 30 patients in their private offices. Stable patients may be given prescriptions for up to a month of medication. The combination buprenorphine/naloxone tablet is expected to have minimal risk for diversion. When taken subhnguaUy, as prescribed, naloxone has minimal biologic activity and does not interfere with the buprenorphine dose. However, if an attempt is made to inject the drug, the addict will experience the full antagonist effect of the naloxone. 

---