John A. Thomas

Important Drug-Nutrient Interactions in the Elderly

Several drug-nutrient interactions can occur, but their prevalence may be accentuated in the elderly. Geriatric patients may experience age-related changes in the pharmacokinetics of a drug — absorption, distribution, metabolism and excretion. When drug-nutrient interactions occur, they usually affect absorptive processes more frequently. Specific transporter systems facilitate the absorption of many drugs. Little is known about how these transporter systems are affected by aging. Co-existing disease states in the elderly may exaggerate the action of a drug and represent a confounding factor in drug-nutrient interactions. While several different drug-nutrient interactions are important in the elderly, those affecting the cardiovascular system warrant special attention.

Interactions Between Drugs and Nutrients

Publisher Summary Certain clinical conditions, where prolonged medication is prescribed, can accentuate such potential interactions. There is, however, no reason to believe that genetically engineered foods differ significantly from natural foodstuffs with regard to drug-nutrient interactions. Perhaps the impact of plant genetic engineering on foods and nutrition is too embryonic to accurately forecast. Plant genetic engineering can improve agronomic and quality traits such as nutritional value, yet virtually nothing is known about potential nutrient-drug interactions. Increasing attention has focused on nutrient-drug interaction due perhaps to drugs becoming more and more potent and having greater specificity. Drugs and nutrients share a host of characteristics including physico-chemical properties that may affect certain biochemical actions and other dose-related toxicities. Frequently, the mechanism of action of a drug may involve a nutrient(s) in a manner comparable to a nonnutrient component(s). Food-induced changes in the bioavailability of some drugs may partially depend on hepatic biotransformation as evidenced by absorbed nutrients competing with drugs for first-pass metabolism in the intestine or in the liver. Altered drug metabolism has been studied extensively among different populations. Among the many conditions to which the human organism must adapt is the nutritional environment. Genetic variation can impact certain nutritional states. Undoubtedly, nutritional status plays a significant role in a drugs pharmacologic response.

Recent developments and perspectives of biotechnology-derived products

Recent advances in molecular biology especially in the area of rDNA, gene transfer, polymerase chain reaction and hybridoma techniques have provided the necessary molecular tools for the development of a new class of biopharmaceuticals. These biopharmaceuticals include antisense drugs, carbohydrate-based macromolecules and agents that interfere with apoptosis pathways. Cytokines and other immunomodulators also represent an exciting class of new therapeutic entities. The safety evaluation, efficacy, manufacturing and quality control of these complex biopharmaceuticals represent a challenge to the pharmacologist and toxicologist. Finally, the regulatory issues associated with the new biopharmaceuticals need to be addressed to insure the safety of these evolving therapeutic substances.

Principles of endocrine pharmacology

1. Introduction and General Mechanisms of Hormonal Actions.- 1.1. History and Scope of Endocrine Pharmacology.- 1.2. General Concepts of Hormone Actions.- 1.2.1. Hormone Receptor/Acceptors.- 1.2.2. Hormone Substitutes.- 1.2.3. Hormone Antagonists.- 1.2.4. Hormone Synthesis Inhibitors.- 1.3. Hormonal Feedback Systems.- Recommended Readings.- 2. Pharmacology of Adenohypophyseal Hormones.- 2.1. Factors Modifying Adenohypophyseal Secretion: Hypophysiotrophic Hormones.- 2.1.1. CRH.- 2.1.2. TRH.- 2.1.3. LH/FSH-RH (GnRH).- 2.1.4. GH-RF and GH-IF (SRIF).- 2.1.5. PRF and PIF.- 2.1.6. MRF and MIF.- 2.2. Pharmacology of Anterior Pituitary Hormones.- 2.2.1. TSH.- 2.2.2. STH or GH.- 2.2.3. ACTH.- 2.2.4. FSH/LH.- 2.2.5. PRL.- Recommended Readings.- 3. Posterior Pituitary Hormones, Oxytocics, and Prostaglandins.- 3.1. Posterior Pituitary Hormones.- 3.1.1. History.- 3.1.2. Synthesis, Transport, and Release.- 3.1.3. Antidiuretic Hormone.- 3.1.4. Oxytocin.- 3.2. Ergot Alkaloids.- 3.2.1. Chemistry.- 3.2.2. Mechanism of Action and Biochemical Effects.- 3.2.3. Therapeutic Uses and Preparations.- 3.2.4. Adverse Effects.- 3.3. Prostaglandins: Reproductive Actions.- 3.3.1. Chemistry.- 3.3.2. Mechanism of Action and Biochemical Effects.- 3.3.3. Therapeutic Uses and Preparations.- 3.3.4. Adverse Effects.- 3.3.5. Prostaglandin Inhibitors.- 3.3.6. Uterine Relaxants.- Recommended Readings.- 4. Thyroid and Antithyroidal Drugs.- 4.1. Thyroid.- 4.1.1. History.- 4.1.2. Central Regulation of the Thyroid.- 4.1.3. Chemistry, Biosynthesis, Secretion, and Metabolism.- 4.1.4. Thyroid Hormone Receptors.- 4.1.5. Biochemical Actions.- 4.1.6. Management of Hypothyroidal States.- 4.1.7. Therapeutic Uses and Preparations.- 4.1.8. Adverse Effects.- 4.2. Antithyroidal Agents.- 4.2.1. Thyrotoxicosis (Hyperthyroidism).- 4.2.2. Drugs Used in the Management of Thyrotoxicosis.- 4.3. Drug Interactions and Thyroid Function Tests.- Recommended Readings.- 5. Parathyroid Hormone and Calcitonin.- 5.1. Introduction.- 5.2. History.- 5.3. Parathyroid Hormone.- 5.3.1. Chemistry.- 5.3.2. Biosynthesis, Secretion, and Metabolism.- 5.3.3. Mechanism of Action.- 5.3.4. Physiological and Pharmacological Actions.- 5.3.5. Preparations.- 5.3.6. Therapeutic Uses.- 5.3.7. Adverse Effects.- 5.4. Calcitonin.- 5.4.1. Chemistry.- 5.4.2. Biosynthesis, Secretion, and Metabolism.- 5.4.3. Mechanism of Action.- 5.4.4. Physiological and Pharmacological Actions.- 5.4.5. Preparations.- 5.4.6. Therapeutic Uses.- 5.4.7. Adverse Effects.- Recommended Readings.- 6. Androgenic and Anabolic Steroids.- 6.1. Introduction.- 6.2. History.- 6.3. Chemistry.- 6.4. Biosynthesis, Secretion, and Metabolism.- 6.5. Mechanism of Action.- 6.6. Physiological and Pharmacological Actions of Androgens.- 6.7. Preparations.- 6.8. Therapeutic Uses.- 6.9. Adverse Effects.- 6.10. Weak or Impeded Androgens.- 6.11. Androgen Antagonists.- Recommended Readings.- 7. Estrogens and Antiestrogenic Drugs.- 7.1. Estrogens.- 7.1.1. Introduction.- 7.1.2. History.- 7.1.3. Chemistry.- 7.1.4. Biosynthesis, Secretion, and Metabolism.- 7.1.5. Mechanism of Action.- 7.1.6. Physiological Actions.- 7.1.7. Therapeutic Uses.- 7.1.8. Preparations.- 7.1.9. Adverse Effects.- 7.2. Antiestrogens.- 7.2.1. Clomiphene.- 7.2.2. Tamoxifen.- Recommended Readings.- 8. Progestins and Oral Contraceptives.- 8.1. Progestins.- 8.1.1. Introduction.- 8.1.2. History.- 8.1.3. Chemistry.- 8.1.4. Biosynthesis, Secretion, and Metabolism.- 8.1.5. Mechanism of Action.- 8.1.6. Physiological Effects.- 8.1.7. Therapeutic Uses.- 8.1.8. Preparations.- 8.1.9. Adverse Effects.- 8.2. Oral Contraceptives.- 8.2.1. Preparations.- 8.2.2. Mechanism of Action.- 8.2.3. Adverse Effects.- Recommended Readings.- 9. Adrenocorticosteroid Drugs.- 9.1. Introduction.- 9.2. History.- 9.3. Chemistry.- 9.4. Biosynthesis, Secretion, and Metabolism.- 9.5. Mechanism of Action.- 9.6. Physiological and Pharmacological Actions.- 9.7. Preparations.- 9.8. Therapeutic Uses.- 9.9. Adverse Effects.- 9.10. Inhibitors of Adrenocortical Steroid Biosynthesis.- Recommended Readings.- 10. Insulin and Oral Hypoglycemic Agents.- 10.1. Insulin.- 10.1.1. History of Diabetes Mellitus.- 10.1.2. Chemistry of Insulin.- 10.1.3. Secretion and Metabolism.- 10.1.4. General Biochemical Events and Actions.- 10.1.5. Insulin Receptors.- 10.1.6. Receptor-Mediated Internalization.- 10.1.7. Factors Affecting Insulin and Insulin Resistance.- 10.1.8. Uses and Preparations.- 10.1.9. Adverse Effects.- 10.2. Oral Hypoglycemic Agents.- 10.2.1. Sulfonylureas.- 10.2.2. Biguanides.- 10.3. Glucagon.- 10.4. Somatostatin.- 10.5. Nonhormonal Hyperglycemic Agents.- Recommended Readings.- 11. Effects of Drugs on the Endocrine System.- 11.1. Introduction.- 11.2. Basic Mechanisms of Drug-Hormone Interactions.- 11.3. Effects of Drugs on Adenohypophyseal Function.- 11.4. Effects of Drugs on Neurohypophyseal Function.- 11.5. Effects of Drugs on Lactation and Their Presence in Milk.- 11.6. Effects of Drugs on Hormone Transport.- 11.7. Effects of Drugs on Steroidogenesis.- 11.8. Effects of Drugs on Gonadal Function.- 11.9. Effects of Drugs on Pancreatic Function.- 11.10. Effects of Drugs on Thyroid Function.- 11.11. Effects of Drugs on Laboratory Analyses.- Recommended Readings.

Toxicological Assessment of Zeolites

The zeolites, sometimes referred to as molecular sieves, are a large group of natural and synthetic materials. Their composition may consist of an aluminosilicate framework containing alkali or alkaline earth cations. Zeolites exhibit fibrous, cuboidal, or other crystalline morphologies. Often considered nuisance dusts, these materials may evoke pulmonary changes leading to irritation of the respiratory tract. Pulmonary inflammatory responses, particularly those caused by natural occurring zeolites, can lead to fibrosis and even mesotheliomas. Synthetic zeolite structures, usually cuboidal, produce irritation of the eyes and mucous membranes, but there is no evidence of significant pathologic changes in the lungs. Few nonpulmonary toxicologic changes are produced by either the natural or synthetic zeolites.

Drugs and Chemicals that Affect the Endocrine System

The mammalian endocrine system is very dynamic, and undergoes frequent physiological fluctions due to diurnal variations and cyclical hormonal feedback systems. Both hormonal modulations and chemicall drug perturbations can affect the reproductive systems in males and females. An endocrine disrup-tor, a contemporary term that has been used to define an agent that disrupts the endocrine system, is a hormone or antihormone mimic that can modulate endocrine signaling pathways. Unfortunately, this terminology is confusing and ambiguous and fails to account for the ever-changing endogenous hormonal milieu. The endocrine system can be disrupted or modulated by many physiologic events (e.g., exercise, menstruation, pregnancy), by pharm acologic intervention (e.g., oral contraceptives, antithyroidal medication), and by nutritional states (e.g., iodine deficiencies, vitamin deficiencies and malnutrition). Seasonal changes (e.g., light and temperature) can also modulate endocrine events. Phytoestrogens and xenoestrogens (e.g., chlorinated pesticides) can also affect the dynamics of the endocrine system. Heavy metals and certain anti-cancer agents can interfere with testicular and ovarian function and may cause sterility. Several sites of action can be involved between a drug/chemical and the endocrine system, including the central nervous system, specific target organs or subpopulation of cells, hormone-transporting proteins, and xenobi-otic-m etabolizing enzymes in the liver. At the endocrine target organ level, mechanism(s) of action may involve competition for a cell receptor or affect non-receptor-mediated actions. Some drug!chemicals may act as hormone agonists (i.e., mimic) or conversely act as hormone antagonists (i.e., an antihormone); other agents may act as partial agonists or partial antagonists. Clearly, there are many internal and external factors that can modulate the endocrine system, yet the paracrine and autocrine regulation of specific target organs is finely regulated, and, importantly, is very resilient to drugl chemical perturbation.

Insulin and Oral Hypoglycemic Agents

About 100 years have elapsed since the classic experiments of von Mering and Minkowski demonstrated that pancreatomized dogs exhibited signs and symptoms resembling those seen in diabetes mellitus. The pioneering efforts of Banting and Best revealed that pancreatic extracts could sustain the life of patients suffering from severe diabetes, thereby providing the link between insulin deficiency and the disease. Insulin was subsequently crystallized by Abel and was eventually chemically synthesized in the laboratory. Recently, synthetic insulin derived from recombinant DNA technologies has been approved for clinical trials. Therapy employing animal insulin has been used in the clinical management of diabetes mellitus for many years. Despite the experience with hormone replacement therapies, it is now recognized that diabetes mellitus is a very complex metabolic disorder, and the simple concept that its pathogenesis is due solely to insulin deficiency is no longer tenable. Indeed, contributing to the reduced production of insulin are contributing factors such as excess glucagon, which aggravate both hyperglycemia and ketosis. Insulin resistance, as demonstrated in insulin-dependent diabetes mellitus (IDDM) (i. e., type I), is yet another complicating factor and may be due to both a decrease in insulin receptors and a postreceptor defect.

Biotechnology: Safety Evaluation of Biotherapeutics and Agribiotechnology Products

Publisher Summary The term biotechnology can refer to different things, but classically refers to any technique that uses living organisms to modify or create life forms, to improve plants or animals, or to develop microorganisms for specific uses. Genetic engineering involves the ability to manipulate, modify, or otherwise “engineer” genetic material to produce desired characteristics. This chapter reveals several important milestones in biotechnology; discusses transgene technology in animals and plants and regulatory considerations; outlines biotherapeutics; and describes the new biologics genetics, immunology, and molecular biology. Safety evaluation includes general considerations, antisense drugs, gene products, monoclonal antibodies, and regulatory considerations. Agrobiotechnology includes information on genetically modified foods and world population, field trials and releases, and substantial equivalence. Safety evaluation includes allergenicity and digestible proteins, feeding studies, nutritional improvement, agrobiotechnology, and medicines.

Pharmacologic and Toxicologic Responses in the Neonate

HE POSSIBILITY OF DELETERIOUS EFFECTS of chemicals andlor drugs on the fetus and the T newborn continues to be a major concern in our society.(l-l) During the last few decades a number of agents have been shown to affect the newborn adversely. The thalidomide tragedy of the 1960s emphasized the vulnerability of the human fetus to exposure to drugs and chemicals.(s) The use of diethylstilbestrol by pregnant women also revealed the action of this synthetic estrogen on the fetus. The sciences of embryology, teratology, and developmental toxicology have undergone considerable advances in recent times.

Effects of Drugs on the Endocrine System

Several synthetic steroids and hormonally active substances are able to affect the endocrine system. In such cases, the substance may possess inherent hormonal activity and therefore act rather specifically on a particular target organ of the endocrine system. Some of the so-called 19-norsteroids can effectively inhibit ovulation (e. g., norethynodrel) or can enhance protein-anabolic activity (e. g., norethandrolone). While these steroids are, in fact, drugs, they nevertheless possess inherent hormonal activity. On the other hand, drugs without inherent hormonal activity are able to affect particular target organs of the endocrine system. Some of these drugs are used for the explicit purpose of affecting an endocrine process, while still others affect a hormonal action, usually as a result of some side effect or toxic reaction. Several antithyroidal agents have no inherent hormonal activity, yet exert pharmacological effects on the endocrine system. Conversely, several CNS-depressant drugs without inherent hormonal activity are capable of affecting hormonal balance as a result of some side effect, or their ability to interfere with hypothalamic-pituitary relationships.