- Capillaries of the central nervous system (CNS) and a variety of epithelial tissues have tight junctions (see below). - participation of components of the membrane. - Such transfer is directly proportional to the magnitude of the concentration gradient across the. - However, some enteric-coated preparations of a drug also may resist dissolution in the intestine, and very little of the drug may be absorbed.. - pharmaceutical preparations that are designed to produce slow, uniform absorption of the drug for 8. - Approximately 50% of the drug that is absorbed from the rectum will bypass the liver. - In some instances, as in the induction of surgical anesthesia, the dose of a drug is not predetermined but is adjusted to the response of the patient. - Local effects usually require absorption of the drug through the cornea. - concentrations of drug (less than the plasma-protein binding dissociation constant), the fraction bound is a function of the concentration of binding sites and the dissociation constant. - acidification of the urine. - The relative contributions of the various CYP isoforms in the metabolism of drugs is illustrated in Figure 1–3. - The reactions of the major hydrolytic enzymes are illustrated in Table 1–2. - This involves activation of the cytosolic. - In general, the severity of the liver damage. - volume of distribution, a measure of the apparent space in the body available to contain the drug;. - elimination half-life, a measure of the rate of removal of drug from the body. - is independent of the drug's concentration (see below).. - Division of the rate of. - in predictions of the appropriate dosage. - This rate constant is inversely related to the half-life of the drug (k=. - Clearance is the measure of the body's ability to eliminate a drug. - where F= fractional bioavailability of the dose and T= dosage interval (time). - concentration of the drug in plasma, it may still influence drug therapy. - Thus, calculation of the appropriate maintenance dosage is a primary goal. - and is expressed here in terms of the desired target concentration:. - similarity of the dosage interval to digoxin's half-life. - The first of these relates to the time of sampling for measurement of the drug concentration.. - component of the organism has several fundamental corollaries. - Note also that, even if the primary action of a drug is localized, the consequent physiological effects of the drug may be widespread.. - Regulation of the Activity of a Receptor with Conformation-Selective Drugs. - cytoplasmic face of the plasma membrane. - G proteins bind to the cytoplasmic face of the receptors. - Discovery of the endogenous ligands and. - it reaches a maximal asymptote value when the drug occupies all of the receptor sites. - these parameters characterize and quantitate the activity of the drug.. - Graded Responses (Y Axis As a Percent of Maximal Response) Expressed As a Function of the Concentration of Drug A Present at the. - Affinity is measured by the equilibrium dissociation constant of the drug–receptor complex (denoted K d. - Occupancy of the receptor is given by the Langmuir adsorption isotherm: [A]/([A] +K d. - only the efficiency of the signaling system has changed. - mechanisms of the tissue) and two relate to the interaction of drug with its receptor (affinity and efficacy). - In the case of an allosteric antagonist, the affinity of the receptor for the agonist is decreased by the antagonist (see Figure 2–8 C. - disease of the organs of drug elimination (kidney, liver). - data in favor of the objective "hard". - doses will be the order of the day. - because they are not generated by application of the scientific method. - (2) The accuracy of diagnosis and the severity of the disease must be comparable in the groups being contrasted. - reflects only the natural course of the disease. - (3) It should be difficult to monitor intended or unintended effects of the drug. - coagulation), such assessments should be preferred in the decision to make any necessary adjustment of dosage of the drug. - measurements of concentrations of the drug in blood (4). - pharmacological effects of the drug can provide an indication of probable lack of efficacy. - Considerable interindividual variation in the response to drugs remains after the concentration of the drug in plasma has been adjusted to a target value. - Similar relationships also can be plotted as a function of the dose of drug administered. - Receptors are not static components of the cell. - At each extreme of the age spectrum, individuals differ both in the way they handle drugs (pharmacokinetics) and in their response to drugs (pharmacodynamics). - would greatly improve the health of the elderly population. - Another common expression of the. - efficacious and toxic effects of the drug). - A definitive evaluation of the utility of a drug is not easy;. - nevertheless, some sense of the value of a regimen must be established in the minds of the physician and the patient. - The reaction to the dramatic demonstration of the teratogenicity of a needless drug was worldwide. - Physicians and patients alike should be aware of the lack of. - adverse reactions, which result from an interaction of the drug with unique host. - the term used to refer to the combination of the overwhelming number of drugs, the. - The use of the nonproprietary name is clearly less. - Toxicology is the science of the adverse effects of chemicals on living organisms. - chemicals, and for rational treatment of the manifestations of toxicity. - Employers must keep the concentration of each chemical in the air of the workplace below a threshold limit value (TLV). - Many of the adverse effects of drugs mimic symptoms of disease. - The slope of the dose–effect curve also is important. - However, the slopes of the dose–. - Classification of the Effects of Chemicals.. - concentration of the toxic chemical in the body. - Systemic toxicity requires absorption and distribution of the toxicant. - systematic surveillance of the long-term effects of marketed drugs and other chemicals (see Chapter 3: Principles of Therapeutics).. - Dispositional antagonism is the alteration of the disposition of a substance (its absorption, biotransformation, distribution, or excretion) so that less of the agent reaches the target organ or its persistence there is reduced (see below). - The validity of the necessary extrapolation is clearly a crucial question.. - of the poisoning incidents reported but only 2% of the deaths. - If possible, the foot of the table should be elevated. - Enhanced Elimination of the Poison Biotransformation. - constituents of the hepatocyte, resulting in cell death. - Extensive binding of the compound to plasma proteins impairs dialysis greatly. - Functional antagonism also can be valuable for support of the patient's vital functions. - (3) the trafficking of the genetic material within cellular organelles. - (4) the rate of degradation of the DNA;. - (6) the stability of the mRNA produced. - (7) the amount and stability of the protein produced. - Nonetheless, some specific events can be anticipated independent of the transgene employed. - Retroviral vectors are constructed from the proviral form of the virus. - Pharmacokinetics are generally independent of the oligonucleotide sequence and length. - and (3) a transgene under direct control of the artificial transcription factor. - The sirolimus-reconstituted transcription factor drives expression of the. - The molecular components illustrated in the upper portion of the figure include (1) an expression vector encoding the gene of interest under the transcriptional control of a promoter, (2) FKBP12 (see text) fused to a transcription factor DNA binding domain, (3) the FRB domain of FRAP (see text) fused to a transcription factor activation domain, and (4). - nontransduced tumor cells by local dissemination of the compound. - toxic effects of the chemotherapy (Aran et al. - In most gene therapy applications, the ability of the virus to replicate in the host cell is disabled. - This phenomenon provides amplification of the initial viral dose. - In a similar strategy, deletion of the gene encoding. - Various combinations of the interleukins, interferon. - Two of the genes that cause CGD (gp91 phox and p47 phox ) are targeted in gene therapy trials (Kume and Dinauer, 2000)
Xem thử không khả dụng, vui lòng xem tại trang nguồn hoặc xem
Tóm tắt