Ebook Pharmacology (4th edition): Part 2

(BQ) Part 2 book Pharmacology presents the following contents: Pharmacology of the respiratory and other systems (autacoid drugs, drugs for respiratory tract disorders, drugs for headache disorders,...), pharmacology of the respiratory and other systems (thyroid drugs, adrenal steroids and related drugs, drugs for diabetes mellitus, drugs affecting calcium and bone,...), chemotherapy.

V Section PHARMACOLOGY OF THE RESPIRATORY AND OTHER SYSTEMS Autacoid Drugs  274 Drugs for Respiratory Tract Disorders  284 Drugs for Gastrointestinal Tract Disorders  295 Drugs for Headache Disorders  307 Drugs for Pain, Inflammation, and Arthritic Disorders  314 CHAPTER 26 Autacoid Drugs CLASSIFICATION OF AUTACOID DRUGS Histamine H1 Receptor Antagonists First-Generation Antihistamines • Promethazine (Phenergan) • Diphenhydramine (Benadryl) • Chlorpheniramine (Chlor-Trimeton) • Clemastine (Tavist) • Dimenhydrinate (Dramamine) • Doxepin (Silenor) • Hydroxyzine (Atarax) • Meclizine (Antivert) Second-Generation Antihistamines • Cetirizine (Zyrtec) • Desloratadine (Clarinex) • Fexofenadine (Allegra) • Levocetirizine (Xyzal) • Loratadine (Claritin) Intranasal Antihistamines • Azelastine (Astelin) Ophthalmic Antihistamines • Ketotifen (Zaditor) • Levocabastine (Livostin)a Serotonergic Drugs Serotonin Agonists • Buspirone (BuSpar) • Sumatriptan (Imitrex)b • Tegaserod (Zelnorm) Serotonin Antagonists • Clozapine (Clozaril) • Cyproheptadine (Periactin) • Methysergide (Sansert)c • Ondansetron (Zofran)d Prostaglandin Drugs • Alprostadil (Caverject, Muse) • Carboprost Tromethamine (Hemabate) • Dinoprostone (Cervidil) • Misoprostol (Cytotec) • Epoprostenol (Flolan) • Treprostinil (Remodulin) • Latanoprost (Xalatan)e Endothelin-1 Antagonists • Bosentan (Tracleer) • Ambrisentan (Letairis) a Also epinastine (Elestat) and olopatadine (Patanol) Also zolmitriptan (Zomig), rizatriptan (Maxalt), naratriptan (Amerge), frovatriptan (Frova), almotriptan (Axert), and eletriptan (Relpax) c Recently withdrawn from the market in the United States d Also granisetron (Kytril), palonosetron (Aloxi), alosetron (Lotronex), and dolasetron (Anzemet) e Also bimatoprost (Lumigan) and travoprost (Travatan) b 274 OVERVIEW Autacoids (also spelled autocoids) are substances produced by neural and nonneural tissues throughout the body that act locally to modulate the activity of smooth muscles, nerves, glands, platelets, and other tissues (Table 26-1) Several autacoids also serve as neurotransmitters in the central nervous system (CNS) or enteric nervous system Autacoids regulate certain aspects of gastrointestinal, uterine, and renal function, and they are involved in pain, fever, inflammation, allergic reactions, asthma, thromboembolic disorders, and other pathologic conditions Drugs that inhibit autacoid synthesis or block autacoid receptors are helpful in treating these conditions, whereas drugs that activate autacoid receptors are useful for inducing labor, alleviating migraine headaches, counteracting drug-induced peptic ulcers, and other purposes Autacoids include monoamines, such as histamine and serotonin, as well as fatty acid derivatives, including pro­ staglandins and leukotrienes Autacoids activate specific membrane receptors in target tissues, mostly of the G protein–coupled receptor (GPCR) type Their effects are usually restricted to the tissue in which they are formed, but under pathologic conditions, extraordinarily large amounts of autacoids can be released into the systemic circulation These disorders include carcinoid tumor and anaphylactic shock, which cause the release of copious amounts of serotonin and histamine, respectively, and exert systemic effects including CNS effects Most autacoids are rapidly metabolized to inactive compounds, as seen with prostaglandins, and some autacoids undergo tissue reuptake, as evidenced by 5-hydroxytryptamine (5-HT) reuptake transporter proteins in neurons and peripheral cells This chapter provides basic information about autacoids and reviews the many types of drugs that influence their effects Some autacoid drugs are covered completely here, whereas other chapters provide more details on other agents HISTAMINE AND RELATED DRUGS Histamine Biosynthesis and Release Histamine is a biogenic amine produced primarily by mast cells and basophils, which are particularly abundant in the skin, gastrointestinal tract, and respiratory tract Histamine is also produced by paracrine cells in the gastric fundus, where it stimulates acid secretion by parietal cells Histamine also functions as a neurotransmitter in the CNS (see Chapter 18) Histamine is formed when the amino acid histidine is decarboxylated in a reaction catalyzed by the enzyme l– histidine decarboxylase Histamine is stored in granules (vesicles) in mast cells and basophils until it is released It is released from mast cells when membrane-bound immuno­ globulin E (IgE) interacts with an IgE antigen to cause mast cell degranulation This process can be blocked by cromolyn sodium and related respiratory drugs, as described in Chapter 27 A number of other stimuli can also cause the Chapter 26  y  Autacoid Drugs   275 Antigens Inhalants Food Drugs Nonimmunologic histamine releasers Morphine Cholinergic Codeine agents Polymyxin-B Acetylcholine Lobster Strawberries Blocked by atropine Activation Anaphylatoxins C3a + C5a Physical stimuli GTP cGMP Enzymes Activated enzymes cAMP Activation ATP Exocytosis and degranulation Histamine release Mast cell Complement activation Beta adrenergic agents Epinephrine Isoproterenol Prostaglandins NOTE: Aspirin inhibits synthesis of prostaglandins = Surface receptors = IgE antibody Figure 26-1.  Release of histamine from mast cells Numerous chemical and physical stimuli activate histamine release from mast cells Complement activation from serum sickness or bacterial endotoxins produces the anaphylactic peptides C3a and C5a, allergic antigens bind to immunoglobulin E (IgE) antibodies, and chemicals and other substances increase guanosine triphosphate (GTP) and cyclic guanosine monophosphate (cGMP) to activate enzymes causing increased intracellular calcium and release of histamine granules β-Adrenoceptor agents and some prostaglandins increase adenosine triphosphate (ATP) and cyclic adenosine monophosphate (cAMP) and reduce activated enzymes TABLE 26-1  Effects of Selected Autacoids AUTACOID EFFECTS ON VSM EFFECTS ON NVSM OTHER EFFECTS Histamine Vasodilation and edema Contraction of bronchial and other NVSMs Itching, increase in gastric acid secretion Serotonin Vasoconstriction in most vascular beds Contraction of gastrointestinal and other NVSMs Central nervous system neurotransmission, stimulation of platelet aggregation Leukotrienes Vasoconstriction or vasodilation Contraction of bronchial and other NVSMs Inflammatory effects, increase in vascular permeability Prostaglandin E Vasodilation Relaxation of bronchial muscle and contraction of uterine muscle Inhibition of gastric acid secretion Prostaglandin F Vasoconstriction in most vascular beds Contraction of bronchial and uterine muscle Increase in aqueous humor outflow Prostaglandin I Vasodilation Contraction Inhibition of platelet aggregation Thromboxane A2 Vasoconstriction Contraction Stimulation of platelet aggregation Eicosanoids NVSM, Nonvascular smooth muscle; VSM, vascular smooth muscle release of histamine from mast cells (Fig 26-1) Stimuli that increase cyclic guanosine monophosphate increase histamine release, whereas those that increase cyclic adenosine monophosphate oppose this action Mast cell degranulation can also be triggered by bacterial toxins and by drugs such as morphine and tubocurarine Some of these stimuli result in the formation of inositol triphosphate (IP3) and diacylglycerol (DAG) As with neurons, this causes the release of intracellular calcium and the fusion of granule membranes with the plasma membrane, thereby releasing histamine and other compounds The release of histamine that can occur with morphine administration does not appear to be mediated by opioid receptors because the opioid antagonist naloxone does not inhibit morphine-induced histamine release from mast cells 276   Section V  y  Pharmacology of the Respiratory and Other Systems Histamine is inactivated by methylation and oxidation reactions that are catalyzed by a methyltransferase enzyme and diamine oxidase, respectively Histamine Receptors and Effects Histamine receptors have been classified as H1, H2, and H3 All three types are typical, seven-transmembrane GPCR proteins H1 receptors are involved in allergic reactions that cause dermatitis, rhinitis, conjunctivitis, and other forms of allergy Activation of H1 receptors in the skin and mucous membranes causes vasodilation; increases vascular permeability; and leads to erythema (heat and redness), congestion, edema, and inflammation Stimulation of H1 receptors on mucocutaneous nerve endings can cause pruritus (itching), and in the lungs it initiates the cough reflex If sufficient histamine is released into the circulation, total peripheral resistance and blood pressure fall and the individual may progress to anaphylactic shock Activation of H1 receptors also causes bronchoconstriction and contraction of most gastrointestinal smooth muscles H2 receptors are most noted for increasing gastric acid secretion, but they are also involved in allergic reactions For this reason, H2 receptor antagonists are sometimes used in combination with H1 receptor antagonists in the treatment of allergies Activation of H2 receptors in the heart increases the heart rate and contractility, but the cardiac effects of histamine are not prominent under most conditions H3 receptors are located in various tissues in the periphery and on nerve terminals Activation of these presynaptic receptors in the brain inhibits the release of histamine and other neurotransmitters ANTIHISTAMINE DRUGS Antihistamines, or histamine receptor antagonists, have been categorized on the basis of their receptor selectivity as H1 receptor antagonists or H2 receptor antagonists Chapter 28 outlines the properties of H2 receptor antagonists, which are used primarily to treat peptic ulcer disease There are presently no approved H3 receptor agents, although clinical trials are underway Histamine H1 Receptor Antagonists Classification The following discussion focuses on the properties and uses of four groups of H1 receptor antagonists Chlorpheni­ ramine, clemastine, dimenhydrinate, diphenhydramine, hydroxyzine, meclizine, and promethazine are examples of first-generation drugs Cetirizine, fexofenadine, loratadine, and desloratadine are examples of second-generation drugs Drugs in these two groups are administered orally or parenterally A major difference in the two groups is that the first-generation antihistamines are distributed to the CNS and can cause sedation, whereas the second-generation antihistamines not cross the blood-brain barrier significantly Azelastine is an example of an intranasal antihi­ stamine, and levocabastine, ketotifen, epinastine, and olopatadine are used for ophthalmic treatment Mechanisms and Pharmacokinetics.  The H1 antihistamines contain an alkylamine group that resembles the side chain of histamine and permits them to bind to the H1 receptor and act as competitive receptor antagonists The drugs can block most of the effects of histamine on vascular smooth muscles and nerves and thereby prevent or counteract allergic reactions When antihistamines are administered orally, they are rapidly absorbed and are widely distributed to tissues Many of them are extensively metabolized in the liver by cytochrome P450 enzymes Hydroxyzine has an active metabolite that is also available as the drug cetirizine, and this drug is excreted unchanged in the urine and feces Azelastine is an H1 antihistamine that is marketed as a nasal spray for the treatment of allergic rhinitis It blocks H1 receptors and inhibits the release of histamine from mast cells, and it is much more potent than either sodium cro­ moglycate or theophylline in its inhibition The systemic bioavailability of azelastine after intranasal administration is about 40%, and the plasma half-life is about 22 hours Azelastine is metabolized by cytochrome P450 enzymes to an active metabolite, desmethylazelastine, a substance whose plasma concentrations are 20% to 30% of azelastine concentrations Azelastine and its principal metabolite are both H1 receptor antagonists The unchanged drug and its active metabolite are excreted primarily in the feces Pharmacologic Effects and Indications.  The H1 antihistamines are all equally effective in treating allergies, but they differ markedly in their sedative, antiemetic, and anti­ cholinergic properties (Table 26-2) The second-generation antihistamines cause little or no sedation, so they are often preferred for the treatment of allergies Antihistamines are usually more effective when administered before exposure to an allergen than afterward Hence persons with seasonal allergies, such as allergic rhinitis (see Chapter 27), should take them on a regular basis throughout the allergy season First-Generation Antihistamines Because the first-generation antihistamines have sedative effects, they are occasionally used to produce sedation They are also used to treat nausea and vomiting, to prevent motion sickness in persons traveling by plane or boat, and to treat vertigo (an illusory sense that the environment or one’s own body is revolving) The most sedating antihistamines are diphenhydramine, hydroxyzine, and promethazine Doxepin has antidepressant and anxiolytic effects, but because of its high affinity for blocking central H1 receptors, it was recently approved at low doses for the treatment of insomnia These drugs have been used to induce sleep or for preoperative sedation Their sedating properties can also be useful in relieving distress caused by the severe pruritus associated with some allergic reactions Persons taking these drugs should be cautioned against driving or operating machinery Pheniramine drugs, such as chlorpheniramine, are less sedating than other first-generation drugs and are used primarily in the treatment of allergic reactions to pollen, mold spores, and other environmental allergens Meclizine, diphenhydramine, hydroxyzine, and pro­ methazine have higher antiemetic activity than other antihistamines Meclizine is less sedating than diphenhydramine, hydroxyzine, and promethazine, so it is frequently used to prevent motion sickness or treat vertigo Dimenhydrinate is a mixture of diphenhydramine and 8-chlorotheophylline and is also used for these purposes Promethazine Chapter 26  y  Autacoid Drugs   277 TABLE 26-2  Pharmacologic Properties of Selected Histamine H1 Receptor Antagonists DRUG DURATION OF ACTION (HOURS) SEDATIVE EFFECTS ANTIEMETIC EFFECTS ANTICHOLINERGIC EFFECTS First-Generation Antihistamines Chlorpheniramine Medium None Medium Dimenhydrinate High Medium High Diphenhydramine High Medium High Hydroxyzine High High Medium Meclizine 12 Medium High Medium Promethazine 12 High High High Cetirizine 24 Low None Very low Fexofenadine 12 Very low None Very low Loratadine 24 Very low None Very low 12 Low None Very low Second-Generation Antihistamines Intranasal Antihistamines Azelastine suppositories are often used to relieve nausea and vomiting associated with various conditions (see Chapter 28) Second-Generation Antihistamines The second-generation drugs lack antiemetic activity, so their use is limited to the treatment of allergies None of these drugs causes substantial sedation; however, cetirizine is more likely than the other second-generation antihistamines to cause some sedation Following a common trend in the pharmaceutical industry to market the active enantiomer of racemic drugs already approved, levocetirizine is now also available Because fexofenadine has a shorter halflife, it must be taken twice a day, whereas the other secondgeneration drugs are taken once a day Fexofenadine and cetirizine are eliminated primarily as the unchanged drug in the feces and urine, respectively Loratadine and deslorata­ dine are metabolized to active metabolites that are excreted in the urine and feces Intranasal Antihistamines Azelastine is indicated for the treatment of symptoms of allergic rhinitis, including sneezing, nasal itching, and nasal discharge It is administered as two sprays per nostril twice daily The drug can cause drowsiness so should be used cautiously when patients are driving or operating machinery Ophthalmic Antihistamines.  Currently, four antihistamine eyedrop formulations are available Levocabastine, epinastine, and olopatadine are selective H1 antagonists for topical ophthalmic use They are indicated for the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis Ketotifen is a selective, noncompetitive H1 antago­ nist and mast cell stabilizer The action of ketotifen occurs rapidly, with an effect seen within minutes after administration; because of the noncompetitive nature of the H1 receptor antagonism, it has a longer duration of action than the other agents It is indicated for the temporary prevention of itching of the eye caused by allergic conjunctivitis Adverse Effects and Interactions.  The H1 antihistamines produce few serious side effects First-Generation Antihistamines.  Sedation is the most common side effect of the first-generation antihistamines Paradoxically, however, the drugs can produce excitement in infants and children and should be used with caution in these patients Diphenhydramine and promethazine have the highest anticholinergic activity (see Table 26-2), but other firstgeneration drugs also block cholinergic muscarinic receptors As a result, the drugs can cause dry mouth, blurred vision, tachycardia, urinary retention, and other atropinelike side effects, including hallucinations Owing to easy over-the-counter access of some agents (e.g., Benadryl), there is a significant incidence of drug abuse and overdose with antihistamines Anticholinergic toxicity is the principal manifestation of an overdose of first-generation antihistamines Admini­ stration of physostigmine, a cholinesterase inhibitor that crosses the blood-brain barrier, may be required to counteract the anticholinergic effects of antihistamines in the CNS Second-Generation Antihistamines.  Astemizole (Hismanal) also caused prolongation of the QT interval and was removed from the market Fexofenadine is the active metabolite of terfenadine (Seldane) Terfenadine was the first nonsedating H1 blocker but was withdrawn from the market by the U.S Food and Drug Administration because it prolonged the QT interval on the electrocardiogram, leading to a type of cardiac arrhythmia called torsades de pointes Fexofenadine does not appear to cause cardiac abnormalities Cetirizine and loratadine also lack cardiac effects (Box 26-1) Intranasal Antihistamines.  Adverse effects of azelastine are rare and include dizziness, fatigue, headache, nasal irritation, dry mouth, and weight gain Ophthalmic Antihistamines.  Adverse effects of levocabastine, epinastine, olopatadine, and ketotifen are usually limited to the eyes and include transient stinging and burning These occur in less than 5% of patients SEROTONIN AND RELATED DRUGS Serotonin Biosynthesis and Release Serotonin, or 5-HT, is an autacoid and a neurotransmitter that is produced primarily by platelets, enterochromaffin cells in the gut, and neurons The greatest concentration of serotonin is in the enterochromaffin cells of the gastro­ intestinal tract As illustrated in Figure 18-3C, serotonin is 278   Section V  y  Pharmacology of the Respiratory and Other Systems BOX 26-1.  THE CASE OF THE SNEEZING STOCKBROKER CASE PRESENTATION A 35-year-old man working as a stockbroker tells his physician that he is constantly sneezing and has a runny nose and itchy, watery eyes whenever he is at his home in the country He tells his physician that he tried an over-thecounter allergy medicine but that it made him drowsy and feel “like he was living in a fog.” His doctor tells him that he has allergic rhinitis, or “hay fever,” and prescribes a nasal spray containing azelastine CASE DISCUSSION The most common symptom of seasonal allergies is allergic rhinitis, otherwise known as hay fever Symptoms of allergic rhinitis closely mimic those of the common cold, but with a cold, nasal discharge may be thick and yellow With allergies, it is generally thin and clear An allergy is also often accompanied by itchy, watery eyes Most over-the-counter medications include diphenhydramine, a first-generation antihistamine, but these preparations are known to cause drowsiness The newer, second-generation antihistamines are fexofenadine and loratadine, which not cause drowsiness, because they not readily gain access into the central nervous system Among the different types of nose sprays are azelastine, an antihistamine, and sprays that contain steroids, such as beclomethasone, fluticasone, or triamcinolone The drawback to steroid medications is that they may take a week or so to be maximally effective There is also a nasal spray containing cromolyn sodium, a mast cell stabilizer, available without a prescription synthesized from the amino acid tryptophan and is converted to 5-hydroxyindoleacetic acid (5-HIAA) by monoamine oxidase and aldehyde dehydrogenase 5-HIAA is then excreted in the urine Serotonin is concentrated in vesicles within the cell and released by calcium-mediated exocytosis Serotonin Receptors and Effects The four main types of serotonin receptors are designated as 5-HT1 through 5-HT4 The 5-HT1 and 5-HT2 receptors have several subtypes that are designated by letters (e.g., 5-HT1A and 5-HT1D) Although most serotonin receptors are GPCRs, the 5-HT3 receptor is a ligand-gated ion channel The mechanisms of signal transduction for serotonin receptors are outlined in Table 18-1 In the peripheral tissues, the physiologic effects of serotonin include platelet aggregation, stimulation of gastrointestinal motility, and modulation of vascular smooth muscle contraction Serotonin causes vasoconstriction in most vascular beds and contraction of most smooth muscles In the CNS, serotonin is involved in the regulation of mood, appetite, sleep, emotional processing, and pain processing (see Chapter 18) Drugs that affect serotonin activity are classified as serotonin agonists, serotonin antagonists, and serotonin reuptake inhibitors Examples are mentioned later in this chapter and discussed in detail in other chapters Serotonin Agonists Serotonin agonists have been developed for use in the management of several specific disorders (Table 26-3) TABLE 26-3  Serotonin Receptors and Clinical Uses of Serotonin Agonists and Antagonists DRUG 5-HT RECEPTOR CLINICAL USE Serotonin Agonists Buspirone 5-HT1A Anxiety, depression (In development) 5-HT4 Irritable bowel syndrome with constipation Sumatriptan 5-HT1D/1B Migraine headaches Serotonin Antagonists Clozapine 5-HT2 Schizophrenia Cyproheptadine 5-HT2 Carcinoid syndrome, pruritus, urticaria Methysergide* 5-HT2 Carcinoid syndrome, migraine headaches Ondansetron 5-HT3 Nausea and vomiting 5-HT, 5-Hydroxytryptamine (serotonin) *Withdrawn from the market Buspirone, a partial agonist that acts at the 5-HT1A receptor, is used to treat anxiety and depression (see Chapter 19) Sumatriptan and related triptan compounds, and some ergot drugs, are 5-HT1D/1B receptor agonists that are used to treat migraine headaches (see Chapter 29) Cisapride was the first 5-HT4 receptor agonist used for the treatment of gastroesophageal reflux disease and gas­ trointestinal hypomotility (see Chapter 28) Activation of 5-HT4 receptors increases the peristaltic action of the gastrointestinal tract, which is helpful in the treatment of both gastroesophageal reflux disease and gastrointestinal hypomotility However, cisapride (Propulsid) was pulled from the market in the United States in 2000 after postmarketing surveillance revealed a risk of rare but sometimes fatal prolongation of the QT interval on electrocardiogram records (long QT syndrome) A newer 5-HT4 agonist, tegaserod (Zelnorm), was approved for a narrower indication for women who have irritable bowel syndrome with constipation as their main symptom, but it was recently withdrawn from the open market owing to increased risk of heart attack or stroke It is still available under an emergency treatment, investigational new drug (IND) protocol for patients who cannot be effectively treated with any other agent Serotonin Antagonists.  Examples of serotonin antagonists include clozapine, cyproheptadine, methysergide, and ondansetron (see Table 26-3) Clozapine and other drugs are classified as atypical anti­ psychotics that act partly by blocking 5-HT2 receptors in the CNS They are used in the treatment of schizophrenia (see Chapter 22) Cyproheptadine is a 5-HT2 receptor antagonist that also has H1 antihistamine activity This makes it useful in managing urticaria (hives) and other allergic reactions in which pruritus is a prominent feature Cyproheptadine is admini­ stered orally every to 12 hours and can cause slight to moderate drowsiness Methysergide is a 5-HT2 receptor antagonist that was used to prevent migraine headaches (see Chapter 29) Cyproheptadine is also indicated and useful for the care of patients with carcinoid tumor This tumor can produce Chapter 26  y  Autacoid Drugs   279 Injury or other stimulus Phospholipase A Arachidonic acid Cyclooxygenase (COX) Prostaglandin I2 5-Lipoxygenase Prostaglandin G2 5-HPETE Prostaglandin H2 Leukotriene A Prostaglandin E2 Thromboxane A2 Prostaglandin F2α Leukotriene B4 Leukotriene C4 Leukotriene D4 Leukotriene E4 Figure 26-2.  Synthesis of eicosanoids When phospholipase A2 is activated by an injury or other stimulus, it catalyzes the hydrolysis of arachidonic acid and other 20-carbon fatty acids from cell membrane phospholipids Arachidonic acid is converted to prostaglandins and leukotrienes by cyclooxygenase and 5-lipoxygenase, respectively Other enzymes complete the synthesis of specific eicosanoids 5-HPETE, 5-Hydroperoxyeicosatetraenoic acid huge quantities of serotonin, histamine, and other vasoactive substances that cause a constellation of clinical effects called the carcinoid syndrome Affected patients experience malabsorption, violent attacks of watery diarrhea and cramping, and paroxysmal vasomotor attacks characterized by sudden red to purple flushing of the face and neck The malabsorption and diarrhea can be managed by giving cyproheptadine in combination with opioid antidiarrheal drugs Ondansetron was the first selective 5-HT3 receptor antagonist used as an antiemetic agent in cancer chemotherapy as well as for treating nausea and vomiting from other causes It prevents nausea and vomiting by blocking the effects of serotonin in the chemoreceptor trigger zone and in vagal afferent nerves in the gastrointestinal tract (see Chapter 28) Closely related gastrointestinal agents sharing the same mechanism of action include granisetron, alose­ tron, palonosetron, and dolasetron Granisetron, like ondansetron, is used to prevent nausea and vomiting caused by cancer chemotherapy and radiation therapy Alosetron is indicated for treatment of women with irritable bowel syndrome whose predominant bowel symptom is diarrhea Palonosetron is an injectable-only formulation for the prevention of acute or delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy Serotonin Reuptake Inhibitors Serotonin reuptake inhibitors are used in the treatment of depression and other CNS disorders (see Chapter 22) EICOSANOIDS AND RELATED DRUGS Eicosanoids are autacoids derived from arachidonic acid (eicosatetraenoic acid) and other 20-carbon fatty acids (eicos in Greek means “twenty”) Eicosanoid Biosynthesis and Release Eicosanoids are made from arachidonic acid and other polyunsaturated fatty acids in the cell membrane They are freed from their esteric attachment to membrane phospholipids by phospholipase A2, an enzyme that is activated by numerous chemical stimuli and by physical stimuli such as cell damage The two main groups of eicosanoids are the prostaglandins and the leukotrienes, whose formation begins with reactions catalyzed by cyclooxygenase and 5-lipoxygenase, respectively As shown in Figure 26-2, subsequent reactions convert the products of these reactions to specific prostaglandins and leukotrienes Each prostaglandin and leukotriene is assigned a letter and subscript number (e.g., PGE2) The letter refers to the specific ring structure of the substance, and the subscript number indicates the number of double bonds in the fatty acid chains Eicosanoid end products made in individuals consuming a typical Western diet come primarily from arachidonic acid, containing four carbon double bonds Because the first double bond is located at the sixth carbon, arachidonic acid is known as an omega-6 fatty acid In diets rich in coldwater fish or plants, cell membranes contain an omega-3 fatty acid, eicosapentaenoic acid, with five double bonds starting at the third carbon position Eicosapentaenoic acid 280   Section V  y  Pharmacology of the Respiratory and Other Systems is also a precursor to eicosanoid products, but these products have different biologic activities than eicosanoids generated from arachidonic acid For example, prostaglandins derived from omega-6 fatty acids have different vasoactive and platelet-aggregating properties than prostaglandins derived from omega-3 fatty acids (see later) After synthesis, eicosanoids are released from the cell to exert local effects on surrounding tissues Unlike other autacoids, no evidence exists of vesicular storage or calciummediated exocytosis for eicosanoid substances within the cell Because of this, the synthesis of eicosanoids coincides with its release though the cell membrane and into the surrounding tissue Eicosanoid Receptors and Effects All of the naturally released eicosanoids are short-lived and locally acting Eicosanoid drugs exist as either purified preparations of the same naturally occurring substance or closely related synthetic analogues Prostaglandins exert their effects on smooth muscle, platelet aggregation, neurotransmission, glandular secretion, and other biologic activities by activating specific prostanoid receptors in target tissues These receptors are GPCR proteins named according to the prostaglandin that binds with the highest affinity and selectivity; the prostanoid receptor for PGD2 is DP, the receptor for PGE2 is EP, and so forth, to identify the ligands for the FP, IP, and TP (thromboxane) receptors To date, four types of EP receptors have been identified, designated EP1 through EP4; two types of DP receptors (D1 and D2); and one type each of FP, IP, and TP receptors The signal transduction pathways of prostanoid receptors are diverse and mediated by G proteins that increase or decrease cyclic adenosine monophosphate, or the DAG-IP3 pathway (see Chapter 3) Thromboxanes, which are substances derived from prostaglandin synthesis (see Fig 26-2), also act on smooth muscle and platelet aggregation Different types of thromboxanes and prostaglandins have different physiologic effects, and often have opposing effects The eicosanoid released from a tissue or cell will depend on the particular set of synthetic enzymes contained within the cell Whereas platelet aggregation is stimulated by throm­ boxane A2 (TXA2), it is inhibited by prostacyclin (prostaglandin I2 [PGI2]) Prostacyclin is released primarily from vascular endothelial cells and serves to prevent platelet aggregation under normal conditions In contrast, TXA2 is produced and released only when a blood vessel is injured, at which time the adherence of platelets to vascular endothelium activates the platelets and leads to the synthesis and release of TXA2 (see Chapter 16 and Fig 16-5) In some cases the fatty acid precursor of a prostaglandin or thromboxane has a major impact on its biologic activity For example, thromboxane A3 (TXA3), which is synthesized from eicosapentaenoic acid, an omega-3 fatty acid found in fish oils, produces relatively little platelet aggregation or vasoconstriction in comparison with TXA2 This difference can largely explain the correlation between increased fish oil consumption and a decreased incidence of throm­­ botic events (strokes and heart attacks) in certain native populations Both PGE2 and PGI2 cause vasodilation in several vascular beds These prostaglandins appear to play a role in maintaining pulmonary blood flow, and they also serve to maintain the patency of the ductus arteriosus until it is time for its closure In the kidneys, PGE2 and PGI2 produce vasodilation and have important roles in modulating renal blood flow and glomerular filtration These actions are particularly important in persons with renal insufficiency and in the elderly The renal actions of prostaglandin also appear to exert an antihypertensive effect, partly by increasing water and sodium excretion Because nonsteroidal antiinflammatory drugs (NSAIDs) inhibit prostaglandin synthesis, their use can cause or exacerbate renal disorders and may counteract the antihypertensive effect of antihypertensive medications taken concurrently Many prostaglandins, including PGE2 and prostaglandin F2α (PGF2α), stimulate uterine contractions and increase gastrointestinal motility Their uterine activity is the basis for several therapeutic applications, whereas their gastrointestinal actions can lead to adverse effects (e.g., diarrhea and intestinal cramping) Several prostaglandins also produce a cytoprotective effect on the gastrointestinal mucosa The leukotrienes are produced primarily in inflammatory cells, including mast cells, basophils, eosinophils, macrophages, and polymorphonuclear leukocytes Leukotrienes C4 and D4 (LTC4 and LTD4) are the main components of the slow-reacting substance of anaphylaxis These two leukotrienes are secreted in the presence of asthma and anaphylaxis and play a major role in bronchospastic disease EICOSANOID DRUGS The effects and clinical uses of prostaglandin drugs are outlined in Table 26-4 and summarized in the following paragraphs Eicosanoid Synthesis Inhibitors Among the groups of drugs that inhibit eicosanoid synthesis are leukotriene inhibitors (see Chapter 27), NSAIDs (see Chapter 30), and corticosteroids (see Chapter 33) TABLE 26-4  Effects and Clinical Uses of Selected Prostaglandin Drugs DRUG PG CLASS EFFECT CLINICAL USE Alprostadil PGE1 Vasodilation Erectile dysfunction; patency of the ductus arteriosus Carboprost tromethamine PGF2α analogue Contraction of uterine muscle Abortifacient; postpartum bleeding Dinoprostone PGE2 Contraction of uterine muscle Abortifacient; cervical ripening Epoprostenol PGI2 Vasodilation Pulmonary hypertension Latanoprost PGF2α analogue Increase in aqueous humor outflow Glaucoma Misoprostol PGE1 analogue Gastric cytoprotection Gastric and duodenal ulcers induced by use of NSAIDs NSAIDs, Nonsteroidal antiinflammatory drugs; PG, prostaglandin Chapter 26  y  Autacoid Drugs   281 Leukotriene inhibitors act either by inhibiting 5-lipoxygenase or by blocking leukotriene receptors They are currently used in the management of asthma, but other therapeutic applications are being explored The NSAIDs act by inhibiting cyclooxygenase and are used primarily to alleviate pain and inflammation Corticosteroids block the formation of all eicosanoids, partly by inhibiting phospholipase A2 They have anti­ inflammatory, antiallergic, and antineoplastic effects and are used in the treatment of a wide variety of adrenal diseases and nonadrenal disorders Prostaglandin Drugs Prostaglandin E1 and Prostaglandin E1 Derivatives Alprostadil is identical to naturally occurring PGE1 and is available in several formulations for specific clinical uses Alprostadil is given by continuous intravenous infusion to maintain the patency of the ductus arteriosus in neonates who are awaiting surgery for some types of congenital heart diseases These include cyanotic heart defects (pulmonary atresia or stenosis, tricuspid atresia, tetralogy of Fallot, and transposition of the great vessels) and acyanotic heart defects (coarctation of the aorta and hypoplastic left ventricle) Alprostadil is available in injectable, pellet, and cream formulations to treat erectile dysfunction in men For this purpose, the drug is injected into the cavernosa of the penis, or slow-release pellets or drops of cream are inserted into the meatus of the urethra Adverse effects in men treated with alprostadil include penile pain, penile fibrosis, priapism (persistent erection), flushing, diarrhea, headache, and fever Given the rise in the use of oral drugs to treat erectile dysfunction, for example, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) (see Chapter 6), it is likely that alprostadil will be limited to those patients in whom the aforementioned popular drugs are contraindicated Misoprostol is a synthetic PGE1 analogue available in an orally administered formulation for the prevention of NSAID-induced gastric ulcers and duodenal ulcers (see Chapter 28) Misoprostol treatment is particularly useful in patients who take NSAIDs on a long-term basis to alleviate the symptoms of arthritis and other inflammatory conditions Misoprostol acts locally on the gastrointestinal mucosa to exert a cytoprotective effect by inhibiting gastric acid secretion and by increasing bicarbonate secretion from mucosal cells Diarrhea, one of the most common adverse effects of misoprostol use, can be minimized by starting patients on a low dose of the drug and then gradually increasing the dose In pregnant women, misoprostol is absolutely contraindicated because it can stimulate uterine contractions and cause premature labor Misoprostol is also approved for use as an abortifacient in combination with the progesterone receptor antagonist mifepristone (RU-486, Mifeprex) When used in combination, mifepristone and misoprostol are 95% to 97% effective within the first weeks of pregnancy Prostaglandin E2 and Prostaglandin F2α Derivatives Dinoprostone and carboprost tromethamine are prostaglandin drugs that have oxytocic activity and increase the uterine contractions of pregnant women Dinoprostone is a formulation of naturally occurring PGE2, whereas carboprost is a synthetic derivative of PGF2α Dinoprostone is available as a vaginal insert, gel, or suppository In pregnant women the vaginal insert or gel is applied to the vagina or cervix to produce cervical ripening before labor induction The insert may provide more accurate dosing than the gel The suppository is used to evacuate the uterine contents in cases of intrauterine fetal death, benign hydatidiform mole, or second-trimester termination of pregnancy Carboprost is administered intramuscularly to control postpartum bleeding when other measures have failed and to terminate pregnancy (abortifacient) It can cause flushing, diarrhea, vomiting, altered blood pressure, blurred vision, respiratory distress, and other adverse reactions Latanoprost was the first prostaglandin drug indicated for the treatment of glaucoma It is administered topically as eyedrops and is used to treat open-angle glaucoma that is resistant to other pharmacologic treatments Latanoprost is a PGF2α analogue that acts on FP receptors to increase aqueous humor outflow via the uveoscleral pathway (see Box 6-1) It can alter the color of the iris and cause a permanent eye color change by increasing the amount of melanin in melanocytes Other synthetic FP receptor agonists developed for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension are bima­ toprost and travoprost Prostaglandin I2 and Prostaglandin I2 Derivatives Epoprostenol is a formulation of naturally occurring PGI2 (prostacyclin) that is used to treat pulmonary arterial hypertension Epoprostenol acts on IP receptors to dilate pulmonary blood vessels and increase pulmonary blood flow, thereby counteracting the pathophysiologic consequences of pulmonary hypertension The drug is administered by continuous intravenous infusion, and the dosage is titrated on the basis of clinical improvement and adverse effects The most common adverse reactions include flushing, tachycardia, hypotension, diarrhea, nausea, vomiting, and flulike symptoms Treprostinil is a stable analogue of prostacyclin that has a half-life of to hours and can be safely administered by a continuous subcutaneous infusion via a self-inserted subcutaneous catheter using a microinfusion pump designed specifically for subcutaneous drug delivery It is approved to diminish the symptoms (e.g., shortness of breath) associated with physical activity in patients with pulmonary arterial hypertension ENDOTHELIN-1 ANTAGONISTS Endothelin-1 (ET-1) is a peptide autacoid produced by vascular endothelial cells It activates ETA and ETB recep­ tors in vascular smooth muscle and other tissues The results of ETA receptor activation are vasoconstriction and cell proliferation, and ETB receptors mediate vasodilation, antiproliferation, and increased ET-1 clearance ET-1 may serve physiologically to counteract the vasodilation produced by the endothelin-relaxing factor (nitric oxide), but levels of ET-1 peptide are increased 10-fold in pulmonary arteries of patients with pulmonary arterial hypertension ET-1 also appears to contribute to cardiac dysfunction during 282   Section V  y  Pharmacology of the Respiratory and Other Systems reperfusion after thrombolytic treatment in patients undergoing acute myocardial infarction Bosentan (Tracleer) is a dual ETA and ETB receptor antagonist that is approved for treating pulmonary arterial hypertension Clinical trials have shown that bosentan significantly improves 6-minute walking distances in persons with class III or IV pulmonary arterial hypertension, while decreasing pulmonary vascular resistance and dyspnea Bosentan is administered orally and is generally well tolerated, but 11% of patients have experienced elevated serum aminotransferase levels For this reason, liver function tests should be monitored at baseline and then monthly in persons taking bosentan Based on animal studies, bosentan is very likely to cause major birth defects if used by pregnant women, and it is contraindicated in pregnancy and in women of childbearing age who are not using hormonal contraceptives A second ET receptor antagonist, ambrisentan, was recently approved for the treatment of pulmonary arterial hypertension Ambrisentan has much greater selectivity for ETA receptors than for ETB receptors (>4000-fold), although the clinical impact of such high selectivity is not known As with bosentan, warnings are made regarding hepatic function and enzyme level monitoring Although not an endothelin drug, sildenafil has been marketed under a new trade name, Revatio, for the treatment of pulmonary arterial hypertension As sildenafil inhibits phosphodiesterase type 5, an increase of cyclic guanosine monophosphate within pulmonary vascular smooth muscle cells results in relaxation and vasodilation of the pulmonary vascular bed SUMMARY OF IMPORTANT POINTS • Autacoids include histamine, serotonin, prostaglandins, and leukotrienes These substances usually act on the same tissue in which they are produced • Histamine is the primary mediator of allergic reactions Stimulation of H1 receptors causes vasodilation, edema, congestion, and pruritus Stimulation of H2 receptors mediates gastric acid secretion • The first-generation H1 receptor antagonists (chlorpheniramine, diphenhydramine, meclizine, promethazine, and others) produce varying degrees of sedation and also have anticholinergic side effects The secondgeneration drugs (cetirizine, loratadine, fexofenadine, and desloratadine) are largely devoid of CNS effects • The H1 receptor antagonists are used primarily to treat allergies, but meclizine is used to prevent motion sickness and promethazine is used to treat nausea and vomiting • Fexofenadine is the active metabolite of the nowbanned terfenadine Unlike terfenadine, fexofenadine does not prolong the QT interval or cause torsades de pointes Cetirizine, desloratadine, and loratadine also lack cardiac effects • Drugs that affect serotonin (5-hydroxytryptamine, or 5-HT) are classified as serotonin agonists, serotonin antagonists, and serotonin reuptake inhibitors • Some 5-HT1 receptor agonists (previously sumatriptan) can be used to treat migraine headaches, whereas some 5-HT2 receptor antagonists (previously methysergide) can be used to prevent migraine headaches • Cyproheptadine, which is a 5-HT2 receptor antagonists, is used in the management of carcinoid syndrome, which is caused by excessive production of serotonin and other vasoactive substances in patients with carcinoid tumors from enterochromaffin tissue • Ondansetron, granisetron, and many others “setron” drugs are 5-HT3 receptor antagonists used in the treatment of nausea and vomiting • Eicosanoids are derived from arachidonic acid and other precursor 20-carbon fatty acids The two main groups of eicosanoids are prostaglandins and leukotrienes The ratio of omega-6 and omega-3 fatty acids in the diet plays an important role in the activity of eicosanoid end products • Alprostadil is PGE1 and misoprostol is a PGE1 derivative Alprostadil is used to maintain patency of the ductus arteriosus in neonates awaiting surgery for heart defects It is also used to treat erectile dysfunction in men Misoprostol is used to prevent gastric and duodenal ulcers in persons taking NSAIDs • Dinoprostone, the same as PGE2, is used for cervical ripening before induction of labor and for evacuation of the uterine contents • Carboprost and latanoprost are PGF2α derivatives Carboprost is used to control postpartum bleeding and to terminate pregnancy Latanoprost and other prostaglandin antiglaucoma drugs that increase the aqueous humor outflow are used to treat glaucoma • Epoprostenol is PGI2 (prostacyclin) and treprostinil is a PGI2 derivative; both are used to treat pulmonary arterial hypertension In addition, bosentan and ambrisentan, endothelin-1 receptor antagonists, and a new formulation of sildenafil are indicated for pulmonary arterial hypertension Review Questions Which of the following antihistamines would be best used to treat mild nausea and vomiting caused by motion sickness? (A) cetirizine (B) fexofenadine (C) loratadine (D) diphenhydramine (E) meclizine Which of the following describes the major difference between a first- and second-generation antihistamine? (A) selectivity at H1 receptors (B) ability to cross the blood-brain barrier (C) effectiveness in treating allergies (D) potency at blocking H1 receptors (E) indications for use 506    Index Multidrug resistance protein, 464 Multidrug-resistant tuberculosis (MDR-TB), 424 Multiple action neuroendocrine antagonist, 117 Multiple dose kinetics, 21-23 Multiple myeloma chemotherapy, 472t Multiple sclerosis, 257 etiology and pathogenesis of, 257 management of, 254t, 257, 347 Mupirocin, 410t, 415 indications for use, 410t Muromonab-CD3, 478 Muscarine, 55t, 57 indications for use, 55t, 57 sources of, and effects, 57 Muscarinic receptor(s), 47, 48f, 53, 54t in physiology of emesis, 302-305, 303f subtypes of, 53 Muscarinic receptor antagonists, 50, 63-66 antiemetic effects of, 305 belladonna alkaloids, 63-65 for gastrointestinal hyperactivity, 301 ipratropium and tiotropium, 290-291 semisynthetic and synthetic, 65-66 Muscle relaxants See Neuromuscular blocking agents Muscle spasms, agents for, 257-258 Musculoskeletal pain and inflammation, 314 See also Gout; Osteoarthritis; Rheumatoid arthritis classification of drugs for, 314, 314b disease modifying antirheumatic drugs, 322-324 drugs for gout, 324-325 nonsteroidal antiinflammatory drugs, 316-317 summary of important points, 325-326 MUSE See Alprostadil MYAMBUTOL See Ethambutol MYCAMINE See Micafungin MYCELEX See Clotrimazole Mycobacterial infections, 424 treatment regimens for, 426t See also Antimycobacterial drugs Mycobacterium avium-intracellulare infection, 424 treatment of, 428 MYCOBUTIN See Rifabutin Mycophenolate, 477-478 Mycoses, 431 causes of, and treatment, 434t MYCOSTATIN See Nystatin MYDRIACYL See Tropicamide Myelosuppression, 465 Myocardial infarction, 102, 103t acute, 163, 163b thromboembolic management in, 156 Myocardial metabolism, modifiers of, 107 Myocardial oxygen demand, 102 reduction of, 102-103 Myocardial oxygen supply, 102 MYOCHRYSINE See Gold sodium thiomalate Myoclonic seizures, 198 MYSOLINE See Primidone Myxedema coma, 339 N Nabilone, 267 Nabumetone, 321 Nadolol, 81 for angina pectoris, 107 clinical uses of, 83 Nafarelin, 333 Nafcillin, 399-400, 401t indications for use, 402t Naftifine, 432t, 434t, 436 NAFTIN See Naftifine Nalbuphine, 245 Naloxone, 245-246, 268-269 Naltrexone, 245-246 for opioid and alcohol dependence therapy, 269 NAMENDA See Memantine NAPROSYN See Naproxen Naproxen, 319-320 adverse effects of, 320 for migraine termination, 311 pharmacokinetics of, 319-320 pharmacologic effects of, and indications for use, 319 Naproxen-esomeprazole, 319 Naratriptan, 311 adverse effects of, and interactions, 311 mechanism of action of, 311 pharmacokinetics and effects of, 311 NARCAN See Naloxone Narcolepsy, 235 NARDIL See Phenelzine NAROPIN See Ropivacaine Narrow spectrum penicillins, 397b, 399 NASACORT See Triamcinolone NASCOBAL See Cyanocobalamin; Vitamin B12 NASONEX See Mometasone NATACYN See Natamycin Natalizumab, 257 Natamycin, 432t, 434t, 435 NATAZIA See Oral contraceptives (estrogen-progestin) Nateglinide, 371 National Cholesterol Education Program (NCEP), 148-149 NATRECOR See Nesiritide Natriuretic effect, 89-91 NATROBA See Spinosad Natural sources, of drugs, NAVANE See Thiothixene Nebivolol, 93 NEBUPENT See Pentamidine Nedocromil, 287 Nelarabine, 468 Nematode infections, 457-459 treatment of, 453t, 458-459 NEMBUTAL See Pentobarbital NEO-SYNEPHRINE See Phenylephrine Neomycin, 408-411, 410t Neoplastic disease See Cancer entries Neostigmine, 50, 59 chemistry and pharmacokinetics of, 59 indications for use, 59 mechanism and effects of, 59 Nephron units, function of, 120-121 Nephrotoxicity, 39 Nerve block anesthesia, 213 NESACAINE See Chloroprocaine Nesiritide, for heart failure, 112t, 116t, 117 NEULASTA See Pegfilgrastim NEUPOGEN See Filgrastim NEUPRO See Rotigotine Neuraminidase inhibitors, 447-448 Neuroadaptation, 242, 261 Neurodegenerative disease(s), 249 classification of drugs for, 249b summary of important points, 258 treatment of specific See also specific disease adverse effects, and interactions, 254t Alzheimer disease, 256-257 amyotrophic lateral sclerosis, 257 antispastic agents in, 257-258 Huntington disease, 255 multiple sclerosis, 257 Parkinson disease, 249-255 Neurogenesis, 228-229 Neurohypophysis, 330 Neurokinin(s), 180 Neurokinin-1 receptor antagonist, antiemetic effects of, 305 Neuroleptic drugs See Antipsychotic drugs Neuroleptic malignant syndrome, 224-225, 258 Neuromodulator(s), 174, 176 Index    507 Neuromuscular blocking agents, 50, 66-68, 66t depolarizing, 67-68 nondepolarizing, 66-67 Neuronal adaptation, 260, 261f Neuronal reuptake inhibitors, 229-234 mechanisms of action of, 229f NEURONTIN See Gabapentin Neuropathic pain, 238 Neuropeptide(s), 180 Neuropeptide receptors, of central nervous system, 177t Neuropeptide Y, 47, 180 Neurotransmission in central nervous system excitatory and inhibitory, 174-176 patterns of, 175b and sites of drug action, 174180, 175f in peripheral nervous system, and sites of drug action, 48-51 Neurotransmitters, 174-176 central nervous system, 176-180 peripheral nervous system, 47-48 synthesis and metabolism of, 174 Nevirapine, 441t, 445-446 New drug application (NDA), 35-36 NEXIUM See Esomeprazole NEXPLANON See Contraceptive implants NEXT CHOICE See Emergency (postcoital) contraceptive Niacin, 152-153 adverse effects of, and interactions, 153 chemistry and pharmacokinetics of, 150t, 152-153 indications for use, 153 mechanisms and effects of, 153 NIASPAN See Niacin Nicardipine, 106, 106t for angina pectoris, 106 for hypertension, 97-98 Niclosamide, 459 NICODERM See Nicotine NICORETTE See Nicotine Nicotine, 55t, 57 indications for use, 57, 269 sources of, and effects, 57 Nicotine dependence, 266 withdrawal signs and symptoms, 262t Nicotinic acid See Niacin Nicotinic receptor(s), 47, 47f, 53-54, 54t Nicotinic receptor antagonists, 50, 66-68 depolarizing neuromuscular blocking agents, 67-68 nondepolarizing neuromuscular blocking agents, 66-67 Nifedipine, 106, 106t for angina pectoris, 106 for hypertension, 97-98 Nifurtimox, 457 NILANDRON See Nilutamide Nilotinib, 474-475 Nilutamide, 361 NIMBEX See Cisatracurium Nimodipine, 107 pharmacokinetics of, 106, 106t NIMOTOP See Nimodipine Nitazoxanide, 454 Nitric oxide, 47 neuromodulatory effects of, 180 Nitrites and nitrates, organic, 103-105, 108 amyl nitrite, 103-104 nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, 104-105 Nitrofurantoin, 418t, 421-422 indications for use, 419t Nitrogen mustards, 469-471 chlorambucil, 469-470 cyclophosphamide, 469-471 ifosfamide, 469-471 mechlorethamine, 469-470 melphalan, 469-470 Nitroglycerin, 104-105 for angina pectoris, 107-108 mechanisms and effects of, 104 adverse, and interactions, 105 pharmacokinetics of, 104 tolerance to, 104-105 NITROPRESS See Nitroprusside Nitroprusside, 98 Nitrosourea drugs, 470 NITROSTAT See Nitroglycerin Nitrous oxide, 214t, 217 adverse effects of, 215t NIX See Permethrin Nizatidine, 296-297 adverse effects of, and interactions, 297 chemistry, mechanisms, and effects of, 296-297 indications for use, 297 pharmacokinetics of, 297 NIZORAL See Ketoconazole NMDA (N-methyl-d aspartate) receptor-calcium ion channels, 198-199 Nocturnal asthma, 289 Nocturnal enuresis, 334 Non-Hodgkin lymphoma chemotherapy, 472t Noncatecholamines, 74-76 Nondepolarizing neuromuscular blocking agents, 66-67 chemistry and pharmacokinetics of, 66-67 indications for use, 67 Nondepolarizing neuromuscular blocking agents (Continued) interactions of, 67 mechanisms and effects of, 67 reversal of effects of, 67 selection of, for clinical application, 67 Nonnucleoside reverse transcriptase inhibitors, 445-446 action of, and viral resistance, 445 adverse effects and interactions of, 445-446, 445t indications for use of, 445 pharmacokinetics of, 441t, 445-446 therapeutic regimens based on, 443t Nonoxynol-9, 359 Nonproprietary name, of drug, Nonsedating anxiolytic drugs, 195 Nonselective β-blockers, 78-79, 81 chemistry and pharmacokinetics of, 81, 83t mechanisms and effects of, 81 specific, 82-84 Nonsquamous non–small cell lung cancer, 467-468 Nonsteroidal antiinflammatory drugs, 238, 316-317, 317t adverse effects of, 317 interactions of, 317-318 mechanisms of action of, 316, 316f and effect on prostaglandin release, 316-317 for migraine termination, 311-312 nonselective cyclooxygenase inhibitors, 317-321 acetaminophen, 319 aspirin and other salicylates, 318-319 diclofenac, 321 etodolac, meloxicam, 321 ibuprofen, ketoprofen, naproxen, 319-320 indomethacin, sulindac, ketorolac, 320-321 piroxicam, nabumetone, 321 and opioids, for postoperative pain, 317 for prevention of migraine headache, 309 safety of, during pregnancy, 318 selective cyclooxygenase inhibitors, 321-322 celecoxib, rofecoxib, valdecoxib, 321-322 NOR-QD See Progestin-only contraceptives Noradrenaline See Norepinephrine NORDETTE See Oral contraceptives (estrogen-progestin) 508    Index Norepinephrine, 71-74, 179-180 in autonomic neurotransmission, 46-47, 50 receptors for, 47-48 See also Adrenergic neurotransmission cardiovascular effects of, 72, 74f, 82f pharmacologic effects, and clinical uses, 72, 73t reuptake inhibitors of, 229-234, 229f synthesis and degradation of, 179f Norethindrone, 358-359 NORFLEX See Orphenadrine Norfloxacin, 418t indications for use, 419t Norgestimate, 355 Norgestrel, 355, 358 NORINYL See Oral contraceptives (estrogen-progestin) NORINYL 1+50 See Oral contraceptives (estrogen-progestin) NORMODYNE See Labetalol NOROXIN See Norfloxacin NORPACE See Disopyramide NORPRAMIN See Desipramine Nortriptyline, 230 adverse effects of, 230 treatment of, 230 indications for use, 230 mechanisms and effects of, 230 pharmacokinetics of, 230 NORVASC See Amlodipine NORVIR See Ritonavir NOVANTRONE See Mitoxantrone NOVOLOG See Insulin NOXAFIL See Posaconazole NPH (neutral protamine Hagedorn) insulin, 368, 368t NSAIDS See Nonsteroidal antiinflammatory drugs NUBAIN See Nalbuphine Nuclear reactor accident, potassium iodide preparations for, 340 Nuclear (hormone) receptors, 26, 27t examples of, 29t signal transduction via, 27f Nucleoside analogues, 439-442 acyclovir, famciclovir, valacyclovir, 440-442 chemistry and mechanisms of, 439-440, 440f ganciclovir, valganciclovir, cidofovir, 442 penciclovir, 442 pharmacokinetics of, and indications for use, 440, 441t-442t trifluridine, 442 viral resistance to, 440 Nucleoside reverse transcriptase inhibitors, 444-445 adverse effects of, and interactions, 444, 445t chemistry and pharmacokinetics of, 441t, 444 specific, 444-445 spectrum of, and indications for use, 444 viral resistance to, 444 Nucleotide reverse transcriptase inhibitor, 443-444 NUCYNTA See Tapentadol NUEDEXTA See Dextromethorphan-quinidine NUPERCAINAL See Dibucaine NUTROPIN See Somatropin NUVARING See Vaginal ring contraceptive NUVIGIL See Armodafinil Nystatin, 432t, 434t, 435 O Obesity, 235 Obsessive-compulsive disorder, 187 Obstructive sleep apnea, 235, 292 Octreotide, 332 Ocular bacterial infections, 422 Ocular herpes infections, 442 OFIRMEV See Acetaminophen, injectable form of Oil/gas partition coefficient, 215, 216b Ointments, Olanzapine, 226t, 227 adverse effects of, 225t for bipolar disorder, 234-235 considerations in use of, 228 Olopatadine, 276-277 Omalizumab, 292 Omeprazole, 297-298 adverse effects of, 298 chemistry and pharmacokinetics of, 298 indications for use, 298 mechanisms and effects of, 298 OMNARIS See Ciclesonide Onchocerciasis, 458 Ondansetron, 278t, 279, 304 adverse effects of, and interactions, 304 chemistry, mechanisms, and effects of, 304 pharmacokinetics of, and indications for use, 304 ONFI See Clobazam ONGLYZA See Saxagliptin Onychomycosis, 431 Ophthalmic antihistamines, 277 Opioid analgesics, 238, 240 Opioid dependence, 264-265 treatment of, 269-270 withdrawal signs and symptoms, 262t Opioid intoxication, 245-246, 262t, 265b treatment of, 262t Opioid receptor(s), 240-241 Opioid receptor agonists analgesic, 238, 240-243, 243t for acute pain, 246 adverse effects of, 242 for cancer induced pain, 247 for chronic pain, 246-247 classification of, 238b, 241-243 mechanisms and effects of, 241-243, 241f, 242b in cardiovascular system, 241 in central nervous system, 241 in gastrointestinal, biliary, genitourinary system, 241-242 mixed, 245 moderate, 244 other, 244-245 strong, 243-246, 243t summary of important points, 247 tolerance to, and physical dependence, 242-243 antidiarrheal effects of, 302 antitussive effects of, 292-293 for migraine termination, 311 parenteral, for anesthesia, 217-219 Opioid receptor antagonists, 243t, 245-246 OPTICROM See Cromolyn Oral administration, of drugs, Oral antidiabetic agents, 369-373, 369t Oral contraceptives (estrogenprogestin), 355-358, 357t adverse effects of, 358, 358b and interactions, 358 extended cycle, 357 other therapeutic uses of, 357 ORENCIA See Abatacept Orexin, 180 Organ toxicity(ies), 38, 38t genetically determined, 39 specific cardiotoxicity, 39 hematopoietic toxicity, 38-39 hepatotoxicity, 39 nephrotoxicity, 39 pulmonary toxicity, 39 Organ transplant/graft rejection, suppression of, 348, 478 Organophosphate compounds, 59-60 See also Quasi-reversible cholinesterase inhibitors clinical uses of, 60 Index    509 Organophosphate poisoning, management of, 60, 60b Orphan Drug amendments, to Food, Drug & Cosmetics Act, 36-37 Orphan receptors, 26 Orphenadrine, antispastic effect of, 258 ORTHO-CEPT See Oral contraceptives (estrogen-progestin) ORTHO EVRA See Transdermal contraceptive ORTHO-NOVUM 7/7/7 See Oral contraceptives (estrogen-progestin) ORTHO TRI-CYCEN See Oral contraceptives (estrogen-progestin) ORTHO TRI-SPRINTEC See Oral contraceptives (estrogen-progestin) Orthostatic hypotension, 183 ORUDIS See Ketoprofen Oseltamivir, 441t, 447-448 OSMITROL See Mannitol Osmotic diuretics, 122t, 127 adverse effects and interactions of, 124t Osmotic laxatives, 301 Osteoarthritis, 314-316 Osteomalacia, 377 Osteoporosis, 376 treatment of, 382-383 Ovarian cancer chemotherapy, 472t OVCON See Oral contraceptives (estrogen-progestin) OVIDE See Malathion OVIDREL See Choriogonadotropin alfa Oxacillin, indications for use, 402t Oxaliplatin, 470-471 Oxamniquine, 459 Oxazepam, 193 See also Benzodiazepines Oxazolidinedione compound, 415 Oxcarbazepine, 203 indications for use, 203 interactions of, 203 mechanisms and effects of, 203 pharmacokinetics of, 203 OXECTA See Oxycodone Oxidative reactions, 14 Oxidative stress theory, 249-250 Oxybutynin, 65 Oxycodone, 244 dependence on, 264-265 OXYCONTIN See Oxycodone Oxymetazoline, 75-76 pharmacologic effects, and clinical uses, 73t Oxytocin, and related drugs, 334 P P-glycoprotein (Pgp) efflux pump, 11, 464, 465f P2X receptors, 180 P2Y receptors, 180 Paclitaxel, 474 Paget disease of bone, 376 treatment of, 383 Pain, 238 analgesics for, 238 See also Mixed opioid agonist-antagonists; Opioid receptor agonists; Opioid receptor antagonists cancer-related, 247 headache, 307, 308t cluster, 312 migraine, 307-308 See also Migraine headache tension, 312 musculoskeletal, and inflammation, 314 See also Gout; Osteoarthritis; Rheumatoid arthritis neural pathways of, 238-240, 239f and sites of drug action, 239b treatment of, 246-247 Paliperidone, 227-228 Palivizumab, 477 Palonosetron, 279, 304 adverse effects of, and interactions, 304 chemistry, mechanisms, and effects of, 304 pharmacokinetics of, and indications for use, 304 PAMELOR See Nortriptyline Pamidronate, 380-381 adverse effects of, 380 and interactions, 380 chemistry and pharmacokinetics of, 380 indications for use, 380-381 mechanisms and effects of, 380 PAMINE See Scopolamine Pancreatic carcinoma, 469 Pancreatic hormones, 364 glucagon, 365 insulin, 364 Pancreatic islet cell tumor, 470 Pancreatitis, 144-149 Pancuronium, 66-67, 66t Panic disorder, 187 Panitumumab, 476 Pantoprazole, 297-298 adverse effects of, 298 chemistry and pharmacokinetics of, 298 indications for use, 298 mechanisms and effects of, 298 Papillomavirus infections, 449 Paralytics See Neuromuscular blocking agents Parasitic infections, and infestations, 451 causes and treatment of, 453t blood and tissue-dwelling protozoa, 454-457 ectoparasites, 459-460 helminths, 457-459 lumen- and tissue-dwelling protozoa, 451-454 Parasympathetic nervous system, 46 and effect on organs, 48f Parathyroid hormone (PTH), 376 recombinant form of, 382 PARCOPA See Levodopa-carbidopa Parenteral administration, of drugs, 6-7 Parenteral anesthetics, 217-219, 218t Parkinson disease, 183, 249-255 etiology and pathogenesis of, 249-250, 250f treatment of, 254t, 255 with acetylcholine receptor antagonists, 255 with dopamine receptor agonists, 253-255 with drugs increasing dopamine levels, 250-253 PARLODEL See Bromocriptine PARNATE See Tranylcypromine Paromomycin, 454 Paroxetine, 230-232 adverse effects of, 231, 231t mechanisms and effects of, 231 pharmacokinetics of, 231 Partial seizures, 198, 200f management of, 207 treatment of, 203-205 adjunct, 205-206 Passive diffusion, PATANOL See Olopatadine Patent ductus arteriosus, 320 Patient controlled analgesia, 246 PAVULON See Pancuronium PAXIL See Paroxetine PCP See Phencyclidine Pediatric tumors, 473 Pediculosis, 459 Pegfilgrastim, 171-172 Peginterferon alfa-2b, 441t, 448-449 PEGINTRON See Peginterferon alfa-2b Pegloticase, 325 Pegvisomant, 333 Pelvic inflammatory disease, 421 Pemetrexed, 467-468 Penciclovir, 442, 442t Penicillamine, for rheumatoid arthritis, 324 Penicillamine resistant penicillins, 400, 401t Penicillin allergy, 404 510    Index Penicillin G, 399-400 indications for use, 402t long-acting forms of, 400 pharmacokinetics of, 400f, 401t renal excretion of, 16b Penicillin V, 399-400, 401t indications for use, 402t Penicillinase resistant penicillins, 397b, 399 pharmacokinetics of, 401t Penicillins, 398-404 adverse effects of, 404 bacterial mechanisms of resistance to, 402-403, 403b, 403t chemistry of, 399, 400f extended spectrum, 400-401 grouping of, 397b, 399 narrow spectrum, 400 penicillinase resistant, 400 pharmacokinetics of, 399-400, 401t sites of action of, 398, 399f spectrum of, and indications for use, 400-402, 402t Pentamidine, 457 Pentazocine, 245 Pentobarbital, 194, 264 PENTOTHAL See Thiopental PEPCID See Famotidine Peptic ulcer disease, 295-299, 297t, 412-413 Peptidoglycan(s), 397-398 PERCOCET See Hydrocodone PERCODAN See Hydrocodone Pergolide, 253 PERIACTIN See Cyproheptadine Peripheral nervous system, 46 autonomic, 46 enteric, 46 neurotransmission and sites of drug action in, 48-51 neurotransmitters and receptors of, 47-48 somatic, 46 Peripheral vascular resistance (PVR), 89, 90f Permethrin, 459 Pernicious anemia, 170 Perphenazine, antiemetic effects of, 304-305 Petit mal seizures, 198 PFIZERPEN See Penicillin G pH, and effect on drug absorption, 9, 10b Pharmaceutical chemistry, Pharmaceutical drug interactions, 39, 40t Pharmaceutical preparations, 4-6 aerosols, ointments, creams, lotions, suppositories, skin patches, Pharmaceutical preparations (Continued) solutions and suspensions, tablets and capsules, Pharmacodynamic drug interactions, 39-40, 40t Pharmacodynamic tolerance, 30, 242-243 Pharmacodynamics, 3f, 26 dose-response relationship in, 30-32 drug receptor interactions in, 26-30 drug receptors in, 26 summary of important points in, 32 Pharmacogenomics, 15 Pharmacognosy, Pharmacokinetic tolerance, 30, 266 Pharmacokinetics, 3f, 9, 10f alterations in, 40, 40t clinically significant, management of, 40t drug absorption, 40 drug biotransformation, 41 drug distribution, 40-41 drug excretion, 41 drug absorption in, drug biotransformation in, 11-15 drug distribution in, 9-11 drug excretion in, 15-17 quantitative, 17-21 bioavailability in, 18 continuous dose and multiple dose, 21-23 drug clearance in, 20-21 drug dosage calculations in, 19b one compartment and two compartment models in, 17, 18f plasma drug concentration curves in, 17-18 single dose, 21 volume of distribution in, 18-20 summary of important points, 23-25 Pharmacology, 2-3 of antimicrobial chemotherapy, 386-396 See also Antimicrobial therapy of autacoid drugs, 274-283 See also Autacoid drugs; Autacoid pharmacology autonomic and neuromuscular, 46-52 See also Autonomic and neuromuscular pharmacology cardiovascular, renal, and hematologic, 88-101 See also Cardiovascular, renal, and hematologic pharmacology Pharmacology (Continued) central nervous system, 174-185 See also Central nervous system pharmacology drug development and safety in, 34-44 See also Drug development; Drug safety and efficacy laws drug naming in, drug sources and preparations in, 4-6 dual aspects of, 2-3 See also Pharmacodynamics; Pharmacokinetics endocrine, 330-335 See also Endocrine pharmacology gastrointestinal, 295-306 See also Gastrointestinal tract pharmacology goal of, for headache disorders, 307-313 See also Headache pharmacotherapy history and role of, for pain, inflammation, and arthritic disorders, 314-327 and pharmacy, respiratory, 284-294 See also Respiratory tract pharmacology routes of drug administration in, 6-7 summary of important points, 7-8 and toxicology, in treatment of disease, Pharmacotherapeutics, Pharmacy, Phencyclidine, 268 Phencyclidine intoxication, 262t treatment of, 262t Phenelzine, 232 adverse effects of, 231t for migraine prophylaxis, 309 PHENERGAN See Promethazine Phenobarbital, 194, 204 adverse effects of, 202t CYP enzyme induction by, 12 interactions of, 203t mechanisms and effects of, 201t Phenothiazine drugs, 304-305 Phenoxybenzamine, 78, 100 mechanisms and pharmacokinetics of, 78 pharmacologic effects of, and indications for use, 78 Phentermine, 235 Phentolamine, 49t, 50, 78-79 chemistry and pharmacokinetics of, 78 mechanisms and effects of, and indications for use, 78-79, 82f tahir99-VRG & vip.persianss.ir Index    511 Phenylephrine, 75 indications for use, 75 mechanisms and effects of, 73t, 75 pharmacokinetics of, 75 Phenytoin, 204 adverse effects of, 202t and interactions, 203t, 204 indications for use, 204 mechanisms and effects of, 199, 201t, 204 pharmacokinetics of, 204 Pheochromocytoma, 50, 79b causing hypertensive crisis, 100 Phobic disorders, 187 Phosphodiesterase inhibitor(s), 58t for heart failure and myocardial stimulation, 116 See also Milrinone for respiratory disorders, 288-289 PHOSPHOLINE IODIDE See Echothiophate Physical dependence, 261 Physostigmine, 50, 59 for anticholinergic effects of antihistamines, 277 chemistry and pharmacokinetics of, 59 indications for use, 59 mechanism and effects of, 59 Phytonadione (vitamin K1), 158, 160 for bleeding caused by warfarin, 160 Pilocarpine, 49t, 50, 57 indications for use, and effects, 55f, 55t, 57, 58b Pindolol, 81 clinical uses of, 82-83 Pinworm infection, 458-459 Pioglitazone, 371-372 adverse effects of, 372 chemistry and pharmacokinetics of, 371 indications for use, 372 mechanisms and effects of, 371-372 Piperacillin, 399-401, 401t indications for use, 402, 402t Pirbuterol, 75 chemistry and pharmacokinetics of, 75 indications for use, 75 mechanisms and effects of, 73t, 75 for respiratory disorders, 289-290, 289t Pirenzepine, 66, 301 Piroxicam, 321 Pitavastatin, 149-151 PITOCIN See Oxytocin PLAN B See Emergency (postcoital) contraceptive PLAN B ONE-STEP See Emergency (postcoital) contraceptive Plant alkaloids, 55t, 57 muscarine and nicotine, 57 pilocarpine, 57 PLAQUENIL See Hydroxychloroquine Plasma drug concentration curve, 17-18, 19f See also Pharmacokinetics Plasma glucose and insulin concentrations, time course, 366f Plasma protein binding, and drug distribution, 11 Platelet aggregation, 162, 163f Platinum compounds, 470-471 PLAVIX See Clopidogrel PLENDIL See Felodipine PLETAL See Cilostazol Pneumocystis jiroveci infection, treatment of, 419, 456-457 Pneumonia, 401, 413 fungal, 431 Podophyllotoxins, 473 Polyarteritis nodosa, 347 Polyene antibiotics, 433-435, 434t mechanisms of, and clinical applications, 432, 432t Polyethylene glycol, 300-301 Polymorphism, gene, 15 Polymyositis, 347 Polymyxin B, 418t, 422 indications for use, 419t Polypharmacy, 41 PONTOCAINE See Tetracaine Posaconazole, 432t, 434t, 435-436 Positively inotropic drugs, 112-116, 113t adverse effects and interactions of, 115t for heart failure, 112-116 digoxin, 112-115 dobutamine, 115-116 milrinone, 116 Postantibiotic effect (PAE), 388 Posterior pituitary hormones, 334 Postherpetic neuralgia, 238, 240b, 246-247 Postmarketing surveillance, 36 Postoperative analgesia, 245, 317 Posttraumatic stress disorder, 187 Postural tachycardia syndrome, 183 Potassium channel blockers (Class III antiarrhythmics), 136t, 138-140 electrophysiologic effects of, 135f, 136t specific, 138 amiodarone and dronedarone, 138-139 ibutilide and dofetilide, 139-140 sotalol, 140 Potassium iodide solution, 340 Potassium iodide tablets, 340 Potassium sparing diuretics, 122t, 126-127 adverse effects and interactions of, 124t amiloride and triamterene, 126 in hypertension therapy, 91, 91t spironolactone, 126-127 Potency, drug, 27, 31 POTIGA See Ezogabine PRADAXA See Dabigatran Pralidoxime, 60 Pramipexole, 253-255 Pramlintide acetate, 373-374 PRANDIN See Repaglinide Prasugrel, 164 PRAVACHOL See Pravastatin Pravastatin, 149-151 adverse effects of, 150-151 and interactions, 151 chemistry and pharmacokinetics of, 149, 150t indications for use, 149-150 mechanisms and effects of, 149, 150f Praziquantel, 459 Prazosin, 79-81 effects of, on heart rate, 82f PRECEDEX See Dexmedetomidine PRECOSE See Acarbose Prednisolone, 346 Prednisone, 346 for acute exacerbation of multiple sclerosis, 257 antineoplastic effect of, 477 immunomodulating effect of, 477 in pulmonary inflammation therapy, 456-457 for rheumatoid arthritis therapy, 322 PREDNISONE INTENSOL See Prednisone Pregabalin, 199, 206 Pregnancy, and lactation and altered drug disposition, 42-43 categories of drug safety in, 42 drugs of choice in, 42-43 PREGNYL See Chorionic gonadotropin PREMARIN See Conjugated equine estrogens Preoperative/postoperative analgesia, 245, 317 Prescription drug abuse, 264-265, 268 PREZISTA See Darunavir PRIFTIN See Rifapentine Prilocaine, 211t, 214 PRILOSEC See Omeprazole Primaquine, 454-456 tahir99-VRG & vip.persianss.ir 512    Index PRIMAXIN See Imipenem-cilastatin Primidone, 204 adverse effects of, 202t interactions of, 203t mechanisms and effects of, 201t Priming dose See Loading dose PRINIVIL See Lisinopril PRISTIQ See Desvenlafaxine PROAMATINE See Milodrine Probenecid, 324-325, 399 Procainamide, Class IA antiarrhythmic, 134-137 Procaine, 211t, 213-214 Procaine penicillin G, 400 PROCARDIA See Nifedipine Prochlorperazine antiemetic effects of, 304-305 for migraine termination, 311 PROCRIT See Epoetin alfa Prodrugs, 11, 439-440 Progesterone, and progestins, 351-354 biosynthesis of, 351, 352f derivatives of, 355 physiologic action of, 351-353 Progesterone receptor antagonist, 360 Progestin(s), 351-354 in contraception, 356-359 and estrogen, in oral contraceptives, 357-358 synthetic, 355 Progestin-only contraceptives, 356-359, 357t indications for use, 359 Prokinetic drugs, 300 Prolactin, and related drugs, 333-334 PROLIA See Denosumab Promethazine, 276-277 adverse effects of, and interactions, 277 antiemetic effects of, 305 PROMETRIUM See Progesterone Propafenone, Class IC antiarrhythmic, 137 Proparacaine, 214 PROPECIA See Finasteride Propofol, for induction of anesthesia, 218, 218t Propoxyphene, 244 Propranolol, 49t, 50, 81 for angina pectoris, 107 as Class II antiarrhythmic, 138 clinical uses of, 83 as nonsedating anxiolytic, 195 for prevention of migraine headache, 310 Proprietary name, of drug, Propylthiouracil, 339-340 adverse effects of, 340 indications for use, 340 mechanisms of, 339-340 pharmacokinetics of, 340 PROSCAR See Finasteride PROSOM See Estazolam Prostacyclin, 280 Prostaglandin(s), 279-280, 284 autacoid effects of, 275t Prostaglandin drugs, 281 effects of, and clinical uses, 280-281, 280t inhibition of, by nonsteroidal antiinflammatory drugs, 316-317 Prostanoid receptors, 280 Prostate cancer chemotherapy, 472t hormone antagonists in, 333, 477 Prostate infections, 419, 421 PROSTIGMIN See Neostigmine PROSTIN VR PEDIATRIC See Alprostadil Protamine sulfate, 161 Protease inhibitors, 446 action of, and viral resistance, 446 adverse effects and interactions of, 445t, 446 indications for use of, 446 pharmacokinetics of, 441t, 446 therapeutic regimens based on, 443t Proteasome inhibitor, 475 Protein kinase inhibitors, 474-475 clinical uses of, and adverse effects, 466t-467t mechanism of action of, 475f PROTELOS See Strontium ranelate Proton pump inhibitors, 297-298 adverse effects of, 298 chemistry and pharmacokinetics of, 298 indications for use, 298 mechanisms and effects of, 298 PROTONIX See Pantoprazole PROTOPAM See Pralidoxime Protozoan infections, treatment of, 453t blood and tissue-dwelling, 454-457 lumen and tissue-dwelling, 451-454 other, 457 PROVENTIL See Albuterol PROVERA See Medroxyprogesterone PROVIGIL See Modafinil PROZAC See Fluoxetine Pruritus, 347-348 Pseudallescheriasis, 431 Pseudobulbar affect, 245, 256-257 Pseudoephedrine, 76 for allergic rhinitis, 293 mechanism and effects of, and indications for use, 73t, 76 pharmacokinetics of, 76 Pseudomonas spp infections, 402 Pseudoparkinsonism, 225-226 Psilocybin, 267-268 Psychiatric disorders, 221 affective, 228-229 schizophrenia in, 221-228 Psychological dependence, 260-261 Psychomotor epilepsy, 198 Psychotherapeutic drugs, 221 classification of, 221b antidepressant drugs, 229-234 antipsychotic drugs, 223 central nervous system stimulants, 235-236 mood stabilizing drugs, 234-235 summary of important points, 236 Psyllium hydrophilic mucilloid, 301-302 PTU See Propylthiouracil PULMICORT See Budesonide Pulmonary embolism, 156, 159t, 160-162, 165 Pulmonary toxicity, 39 Pure drug compounds, Pure Food and Drug Act (1906), 36 Purine analogues, 468 Purine neurotransmitters, 180 PURINETHOL See Mercaptopurine Pyrantel pamoate, 458 Pyrazinamide, 424-425, 425t, 427 Pyridostigmine, 50, 59 chemistry and pharmacokinetics of, 59 indications for use, 59 mechanism and effects of, 59 Pyrimethamine-sulfadiazine, 456 Pyrimethamine-sulfadoxine, 456 Pyrimidine analogues, 468-469 Pyrogen secretion, prostaglandin effects on, 316-317 Q Quantal dose-response relationship, 31-32, 31f Quantitative pharmacokinetics, 17-21 bioavailability in, 18 continuous dose and multiple dose, 21-23 drug clearance in, 20-21 drug dosage calculations in, 19b one compartment and two compartment models in, 17, 18f plasma drug concentration curves in, 17-18 single dose, 21 volume of distribution in, 18-20 Quasi-reversible cholinesterase inhibitors, 59-60 chemistry and pharmacokinetics of, 59 clinical use of, 60 mechanisms and effects of, 59 tahir99-VRG & vip.persianss.ir Index    513 QUESTRAN See Cholestyramine Quinapril, 95t, 97 QUINIDEX EXTENTABS See Quinidine Quinidine, as Class IA antiarrhythmic, 134-137 Quinine, 455 Quinupristin-dalfopristin, 410t, 415 indications for use, 410t QVAR See Beclomethasone R Rabeprazole, 297-298 adverse effects of, 298 chemistry and pharmacokinetics of, 298 indications for use, 298 mechanisms and effects of, 298 Radioactive iodine, 341 Raloxifene, 360 in prevention of bone resorption, 381 Raltegravir, 441t, 446 adverse effects and interactions of, 445t Ramelteon, 195 Ramipril, 95t, 97, 116-117 RANEXA See Ranolazine Ranitidine, 296-297 adverse effects of, and interactions, 297 chemistry, mechanisms, and effects of, 296-297 indications for use, 297 pharmacokinetics of, 297 RANKL antibody, 381-382 Ranolazine, for chronic stable angina, 107 RAPAFLO See Silodosin RAPAMUNE See Sirolimus Rapamycin, 478 Rapid-acting insulin preparations, 368, 368t, 374 Rasagiline, 253 Rasburicase, 325 RAZADYNE See Galantamine Reabsorption rate, drug, 10b Rebound seizures, 208 Receptor(s), 26 for acetylcholine, 28 alteration of, 182f in disease states, 30 by drug therapy, 181 in drug tolerance, 30 classification of, 26 for epinephrine and norepinephrine, 28 interaction of, 26-30 binding and affinity in, 26-27 efficacy of, 30 in signal transduction, 28-30, 28f Receptor(s) (Continued) for neurotransmitters, 26, 27t, 28 types of, 26, 27t and signal transduction pathways, 28-30, 29t Receptor guanyl cyclases, 29 Receptor serine/threonine kinases, 29 Receptor tyrosine kinases, 29-30 Receptor tyrosine phosphatases, 29 Recombinant somatotropin, 332 Rectal administration, of drugs, Recurrent apnea, in premature infants, 292 Reflex bradycardia, 51 REFLUDAN See Lepirudin REGITINE See Phentolamine REGLAN See Metoclopramide Regular insulin (insulin injection USP), 368, 368t RELAFEN See Nabumetone RELENZA See Zanamivir RELISTOR See Methylnaltrexone bromide RELPAX See Eletriptan REMERON See Mirtazapine REMICADE See Infliximab Remifentanil, 218, 218t, 243-244 REMODULIN See Treprostinil Renal cell carcinoma chemotherapy, 472t Renal clearance, 10b, 20 Renal excretion, of drugs, 15, 16b active tubular secretion in, 15 glomerular filtration in, 15 passive tubular reabsorption in, 15-16 Renal function improvement, osmotic diuretics in, 127 Renal pharmacology See Cardiovascular, renal, and hematologic pharmacology Renal toxicity, 39 Renal tubular pH, 16 manipulation of, in drug overdose, 17b REOPRO See Abciximab Repaglinide, 371 REQUIP See Ropinirole Resistance to drugs fungal, 433 microbial, 388-391 See also Bacterial resistance mechanisms of, 391, 391t mutation and selection in, 388-391 transferable, 391 tumor cell, 395 viral See Viral resistance Respiratory inflammatory disorders, 284-285 See also Allergic rhinitis; Asthma; Chronic obstructive pulmonary disease; Viral rhinitis Respiratory syncytial viral infection, 448 Respiratory tract infections, 401, 413 fungal, 431 Respiratory tract pharmacology, 284-285 antiinflammatory drugs in corticosteroids, 285-287 leukotriene inhibitors, 287-288 mast cell stabilizers, 287 phosphodiesterase inhibitor, 288-289 sites of action of, 286f antitussives in, 292-293 bronchodilators in, 289-292 β2-adrenoceptor agonists, 289-290 ipratropium and tiotropium, 290-291 theophylline, 291-292 classification of drugs in, 284b efficacy of drugs used in, 285t expectorants in, 293 summary of important points, 293-294 Restless leg syndrome, 253 RESTORIL See Temazepam RETAVASE See Reteplase Reteplase, 165-166 RETROVIR See Zidovudine Reuptake inhibitors, 26 REVATIO See Sildenafil, for pulmonary hypertension Reverse transcriptase inhibitors, 443-444 REVIA See Naltrexone REYATAZ See Atazanavir Rheumatoid arthritis, 314, 315b, 469 pathogenesis of, 315f RHEUMATREX See Methotrexate Rhinitis, 284-285 treatment of, 293 RHINOCORT See Budesonide Rhinorrhea, treatment of, 293 Ribavirin, 441t, 448 adverse effects of, and interactions, 448 mechanism of action of, 448 pharmacokinetics of, 448 spectrum of, and indications for use, 448 Ribonucleotide reductase inhibitor, 469 Rickettsial infections, 412 RIDAURA See Auranofin tahir99-VRG & vip.persianss.ir 514    Index Rifabutin, 425, 425t, 428 for Mycobacterium aviumintracellulare infection, 428 RIFADIN See Rifampin Rifampicin See Rifampin Rifampin, 424-425, 427-428 adverse effects of, and interactions, 428 bacterial resistance to, 428 chemistry and pharmacokinetics of, 425t, 427-428 CYP enzyme induction by, 12, 428 mechanism of action of, 427-428 spectrum of, and indications for use, 427-428 leprosy treatment, 429 Mycobacterium aviumintracellulare infection, 428 Rifamycin See Rifampin Rifapentine, 425, 425t, 428 Rifaximin, 422 indications for use, 419t RILUTEK See Riluzole Riluzole, 257 Rimantadine, 448 Ringworm, 431 Risedronate, 380-381 adverse effects of, 380 and interactions, 380 chemistry and pharmacokinetics of, 380 indications for use, 380-381 mechanisms and effects of, 380 RISPERDAL See Risperidone Risperidone, 226t, 227-228 adverse effects of, 225t for bipolar disorder, 234-235 considerations in use of, 228 RITALIN See Methylphenidate Ritonavir, 441t, 446 Rituximab, 475-476 Rivaroxaban, 159t, 162 Rivastigmine, 59, 256 Rizatriptan, 311 adverse effects of, and interactions, 311 mechanism of action of, 311 pharmacokinetics and effects of, 311 RNA retrovirus, 443 ROBINUL See Glycopyrrolate ROCALTROL See Calcitriol ROCEPHIN See Ceftriaxone Rocky Mountain spotted fever, 412 Rocuronium, 66-67, 66t Rofecoxib, 321 ROFERON-A See Interferon alfa-2a Roflumilast, 288-289 administration and kinetics of, 289 adverse effects of, and interactions, 289 indications for use, 289 mechanism and effects of, 288-289 ROGAINE See Minoxidil ROHYPNOL See Flunitrazepam ROMAZICON See Flumazenil Roofies, 264 Ropinirole, 253-255 Ropivacaine, 211t, 214 Rosacea, 452 Rosiglitazone, 371-372 adverse effects of, 372 chemistry and pharmacokinetics of, 371 indications for use, 372 mechanisms and effects of, 371-372 Rosuvastatin, 149-151 adverse effects of, 150-151 and interactions, 151 chemistry and pharmacokinetics of, 149, 150t indications for use, 149-150 mechanisms and effects of, 149, 150f Rotigotine, 253-255 Route(s) of drug administration, 6-7 advantages and disadvantages of, 6t enteral, inhalation, parenteral, 6-7 topical, transdermal, ROXICODONE See Oxycodone ROZEREM See Ramelteon RU-486 See Misoprostol-mifepristone Rufinamide, 206 RYTHMOL See Propafenone S SABRIL See Vigabatrin SALAGEN See Pilocarpine Salicylates, 318-319 See also Aspirin Salmeterol, 75, 289-290, 289t SAMSCA See Tolvaptan SANCTURA See Trospium SANDOSTATIN See Octreotide SANSERT See Methysergide SAPHRIS See Asenapine Saquinavir, 441t, 446 SARAFEM See Fluoxetine Sarcoidosis, 348 Sarcoma chemotherapy, 472t Sargramostim, 171-172 Saxagliptin, 372-373 Scabies, 459 Schedule of controlled substances, 37f Schistosomiasis, 459 Schizophrenia, 183, 221-228, 223b antipsychotic drug therapy for, 223 neurobiology of, and sites of drug action, 222-223, 222b symptoms of, 222b Scopolamine, 49t, 50, 63-65 chemistry and pharmacokinetics of, 63 indications for use, 65, 305 pharmacologic effects of, 63-65 transdermal formulation of, 65 Seasonal allergies, symptoms and treatment of, 278b SEASONALE See Oral contraceptives (estrogen-progestin) SEASONIQUE See Oral contraceptives (estrogen-progestin) Seborrheic dermatitis, 431 Second messengers, 28, 174-176 Secretion rate, drug, 10b SECTRAL See Acebutolol Sedative-hypnotic and anxiolytic drugs, 186, 189-195 adverse effects of, and interactions, 190t classification of, 186b antihistamines, 194-195 barbiturates, 194 benzodiazepines, 189-194 chloral hydrate, 195 melatonin, ramelteon, 195 nonsedating anxiolytics, 195 zolpidem, zaleplon, eszopiclone, 195 pharmacokinetics and clinical uses of, 189t summary of important points, 195-196 Seizures, 198-199 classification of, 198, 199t electroencephalography of, 200f generalized absence, myoclonic, or atonic, 206-207 management of, 207-208, 207b neurobiology of, 198-199, 201f partial, adjunct drugs, 205-206 partial and generalized tonicclonic, 203-205 status epilepticus, 207 treatment of, 199-207 See also Antiepileptic drugs Selective β-blockers, 79-81 adverse effects of, 80 cardiovascular effects of, 81f mechanisms and effects of, and indications for use, 79-80, 83f pharmacokinetics of, 79 Selective β2-adrenoceptor agonists, 285t Selective β-blockers, 83t, 84 Selective estrogen receptor modulator, 360 tahir99-VRG & vip.persianss.ir Index    515 Selective serotonin reuptake inhibitors (SSRIs), 230-232, 279 adverse effects of, 231, 231t, 233 mechanisms and effects of, 231 pharmacokinetics of, 231 for prevention of migraine headache, 309 Selective toxicity, 386 Selegiline, 232, 252-253 adverse effects of, and interactions, 253 indications for use, 253 mechanisms and effects of, 252 pharmacokinetics of, 252 Selegiline patch, 233 SELZENTRY See Maraviroc SENSIPAR See Cinacalcet Sensory processing, 183 drug effects on, 183 Septicemia, fungal, 431 SEPTRA See Trimethoprim-sulfamethoxazole SERAX See Oxazepam SEREVENT See Salmeterol SEROPHENE See Clomiphene Serotonin (5-HT), 47, 180, 277-279 autacoid effects of, 275t biosynthesis and release of, 277-278 receptors for metabolites of, 180 reuptake inhibitors of, 229-234, 229f structure of, and antagonist, 297f synthesis and degradation of, 179f Serotonin and norepinephrine reuptake inhibitors (SNRIs), 229-234 adverse effects of, 231t Serotonin (5-HT) receptor(s), 278, 308 activation of, 278 and clinical uses of agonists and antagonists, 278t competitive blockade of, by antipsychotic drugs, 223, 224t in physiology of emesis, 302-305, 303f Serotonin (5-HT) receptor agonists, 278-279, 278t for abortion of migraine headache, 310-311 ergot alkaloids, 310-311 triptan drugs, 311 Serotonin (5-HT) receptor antagonists, 278-279 antiemetic effect of, 304 for prevention of migraine headache, 310 Serotonin syndrome, 233 Sertraline, 230-233 adverse effects of, 231, 231t mechanisms and effects of, 231 pharmacokinetics of, 231 Sevoflurane, 214t, 217 adverse effects of, 215t Sex steroids See Gonadal steroids Shift work sleep disorder, 235 Shingles (herpes zoster), 439, 442 Short-acting insulin preparations, 368, 368t Short-course sequential therapy, 299 Sibutramine, 235 Sickle cell anemia, 469 Signal transduction, 28-30, 29t G protein–coupled receptors in, 28, 29f ligand-gated ion channels in, 28-29 Sildenafil, 60-61 adverse effects of, and interactions, 61 indications for use, 60-61 pharmacokinetics of, 61 for pulmonary hypertension, 282 SILENOR See Doxepin Silodosin, 80-81 SILVADENE See Silver sulfadiazine Silver sulfadiazine, 417-418 indications for use, 419t SIMPONI See Golimumab Simvastatin, 149-151 adverse effects of, 150-151 and interactions, 151 chemistry and pharmacokinetics of, 149, 150t indications for use, 149-150 mechanisms and effects of, 149, 150f SINEMET See Levodopa-carbidopa Single dose pharmacokinetics, 21 SINGULAIR See Montelukast Sirolimus, 478 Sitagliptin, 372-373 Sitagliptin-simvastatin, 373 Skeletal muscle spasms, agents for, 257-258 SKELID See Tiludronate Skin infections, bacterial, 411, 413, 415, 422 Skin patches, 5, Sleep, neurologic basis of, 187 Sleep disorders, 183, 187-189 classification and treatment of, 187-189 other, 189 Sleep patterns, 188 drug effects on, 188 Sleep stages, terminology of, 188b, 188t Sniffing, 268 Sodium channel blockers (Class I antiarrhythmics), 134-137, 136t Class IA, 134-137 disopyramide, 137 procainamide, 137 quinidine, 135 Sodium channel blockers (Class I antiarrhythmics) (Continued) Class IB, 137 Class IC, 137 diuretic action of, 126 electrophysiologic properties of, 134t, 135f, 136t Sodium cromoglycate, 276 Sodium ferric gluconate, 169 Sodium fluoride, 382 Sodium hyaluronate, 316 Sodium iodide (131I), 341 Sodium thiosulfate, 465, 470-471 Soft tissue infections, 405, 413, 415 fungal, 431 SOLGANAL See Aurothioglucose Solifenacin, 65 Solution preparation, SOMA See Carisoprodol Somatic nervous system, 46 neurotransmission in, 47, 47f receptors of, 47-48 Somatostatin, 180, 332 Somatotropin, 332-333 Somatropin, 332 SOMATULINE DEPOT See Lanreotide acetate SOMAVERT See Pegvisomant SONATA See Zaleplon Sorafenib, 475 Sotalol, as Class III antiarrhythmic, 140 Special senses, disorders of, 183 Spermatogenesis, stimulation of, 333 Spermicides, 356-357, 359 Spinal intrathecal anesthesia, 213 Spinosad, 459-460 Spiramycin, 456 SPIRIVA See Tiotropium Spironolactone, 126-127, 349 for heart failure therapy, 116t, 118 for hypertension therapy, 91 SPORANOX See Itraconazole Sporotrichosis, 431 SPRIX See Ketorolac nasal spray STADOL NS See Butorphanol STALEVO See Levodopa-carbidopaentacapone STARLIX See Nateglinide Statins (HMG-CoA reductase inhibitors), 149-151 adverse effects of, 150-151 and interactions, 151 chemistry and pharmacokinetics of, 149, 150t indications for use, 149-150 mechanisms and effects of, 149, 150f Status epilepticus, 198 treatment of, 207 Stavudine, 441t, 445 tahir99-VRG & vip.persianss.ir 516    Index STAVZOR See Valproate STAXYN See Vardenafil Steady state equilibrium, 22, 23f desired, 19b, 22-23 dosage calculations for, 22-23 time required for, 22 Stereospecificity, 26 Sterile solutions, and suspensions, Steroid drug abuse, 268 Stimulant laxatives, 301 Stool softeners, 301 STRATTERA See Atomoxetine Streptogramin antibiotics, 415 Streptokinase, 165-166 Streptomycin, 408-411, 410t indications for use, 410t for tuberculosis therapy, 424-425, 428 Streptozocin, 470 Stroke, treatment of thromboembolisms in, 156 STROMECTOL See Ivermectin Strongyloidiasis, 458 Strontium ranelate, 382 Structure-activity relationship, Subcutaneous administration, of drugs, Subcutaneous mycoses, 431 SUBLIMAZE See Fentanyl Sublingual administration, of drugs, SUBOXONE See Buprenorphine Substance abuse disorder, 261 Substance P, 47, 180, 238-240 in pathogenesis of migraine headaches, 307-308 in physiology of emesis, 305 SUBUTEX See Buprenorphine Succinylcholine, 66t, 67-68 Sucralfate, 298 SUDAFED See Pseudoephedrine SUFENTA See Sufentanil Sufentanil, 218, 243-244 Sugammadex, 67 Sulbactam, 403-404 Sulbactam-ampicillin, 401, 404 indications for use, 402, 402t Sulfacetamide, 418 indications for use, 419t pharmacokinetics of, 418t Sulfadiazine, 417-418 Sulfamethoxazole, 417 Sulfasalazine for inflammatory bowel disease, 299 for rheumatoid arthritis, 324 Sulfinpyrazone, 324-325 Sulfisoxazole, 417 Sulfonamides, 417-418 adverse effects of, 418 bacterial resistance to, 417-418 Sulfonamides (Continued) chemistry of, and pharmacokinetics, 417, 418t spectrum of, and indications for use, 417-418, 419t Sulfones, for leprosy treatment, 428-429 Sulfonylurea drugs, 369-371, 369t, 374 adverse effects of, 370 and interactions, 370-371 indications for use, 370 mechanisms and effects of, 369-370 metabolic effects of, 369t pharmacokinetics of, 369 Sulfotransferases, 14 Sulindac, 320-321 Sumatriptan, 278, 278t, 311 adverse effects of, and interactions, 311 mechanism of action of, 311 pharmacokinetics and effects of, 311 Sunitinib, 475 SUPARTZ See Sodium hyaluronate Superficial infections, 411, 413, 415 Superficial mycoses, 431 Suppositories, SUPPRELIN See Histrelin SUPRANE See Desflurane Supraventricular tachycardia, 141-142 Suramin, 457 Surfactant laxatives, 301 SURFAK See Docusate Suspension preparation, Sustained-release products, 5, 5f SUSTIVA See Efavirenz Switch phenomenon, 235 SYMBICORT See Budesonide-formoterol SYMLIN See Pramlintide SYMMETREL See Amantadine Sympathetic nervous system, 46 and effect on organs, 48f neurotransmission in, 50 drug effects on, 50-51 Sympatholytic drugs See also Adrenoceptor antagonists; Centrally acting sympatholytics for hypertension, 91-93 Sympathomimetic drugs, 71, 133 SYNAREL See Nafarelin SYNERCID See Quinupristin-dalfopristin Synergistic effects, of drug interactions, 39-40, 464 Synesthesia, 267 Synthetic drugs, SYNTHROID See Levothyroxine Syrups, Systemic mycoses, treatment of, 431 T Tablet preparation, Tachykinins, 180 Tachyphylaxis, 30 Tacrine, 254t, 256 Tacrolimus, 478 Tacrolimus-mycophenolate, 478 Tadalafil, 60-61 adverse effects of, and interactions, 61 indications for use, 60-61 pharmacokinetics of, 61 TAGAMET See Cimetidine TALWIN See Pentazocine TAMBOCOR See Flecainide TAMIFLU See Oseltamivir Tamoxifen, 360, 477 Tamsulosin, 80-81 TAPAZOLE See Methimazole Tapentadol, 245 Tapeworm infections, 459 Tardive dyskinesia, 223-224, 226 Targeted anticancer drugs, 463 antineoplastic monoclonal antibodies, 475-476 antineoplastic mTOR inhibitors, 476 protein kinase inhibitors, 474-475 Targeted chemotherapy, 463 TASMAR See Tolcapone Taurine receptors, of central nervous system, 176 Taxanes, 474 Tazobactam, 403-404 Tazobactam-piperacillin, 404 indications for use, 402, 402t TEFLARO See Ceftaroline Tegaserod, 278, 301-302 TEGRETOL See Carbamazepine TEKTURNA See Aliskiren Telaprevir, 449 Telavancin, 406 Telithromycin, 410t, 414 indications for use, 410t Telmisartan, 97 Temazepam, 193 See also Benzodiazepines Temozolomide, 471 Temporal lobe epilepsy, 198 Temsirolimus, 476, 478 Tenecteplase, 165-166 Teniposide, 473 Tenofovir disoproxil, 441t, 443-445 TENORMIN See Atenolol TENSILON See Edrophonium Tension headache, 308t, 312 Teratogenic effects, 42-43, 43t Terazosin, 79-81 Terbinafine, 432t, 434t, 436 Terbutaline, 75 chemistry and pharmacokinetics of, 75 tahir99-VRG & vip.persianss.ir Index    517 Terbutaline (Continued) indications for use, 75 mechanisms and effects of, 73t, 75 for respiratory disorders, 289-290, 289t Terfenadine, 277 Teriparatide, 382 Testicular cancer, drugs used for, 472t Testosterone, 351-354, 360-361 biosynthesis of, 351, 352f and derivatives, 361 physiologic actions of, 354 TESTRED See Methyltestosterone Tetrabenazine, antichorea effect of, 255 Tetracaine, 213-214 Tetracycline, 410t, 411-412 Tetracycline antibiotics, 411-413 adverse effects of, 413 bacterial resistance to, 412-413 chemistry of, and pharmacokinetics, 410t, 411-412 sites of action of, 408 spectrum of, and indications for use, 410t, 412 Tetrahydrogestrinone, 361 Thalidomide, 425t, 429 antineoplastic effect of, 477 THALITONE See Chlorthalidone THALOMID See Thalidomide THEOLAIR See Theophylline Theophylline, 276 and caffeine, for recurrent apnea in premature infants, 292 for respiratory disorders, 291-292 adverse effects, 292 chemistry, mechanisms, and effects, 291 efficacy, 285t indications for use, 291-292 interactions, 292 pharmacokinetics, 291 Therapeutic index (TI), 31-32 Therapeutic lifestyle changes, 148-149 Thiazide diuretics, 122t adverse effects of, and interactions, 121-124, 124t, 125f chemistry and pharmacokinetics of, 121 dose-response curve of, 126f for hypertension, 90-91, 93f, 121-125 indications for use, 124 mechanisms and effects of, 121 and related compounds, 125 Thiazolidinediones, 371-372 adverse effects of, 372 chemistry and pharmacokinetics of, 371 indications for use, 372 mechanisms and effects of, 371-372 Thioamide drugs, 339-340 adverse effects of, 340 indications for use, 340 mechanisms of, 339-340 pharmacokinetics of, 340 Thioguanine, 468 Thiopental, 194 for induction of anesthesia, 218, 218t Thioridazine, 225-227 adverse effects of, 225-226, 225t treatment of, 227 mechanisms and effects of, 225 pharmacokinetics of, 225 and interactions, 226t, 227 Thiothixene, 225t-226t Thrombin clotting time (TT), 162 Thromboembolism, and thromboembolic disorders, 156 See also Anticoagulant drugs; Antiplatelet drugs; Fibrinolytic drugs Thromboxane(s), 280 Thromboxane A2, 280 autacoid effects of, 275t Thrombus formation, pathologic, 156 THYROGEN See Thyrotropin alfa Thyroglobulin, 336 Thyroid cancer, 333, 339 Thyroid dessicated, 337-339 Thyroid disorders, 336-337 Thyroid drugs, 336 antithyroid agents, 339-341 summary of important points, 341 thyroid hormone preparations, 337-339 Thyroid hormone synthesis, and sites of drug action, 336, 338f Thyroid nodules, 339 THYROLAR See Liotrix Thyrotoxicosis, 340 Thyrotropin, 333 Thyrotropin alfa, 333 Tiagabine, 199, 202t, 206 Ticagrelor, 164 Ticarcillin, 399, 401t Ticarcillin-clavulanate, 404 TICLID See Ticlopidine Ticlopidine, 164 Tigecycline, 410t, 411-413 indications for use, 410t TIKOSYN See Dofetilide Tiludronate, 380-381 adverse effects of, 380 and interactions, 380 chemistry and pharmacokinetics of, 380 indications for use, 380-381 mechanisms and effects of, 380 TIMENTIN See Clavulanate-ticarcillin TIMOLIDE See Timolol Timolol, 81 clinical uses of, 83-84, 310 TIMOPTIC See Timolol TINACTIN See Tolnaftate TINDAMAX See Tinidazole Tinea infections, 431 Tinidazole, 454 Tinzaparin, 160-161 Tiotropium, 65, 290-291 Tirofiban, 165 TITRALAC See Calcium carbonate Tizanidine, antispastic effect of, 258 Tmax (maximum time), 17-18, 19f TMP-SMX See Trimethoprim-sulfamethoxazole TNKASE See Tenecteplase Tobramycin, 347, 408-411, 410t indications for use, 410t Tocilizumab, 324 TOFRANIL See Imipramine Tolcapone, 253 Tolerance drug, 30 pharmacodynamic, 242-243 pharmacokinetic, 266 Tolnaftate, 434t, 437 mechanism of action of, 432t, 433 Tolterodine, 65 Tolvaptan, 128, 334 TOPAMAX See Topiramate Topical administration, of drugs, Topical anesthesia, 213 Topical steroids, 348 TOPICORT See Desoximetasone Topiramate, 199, 205-206 adverse effects of, 202t and interactions, 203t mechanisms and effects of, 199, 201t Topoisomerase(s), 419-420, 473 Topoisomerase mutations, 464 See also DNA topoisomerase inhibitors Topotecan, 473 TORADOL See Ketorolac Torsades de pointes, 133 management of, 142 Torsemide, 126 for heart failure, 118 131 I-tositumomab, 475-476 Toxicology, Toxoplasmosis, 456 TRACLEER See Bosentan Trade name, of drug, TRADJENTA See Linagliptin Tramadol, 244-245, 247 for migraine termination, 311 TRANDATE See Labetalol Tranexamic acid, 166 TRANSDERM-NITRO See Nitroglycerin tahir99-VRG & vip.persianss.ir 518    Index TRANSDERM SCOP See Scopolamine Transdermal administration, of drugs, Transdermal contraceptive, 357t, 358 Transdermal estradiol systems, 354 Transdermal fentanyl skin patch, 247 Transdermal patch, 214 Transferrin, 168 TRANXENE See Clorazepate Tranylcypromine, 232 adverse effects of, 231t Trastuzumab, 476 TRAVATAN See Travoprost Travoprost, 281 Trazodone, 233-234 adverse effects of, 231t TRELSTAR See Triptorelin Trematode infections, 457-459 treatment of, 453t, 459 Treprostinil, 281 TRI-NORINIL See Oral contraceptives (estrogen-progestin) Triamcinolone, 285-287, 346 topical preparation, 348 Triamterene, 126 for hypertension, 91 Triazolam, 193-194 See also Benzodiazepines Trichinosis, 458 Trichomoniasis, 452 Triclabendazole, 459 TRICOR See Fenofibrate Tricyclic antidepressants (TCAs), 230 adverse effects of, 230, 231t treatment of, 230 for chronic pain, 247 indications for use, 230 mechanisms and effects of, 230 for migraine headache prevention, 309 pharmacokinetics of, 230 Trifluoperazine, 226t adverse effects of, 225t Trifluridine, 442, 442t Trigeminal neuralgia, 238, 246-247 Trihexyphenidyl, 255 TRILAFON See Perphenazine TRILEPTAL See Oxcarbazepine Trimetazidine, for angina pectoris, 107 Trimethoprim, 418, 418t Trimethoprim-sulfamethoxazole (TMP-SMX), 418-419 adverse effects of, 419 pharmacokinetics of, 418-419, 418t for Pneumocystis jiroveci infection, 456-457 spectrum of, and indications for use, 419, 419t Triptan drugs, 311-312 adverse effects of, and interactions, 311 mechanism of action of, 311 pharmacokinetics and pharmacologic effects of, 311 Triptorelin, 333 TRIVORA See Oral contraceptives (estrogen-progestin) Trophoblastic tumors, 473 Tropicamide, 66 Trospium, 65 TRUSOPT See Dorzolamide Trypanosomiasis, 457 Tuberculosis, 424 drug resistant, 421 drugs for, 424-428 ethambutol, 427 isoniazid, 425-427 new, 428 pyrazinamide, 427 rifampin, 427-428 rifapentine, rifabutin, 428 streptomycin, amikacin, 428 latent, treatment of, 427 presentation and treatment of, 425b, 426t Tumor lysis syndrome, 468 Tumor necrosis factor-alpha blocking agents, 323 Tumor suppressor genes, 464 TUMS See Calcium carbonate TYGACIL See Tigecycline TYLENOL See Acetaminophen TYLENOL WITH CODEINE #3 See Acetaminophen with codeine Type phosphodiesterase inhibitors, 60-61 adverse effects of, and interactions, 61 indications for use, 60-61 pharmacokinetics of, 61 Tyramine, 76 Tyrosine kinase associated receptors, 29 TYSABRI See Natalizumab U Ulcerative colitis, 287, 299, 347 ULORIC See Febuxostat ULTANE See Sevoflurane ULTIVA See Remifentanil ULTRAM See Tramadol UNASYN See Sulbactam-ampicillin United States Adopted Name (USAN), United States Pharmacopoeia (USP), drug product standards, 36 Unstable angina, 102, 103t treatment of, 108, 161 Up-regulation, of drug receptors, 30 URECHOLINE See Bethanechol Uric acid metabolism, and sites of drug action, 324f Uricase, 324f, 325, 468 Uricosuric drugs, 324-325 Urinary tract infections, 406, 419, 421 fungal, 417 Urokinase, 165 UROXATRAL See Alfuzosin V Vaginal ring contraceptive, 357t Vaginosis, 454 Valacyclovir, 440-442, 442t VALCYTE See Valganciclovir Valdecoxib, 321 Valganciclovir, 442, 442t VALIUM See Diazepam Valproate, 204-205 adverse effects of, 202t and interactions, 203t, 204-205 indications for use, 205 migraine prophylaxis, 204, 309 mood stabilization, 234-235 mechanisms and effects of, 199, 201t, 204 pharmacokinetics of, 204 Valproic acid, 204-205 See also Valproate Valsartan, 95t, 97, 117 VALTREX See Valacyclovir VANCOCIN See Vancomycin Vancomycin, 401t, 406 indications for use, 402t sites of action of, 398, 399f Vancomycin-resistant bacteria, antibiotics effective against, 422 VAPRISOL See Conivaptan Vardenafil, 60-61 adverse effects and interactions of, 61 indications for use, 60-61 pharmacokinetics of, 61 Varenicline, 55t, 57 for nicotine dependence, 269 Variant angina, 102-103, 103t Varicella zoster virus, 439 See also Chickenpox; Shingles Vascular endothelial cell dysfunction, 88 Vascular smooth muscle contraction, regulation of, 105f Vascular smooth muscle receptors, 334 Vasoactive intestinal polypeptide, 47, 180 Vasodilators, 97-98 for angina pectoris, 103-107 angiotensin inhibiting, 93-97 See also Angiotensin receptor antagonists tahir99-VRG & vip.persianss.ir Index    519 Vasodilators (Continued) antiplatelet action of dipyridamole, 164 β-adrenoceptor antagonist, 81-84, 107 See also β-adrenoceptor antagonists calcium channel blocking, 105-107 See also Calcium channel blockers for heart failure, 116-117 for hypertension, 97-98 organic nitrites and nitrates, 103-105 Vasopressin, and related drugs, 334 Vasospasm, 156, 157f VASOTEC See Enalapril Vecuronium, 66-67, 66t Vemurafenib, 475 Venlafaxine, 231t, 232 Venous thromboembolism, 156, 159t, 160-162 VENTOLIN See Albuterol Ventricular tachycardia and fibrillation, 142 Verapamil, 106t for angina pectoris, 106-107 as Class IV antiarrhythmic, 140 for cluster headache, 312 for hypertension, 97-98 for migraine prophylaxis, 310 Vernal conjunctivitis, 287 Vernal keratitis, 287 VERSED See Midazolam Very low density lipoproteins, 145 VESICARE See Solifenacin VFEND See Voriconazole VIAGRA See Sildenafil VIBATIV See Telavancin VIBRAMYCIN See Doxycycline VIBRYD See Vilazodone VICODIN See Hydrocodone VICTOZA See Liraglutide VICTRELIS See Boceprevir VIDEX See Didanosine Vigabatrin, 202t, 206 Vilazodone, 233-234 VIMOVO See Naproxen-esomeprazole VIMPAT See Lacosamide Vinblastine, 473-474 Vinca alkaloids, 473-474 Vincristine, 473-474 Vinorelbine, 474 Viral infections, 439 Viral resistance to nonnucleoside reverse transcriptase inhibitors, 445 to nucleoside analogues, 440 to nucleoside reverse transcriptase inhibitors, 444 to protease inhibitors, 446 Viral rhinitis, 285, 293 VIRAMUNE See Nevirapine VIRAZOLE See Ribavirin VIREAD See Tenofovir disoproxil VIROPTIC See Trifluridine VISKEN See Pindolol VISTIDE See Cidofovir Vitamin B3 See Niacin Vitamin B12, 170-171 biochemical reactions involving folic acid and, 170, 171f structure of, 170f Vitamin D, 376-379 adverse effects of, and interactions, 379 chemistry and pharmacokinetics of, 379 indications for use, 379 recommended dietary allowances for, 377t synthesis of, 378f Vitamin D preparations, 379 Vitamin D2 See Ergocalciferol Vitamin D3 See Cholecalciferol Vitamin K agonist See Warfarin Vitamin K1 See Phytonadione VIVITROL See Naltrexone Voltage sensitive sodium channels, 199 VOLTAREN GEL See Diclofenac Volume of distribution (Vd), 18-20 calculation of, 18-19, 20f in drug dosage calculations, 19b interpretation of, 19-20 von Willebrand disease, 334 Voriconazole, 432t, 434t, 435-436 VYVANSE See Lisdexamfetamine W Warfarin, 157-160 adverse effects of, and interactions, 158, 159t chemistry and mechanisms of, 157-158, 158f indications for use, 159-160 management of bleeding caused by, 160 pharmacokinetics and pharmacologic effects of, 158 WELCHOL See Colesevelam WELLBUTRIN See Bupropion Whipworm infection, 458 Wilms tumor, 473 Wolff-Parkinson-White syndrome, 133, 141 X XALATAN See Latanoprost XANAX See Alprazolam Xanthine oxidase inhibitors, 325 XARELTO See Rivaroxaban XENAZINE See Tetrabenazine XGEVA See Denosumab XIFAXAN See Rifaximin XOLAIR See Omalizumab XOPENEX See Levalbuterol XYLOCAINE See Lidocaine XYZAL See Levocetirizine Y YASMIN See Oral contraceptives (estrogen-progestin) Yeast infections, 431 YODOXIN See Iodoquinol Z ZADITOR See Ketotifen Zafirlukast, 287-288 adverse effects of, and interactions, 288 mechanisms of, 287 pharmacokinetics of, 287 pharmacologic effects of, and indications for use, 287-288 Zaleplon, 195 ZANAFLEX See Tizanidine Zanamivir, 441t, 447-448 ZANTAC See Ranitidine ZARONTIN See Ethosuximide ZAROXOLYN See Metolazone ZDV See Zidovudine ZEBETA See Bisoprolol ZELNORM See Tegaserod ZEMURON See Rocuronium ZERIT See Stavudine Zero order elimination, 319 Zero order kinetics, 21 ZETIA See Ezetimibe ZIAGEN See Abacavir Zidovudine, 441t, 444-445 Zileuton, 288 adverse effects of, and interactions, 288 pharmacologic effects of, and indications for use, 288 ZINACEF See Cefuroxime Ziprasidone, 227-228 ZIPSOR See Diclofenac ZITHROMAX See Azithromycin ZOCOR See Simvastatin ZOFRAN See Ondansetron ZOLADEX See Goserelin Zoledronic acid, 380-381 adverse effects of, 380 and interactions, 380 chemistry and pharmacokinetics of, 380 indications for use, 380-381 mechanisms and effects of, 380 Zollinger-Ellison syndrome, 298 Zolmitriptan, 311 adverse effects of, and interactions, 311 mechanism of action of, 311 tahir99-VRG & vip.persianss.ir 520    Index Zolmitriptan (Continued) pharmacokinetics and pharmacologic effects of, 311 ZOLOFT See Sertraline Zolpidem, 195 ZOMETA See Zoledronic acid ZOMIG See Zolmitriptan ZONEGRAN See Zonisamide Zonisamide, 199, 202t, 206 ZOSYN See Tazobactam-piperacillin ZOVIRAX See Acyclovir ZYBAN See Bupropion ZYFLO See Zileuton ZYLET See Loteprednol-tobramycin ZYLOPRIM See Allopurinol ZYMAR See Gatifloxacin ZYPREXA See Olanzapine ZYRTEC See Cetirizine ZYVOX See Linezolid tahir99-VRG & vip.persianss.ir ... Gastrointestinal Tract Disorders     29 7 CH2 N CH2 NH2 HO N CH2 CH2 NH2 N Histamine Serotonin O CH3 N CH2SCH2CH2N HN N CH2 CNHCH3 C N N H3C N N CH3 Cimetidine Ondansetron Figure 28 -2.   Structures of histamine... Ca2+-calmodulin complex PDE cAMP Ca2+ Selective β2adrenoceptor agonists ATP Ca2+ L-type calcium channel Sarcoplasmic reticulum + + 2- adrenoceptor Ca2+ IP3 Adenylyl cyclase Phospholipase C PIP2... puffs every 4-6 hours Formoterol 12 inhalation every 12 hours Indacaterol 15 >24 inhalation every 24 hours 5 puffs every 4-6 hours Salmeterol 20 12 puffs every 12 hours Terbutaline 5-15 DRUG Pirbuterol