Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.United States Food and Drug Administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.Drug Administration Routes: The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Administration, Intranasal: Delivery of medications through the nasal mucosa.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Injections, Subcutaneous: Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.Administration, Rectal: The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Mice, Inbred C57BLBiological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Injections, Intramuscular: Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it.Administration, Topical: The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example.Infusions, Intravenous: The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Administration, Intravenous: Delivery of substances through VENIPUNCTURE into the VEINS.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Injections, Intraventricular: Injections into the cerebral ventricles.Mice, Inbred BALB CRats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Administration, Cutaneous: The application of suitable drug dosage forms to the skin for either local or systemic effects.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Administration, Sublingual: Administration of a soluble dosage form by placement under the tongue.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Administration, Inhalation: The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Infusions, Parenteral: The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.Behavior, Animal: The observable response an animal makes to any situation.Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Injections: Introduction of substances into the body using a needle and syringe.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Injections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Organ Size: The measurement of an organ in volume, mass, or heaviness.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Mice, Inbred ICRLung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Rats, Inbred F344Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Estradiol: The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Injections, Intra-Arterial: Delivery of drugs into an artery.Administration, Buccal: Administration of a soluble dosage form between the cheek and gingiva. It may involve direct application of a drug onto the buccal mucosa, as by painting or spraying.Spleen: An encapsulated lymphatic organ through which venous blood filters.Piperidines: A family of hexahydropyridines.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Blood Glucose: Glucose in blood.Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Eating: The consumption of edible substances.United StatesDopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Absorption: The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Delayed-Action Preparations: Dosage forms of a drug that act over a period of time by controlled-release processes or technology.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Progesterone: The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Growth Hormone: A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.Administration, Intravaginal: The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Animals, Newborn: Refers to animals in the period of time just after birth.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Body Temperature: The measure of the level of heat of a human or animal.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Kinetics: The rate dynamics in chemical or physical systems.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.United States Department of Veterans Affairs: A cabinet department in the Executive Branch of the United States Government concerned with overall planning, promoting, and administering programs pertaining to VETERANS. It was established March 15, 1989 as a Cabinet-level position.Gonadotropin-Releasing Hormone: A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.Drugs, Chinese Herbal: Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Luteinizing Hormone: A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.PiperazinesNeoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Device Approval: Process that is gone through in order for a device to receive approval by a government regulatory agency. This includes any required preclinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance. It is not restricted to FDA.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Infusion Pumps: Fluid propulsion systems driven mechanically, electrically, or osmotically that are used to inject (or infuse) over time agents into a patient or experimental animal; used routinely in hospitals to maintain a patent intravenous line, to administer antineoplastic agents and other drugs in thromboembolism, heart disease, diabetes mellitus (INSULIN INFUSION SYSTEMS is also available), and other disorders.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Glucocorticoids: A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Diazepam: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.Corticosterone: An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.Chemistry, Pharmaceutical: Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Drug Carriers: Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.Ovariectomy: The surgical removal of one or both ovaries.Hyperalgesia: An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Mice, Inbred C3HLeukocyte Count: The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)Drug-Induced Liver Injury: A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Anti-Anxiety Agents: Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.Suppositories: Medicated dosage forms that are designed to be inserted into the rectal, vaginal, or urethral orifice of the body for absorption. Generally, the active ingredients are packaged in dosage forms containing fatty bases such as cocoa butter, hydrogenated oil, or glycerogelatin that are solid at room temperature but melt or dissolve at body temperature.Hypothalamus: Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Infusion Pumps, Implantable: Implanted fluid propulsion systems with self-contained power source for providing long-term controlled-rate delivery of drugs such as chemotherapeutic agents or analgesics. Delivery rate may be externally controlled or osmotically or peristatically controlled with the aid of transcutaneous monitoring.Chorionic Gonadotropin: A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN).Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Narcotics: Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Clinical Trials as Topic: Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.Acute Disease: Disease having a short and relatively severe course.Hypoglycemic Agents: Substances which lower blood glucose levels.Rats, Inbred LewEndotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.Sulfonamides: A group of compounds that contain the structure SO2NH2.Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.Injections, Intradermal: The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.
(1/247) Exercise training enhances endothelial function in young men.

OBJECTIVES: The present study was designed to assess whether exercise training can enhance endothelium-dependent dilatation in healthy young men. BACKGROUND: Exercise has been shown to reduce cardiovascular morbidity and mortality, but the mechanisms for this benefit are unclear. Endothelial dysfunction is an early event in atherogenesis, and animal studies have shown that exercise training can enhance endothelial function. METHODS: We have examined the effect of a standardized, 10-week, aerobic and anaerobic exercise training program on arterial physiology in 25 healthy male military recruits, aged 17 to 24 (mean 20) years, of average fitness levels. Each subject was studied before starting, and after completing the exercise program. Baseline vascular reactivity was compared with that of 20 matched civilian controls. At each visit, the diameter of the right brachial artery was measured at rest, during reactive hyperemia (increased flow causing endothelium-dependent dilation) and after sublingual glyceryltrinitrate (GTN; an endothelium-independent dilator), using high-resolution external vascular ultrasound. RESULTS: At baseline, flow-mediated dilatation (FMD) and GTN-mediated dilatation were similar in the exercise and control groups (FMD 2.2+/-2.4% and 2.4+/-2.8%, respectively, p = 0.33; GTN 13.4+/-6.2 vs. 16.7+/-5.9, respectively, p = 0.53). In the military recruits, FMD improved from 2.2+/-2.4% to 3.9+/-2.5% (p = 0.01), with no change in the GTN-mediated dilation (13.4+/-6.2% vs. 13.9+/-5.8%, p = 0.31) following the exercise program. CONCLUSION: Exercise training enhances endothelium-dependent dilation in young men of average fitness. This may contribute to the benefit of regular exercise in preventing cardiovascular disease.  (+info)

(2/247) A retrospective study of buprenorphine and norbuprenorphine in human hair after multiple doses.

The analysis of hair has been proposed as a tool for monitoring drug-treatment compliance. This study was performed to determine if buprenorphine (BPR) and norbuprenorphine (NBPR) could be detected in human hair after controlled administration of drug and to determine if segmental analysis of hair was an accurate record of the dosing history. Subjects with dark hair (six males, six females) received 8 mg sublingual BPR for a maximum of 180 days. Single hair collections were made once after BPR treatment and stored at -20 degrees C until analysis. Hair was aligned scalp-end to tip and then segmented in 3-cm sections. For this study, it was assumed that the mean hair growth rate was 1.0 cm/month. Deuterated internal standard was added to hair segments (2-20 mg of hair) and digested overnight at room temperature with 1 N NaOH. Specimens were extracted with a liquid-liquid procedure and analyzed by liquid chromatography-tandem mass spectrometry. The limits of quantitation for BPR and NBPR were 3 pg/mg and 5 pg/mg, respectively, for 20 mg of hair. BPR and NBPR concentrations were highest for all subjects in hair segments estimated to correspond to the subject's period of drug treatment. With one exception, NBPR was present in higher concentrations in hair than was the parent compound. BPR concentrations in hair segments ranged from 3.1 pg/mg to 123.8 pg/mg. NBPR concentrations ranged from 4.8 pg/mg to 1517.8 pg/mg. In one subject, BPR and NBPR were not detected in any hair segment. In some subjects, BPR and NBPR were detected in hair segments that did not correspond to the period of drug treatment, suggesting that drug movement may have occurred by diffusion in sweat and other mechanisms. The data from this study also indicate that there is a high degree of intersubject variability in measured concentration of BPR and NBPR in hair segments, even when subjects receive the same dose for an equivalent number of treatment days. Future prospective studies involving controlled drug administration will be necessary to evaluate whether hair can serve as an accurate historical record of variations in the pattern of drug use.  (+info)

(3/247) Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam.

We have evaluated the perioperative effects of melatonin with those of midazolam in 75 women in a prospective, randomized, double-blind, placebo-controlled study. Patients were given sublingual midazolam 15 mg, melatonin 5 mg or placebo, approximately 100 min before a standard anaesthetic. Sedation, anxiety and orientation were quantified before, and 10, 30, 60 and 90 min after premedication, and 15, 30, 60 and 90 min after admission to the recovery room. Psychomotor performance was evaluated at these times also, using the digit-symbol substitution test (DSST) and the Trieger dot test (TDT). Patients who received premedication with either midazolam or melatonin had a significant decrease in anxiety levels and increase in levels of sedation before operation compared with controls. Midazolam produced the highest scores for sedation at 30 and 60 min after administration and significant psychomotor impairment in the preoperative period compared with melatonin or placebo. After operation, patients who received midazolam or melatonin premedication had increased levels of sedation at 30 min and impairment in performance on the DSST at 15, 30 and 90 min compared with controls. There were no significant differences between the three groups for anxiety levels or TDT performance after operation. Amnesia was notable only in the midazolam group for one preoperative event (entry into the operating room). Patient satisfaction was noted in the midazolam and melatonin groups only. We have demonstrated that melatonin can be used effectively for premedication of adult patients.  (+info)

(4/247) The impact of heavy passive smoking on arterial endothelial function in modernized Chinese.

OBJECTIVES: The study evaluated whether heavy exposure to environmental tobacco smoke (passive smoking) might damage arterial function in modernized Chinese. BACKGROUND: Heavy passive smoking is associated with arterial endothelial dysfunction in Caucasian, but not rural Chinese, subjects. METHODS: We studied 20 young (mean age 36.6 +/- 7.0 years) nonsmoking asymptomatic casino workers (9 men) in Macau who were exposed to environmental tobacco smoke for over 8 h/day for at least two years and 20 normal subjects (control subjects). These two groups were carefully matched for age, gender, body mass index (BMI), blood pressure, vessel diameter, cholesterol and glucose levels. Brachial artery diameter was measured by high-resolution B-mode ultrasound at rest, after flow increase (causing flow-mediated endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). RESULTS: Flow-mediated dilation (mean +/- SD% of diameter changes) was significantly lower in passive smokers (6.6 +/- 3.4%) compared with the controls (10.6 +/- 2.3%) (p < 0.0001). Nitroglycerin-induced dilation of the two groups were similar. Upon multivariate analysis, passive smoking exposure was the strongest independent predictor (beta = -0.59; p = 0.0001) for impaired flow-mediated endothelium-dependent dilation (model R2 = 0.75, F value = 6.1, p = 0.0001). CONCLUSIONS: In modernized Chinese, as in Caucasians, exposure to heavy environmental tobacco smoke causes arterial endothelial dysfunction, a key early event in atherosclerosis. This may have serious implications for cardiovascular health in China, currently in a process of rapid modernization.  (+info)

(5/247) Responses to the prolonged head-up tilt followed by sublingual nitrate provocation in asymptomatic older adults.

BACKGROUND: prolonged head-up tilt testing and sublingual nitrate provocation are increasingly used in the diagnosis of neurocardiogenic syncope. However there are few data regarding the results of these tests in asymptomatic older subjects. OBJECTIVE: to assess the responses to the prolonged head-up tilt test followed by sublingual glyceryl trinitrate provocation in asymptomatic subjects over the age of 60 years. DESIGN: observational study. METHODS: we recruited 64 asymptomatic subjects over the age of 60 (39 men, 25 women) from two general practice lists in Nottingham and Leicester. Exclusion criteria were: history of syncope, ischaemic heart disease, cerebrovascular disease, marked aortic stenosis, carotid artery disease and being unable to stand for the duration of the test. All subjects underwent a full clinical examination, a 12-lead electrocardiogram and a 30-40-min head-up tilt test, during which we monitored the heart rate and blood pressure continuously. We ended the test prematurely if the subjects developed syncope or symptoms of presyncope associated with hypotension with or without bradycardia. If they remained asymptomatic at the end of this period, they received 400 microg of sublingual glyceryl trinitrate and monitoring continued for another 15 min. SETTINGS: two teaching hospitals in Nottingham and Leicester. RESULTS: six (9%) of the subjects had a positive response (syncope or presyncope) to the prolonged head-up tilt test prior to glyceryl trinitrate provocation. After provocation, 30 (52%) of the remaining 58 subjects had a positive response. CONCLUSION: the role of sublingual glyceryl trinitrate provocation following prolonged head-up tilt testing in the diagnosis of neurocardiogenic (vasovagal) syncope in older people is questionable, as many asymptomatic older subjects demonstrate syncopal or presyncopal symptoms.  (+info)

(6/247) Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope.

AIMS: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients. METHODS: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min. RESULTS: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards). CONCLUSIONS: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.  (+info)

(7/247) Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women.

OBJECTIVES: We sought to evaluate the relationship between the angiotensin-converting enzyme (ACE) genotype and the change in forearm vasoreactivity in response to a three-month course of oral estrogen in postmenopausal women. BACKGROUND: The ACE genotype is a known predictor of the response to an ACE inhibitor drug; however, it is not clear whether it can modify the effect of estrogen replacement therapy (ERT) on endothelial function in postmenopausal women. METHODS: Fifty-five postmenopausal women received 0.625 mg of conjugated equine estrogen daily for three months. Forearm blood flow (FBF) was measured by strain-gauge plethysmography. RESULTS: Twenty-one, 25 and 9 patients had the insertion/deletion (ID), II and DD genotypes, respectively. Plasma ACE activity was significantly higher at baseline in patients with either the DD or ID genotype than in those with the II genotype (p < 0.05). A significant decrease in plasma ACE activity with ERT was seen in the ID and II genotypes (p < 0.05), but not in the DD genotype. There were no significant differences in the FBF responses to reactive hyperemia at baseline between the three groups. Estrogen replacement therapy did not alter the FBF response to reactive hyperemia in the DD genotype (4.0 +/- 1.3%), although ERT significantly increased the FBF response in the ID and II genotypes (32.6 +/- 7.5% and 30.6 +/- 6.5%, respectively; p < 0.05). Forearm blood flow after administration of sublingual nitroglycerin did not change over three months in any of the three groups. CONCLUSIONS: These findings suggest that the effect of ERT in postmenopausal women on forearm endothelial function may be determined in part by the genotype of the ACE gene.  (+info)

(8/247) Evaluation of the method for nifedipine administration for a rapid onset of clinical effect: a clinical study in normal volunteers.

Nifedipine is frequently used for patients who require an immediate reduction of blood pressure elevated temporarily by various administration techniques including sublingual route without administrating intravenous infusion of vasodilator. A cross-over clinical study was conducted to investigate the optimal administration method of nifedipine for rapid management of hypertension. Four method of administering 10 mg nifedipine (the capsule was bitten and swallowed, sublingually with a hole in it or the contents administered orally or intranasally with a syringe) were evaluated with regarded efficacy, safety, and usefulness in 6 normal volunteers. Systolic and diastolic blood pressures were correlated with the nifedipine serum concentration in each method. Nifedipine pharmacokinetic parameters differed among the 4 administration methods. Nifedipine was absorbed rapidly by not only intestinal mucosa but also the nasal or oral mucosa. The pharmacological effect of intranasal or sublingual administration was superior. However, mint oil which is present in nifedipine capsules stimulates nasal mucosa when administered intranasally. For clinical usage, nifedipine capsules in which a hole is made with a needle, administered sublingually, can be effectively and safely used for rapid management of systemic hypertension.  (+info)

*  Sublingual administration
... has certain advantages over oral administration. Being more direct, it is often faster,[quantify] and ... but sublingual administration may also be used for vaccines against other infectious diseases. "ATIVAN® 1 mg SUBLINGUAL TABLETS ... Pharmaceutical preparations for sublingual administration are manufactured in the form of: Sublingual tablets-tablets which ... Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by ...
*  Buccal administration
Sublabial administration Sublingual administration Route of administration Pharmacology Sattar, M; Sayed, OM; Lane, ME (Aug ... Buccal administration refers to a topical route of administration by which drugs held or applied in the buccal (/ˈbʌkəl/) area ... Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral ... Buccal administration of vaccines has been studied, but there are challenges to this approach due to immune tolerance ...
*  Clotiazepam
The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially ... "The pharmacokinetics of clotiazepam after oral and sublingual administration to volunteers". European Journal of Clinical ... and sublingual tablets. The formulations had similar systemic availability. Compared with oral tablets, the sublingual route ...
*  Sublabial administration
... should not be confused with sublingual administration, which is under the tongue. The frenulum of the ... Sublabial administration, literally "under the lip", from Latin, refers to the pharmacological route of administration by which ...
*  Hydromorphone
Sublingual administration (under the tongue) is usually superior to swallowing for bioavailability and effects; however, ... A particular problem that may occur with hydromorphone is accidental administration in place of morphine due to a mix-up ... Gagnon, DJ; Jwo, K (2013). "Tremors and agitation following low-dose intravenous hydromorphone administration in a patient with ... the Drug Enforcement Administration, reports an increase in annual aggregate production quotas of hydromorphone from 766 ...
*  Palliative care
Other routes of administration include sublingual, intramuscular and transdermal. Medications are often managed at home by ... Routes of administration may differ from acute or chronic care, as many people in palliative care lose the ability to swallow. ... A common alternative route of administration is subcutaneous, as it is less traumatic and less difficult to maintain than ...
*  Hydrophile
Stuenkel CA, Dudley RE, Yen SS (May 1991). "Sublingual Administration of Testosterone-Hydroxypropyl-β-Cyclodextrin Inclusion ... normally via sublingual route. Hydrophilic membrane filtration is used in several industries to filter various liquids. These ... absorption of testosterone was achieved in 20 minutes via the sublingual route but HPBCD was not absorbed, whereas normally ...
*  Schering-Plough
"Liquid chromatographic assay and pharmacokinetics of quazepam and its metabolites following sublingual administration of ...
*  Influenza treatment
July 2008). "Effect of sublingual administration of interferon-alpha on the immune response to influenza vaccination in ... On October 23, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization for Peramivir (now expired), ... CS1 maint: Multiple names: authors list (link) - see also "Systemic effects of interferons after oral administration in animals ... be particularly useful in serious cases of influenza where the patient is unconscious and oral or inhaled drug administration ...
*  Comorbidity
... but they always disappeared after a few minutes of sublingual administration of organic nitrates. This time taking three ...
*  Route of administration
sublingual and buccal medication administration is a way of giving someone medicine orally (by mouth). Sublingual ... The word "sublingual" means "under the tongue." Buccal administration involves placement of the drug between the gums and the ... Strictly enteral administration (directly into the intestines) can be used for systemic administration, as well as local ( ... extra-amniotic administration, between the endometrium and fetal membranes nasal administration (through the nose) can be used ...
*  Normethandrone
With sublingual administration, it has at least 150 times the potency of progesterone and 50 times the potency of ethisterone ...
*  Oxycodone
... is available in a variety of formulations for oral or sublingual administration: Immediate-release oxycodone (OxyFast ... The bioavailability of oral administration of oxycodone averages 60-87%, with rectal administration yielding the same results; ... Therapeutic Goods Administration (June 2008). Standard for the uniform scheduling of drugs and poisons no. 23 (PDF). Canberra: ... Drug Enforcerment Administration. Retrieved 23 November 2015. "DEA Diversion Control CSA". US Dept of Justice - DEA. Retrieved ...
*  Anxiolytic
Sublingual administration of Validol produces a sedative effect, and has moderate reflex and vascular dilative action caused by ...
*  Blotting paper
Blotter as a delivery method allows for easy dosing of potent substances and easy sublingual administration of drugs which has ...
*  Oral administration
... dissolved under the lip Sublingual administration, dissolved under the tongue, but due to rapid absorption many consider SL a ... Oral administration is a route of administration where a substance is taken through the mouth. Per os (P.O.) is sometimes used ... Oral administration is a part of enteral administration, which also includes Buccal, dissolved inside the cheek Sublabial, ... TheFreeDictionary > oral administration of medication Citing: Mosby's Medical Dictionary, 8th edition. 2009. ...
*  Tonix Pharmaceuticals
As of 2013 its lead candidates were a reformulation of cyclobenzaprine as a tablet for sublingual administration called TNX-102 ...
*  Seth Lederman
5.6 mg tablets for sublingual administration) for the treatment of post-traumatic stress disorder (PTSD). TNX-102 SL 5.6 mg was ... Low-Dose Sublingual Cyclobenzaprine (TNX-102 SL*) in Military-Related PTSD: Results of a Phase 2 Randomized, Placebo-Controlled ... A Randomized Placebo-Controlled Multicenter Trial of a Low-Dose Bedtime Sublingual Formulation of Cyclobenzaprine (TNX-102 SL) ... A Randomized Placebo-Controlled Multicenter Trial of a Low-Dose Bedtime Sublingual Formulation of Cyclobenzaprine (TNX-102 SL) ...
*  Flumazenil
Administration of flumazenil by sublingual lozenge and topical cream has also been tested. Flumazenil is of benefit in patients ... upon rapid administration of flumazenil. It is not recommended for routine use in those with a decreased level of consciousness ...
*  25C-NBOMe
Buccal, sublingual or insufflated routes of administration are all viable options. Absorption rate buccally and sublingually ... "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015. " ... Drug Enforcement Administration (2015). "Schedules of Controlled Substances: Extension of Temporary Placement of Three ... Thomas M. Harrigan (10 October 2013). "Proposed Rules" (PDF). Drug Enforcement Administration (DEA).
*  Angina
... with minimal or non-existent symptoms at rest or after administration of sublingual nitroglycerin. Symptoms typically abate ...
*  Narcolepsy
For one patient, daily administration of flumazenil by sublingual lozenge and topical cream has proven effective for several ... "XYREM® (sodium oxybate)" (PDF). United States Food and Drug Administration. Jazz Pharmaceuticals, Inc. 11 April 2014. Archived ... Administration of acetyl-L-carnitine was shown to improve these symptoms in mice. A subsequent human trial found that ... and administration of the Epworth Sleepiness Scale. These tests are usually performed by a sleep specialist. The polysomnogram ...
*  Idiopathic hypersomnia
For one patient, daily administration of flumazenil by sublingual lozenge and topical cream has proven effective for several ... Administration of acetyl-L-carnitine was shown to improve these symptoms in mice. A subsequent human trial found that ... "Effects of oral L-carnitine administration in narcolepsy patients: A randomized, double-blind, cross-over and placebo- ...
*  British Columbia Ambulance Service
... administration of the following oral, sublingual or inhaled medications; anti-anginal; anti-hypoglycemic agent; analgesic; ... administration of the following intravenous, intra-muscular, subcutaneous, oral, sublingual, inhaled or nebulized medications: ... administration of oxygen; administration of oral glucose; emergency childbirth; ventilation using pocket mask and bag/valve/ ... oxygen administration and equipment; administration of semi-automatic or automatic external defibrillator; soft tissue injury ...
*  Bioavailability
... or sublingual administration), with the bioavailability of the same drug following intravenous administration. It is the ... The reason for this is that its assessment requires an intravenous reference, that is, a route of administration that ... Intravenous administration of a developmental drug can provide valuable information on the fundamental pharmacokinetic ... For dietary supplements, herbs and other nutrients in which the route of administration is nearly always oral, bioavailability ...
*  Emergency department
... sub lingual (under the tongue) or buccal (between cheek and upper gum) glyceryl trinitrate (nitroglycerin) (GTN or NTG) will be ... medication administration, foley catheter insertion, and obtaining intravenous access) and also perform splinting of injured ...
Sublingual administration - Wikipedia  Sublingual administration - Wikipedia
Sublingual administration has certain advantages over oral administration. Being more direct, it is often faster,[quantify] and ... Pharmaceutical preparations for sublingual administration are manufactured in the form of:. *Sublingual tablets-tablets which ... Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by ... "ATIVAN® 1 mg SUBLINGUAL TABLETS; ATIVAN® 2 mg SUBLINGUAL TABLETS". home.intekom.com. Retrieved 2016-07-08.. ...
more infohttps://en.wikipedia.org/wiki/Sublingual
Sublingual administration - Wikipedia  Sublingual administration - Wikipedia
Sublingual administration has certain advantages over oral administration. Being more direct, it is often faster,[quantify] and ... but sublingual administration may also be used for vaccines against other infectious diseases. "ATIVAN® 1 mg SUBLINGUAL TABLETS ... Pharmaceutical preparations for sublingual administration are manufactured in the form of: Sublingual tablets-tablets which ... Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by ...
more infohttps://en.wikipedia.org/wiki/Sublingual_administration
Sublingual administration of a helper-dependent adenoviral vector expressing the codon-optimized soluble fusion glycoprotein of...  Sublingual administration of a helper-dependent adenoviral vector expressing the codon-optimized soluble fusion glycoprotein of...
Sublingual (s.l.) immunization has been described as a convenient and safe way to induce mucosal immune responses in the ... Sublingual administration of a helper-dependent adenoviral vector expressing the codon-optimized soluble fusion glycoprotein of ... Sublingual (s.l.) immunization has been described as a convenient and safe way to induce mucosal immune responses in the ... These findings suggest that s.l. administration of HDAd-sFsyn acts as an effective and safe mucosal vaccine against RSV ...
more infohttp://www.biomedsearch.com/nih/Sublingual-administration-helper-dependent-adenoviral/24560779.html
About Sublingual and Buccal Medication Administration  About Sublingual and Buccal Medication Administration
Sublingual and buccal medication administration are ways to take certain oral drugs. Learn the differences, pros, cons, and ... Sublingual and buccal medication administration are two different ways of giving medication by mouth. Sublingual administration ... Sublingual and Buccal Medication Administration. Medically reviewed by Zara Risoldi Cochrane, PharmD, MS, FASCP on December 5, ... When sublingual and buccal drugs are given. Your doctor may prescribe sublingual or buccal drugs under any of the following ...
more infohttps://www.healthline.com/health/sublingual-and-buccal-medication-administration
Sublingual steroids | Sublingual administration - Wikipedia  Sublingual steroids | Sublingual administration - Wikipedia
I would recommend asking your veterinarian about sublingual immunotherapy (SLIT), which can often successfully resolve the ... Sublingual steroids. This information should not be used to decide whether or not to take this medicine or any other medicine. ... Sublingual steroids. If your dog or cat has been diagnosed with atopic dermatitis - an allergic skin condition - I would ... This is only a brief summary of general information about this medicine (buprenorphine and naloxone sublingual tablets). It ...
more infohttp://evn.stoynev.us/sublingual-steroids.html
Optimization of Epinephrine Sublingual Tablet for Pediatric Administration  Optimization of Epinephrine Sublingual Tablet for Pediatric Administration
... Grant Winners. *Mutasem Rawas-Qalaji, Ph.D. - ... A fast-disintegrating sublingual tablet (FDST) of epinephrine (Epi) for the treatment of anaphylaxis has been successfully ... We hypothesized that the evaluation and understanding of the effect of the medium's pH in the sublingual cavity and various ... Epi microcrystals and nanocrystals were developed and used to enhance drug permeation and absorption from the sublingual route ...
more infohttp://www.nova.edu/academic-affairs/faculty-research-grant/winners1718/optimization-of-epinephrine-sublingual-tablet-for-pediatric-administration.html
Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12...  Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12...
... sublingual (SL), and intranasal vitamin B12 (VB12) preparations. Large studies comparing the efficacy of... ... Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 ... Vitamin B12 Intramuscular (IM) Oral Sublingual (SL) Efficacy This is a preview of subscription content, log in to check access. ... Successful sublingual cobalamin treatment in a child with short-bowel syndrome. J Pediatr Pharmacol Ther. 2014;19(1):60-3. ...
more infohttps://rd.springer.com/article/10.1007%2Fs13346-018-00613-y
Vitamins & Supplements Help - Forums and Discussions - MedHelp  Vitamins & Supplements Help - Forums and Discussions - MedHelp
Sublingual administration Krsna108 So I have some 5htp capsules which I want to take sublingually by emptying the capsule ...
more infohttps://www.medhelp.org/forums/Vitamins--Supplements/show/1206
Drug Treatment of Urogenital Disease Flashcards by Katie Browse | Brainscape  Drug Treatment of Urogenital Disease Flashcards by Katie Browse | Brainscape
Painful, prolonged erection for more than 4 hours - if great than 6, treat...aspiration of blood, administration of ... Sublingual administration - but vomitting. 12 Give some example of female sexual dysfunction. ...
more infohttps://www.brainscape.com/flashcards/drug-treatment-of-urogenital-disease-812310/packs/1347625
Buprenorphine and Naloxone Sublingual Film - FDA prescribing information, side effects and uses  Buprenorphine and Naloxone Sublingual Film - FDA prescribing information, side effects and uses
Buprenorphine and Naloxone Sublingual Film official prescribing information for healthcare professionals. Includes: indications ... Sublingual Film for sublingual or buccal administration (CIII). IMPORTANT:. Keep buprenorphine and naloxone sublingual film in ... The most common adverse event (, 1%) associated with the sublingual administration of the Buprenorphine and Naloxone Sublingual ... The systemic exposure of buprenorphine between buccal and sublingual administration of Buprenorphine and Naloxone Sublingual ...
more infohttps://www.drugs.com/pro/buprenorphine-and-naloxone-sublingual-film.html
Wiley-VCH - Impacted Third Molars  Wiley-VCH - Impacted Third Molars
Routes of Administration 174. Inhalation (N2O) 176. Oral Sedation 183. Sublingual Administration 184. Intravenous Sedation 185 ...
more infohttp://www.wiley-vch.de/en?option=com_eshop&view=product&isbn=9781119118336&title=Impacted%20Third%20Molars
Pharm Anti-Anginal Agents Linger Flashcards by Stephen Schaffner | Brainscape  Pharm Anti-Anginal Agents Linger Flashcards by Stephen Schaffner | Brainscape
NTG typically sublingual administration, spray equally effective. 21 NTG formulations that improve exercise tolerance and time ...
more infohttps://www.brainscape.com/flashcards/pharm-anti-anginal-agents-linger-4184982/packs/6283968
Free Medical Flashcards about Bonewit chap 11  Free Medical Flashcards about Bonewit chap 11
sublingual administration administration of medication by placing it under the tongue, where it dissolves and is absorbed ... administration of whole blood or blood products through the intravenous route. vial. closed glass container with a rubber ... administration of a liquid agent directly into a patients vein, where it is distributed throughout the body via the circulatory ... the administration of medication by way of air or other vapor being drawn into the lungs ...
more infohttps://www.studystack.com/flashcard-1028898
Free Pharmacology Flashcards about Drug Law Review  Free Pharmacology Flashcards about Drug Law Review
sublingual administration. Most dangerous route for medication administration. intraveous. Drug applied directly to a body site ... Which type of administration produces the slowest onset of action?. Oral. True or False:Drugs are bound irreversibly to plasma ... What type of administration produces the most rapid drug response, with an almost immediate onset of action?. Intravenous Route ... Which route of administration results in fast absorption, thereby producing rapid onset and a more predictable response?. ...
more infohttps://www.studystack.com/flashcard-14270
Sublingual misoprostol for the prevention of postpartum hemorrhage.  Sublingual misoprostol for the prevention of postpartum hemorrhage.
Administration, Rectal. Administration, Sublingual. Adult. Female. Humans. Misoprostol / administration & dosage*. Oxytocics / ... CONCLUSION: Postpartum use of 600 microg misoprostol by sublingual route has a comparable effect in reducing PPH, as that of ...
more infohttp://www.biomedsearch.com/nih/Sublingual-misoprostol-prevention-postpartum-hemorrhage/19618006.html
Search of: ZOLPIDEM AND Primary Insomnia - List Results - ClinicalTrials.gov  Search of: ZOLPIDEM AND Primary Insomnia - List Results - ClinicalTrials.gov
Dietary Supplement: Melatonin sublingual administration. Interventional. Phase 2. *Technological Centre of Nutrition and Health ... Efficacy and Safety of 5 mg Sublingual Zolpidem vs 10mg Oral Zolpidem in the Induction and Maintenance of Sleep in Patients ... A Study of Zolpidem Tartrate Sublingual Tablet in Adult Patients With Insomnia. *Insomnia ... A Study of Zolpidem Tartrate Sublingual Tablet in Adult Patients With Insomnia. *Insomnia ...
more infohttps://www.clinicaltrials.gov/ct2/results?term=ZOLPIDEM+AND+Primary+Insomnia
Sublingual Milk Immunotherapy in Children - Full Text View - ClinicalTrials.gov  Sublingual Milk Immunotherapy in Children - Full Text View - ClinicalTrials.gov
Administration of Milk. Other: Milk sublingual administration of milk. Other Name: sublingual administration of milk ... Sublingual immunotherapy is developing in the treatment of aeroallergens allergy. The hypothesis is that such process may be ... Sublingual Milk Immunotherapy in Children With IgE-mediated Cow Milk Protein Allergy. ... Children with disabling disease, preventing from a correct practice of sublingual treatment ...
more infohttps://clinicaltrials.gov/ct2/show/NCT00874627
Sublingual Milk Immunotherapy in Children - Full Text View - ClinicalTrials.gov  Sublingual Milk Immunotherapy in Children - Full Text View - ClinicalTrials.gov
Administration of Milk. Other: Milk sublingual administration of milk. Other Name: sublingual administration of milk ... Sublingual Milk Immunotherapy in Children (Lactaide). The safety and scientific validity of this study is the responsibility of ... Sublingual immunotherapy is developing in the treatment of aeroallergens allergy. The hypothesis is that such process may be ... Sublingual Milk Immunotherapy in Children With IgE-mediated Cow Milk Protein Allergy. ...
more infohttps://clinicaltrials.gov/show/NCT00874627
Buccal | definition of buccal by Medical dictionary  Buccal | definition of buccal by Medical dictionary
buccal administration. drugs may be absorbed across buccal mucosa, directly into the venous circulation. Called also sublingual ...
more infohttp://medical-dictionary.thefreedictionary.com/buccal
  • LSD , MDMA , morphine , alprazolam , clonazepam , and many other substances including the psychedelic tryptamines and phenethylamines are all viable candidates for administration via this route. (wikipedia.org)
  • In this formulation, Epi microcrystals and nanocrystals were developed and used to enhance drug permeation and absorption from the sublingual route using our developed taste-masked FDST platform. (nova.edu)
  • Upon the completion of this project, the new optimized FDST formulation will not only have better physical properties but hopefully should allow for the reduction of the tablet size for pediatric population and the reduction of the required Epi dose through delivering Epi more efficiently through the sublingual route. (nova.edu)
  • Administration of tacrolimus by the sublingual route may allow for direct entry into the systemic circulation and bypasses problems associated with drug absorption and breakdown that take place in the small intestine. (clinicaltrials.gov)
  • The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly. (wikipedia.org)
  • For example, the Joseph Pitha study showed that when testosterone was complexed with hydroxy-propyl-beta-cyclodextrin (HPBCD), that 95% absorption of testosterone was achieved in 20 minutes via the sublingual route but HPBCD was not absorbed, whereas normally hydrophobic testosterone is absorbed less than around 40% normally via sublingual route. (wikipedia.org)
  • A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body. (wikipedia.org)
  • However, uptake of drugs administered orally may also occur already in the stomach, and as such gastrointestinal (along the gastrointestinal tract) may be a more fitting term for this route of administration. (wikipedia.org)
  • With sublingual administration, it has at least 150 times the potency of progesterone and 50 times the potency of ethisterone when administered to women via the same route. (wikipedia.org)
  • In pharmacology, the route of drug administration is important because it affects drug metabolism, drug clearance, and thus dosage. (wikipedia.org)
  • A fast-disintegrating sublingual tablet (FDST) of epinephrine (Epi) for the treatment of anaphylaxis has been successfully developed and evaluated in vitro and in vivo. (nova.edu)
  • If your dog or cat has been diagnosed with atopic dermatitis - an allergic skin condition - I would recommend asking your veterinarian about sublingual immunotherapy (SLIT), which can often successfully resolve the underlying problem instead of just addressing the symptoms. (stoynev.us)
  • Sublingual immunotherapy is developing in the treatment of aeroallergens allergy. (clinicaltrials.gov)
  • We hypothesized that the evaluation and understanding of the effect of the medium's pH in the sublingual cavity and various penetration enhancers on Epi permeability can result in further optimization of the FDST formulation in order to further reduce the required bioequivalent sublingual Epi dose. (nova.edu)
  • The convenience of administering a single dose of a medication which releases active ingredients in a controlled fashion over an extended period of time, as opposed to the administration of a number of single doses at regular intervals, has long been recognized in the pharmaceutical arts. (google.ca)
  • A dose regimes comprising the simultaneous administration of two pharmaceutical compositions, wherein the first pharmaceutical composition is a composition. (patents.com)
  • The aim of the present study was to compare the efficacy of SL versus the standard IM administration of VB12 in restoring B12 levels. (springer.com)
  • The 1000mg CBD Oil Tincture is a sublingual oil that is vegetable glycerin based and infused with pharmaceutical-grade cannabidiol (CBD). (drugs-forum.com)
  • On October 23, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization for Peramivir (now expired), leading to wider and faster availability for patients. (wikipedia.org)