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CHAPTER 28 ESTROGENS order on line mycelex-g antifungal ketoconazole, PROGESTINS order mycelex-g online from canada fungus gnat eggs, AND HORMONAL CONTRACEPTIVES 413 ovarian function in dysmenorrhea discount mycelex-g 100 mg on line fungus on skin, endometriosis, and uter- • Known or suspected cancers of breast or genital tissues, ine bleeding. These uses of progestins are extensions of the because the drugs may stimulate tumor growth. An ex- physiologic actions of progesterone on the neuroendocrine ception is the use of estrogens for treatment of metastatic control of ovarian function and on the endometrium. With HRT, the purpose of a pro- • Active liver disease or impaired liver function gestin is to prevent endometrial cancer, which can occur with • History of cerebrovascular disease, coronary artery dis- unopposed estrogenic stimulation. Currently, however, the ease, thrombophlebitis, hypertension, or conditions combination is not recommended for long-term use because predisposing to these disease processes a research study indicated that the adverse effects outweigh • Women older than 35 years of age who smoke cigarettes. These women have a greater risk of thromboembolic dis- orders if they take hormonal contraceptives, possibly be- cause of increased platelet aggregation with estrogen Hormonal Contraceptives ingestion and cigarette smoking. In addition, estrogen in- the primary clinical indication for the use of hormonal con- creases hepatic production of blood clotting factors. Some • Family history of breast or reproductive system cancer products are used for contraception after unprotected sexual intercourse. These preparations also are used to treat men- strual disorders (eg, amenorrhea, dysmenorrhea). INDIVIDUAL ESTROGENS, PROGESTINS, AND Contraindications to Use COMBINATION PRODUCTS Because of their widespread effects on body tissues and re- Clinical indications, routes of administration, and dosages are ported adverse reactions, estrogens, progestins, and hormonal discussed in the estrogens and progestins Drugs at a Glance contraceptives are contraindicated in: tables. Combination noncontraceptive products are listed in • Known or suspected pregnancy, because damage to the Drugs at a Glance: Noncontraceptive Estrogen-Progestin fetus may result Combinations, and hormonal contraceptive agents are listed • Thromboembolic disorders, such as thrombophlebitis, in Table 28–1. Atrophic vaginitis: topi- cally, 1–2 g vaginal cream daily Ethinyl estradiol (Estinyl) PO 0. If no bleed- repeat one or more ing after 21 d, begin times each week (maxi- cyclic therapy with mum, 7 g/wk). Stop estradiol and repeat when relapse occurs every 4 wk for 4 cycles or after 12 wk with no response. Then menstrual cycle and give 10–15 mg daily for ending on 25th d maintenance. Progesterone Amenorrhea, dysfunc- tional uterine bleeding: IM 5–10 mg for 6–8 consecutive d Drugs at a Glance: Noncontraceptive Estrogen-Progestin Combinations Trade Name Estrogen Progestin Indications for Use Routes and Dosage Ranges Activelle Estradiol 1 mg Norethindrone 0. Premphase Conjugated estrogens Medroxyprogesterone Menopausal symptoms; PO 1 tablet of estrogen-only 0. It is reportedly effective in relieving vasomo- Assessment tor instability. Most information is derived from small German Before drug therapy is started, clients need a thorough his- studies using Remifemin, the brand name of a standardized tory and physical examination, including measurements of extract that is marketed as an alternative to estrogen ther- blood pressure, serum cholesterol, and triglycerides. The product apparently does parameters must be monitored periodically as long as the not affect the endometrium or estrogen-dependent cancers; drugs are taken. Animal • Assess for conditions in which estrogens and progestins are studies indicate binding to estrogen receptors and suppres- used (eg, menstrual disorders, menopausal symptoms).

Metabolism is the method by which drugs are inactivated or An important factor in drug distribution is protein bind- biotransformed by the body 100mg mycelex-g otc antifungal pen. Most drugs form a complex with plasma changed into one or more inactive metabolites mycelex-g 100 mg lowest price fungus gnats definition, which are Cell membrane Lipid-soluble drugs dissolve in the lipid layer of the cell membrane and diffuse into or out of the cell mycelex-g 100mg cheap antifungal bacteria. Drug molecules cross cell Carrier proteins attach to membranes to move into and out of body cells by directly pene- drug molecules and move them across cell membranes. CHAPTER 2 BASIC CONCEPTS AND PROCESSES 13 BOX 2–2 DRUG TRANSPORT PATHWAYS AND MECHANISMS Pathways the third pathway involves carrier proteins that transport mol- There are three main pathways of drug movement across cell mem- ecules from one side of the cell membrane to the other. Most systemic drugs are formulated transport systems are an important means of moving drug mole- to be lipid soluble so they can move through cell membranes, even cules through the body. They are used, for example, to carry oral oral tablets and capsules that must be sufficiently water soluble to drugs from the intestine to the bloodstream, to carry hormones to dissolve in the aqueous fluids of the stomach and small intestine. Only a few drugs Mechanisms are able to use this pathway because most drug molecules are too large to pass through the small channels. Small ions (eg, sodium Once absorbed into the body, drugs are transported to and from and potassium) use this pathway, but their movement is regulated target cells by such mechanisms as passive diffusion, facilitated by specific channels with a gating mechanism. For example, after oral administration, the gates are located on the outside of the cell membrane; when the initial concentration of a drug is higher in the gastrointestinal tract gates open, sodium ions (Na+) move from extracellular fluid into than in the blood. When the drug is circulated, the concentration is of the cell membrane; when the gates open, potassium ions (K+) higher in the blood than in body cells, so that the drug moves (from move from the cell into extracellular fluid. Passive diffusion continues until a state of equilibrium gating or chemical (also called ligand) gating. With voltage gating, is reached between the amount of drug in the tissues and the amount the electrical potential across the cell membrane determines whether in the blood. With chemical gating, a chemical sub- Facilitated diffusion is a similar process, except that drug mol- stance (a ligand) binds with the protein forming the channel and ecules combine with a carrier substance, such as an enzyme or changes the shape of the protein to open or close the gate. This process and from nerve cells to muscle cells to cause muscle contraction. Some active drugs yield metabolites that are Most drugs are lipid soluble, a characteristic that aids their also active and that continue to exert their effects on body movement across cell membranes. However, the kidneys, cells until they are metabolized further or excreted. Other which are the primary excretory organs, can excrete only drugs (called prodrugs) are initially inactive and exert no water-soluble substances. Therefore, one function of metabo- pharmacologic effects until they are metabolized. Hepatic drug metabolism or clearance is a major mechanism for terminating drug action and eliminating drug Bloodstream molecules from the body. Most drugs are metabolized by enzymes in the liver (called the cytochrome P450 [CYP] or the microsomal en- zyme system); red blood cells, plasma, kidneys, lungs, and A D A D GI mucosa also contain drug-metabolizing enzymes. The cy- tochrome P450 system consists of 12 groups or families, nine of which metabolize endogenous substances and three of A D which metabolize drugs.

CHAPTER 47 DRUGS FOR ASTHMA AND OTHER BRONCHOCONSTRICTIVE DISORDERS 699 BOX 47–1 NATIONAL ASTHMA EDUCATION AND PREVENTION PROGRAM (NAEPP) EXPERT PANEL GUIDELINES* Definition modifier discount mycelex-g 100 mg fast delivery fungus gnats egg shells, or sustained-release theophylline to maintain a serum Asthma is a chronic inflammatory disorder of the airways in drug level of 5–15 mcg/mL generic mycelex-g 100mg free shipping fungus life cycle. Alternatives: cromolyn (via nebulizer or Goals of Therapy MDI with holding chamber) or a leukotriene modifier purchase mycelex-g no prescription fungus gnats eat leaves. Minimal or no chronic symptoms day or night • Step 3 Moderate Persistent (symptoms daily and >1 night/ 2. Minimal use of short-acting inhaled beta agonist (<1 time per natives: increase corticosteroid dose or continue low to 2 day, <1 canister/month) medium dose of corticosteroid and add a leukotriene modi- 5. Assist to identify hours and frequent at night): and control environmental factors that aggravate asthma. If control is • Children < 5 years: Same as for adults and older children. If control is inadequate, the Low (L), Medium (M), and High (H) Doses treatment regimen may need to be changed. For example, fre- of Inhaled Corticosteroids: quent or increasing use of a short-acting beta2 agonist (>2 times Adults Children (12 y and a week with intermittent asthma; daily or increasing use with (mcg) younger) (mcg) persistent asthma) may indicate the need to initiate or increase long-term control therapy. H: >840 H: >672 Beclomethasone L: 80–240 L: 80–160 Quick Relief for Acute Exacerbations (40–80 mcg/puff) M: 240–480 M: 160–320 • Adults and children > 5 years: Short-acting, inhaled, beta2 ag- H: >480 H: >320 onist, 2–4 puffs as needed. If symptoms are severe, patients may Budesonide (200 mcg/ L: 200–600 L: 200–400 need up to 3 treatments at 20-minute intervals or a nebulizer inhalation) M: 600–1200 M: 400–800 treatment. A short course of a systemic corticosteroid may also H: >1200 H: >800 be needed. With viral respiratory infections, the dose only) beta agonist may be needed q4–6h up to 24 hours or longer and Flunisolide L: 500–1000 L: 500–750 2 a systemic corticosteroid may be needed. Alternatives: cromolyn or nedocromil, a leukotriene *Adapted from NAEPP Expert Panel Report 2 (NIH Publication No. However, an inhaled selective beta2 agonist is the drug of Two major groups of drugs used to treat asthma, acute and choice in this situation. Epinephrine is also available without chronic bronchitis, and emphysema are bronchodilators and prescription in a pressurized aerosol form (eg, Primatene). Bronchodilators are used to prevent Almost all over-the-counter aerosol products promoted for and treat bronchoconstriction; anti-inflammatory drugs are use in asthma contain epinephrine. These products are often used to prevent and treat inflammation of the airways. Re- abused and may delay the client from seeking medical ducing inflammation also reduces bronchoconstriction by attention. Clients should be cautioned that excessive use decreasing mucosal edema and mucus secretions that narrow may produce hazardous cardiac stimulation and other ad- airways and by decreasing airway hyperreactivity to various verse effects. The drugs are described in the following sections; Albuterol, bitolterol, levalbuterol, and pirbuterol are pharmacokinetic characteristics of inhaled drugs are listed short-acting beta2-adrenergic agonists used for prevention in Table 47–1 and dosage ranges are listed in Drugs at a and treatment of bronchoconstriction. These drugs act more Glance: Bronchodilating Drugs and Drugs at a Glance: Anti- selectively on beta2 receptors and cause less cardiac stimula- inflammatory Antiasthmatic Drugs. Most often taken by inhalation, they are also the most effective bronchodilators and the treatment of first choice to relieve acute asthma.

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