C. E. Hobbs' Botanical hand-book : of common local, English, botanical and pharmacopœial names arranged in alphabetical order, of most of the crude vegetable drugs, etc., in common use. Especially designed as a reference book for druggists and apothecaries /

Mode of access: Internet.

Experimental pharmacology. A hand-book of methods for studying the physiological actions of drugs.

Mode of access: Internet.

Drugs & driving : why take the risk?

Mode of access: Internet.

Regulation of trade in drugs: hearings, Ninety-first Congress, second session, on S. 1575, to regulate trade in drugs and devices by prohibiting the dispensing of drugs or devices by medical practitioners and their participation in profits from the dispensing of such products, except under certain circumstances, and for other purposes, June 16 and 17, 1970.

"Serial no. 91-81."

Notices of Judgment under the Federal Food, Drug, and Cosmetic Act. Drugs and Devices

Mode of access: Internet.

Drugs and heart disease; a review of research grants supported by the National Heart Institute July 1, 1949 to June 30, 1962.

Includes bibliographies.

Value Assessment of Orphan Drugs and Treatments for Rare Diseases

Thesis (Master's)--University of Washington, 2016-06

Treatment of dementia with neurotransmission modulation

The prevalence of dementia is growing in developed countries where elderly patients are increasing in numbers. Neurotransmission modulation is one approach to the treatment of dementia. Cholinergic precursors, anticholinesterases, nicotine receptor agonists and muscarinic M-2 receptor antagonists are agents that enhance cholinergic neurotransmission and that depend on having some intact cholinergic innervation to be effective in the treatment of dementia. The cholinergic precursor choline alfoscerate may be emerging as a potential useful drug in the treatment of dementia, with few adverse effects. Of the anticholinesterases, donepezil, in addition to having a similar efficacy to tacrine in mild-to-moderate Alzheimer's disease (AD), appears to have major advantages; its use is associated with lower drop-out rates in clinical trials, a lower incidence of cholinergic-like side effects and no liver toxicity. Rivastigmine is efficacious in the treatment in dementia with Lewy bodies, a condition in which the other anticholinesterases have not been tested extensively to date. Galantamine is an anticholinesterase and also acts as an allosteric potentiating modulator at nicotinic receptors to increase the release of acetylcholine. Pooled data from clinical trials of patients with mild-to-moderate AD suggest that the benefits and safety profile of galantamine are similar to those of the anticholinesterases. Selective nicotine receptor agonists are being developed that enhance cognitive performance without influencing autonomic and skeletal muscle function, but these have not yet entered clinical trial for dementia. Unlike the cholinergic enhancers, the M, receptor agonists do not depend upon intact cholinergic nerves but on intact M, receptors for their action, which are mainly preserved in AD and dementia with Lewy bodies. The M, receptor-selective agonists developed to date have shown limited efficacy in clinical trials and have a high incidence of side effects. A major recent advancement in the treatment of dementia is memantine, a non-competitive antagonist at NMDA receptors. Memantine is beneficial in the treatment of severe and moderate to-severe AD and may also be of some benefit in the treatment of mild-to-moderate vascular dementia. Drugs that modulate 5-HT, somatostatin and noradrenergic neurotransmission are also being considered for the treatment of dementia.

Ion-trapping, microsomal binding, and unbound drug distribution in the hepatic retention of basic drugs

This study investigated the relative contribution of ion-trapping, microsomal binding, and distribution of unbound drug as determinants in the hepatic retention of basic drugs in the isolated perfused rat liver. The ionophore monensin was used to abolish the vesicular proton gradient and thus allow an estimation of ion-trapping by acidic hepatic vesicles of cationic drugs. In vitro microsomal studies were used to independently estimate microsomal binding and metabolism. Hepatic vesicular ion-trapping, intrinsic elimination clearance, permeability-surface area product, and intracellular binding were derived using a physiologically based pharmacokinetic model. Modeling showed that the ion-trapping was significantly lower after monensin treatment for atenolol and propranolol, but not for antipyrine. However, no changes induced by monensin treatment were observed in intrinsic clearance, permeability, or binding for the three model drugs. Monensin did not affect binding or metabolic activity in vitro for the drugs. The observed ion-trapping was similar to theoretical values estimated using the pHs and fractional volumes of the acidic vesicles and the pK(a) values of drugs. Lipophilicity and pK(a) determined hepatic drug retention: a drug with low pK(a) and low lipophilicity (e.g., antipyrine) distributes as unbound drug, a drug with high pK(a) and low lipophilicity (e.g., atenolol) by ion-trapping, and a drug with a high pK(a) and high lipophilicity (e.g., propranolol) is retained by ion-trapping and intracellular binding. In conclusion, monensin inhibits the ion-trapping of high pK(a) basic drugs, leading to a reduction in hepatic retention but with no effect on hepatic drug extraction.

Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy

To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study. Methods. A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes. Results. 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (116.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1 %, P < 0.01). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (11975 vs: 1128 mg, P < 0.01). The incidence of FM with VPA doses greater than or equal to 1100 mg was 30.2% vs. 3.2% with doses < 1100 mg (P < 0.01). Conclusions. There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy. (C) 2004 Elsevier Ltd. All rights reserved.

A commentary on the impacts of metals and metalloids in the environment upon the metabolism of drugs and chemicals

The salient feature of metals is that unlike organic compounds they do not degrade in the environment and barely move from one environmental matrix to another. Human interventions take these compounds from their stable and non-bioavailable geological matrix into situations of biological accessibility. Studies in the 1970s and the 1980s of metal bioavailability and impacts of metals and metalloids were driven by the process of abatement of lead in the environment. Humans have clear and identifiable sources of exposure from fuels, food and leaded water pipes to lead. Interventions started at that time have dramatically lowered human lead exposure. Attention has now shifted to other metals, in particular, cadmium, which has seen increasing use. It is generally accepted that food crops grown on cadmium containing soils or soils naturally rich in this metal are the major source of exposure to humans other than exposure from smoking of cigarettes. This mini-review gives a summary and commentary on early studies on effects of lead on haem metabolism that provide us the clue to why investigations of the impacts of other toxic heavy metals and metalloids such as cadmium and arsenic on different human cytochrome P450 forms have become of great interest at the current time. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Conjugation of an antibody to cross-linked fibrin for targeted delivery of anti-restenotic drugs

There is an urgent need to treat restenosis, a major complication of the treatment of arteries blocked by atherosclerotic plaque, using local delivery techniques. We observed that cross-linked fibrin (XLF) is deposited at the site of surgical injury of arteries. An antibody to XLF, conjugated to anti-restenotic agents, should deliver the drugs directly and only to the site of injury. An anti-XLF antibody (H93.7C.1D2/48; 1D2) was conjugated to heparin (using N-succinimidyl 3-(2-pyridyldithio)-propionate), low molecular weight heparin (LMWH) (adipic acid dihydrazide) and rapamycin (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide), and the conjugates purified and tested for activity before use in vivo. Rabbits had their right carotid arteries de-endothelialised and then given a bolus of 1D2-heparin, 1D2-LMWH or 1D2-rapamycin conjugate or controls of saline, heparin, LMWH, rapamycin or 1D2 (+/-heparin bolus) and sacrificed after 2 or 4 weeks (12 groups, n=6/group). Rabbits given any of the conjugates had minimal neointimal development in injured arteries, with up to 59% fewer neointimal cells than those given control drugs. Rabbits given 1D2-heparin or 1D2-LMWH had an increased or insignificant reduction in luminal area, with positive remodelling, while the medial and total arterial areas of rabbits given 1D2-rapamycin were not affected by injury. Arteries exposed to 1D2-heparin or 1D2-rapamycin had more endothelial cells than rabbits given control drugs. Thus, XLF-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall, where the conjugates can influence remodelling, re-endothelialisation and neointimal cell density, with reduced neointimal formation. (C) 2004 Elsevier B.V. All rights reserved.