was synthesized in 1907 and later isolated from mammalian tissue, important mediator of allergic and inflammatory reaction

decarboxylation of the amino acid L-histidine, a reaction catalyzed in mammalian tissues by the enzyme histidine decarboxylase. Once formed, histamine is either stored or rapidly inactivated

rich at sites of potential tissue injury - nose, mouth, and feet

in bothnhumans and guinea pig, histamine causes bronchoconstriction mediated by

When the patient’s history suggests episodic symptoms of hyperreactive airways and airway obstruction, such as seasonal or exercise-induced wheezing, and the results of baseline spirometry are normal, performing a _______ may be indicated.

patients with asthma evaluated in symptoms-free period may have a normal chest x-ray examination and normal pulmonary function tests.

acts by inhibiting the degranulation of mast cells in response to allergic and nonallergic stimuli. This inhibition prevents release of histamine and other mediators of inflammation. These mediators cause bronchospasm and trigger an increasing cascade

it was known that when blood is allowed to clot, a vasoconstrictor (tonic) substance is released from the clot into the serum. This substance was called serotonin

It resembles the phenothiazine antihistaminic agents in chemical structure and has potent H1- receptor–blocking as well as 5-HT2–blocking actions. The actions of cyproheptadine are predictable from its H1 histamine and 5-HT receptor affinities. It prevents the smooth muscle effects of both amines but has no effect on the gastric secretion stimulated by histamine.

The sudden obstruction of a pulmonary arterial branch causes a decrease or total cessation of blood flow to the distal area of the lung. This interruption of blood flow can cause respiratory and hemodynamic alterations.

Respiratory smooth muscle is relaxed by PGE2 and PGI2 and contracted by PGD2, TXA2 (Thromboxane), and PGF2α

The cysteinyl leukotrienes are also bronchoconstrictors. They act principally on smooth muscle in peripheral airways and are a thousand times more potent than histamine, both in vitro and in vivo. They also stimulate bronchial mucus secretion and cause mucosal edema.

At least 5% of adults with asthma experience severe and even fatal exacerbation of asthma after taking aspirin or other non-steroidal antiinflammatory drugs

defined by an elevation in mean pulmonary arterial pressure 25 mm Hg or greater at rest. PGI2 lowers peripheral, pulmonary, and coronary vascular resistance.

The first commercial preparation of PGI2 approved for treatment of primary pulmonary hypertension improves symptoms, prolongs survival, and delays or prevents the need for lung or lung-heart transplantation

The adrenal cortex releases a large number of steroids into the circulation. Some have minimal biologic activity and function primarily as precursors

Those having important effects on intermediary metabolism and immune function.

major glucocorticoids in human

Those having principally salt-retaining activity.

most important mineralocorticoids

Those having androgenic or estrogenic activity.

major endogenous precursors of estrogen in women after menopause and in younger patients in whom ovarian function is deficient or absent

has a large capacity but low affinity for cortisol, and for practical purposes _______-bound cortisol should be considered free. Synthetic corticosteroids such as dexamethasone are largely bound to _______ rather than CBG.

The major undesirable effects of glucocorticoids are the result of their hormonal actions, which lead to the clinical picture of iatrogenic. glucocorticoids are used for short periods <2 weeks to see adverse effects

The major undesirable effects of glucocorticoids are the result of their hormonal actions, which lead to the clinical picture of iatrogenic

which also serves as a precursor of aldosterone, is normally secreted in amounts of about 200 mcg/d. The secretion may be markedly increased in abnormal conditions such as adrenocortical carcinoma and congenital adrenal hyperplasia.

This compound, a potent steroid with both glucocorticoid and mineralocorticoid activity, is the most widely used mineralocorticoid. used in the treatment of adrenocortical insufficiency associated with mineralocorticoid deficiency

blocks the conversion of cholesterol to pregnenolone and causes a reduction in the synthesis of all hormonally active steroids. It has been used in conjunction with dexamethasone or hydrocortisone to reduce or eliminate estrogen production in patients with carcinoma of the breast. In a dosage of 1 g/d it was well tolerated; however, with higher dosages, lethargy and skin rash were common effects.

an antifungal imidazole derivative is a potent and rather nonselective inhibitor of adrenal and gonadal steroid synthesis. This compound inhibits the cholesterol side-chain cleavage, P450c17, C17,20-lyase, 3β-hydroxysteroid dehydrogenase, and P450c11 enzymes required for steroid hormone synthesis. The sensitivity of the P450 enzymes to this compound in mammalian tissues is much lower than that needed to treat fungal infections, so that its inhibitory effects on steroid biosynthesis are seen only at high doses.

relatively selective inhibitor of steroid 11-hydroxylation, interfering with cortisol and orticosterone synthesis. This agent has not been widely used for the treatment of Cushing’s syndrome. it may be useful in the management of severe manifestations of cortisol excess while the cause of this condition is being determined or in conjunction with radiation or surgical treatment. has been withdrawn from the market in the USA but is available on a compassionate basis.

3β-17 hydroxysteroid dehydrogenase inhibitor that interferes with the synthesis of adrenal and gonadal hormones and is comparable to aminoglutethimide. adverse effects are predominantly gastrointestinal

the newest of the steroid synthesis inhibitors to enter clinical trials. It blocks 17α-hydroxylase (P450c17) and 17,20-lyase and predictably reduces synthesis of cortisol and gonadal steroids in the adrenal and gonadal steroids in the gonads. A compensatory increase occurs in ACTH and aldosterone synthesis, but this can be prevented by concomitant administration of dexamethasone. Abiraterone is an orally active steroid prodrug and has been studied in the treatment of refractory prostate cancer.

The search for a glucocorticoid receptor antagonist finally succeeded in the early 1980s with the development of the 11β- aminophenyl-substituted 19-norsteroid. Unlike the enzyme inhibitors, mifepristone is a pharmacologic antagonist at the steroid receptor. This compound has strong antiprogestin activity and initially was proposed as a contraceptive-contragestive agent. High doses of mifepristone exert antiglucocorticoid activity by blocking the glucocorticoid receptor.

drug related to the DDT or dichlorodiphenyltrichloroethane class of insecticides, has a nonselective cytotoxic action on the adrenal cortex in dogs and to a lesser extent in humans. About one third of patients with adrenal carcinoma show a reduction in tumor mass. In 80% of patients, the toxic effects are sufficiently severe to require dose reduction. The drug has been withdrawn from the market in the USA but is available on a compassionate basis

a 7α-acetylthiospironolactone. Its onset of action is slow, and the effects last for 2–3 days after the drug is discontinued. It is used in the treatment of primary aldosteronism in dosages of 50–100 mg/d. This agent reverses many of the manifestations of aldosteronism. Spironolactone is also an androgen antagonist and as such is sometimes used in the treatment of hirsutism in women.

another aldosterone antagonist, is approved for the treatment of hypertension. also been found to reduce mortality in heart failure. This aldosterone receptor antagonist is somewhat more selective than spironolactone and has no reported effects on androgen receptors. The standard dosage in hypertension is 50–100 mg/d. The most common toxicity is hyperkalemia, but this is usually mild.

progestin in an oral contraceptive, also antagonizes the effects of aldosterone

an idiopathic multisystem inflammatory disorder that commonly involves the lung. The tissue inflammation that occurs in _______ has a characteristic pattern in which the inflammatory cells collect in microscopic nodules called granulomas.

is the revised term for bronchiolitis obliterans _________. The term cryptogenic organizing pneumonia is used when this pattern of injury occurs as an IIP, and it is termed organizing pneumonia when found in the setting of connective tissue disease. Diagnosis usually requires surgical lung biopsy, especially if the clinical and radiographic features are uncertain because small areas of organizing pneumonia can be seen in various inflammatory and fibrotic disorders on transbronchial lung biopsy

presents with sudden onset over a few hours to several days. The clinical presentation may be typical or atypical, depending on the pathogen.

community acquired pneumonia can be divided in to two types

The onset is more insidious, often with gradually escalating symptoms over days, weeks, or months. Pneumonia acquired in health care settings is often caused by microorganisms different from those that cause CAP.

Previously termed nosocomial pneumonia, this clinical entity has been further classified as It is defined as pneumonia occurring in any patient hospitalized for 2 or more days in the past 90 days in an acute-care setting or who in the past 30 days has resided in a long-term care or nursing facility; attended a hospital or hemodialysis clinic; or received intravenous antibiotics, chemotherapy, or wound care.

defined as an LRTI that develops in hospitalized patients more than 48 hours after admission and excludes community-acquired infections that are incubating at the time of admission.

defined as an LRTI that develops more than 48 to 72 hours after endotracheal intubation.

hospitalized patients who are not critically ill and who are admitted to the ward

For isolates of S. pneumoniae susceptible to __________ remains the preferred agent.

produce beta-lactamase, making them resistant to penicillin

is the drug of choice for Pneumocystis jiroveci pneumonia. However, 50% of HIV- infected patients may develop fever or a rash while taking this medication.

the only first-generation parenteral cephalosporin still in general use. it penetrates well into most tissues. It is a drug of choice for surgical prophylaxis

These agents have an activity against anaerobes. In general, they are active against organisms inhibited by first-generation drugs, but in addition they have extended gram-negative coverage. Klebsiella sp (including those resistant to cephalothin) are usually sensitive.

the only two drugs with useful activity against P aeruginosa.

active against B fragilis

Compared with second-generation agents, these drugs have expanded gram-negative coverage, and some are able to cross the blood-brain barrier. Third-generation drugs are active against Citrobacter, S marcescens, and Providencia (although resistance can emerge during treatment of infections caused by these species due to selection of mutants that constitutively produce cephalosporinase).

the only monobactam available in the USA. It has structural similarities to ceftazidime; hence, its gram- negative spectrum is similar to that of the third-generation cephalosporins. The half-life is 1–2 hours and is greatly prolonged in renal failure.

The important quinolones are synthetic fluorinated analogs of nalidixic acid. They are active against a variety of gram-positive and gram-negative bacteria.

active against many gram-positive and gram- negative bacteria, including certain anaerobes, rickettsiae, chlamydiae, its the drug of choice in the treatment of infections caused by rickettsiae. broad-spectrum bacteriostatic antibiotics that inhibit protein synthesis. Susceptible organisms concentrate the drug intracellularly.

an antibiotic produced by Streptococcus orientalis and Amycolatopsis orientalis. With the exception of Flavobacterium, it is active only against gram-positive bacteria.

member of the oxazolidinones, a new class of synthetic antimicrobials.

are a group of closely related compounds characterized by a macrocyclic lactone ring (usually containing 14 or 16 atoms) to which deoxy sugars are attached. The prototype drug, erythromycin, which consists of two sugar moieties attached to a 14-atom lactone ring, was obtained in 1952 from Streptomyces erythreus

is a drug of choice in corynebacterial infections (diphtheria, corynebacterial sepsis, erythrasma); in respiratory, neonatal, ocular, or genital chlamydial infections; and in treatment of community-acquired pneumonia because its spectrum of activity includes pneumococcus, M pneumoniae, and L pneumophila.

defined in anatomic terms as a condition characterized by abnormal, permanent enlargement of the airspaces beyond the terminal bronchiole, accompanied by destruction of the walls of the airspaces without fibrosis.

is defined in clinical terms as a condition in which chronic productive cough is present for at least 3 months per year for at least 2 consecutive years

three important methylxanthines are:

as a therapeutic agent in the treatment of asthma has waned as the greater effectiveness of inhaled adrenoceptor agents for acute asthma and of inhaled anti-inflammatory agents for chronic asthma has been established