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The effects of single oral doses of terfenadine, diphenhydramine and placebo, alone or in combination with diazepam or alcohol, on psychomotor performance and subjective feelings were evaluated in a double-blind, crossover study in 20 normal male volunteers. Terfenadine 60, 120 and 240 mg had no effect on psychomotor skills and subjective feelings, whereas diphenhydramine 100 mg slightly impaired certain features of psychomotor performance and severely worsened subjective feelings. Terfenadine 120 mg did not influence the adverse effects of oral diazepam 10 mg or of alcohol 0.75 g/kg on psychomotor performance and subjective feelings. In contrast, diphenhydramine 100 mg significantly enhanced these effects of diazepam and alcohol. [ABSTRACT FROM AUTHOR]

The inhibitory effect of orally administered terfenadine on the area of histamine-induced skin wheals was studied by single dose and multiple dose trials in 12 normal male volunteers. Single doses of 20, 60 and 200 mg of terfenadine produced dose-dependent decreases in histamine wheal area that reached a maximum by the fourth hour after dosing. The 60 and 200 mg doses blocked almost 90% of histamine whealing, and significant reduction of the wheal area persisted for 8 h. During the multiple dose trial histamine whealing was markedly inhibited after the fifth and sixth dose of terfenadine 20, 40 or 60 mg every 8 h and of 60 mg every 12 h. On the last three dosage schedules inhibition persisted for at least 12 h after the final dose. Inhibition of histamine-induced skin whealing appears to be a quantitative index of the time course of histamine H-receptor antagonist action. [ABSTRACT FROM AUTHOR]

Three clinical pharmacologists independently evaluated 500 untoward clinical events reported by physicians as adverse drug reactions (ADRs). They often disagreed with the reporting physicians and with each other. They judged 14.4-28.2% of the events to be definite, 26.4-38.0% probable, 21.4-31.0% possible and 15.8-28.2% unlikely ADRs. In their opinion 19.1-32.4% of the drugs blamed were definitely, 29.8-34.4% probably, 24.9-36.7% possibly and 8.4-14.5% not responsible for the adverse reactions. Evaluators disagreed among themselves about the drug most likely to have been responsible in 36.4% of the events, about ADRs causing hospital admission in 56.8%, about severe ADR morbidity in 55.8%, about ADR prolongation of hospitalization in 67.3% and about ADR contribution to death in 71.0%. The divergence of judgements suggests that suspected ADRs are usually ambiguous clinical events, and that incidence, severity, medical consequences and cost of ADRs can only be estimated. [ABSTRACT FROM AUTHOR]

The importance of individualizing the dosage of potent drugs in order to maximize their therapeutic effectiveness and safety is generally accepted. Whenever possible the dosage of a drug should be 'titrated' directly in each patient against the intensity of its therapeutic or toxic actions. Unfortunately, for many drugs convenient clinical yardsticks of the intensity of their pharmacologic effects are lacking. Determination of the serum concentration of such compounds can help to guide adjustment of dosage during their therapeutic use. By measuring the serum level of drugs one bypasses the largest source of individual differences in doseeffect relationships - the pharmacokinetic variation between subjects. However, the relationship between the serum concentration of a drug and the intensity of its pharmacodynamic action is influenced by many other factors, which must always be considered in interpretation of serum levels. Therapeutic decisions should never be based solely on the serum concentration of a compound, nor can such measurements ever substitute for careful medical observation and judgement. [ABSTRACT FROM AUTHOR]

Of 6673 hospitalized medical patients monitored in a drug surveillance program, 1037 (15.5%) received chlordiazepoxide and 1202 (18.0%) received diazepam. Anxiety was the most common indication for therapy. Unwanted CNS depression was reported in 7.1% of all diazepam recipients, but ranged from 2.9% in patients with normal serum albumin concentrations (≥4.0 g/100 ml) to 9.3% in those with severe hypoalbuminemia (<3.0 g/100 ml) ( p<0.02). A similar trend noted with unwanted CNS depression due to chlordiazepoxide did not reach statistical significance. Age, sex, hospital, renal function, survival, length of hospitalization, diagnosis, use of coffee, alcohol or tobacco, indication for drug therapy, or drug dosage did not influence the association of hypoalbuminemia and diazepam-induced CNS depression. The mechanism of this association remains unclear. [ABSTRACT FROM AUTHOR]

Hospitalized patients treated with warfarin were monitored to identify additional drugs that modify its hypoprothrombinemic action. Twenty-four patients on warfarin therapy received glucagon in daily doses from 2 to 96 mg for treatment of myocardial contractile failure. Eight of nine patients who were given glucagon for 2 or more days in a total dose exceeding 50 mg showed marked enhancement of the hypoprothrombinemic effect of warfarin. In these patients the ratio of prolongation of the one-stage prothrombin time to total warfarin dose during the preceding 72 hr increased three- to twelvefold on glucagon therapy. All patients became excessively hypoprothrombinemic, and three bled while on both warfarin and glucagon. Glucagon does not significantly prolong the prothrombin time in patients not receiving oral anticoagulants. Glucagon may potentiate the hypoprothrombinemic action of warfarin by acting synergistically with the anticoagulant to depress hepatic synthesis of vitamin-K-sensitive clotting proteins or by increasing the affinity of warfarin for its receptor site. [ABSTRACT FROM AUTHOR]

Compares the effects of topical anthralin and difluoromethylornithine on epidermal polyamine concentration in psoriasis. Relation between the metabolism of polyamines and cellular growth and division; Assessment of skin levels of polyamines, mitotic index and epidermal thickness; Association of decreased epidermal proliferation and therapeutic efficacy with diminished concentrations of three polyamines.

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