P.F. Darcy

DIABETES AND SCHIZOPHRENIA—A PRELIMINARY STUDY

The results of a small scale retrospective study are presented. The study was initiated to determine the incidence of diabetes in long‐stay patients in two psychiatric hospitals in Northern Ireland and to attempt to define whether there was a relationship between the two disease states, schizophrenia and diabetes mellitus.

DRUG-ANTACID INTERACTIONS - ASSESSMENT OF CLINICAL IMPORTANCE

Antacids and adsorbents are commonly used preparations that are generally considered to be pharmacologically inert and free from adverse effects. They may, however, interact with a diverse range of primary drugs and the sequelae can be disadvantageous to the efficacy of the primary medication. Many such reports in the literature are based on animal experiments, or on single-dose studies in healthy subjects. Some reports are anecdotal and are unconfirmed; others are based solely on in vitro evidence. Potentially important interactions have been suggested for a relatively small group of drugs: tetracyclines, phenytoin, digoxin, chloroquine, cimetidine, quinidine, nonsteroidal antiinflammatory drugs, and beta-blocking agents. The evidence for these has been critically evaluated, as well as for antacid-anticoagulant and antacid-nitrofurantoin interactions that have been wrongly emphasized in the literature. The majority of literature reports on interactions with antacids have been overemphasized; only ferrous sulfate-, isoniazid-, and tetracycline-antacid interactions fall into a category I importance (scale I–III of descending importance). This category is for those interactions with good evidence of actual or potential importance in patients or in relevant studies on normal subjects.

Drugs taken by mothers in the puerperium: inpatient survey in Northern Ireland.

In an inpatient survey the medication records of 2004 mothers both breast and bottle feeding were examined and the drugs taken in the early postnatal period recorded. No notable differences existed between the types of drugs prescribed for breast feeding and bottle feeding mothers. Iron, vitamins, and mild analgesics were taken routinely by the population, and antibiotics, laxatives, and hypnotics were frequently prescribed. A wide range of other drugs and preparations were taken or used. Although data were available for some of the drugs, there were many whose concentrations in breast milk and potential risk to the suckling infant were unknown. Data are urgently required on hypnotics, narcotic analgesics, antiemetics, antihistaminics, and some antimicrobial agents with respect to their concentrations in breast milk and their safety for the suckling infant.

Displacement of albumin-bound warfarin by anti-inflammatory agents in vitro.

Much work has been done on the examination of warfarin binding to, and displacement from, serum albumin binding sites especially by phenylbutazone (for example, Aggeler et al 1967; Schary et al 1975). Inhibition of the metabolism of the S-isomer of warfarin by phenylbutazone has also been suggested as an alternative mechanism for the increased anticoagulation (Lewis et al 1974; Schary et al 1975). Azapropazone, which is structurally similar to phenylbutazone, has also been implicated in increased warfarin anticoagulation in the clinic (Green et al 1977; Powell-Jackson 1977). Since azapropazone is highly bound (approximately 95O(,) to human serum (Jones 1976) and since i t displaces warfarin in vi t ro from plasma binding (McElnay & D’Arcy 1978) we have compared this displacement quantitatively with that given by a range of other non-steroidal anti-inflammatory agents that have been implicated in warfarin displacement interactions in man as the results might indicate the relative potential of these agents to interact with warfarin at albumin binding sites.

Interaction of digoxin with activated dimethicone and other antacid constituents

A study was made of the effect of activated dimethicone on the absorption of digoxin in relation to other commonly used antacid constituents using an in vitro experimental model. Dimethicone was found not to affect the absorption of digoxin in relation to aluminium hydroxide, bismuth carbonate, light magnesium carbonate and magnesium trisilicate whose effects on the absorption of digoxin were in agreement with values reported in the literature.

An ‘in vitro’ system for the correlation of drug/protein binding with variable plasma protein profile

Abstract Drug binding to plasma proteins is an important determinant on the pharmacological fate of that drug. With the rapid evolution of dosage regimen compilations, more and more pharmacokinetic parameters are being considered. The present study describes a simple system which enables the correlation of drug protein binding with variable plasma protein profile, and suggests how such information may be of value in the regulation of drug dosage.

Binding of chloroquine to glass

Abstract Buffered chloroquine diphosphate solutions of varying pH and concentration were stored in soda or borosilicate glass. Storage in soda glass (test tubes, glass wool) showed a decrease in original drug concentration of up to 60% and 97%, respectively. Borosilicate glass did not show any binding. The highest binding recorded was at physiological pH and at low concentration (7.8 ng· ml −1 ). It is important for laboratory workers to realize that significant reductions in chloroquine concentrations may occur under such conditions.

Interaction between azapropazone and warfarin.

In vitro studies, using 2 separate techniques, have shown that the anti-inflammatory agent azapropazone caused displacement of warfarin from its plasma albumin binding and it is therfore suggested that such a displacement mechanism may be involved in the reported clinical interaction between these 2 drugs.

Comparison of the ototoxic effect of kanamycin on albino and pigmented rats, studied using an operant method.

A study was made of the effect of daily administration of kanamycin (400 mg kg−1) on the hearing of Wistar albino and Lister hooded (pigmented) rats, which had been conditioned to discriminate an acoustic signal. In all animals except one, the drug caused severe, permanent hearing impairment and there was no difference between albino and pigmented rats in onset or degree. Other work has suggested a mediatory role for melanin pigment in such drug ototoxicity but the significance of this must be questioned in view of the failure to find any differences in functional deficit.

The influence of pigmentation of rats and guinea-pigs on the ototoxicity of kanamycin and neomycin

Following the finding that melanin pigment played a role in the accumulation of ototoxic drugs in the inner ear, an investigation was made of the possible influence of the pigmentation of animals on their susceptibility to the ototoxic effects of drugs. Hearing acuity was assessed by measurement of acoustic startle reaction. Preliminary experiments suggested that pigmented animals might be more likely to suffer hearing impairment following ototoxic drug administration. However, in a controlled study using rats treated with kanamycin, it was not possible to confirm this and albino animals appeared no less vulnerable than pigmented animals to kanamycin-induced deafness.