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Ag- cellular functions purchase 20 mg levitra jelly, such as the direct effect of calcium ions in onists may accelerate or slow normal cellular processes purchase levitra jelly 20mg amex, stimulating muscle contraction. For ex- A third reaction may modify the synthesis, release, or ample, epinephrine-like drugs act on the heart to in- inactivation of the neurohormones (eg, acetylcholine, norepi- crease the heart rate, and acetylcholine-like drugs act nephrine, serotonin) that regulate many physiologic processes. Additional elements and characteristics of the receptor Antagonists are drugs that inhibit cell function by oc- theory include the following: cupying receptor sites. The site and extent of drug action on body cells are de- stances or other drugs from occupying the receptor termined primarily by specific characteristics of recep- sites and activating cell functions. Receptors vary in type, location, number, curs, drug molecules may detach from receptor mole- and functional capacity. For example, many different cules (ie, the chemical binding is reversible), return to types of receptors have been identified. Most types the bloodstream, and circulate to the liver for metabo- occur in most body tissues, such as receptors for epi- lism and the kidneys for excretion. Receptors are dynamic cellular components that can be stimulation of the sympathetic nervous system or ad- synthesized by body cells and altered by endogenous ministration of drug formulations) and receptors for substances and exogenous drugs. For example, pro- hormones, including growth hormone, thyroid hormone, longed stimulation of body cells with an excitatory ag- and insulin. Some occur in fewer body tissues, such as onist usually reduces the number or sensitivity of receptors for opiates and benzodiazepines in the brain receptors. As a result, the cell becomes less responsive and subgroups of receptors for epinephrine in the heart to the agonist (a process called receptor desensitization CHAPTER 2 BASIC CONCEPTS AND PROCESSES 17 or down-regulation). Prolonged inhibition of normal cause the drug does not reach an adequate concentration at cellular functions with an antagonist may increase re- target cells. If the amount is too large or administered too ceptor number or sensitivity. Because dosage in- denly reduced or stopped, the cell becomes excessively cludes the amount of the drug and the frequency of adminis- responsive to an agonist (a process called receptor up- tration, overdosage may occur with a single large dose or regulation). These changes in receptors may explain with chronic ingestion of smaller amounts. Doses that pro- why some drugs must be tapered in dosage and dis- duce signs and symptoms of toxicity are called toxic doses. Dosages recommended in drug literature are usually those that produce particular responses in 50% of the people tested. These dosages usually produce a mixture of therapeutic and Nonreceptor Drug Actions adverse effects. The dosage of a particular drug depends on many characteristics of the drug (reason for use, potency, Relatively few drugs act by mechanisms other than combina- pharmacokinetics, route of administration, dosage form, and tion with receptor sites on cells. These include: others) and of the recipient (age, weight, state of health, and 1. Antacids, which act chemically to neutralize the hy- function of cardiovascular, renal, and hepatic systems). Thus, drochloric acid produced by gastric parietal cells and the recommended dosages are intended only as guidelines for thereby raise the pH of gastric fluid individualizing dosages. Osmotic diuretics (eg, mannitol), which increase the osmolarity of plasma and pull water out of tissues into Route of Administration the bloodstream 3. Drugs that are structurally similar to nutrients required Routes of administration affect drug actions and responses by body cells (eg, purines, pyrimidines) and that can be largely by influencing absorption and distribution. For rapid incorporated into cellular constituents, such as nucleic drug action and response, the IV route is most effective be- acids.
The decrease in resorption intracellular signaling order 20 mg levitra jelly with amex, which leads eventually to apopto- is accompanied purchase levitra jelly 20mg fast delivery, at least in the growing animal, by a posi- sis and death. In contrast, some non-nitrogen-containing tive calcium balance, and an increase in the mineral con- bisphosphonates, such as clodronate, and etidronate, can tent of bone and in bone mass. This is possible because of be incorporated into the phosphate chain of ATP-contain- an increase in intestinal calcium absorption. Thus they impair re- be classified into two major groups with different modes sorption induced by many bone resorbing agents such as of action but the same final effect. They also inhibit bone Pharmacokinetics loss induced by different procedures to induce experimen- tal osteoporosis such as immobilization, the first model The bisphosphonates appear to be absorbed, stored, and used, ovariectomy, corticosteroids, or lactation com- excreted unaltered in the body. When not given in excess, nates seem to be nonbiodegradable, at least with respect bisphosphonates have also a positive effect on mechanical to their P-C-P bond. The bioavailability of an oral dose of characteristics both in normal animals and in various ex- a bisphosphonate both in animals and in humans lies be- perimental osteoporosis models. Absorption is substantially be due to alterations in bone mass, architecture and quality. For etidronate nates should never be given at mealtimes and never to- the dose required to inhibit resorption is relatively high, gether with milk or dairy products. One of the absorbed bisphosphonate is taken up very rapidly of the aims of bisphosphonate research has therefore been by bone, the remainder being rapidly excreted in the urine. Compounds have been de- ing why practically only bone is affected in vivo. The ar- veloped that are up to 10,000 times more powerful than eas of deposition are mostly those of bone formation and etidronate in the inhibition of bone resorption in experi- destruction. Once deposited in the skeleton and covered mental animals without being more active in inhibiting under new layers of bone, the bisphosphonates are re- mineralization. The half-life in bone bisphos- phonates is therefore very long, for humans it can be over Inhibition of mineralization 10 years. The renal clearance of bisphosphonates is high, at least in animals higher than that of inulin, indicating ac- When given in larger amounts, bisphosphonates can inhibit tive secretion. Clinical use in osteoporosis Mechanisms of action Bisphosphonates are today the most frequently used drug in metabolic bone disease. This review deals only physicochemical inhibition of crystal dissolution, as was with osteoporosis. A more extended clinical and clinical initially postulated, namely by acting on the osteoclast. Very Definition and pathophysiology of osteoporosis recently the cellular mechanism has been partially unrav- eled. It was found that nitrogen containing bisphospho- Osteoporosis is a disease characterized by a decrease in nates can, by inhibiting farnesyl pyrophosphate synthase, bone mass and a deterioration in the architecture of the 62 bones, which leads to an enhanced fragility of the skeleton sphonates, was estrogen replacement after the menopause. It is defined as However, it has recently been shown that estrogens in- present in women when the bone mass is more than 2. Calcitonin is sometimes mon disorder which will become even more common with used, but parenteral administration can have unpleasant the increase in life expectancy. It is also frequent in men, side effects, and the nasal form is relatively weak in its ef- although less so than in women. Calcium can also de- tinuous loss during life of both cancellous and cortical crease bone turnover and diminish bone loss in certain con- bone, which is exacerbated in women after the menopause. It was found to diminish hip fractures when given The second contributory factor is failure to achieve ade- with vitamin D in the elderly institutionalized patients. The causes of This is why calcium, although it is not effective enough to these changes are not yet clear, although genetic factors affect strongly fractures in most patients with osteoporo- are involved, at least for the latter. Calcium is, however, an obligatory adjunction in all occurring often spontaneously or after minimal trauma, patients who receive an antiresorptive treatment.
Many drugs are given for their most new drugs can be assigned to a group and compared long-term effects discount levitra jelly 20mg with mastercard. However generic levitra jelly 20 mg on line, some groups lack a universally accepted prototype and some prototypes are re- placed over time by newer, more commonly used drugs. Historically, drugs were DRUG NAMES mainly derived from plants (eg, morphine), animals (eg, in- sulin), and minerals (eg, iron). Now, most drugs are synthetic Individual drugs may have several different names, but the chemical compounds manufactured in laboratories. Chemists, two most commonly used are the generic name and the trade for example, can often create a useful new drug by altering the name (also called the brand or proprietary name). The generic chemical structure of an existing drug (eg, adding, deleting, or name (eg, amoxicillin) is related to the chemical or offi- altering a side-chain). Such techniques and other techno- cial name and is independent of the manufacturer. The generic logic advances have enabled the production of new drugs as name often indicates the drug group (eg, drugs with generic well as synthetic versions of many drugs originally derived names ending in cillin are penicillins). Synthetic drugs are more standard- designated and patented by the manufacturer. For example, ized in their chemical characteristics, more consistent in amoxicillin is manufactured by several pharmaceutical com- their effects, and less likely to produce allergic reactions. In drug literature, trade names are capitalized and Biotechnology is also an important source of drugs. This generic names are lowercase unless in a list or at the begin- process involves manipulating deoxyribonucleic acid (DNA) ning of a sentence. Drugs may be prescribed and dispensed by and ribonucleic acid (RNA) and recombining genes into generic or trade name. Each hybrid molecule produces a genetically iden- DRUG MARKETING tical molecule, called a clone. Cloning makes it possible to identify the DNA sequence in a gene and produce the pro- A new drug is protected by patent for 14 years, during which tein product encoded by a gene, including insulin and sev- it can be marketed only by the pharmaceutical manufacturer eral other body proteins. However, for new drugs DRUG CLASSIFICATIONS that are popular and widely used, other companies often pro- AND PROTOTYPES duce similar drugs, with different generic and trade names. For example, the marketing of fluoxetine (Prozac) led to the Drugs are classified according to their effects on particular introduction of similar drugs from different companies, such body systems, their therapeutic uses, and their chemical as citalopram (Celexa), fluvoxamine (Luvox), paroxetine characteristics. For example, morphine can be classified as (Paxil), and sertraline (Zoloft). Prozac was approved in 1987 a central nervous system depressant, a narcotic or opioid and went off patent in 2001, meaning that any pharmaceuti- analgesic, and as an opiate (derived from opium). The names cal company could then manufacture and market the generic of therapeutic classifications usually reflect the conditions for formulation of fluoxetine. Generic drugs are required to be which the drugs are used (eg, antidepressants, antihyperten- therapeutically equivalent and are much less expensive than sives, antidiabetic drugs). Official drugs must meet standards of purity and strength as determined by chemical analysis or Pharmacoeconomics involves the costs of drug therapy, in- animal response to specified doses (bioassay). The Durham- cluding those of purchasing, dispensing (eg, salaries of Humphrey Amendment designated drugs that must be pre- pharmacists, pharmacy technicians), storage, administra- scribed by a physician and dispensed by a pharmacist. The tion (eg, salaries of nurses, costs of supplies), laboratory Food and Drug Administration (FDA) is charged with en- and other tests used to monitor client responses, and losses forcing the law. Length of illness or hospitalization is also lates vaccines and other biologic products, and the Federal considered. Trade Commission can suppress misleading advertisements Costs are increasingly being considered a major factor in of nonprescription drugs.