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A long-acting injectable (Terramycin/LA) forulated to contain 200 mg/ml of oxytetracycline was tested and compared to a commercially available oxytetracycline injectable (Emicina) containing 50 mg/ml in the treatments of experimentally induced Anaplasma marginale infection in Colombian cattle. Group 1, consisting of 10 infected calves, served as non-treated controls. Ten infected calves (Group 2) were treated with two doses of Emicina, each at 10 mg/kg, intramuscularly (IM), and another ten infected calves (Group 3) were treated once IM, with 20 mg/kg of Terramycin/LA. All treatments were given during the acute phase of infection after A. marginale parasitemia was demonstrated and when the packed cell volume (PCV) had decreased to 60-64% of normal value. Two treatments with Emicina and one with Terramycin/LA were both effective in moderating the course of A. marginale infection and in preventing serious clinical signs of disease under laboratory conditions.
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In three male duodenal ulcer patients, the effects of a 4-week treatment with a long-acting synthetic secretin -- daily s.c. administrations of 10 clinical units secretin/kg b.w. -- were assessed symptomatically, endoscopically, immunologically, and by means of gastric and pancreatic secretory analyses. Improvement in epigastric pain was noted within a few days following the onset of secretin therapy. In all cases, duodenoscopy revealed complete healing of ulcers after a 2- to 3-week treatment period. Before therapy, cutaneous anaphylactoid reactions due to intradermal injections of secretin could be elicited in each subject; skin reactions were found mitigated after 4 weeks of therapeutic secretin administration thus suggesting some desensitisation. Neither gastric acid secretion nor pancreatic bicarbonate production were substantially influenced by the 4-week course of secretin therapy; consequently, prevention of ulcer relapse is rather unlikely to be achievable with the conditions employed in this study. However, it seems therapeutically promising that the duodenal ulcers under study showed complete healing already after 2-3 weeks of secretin administration.
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In 2 patients without clinically significant ischemic heart diseases, oral quinidine was used to control supraventricular arrhythmias. In both patients, syncopal attacks occurred, caused by a particular type of ventricular tachyarrhythmia called torsades de pointes. Quinidine plasma concentrations were low (2.6 and 1.2 mg/1, respectively); QRS duration was normal, but the Q-T interval was markedly prolonged.
Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations.
This short outline of drug-drug interactions does not claim to cover the entire field. The task of this paper is to illustrate the most important principles of drug-drug interactions by paradigms taken from the experience of the practitioner. One consequence of drug-drug interactions is the change in pharmacolinetic parameters important for the therapeutical effect of drugs in the organism. Very often the elucidation of the mechanisms of drug-drug interactions in man is impossible; therefore, for clinical pharmacologists experiments on animals remain the tool in order to gain more knowledge in this field.
In recent years, dosage forms with sustained release have obtained a significant importance. The technological possibilities for manufacturing are described as coating, embedding and matrix procedures. The range of auxiliary substances, which are responsible for the retardation of drug activity, reaches from lipophilic compounds as lipoids, fatty alcohols and compounds which are forming hydrogels as cellulose derivatives and natural polysaccharides to synthetic polymers derived from acrylic acid. The formulation of the dosage forms requires particular care in respect to the amount of initial and maintenance doses. On account of technological processes, for example during manufacturing of tablets, under certain circumstances the liberation rate is altered. In vitro test methods allow comparisons only then when the results can be counter-checked by in vitro experiments. The release of drug follows different mechanisms, which are described, entirely or in part, to be reactions following the time law of zero or first order. In special cases, a linear correlation is observed as a function of square root of time. The calculation of given special equations for events within the dosage form is feasible from blood-level values.
During treatment with thioxanthenes or phenothiazines of schizophrenic patients non-protein nitrogen in urine was measured. The values were calculated in relation to the excretion of creatinine. a) Flupentixol or fluphenazine applied in optimal dosage, increased the excretion of urea and the amino acids asp, glu + gln, and gly. b) Moreover, if the drug induced a parkinsonoid (thioridazine) the excretion of ser and thr was increased, too. The usual desalting procedure by ion-exchanging resins before chromatography increases the contents of several amino acids, e.g. asp, asn, ala, gly, cys, ser, thr, indicating a breakdown of some instable products.
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