Chapter 22 Outline. Chapter 22: Respiratory and Gastrointestinal Drugs. Respiratory Drugs. Asthma. Respiratory Diseases 12/12/2011

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1 Chapter 22 Outline Chapter 22: Respiratory and Gastrointestinal Drugs Respiratory and gastrointestinal (GI) drugs Respiratory drugs Drugs used to treat respiratory diseases GI drugs Drugs used to treat GI diseases 2 Respiratory and Gastrointestinal Drugs Respiratory Drugs Haveles (pp ) (Fig. 22-1) Medications given to treat these diseases can affect dental treatment The dental health care worker should be aware of The effect of these drugs on the patient How these drugs may alter the treatment plan Haveles (pp ) (Fig. 22-2) Respiratory diseases treated include asthma, chronic obstructive pulmonary disease (COPD), and upper respiratory tract infections Treated with a wide range of drug groups, from adrenergic drugs for bronchodilation to corticosteroids for reducing inflammation 3 4 Respiratory Diseases Asthma Haveles (pp ) Haveles (pp ) Characterized by reversible airway obstruction and associated with a reduction in expiratory airflow May be precipitated by allergens, pollution, exercise, stress, or upper respiratory tract infection In status asthmaticus, patients have persistent lifethreatening bronchospasm despite drug therapy Signs of asthma include shortness of breath and wheezing Noninfectious respiratory diseases are divided into asthma and COPD COPD is divided further into chronic bronchitis and emphysema Other respiratory problems are related to viral or bacterial respiratory infections 5 6 1

2 Chronic Obstructive Pulmonary Disease Haveles (p. 278) Irreversible airway obstruction; occurs with either chronic bronchitis or emphysema Chronic bronchitis is a result of chronic inflammation of the airways and excessive sputum production Emphysema is characterized by alveolar destruction with airspace enlargement and airway collapse Chronic Obstructive Pulmonary Disease For a normal person, breathing is stimulated by elevated partial pressure of carbon dioxide (PaCO 2 ) For a person with COPD, breathing is stimulated by a decrease in partial pressure of oxygen (PaO 2 ) If this person is given oxygen, the stimulus to breathing may be removed, and the possibility of inducing apnea occurs 7 8 Drugs Used to Treat Respiratory Diseases Haveles (pp ) Metered-dose inhalers Sympathomimetic agents Corticosteroids Leukotriene modifiers Methylxanthines Anticholinergics Anti immunoglobulin E (IgE) antibodies Agents used to manage upper respiratory tract infections Dental implications of the respiratory drugs Metered-Dose Inhalers Haveles (p. 279) (Fig. 22-5) Advantages include It delivers medication directly into the bronchioles Bronchodilator effect is greater than comparable oral dose Inhaled dose can be accurately measured Rapid and predictable onset of action Compact, portable, and sterile 9 10 Sympathomimetic Agents Short-Acting β 2 -Agonists Haveles (p. 279) Produce bronchodilation by stimulation of β- receptors in the lungs β-receptor activation results in accumulation of cyclic adenosine monophosphate (camp) in smooth muscles, producing a reduction in cytoplasmic calcium concentration and relaxation of smooth muscle Selective β 2 -agonists produce bronchodilation with fewer cardiac side effects Haveles (p. 279) (Fig. 22-3; Table 22-1) Have specificity for the respiratory tree Side effects include nervousness, tachycardia, and insomnia Short-acting β 2 -agonists such as albuterol, may be administered by inhalation or orally The first line of treatment for mild occasional asthma is a short-acting β 2 -agonist Short-acting β 2 -agonists are the drug of choice for the emergency treatment of an acute asthma attack

3 Short-Acting β 2 -Agonists Haveles (p. 279) (Fig. 22-3) Recent studies have found that overuse results in airway hyperresponsiveness and a decrease in the lung s response to them Many asthmatics rely on the albuterol inhaler and omit using the steroid inhaler U.S. Food and Drug Administration (FDA)-Approved Drugs Used to Adrenergic agonists (inhaler) β 2 -Agonist Short-acting; used for an acute attack albuterol (Proventil, Ventolin) metaproterenol (Alupent, Metaprel) levalbuterol (Xopenex HFA) pirbuterol (Maxair Autohaler) Long-Acting β 2 -Agonists Haveles (pp ) (Fig. 22-1) A newer long-acting β 2 -agonist is salmeterol (Serevent) Onset is delayed and duration of action is sustained Not used for management of an acute asthmatic episode Adrenergic agonists (inhaler) β 2 -Agonist Long-acting salmeterol (Serevent Diskus) formoterol (Foradil Aerolizer) Haveles (p. 281) Corticosteroids Typical side effects seen with corticosteroid therapy do not occur with topical aerosol administration Patients have a significant improvement in pulmonary function with a decrease in wheezing, tightness, and cough Reduce inflammation, secretions and swelling in the lungs after an asthma attack Prolonged inhalation may cause candidiasis Adrenergic agonists (inhaler) Corticosteroids Corticosteroids, inhaled beclomethasone (QVAR) budesonide (Pulmicort) ciclesonide (Alvesco) flunisolide (AeroBid) fluticasone (Flovent HFA) mometasone furoate (Asmanex Twisthaler) triamcinolone (Azmacort)

4 Adrenergic agonists (inhaler) Corticosteroids Corticosteroids, oral prednisone (Deltasone, Meticorten)[PO] Adrenergic agonists (inhaler) Inhaled corticosteroids/long-acting β 2 -agonists Corticosteroid/β 2 -agonist fluticasone/salmeterol (Advair HFA) budesonide/formoterol (Symbicort HFA) Leukotriene Modifiers Leukotriene Modifiers Haveles (pp ) Overview: leukotrienes (LTs) are produced by inflammatory cells and produce bronchoconstriction, increased mucus secretion, mucosal edema, and increased bronchial hyperreactivity Leukotriene pathway inhibitors block the effects of the release of LTs Used to manage asthma not controlled by β 2 -agonists and corticosteroid inhalers Adverse reactions include irritation of stomach mucosa, headache, and alteration of liver function tests Zafirlukast has an interaction with erythromycin and aspirin Increases the effect of warfarin Cromolyn LT antagonists LT pathway antagonist zafirlukast (Accolate) (PO) montelukast (Singulair) LT pathway synthesis inhibitor (LPI) zileuton (Zyflo) (PO) Haveles (p. 282) Used only for prophylaxis of asthma and not an acute asthma attack Prevents the antigen-induced release of histamine, LTs, and other substances from sensitized mast cells The least toxic of all asthma medications May be used prophylactically by patients with chronic asthma or taken before exercise-induced asthma

5 Mast cell degranulation inhibitors Mast cell stabilizers cromolyn (Intal) (Nasalcrom) IH nedocromil (Tilade) Haveles (p. 282) Methylxanthines Consist of theophylline, caffeine, and theobromine Theophylline is used to treat chronic asthma and the bronchospasm associated with chronic bronchitis and emphysema Mechanism of action of xanthines is complex Involves antagonism of the receptor mediated action of adenosine, inhibition of cyclic nucleotide phosphodiesterase, mobilization of intracellular calcium pools, protein kinase activity modulation, and inhibition of prostaglandins (PGs) Methylxanthines Side effects include central nervous system (CNS) stimulation, cardiac stimulation, increased gastric secretion, and diuresis Erythromycin can increase the serum levels of theophylline Intravenous aminophylline and rapidly absorbed oral liquid preparations are used to manage acute asthmatic attacks and status asthmaticus Methylxanthines Methylxanthines theophylline (Theo-Dur, Slo-Bid) (PO) aminophylline-theophylline ethylene diamine Haveles (p. 282) Anticholinergics Atropine is an old remedy for asthma; newer anticholinergics have fewer side effects; ipratropium (Atrovent) has several advantages over atropine Low lipid solubility limits its bioavailability and makes it bronchoselective, with minimal side effects The drug of choice for long-term management of COPD; also for patients with poorly controlled asthma or those who do not tolerate the side effects of β-agonists Anti Immunoglobulin E Antibodies Haveles (p. 282) omalizumab (Xolair) is the first in a new class of medications introduced to treat asthma due to allergens A recombinant humanized monoclonal antibody Prevents IgE from binding to mast cells and basophils

6 Agents Used to Manage Upper Respiratory Tract Infections Nasal Decongestants Haveles (pp ) Nasal decongestants Expectorants and mucolytics Antitussives Haveles (pp. 44, 282) (Table 4-5) Adrenergic agonists that act by constricting blood vessels in nasal mucous membranes Chronic use may result in rebound swelling and congestion phenylephrine (Neo-Synephrine, Sinex, Allerest) (α) is used topically as a nasal spray phenylpropanolamine is used systemically as a decongestant (α-agonist action) pseudoephedrine (Sudafed, Sucrets, in Actifed) (α/β) is used systemically Expectorants and Mucolytics Antitussives Haveles (pp ) Haveles (p. 283) Expectorants promote removal of exudate or mucus from respiratory passages Liquefying expectorants decrease the viscosity of mucus Mucolytics destroy or dissolve mucus May be opioids or related agents used for symptomatic relief of nonproductive cough Codeine-containing cough preparations are commonly used, but their histamine-releasing properties may precipitate bronchospasm Dextromethorphan, an opioid-like compound, suppresses the cough reflex by its direct effect on the cough center It does not cause release of histamine Dental Implications of the Respiratory Drugs Gastrointestinal Drugs Haveles (p. 283) (Box 22-1) About 10% of the population has some form of pulmonary disease With severe COPD, a person can develop pulmonary hypertension, increasing the risk for cardiac arrhythmias Stress should be minimized and adrenal supplementation instituted if the patients are taking certain doses of steroids and the procedure is likely to produce severe stress Haveles (pp ) Both over-the-counter and prescription drugs are used for GI diseases Some are used for specific diseases, others are for symptomatic relief

7 Gastrointestinal Diseases Haveles (p. 283) Ulcers and gastroesophageal reflux disease (GERD) are common GI diseases The GI tract is highly susceptible to emotional changes because it is innervated by the vagus nerve associated with the autonomic nervous system Gastroesophageal Reflux Disease Haveles (p. 283) GERD, or heartburn, is the most prevalent GI disease in the U.S. population Stomach contents flow back up into the esophagus Irritation, inflammation, and erosion can occur Gastroesophageal Reflux Disease Treated by decreasing the acid in the stomach or by constricting the cardiac sphincter Histamine 2 (H 2 )-blockers and proton-pump inhibitors (PPIs) reduce or eliminate stomach acid GI stimulants increase the tone in the cardiac sphincter Antacids are used for relief of acute symptoms Haveles (pp ) Ulcers May occur in the stomach or small intestine Most ulcers are related to the presence of Helicobacter pylori Many can be cured by using a combination of one or more antibiotics and an H 2 -blocker or a PPI to reduce the stomach acid Some are related to chronic use of nonsteroidal antiinflammatory drugs (NSAIDs) because NSAIDs inhibit synthesis of PGs, which are cytoprotective to the stomach Treatment is a PG (PGE 2α ) misoprostol (Cytotec) Drugs Used to Treat Gastrointestinal Diseases Histamine 2 -Blocking Agents Haveles (pp ) H 2 -blocking agents PPIs Mixed antiinfective therapy for ulcer treatment Antacids Miscellaneous GI drugs Laxative and antidiarrheals Antiemetics Agents used to manage chronic inflammatory bowel disease Block and inhibit gastric acid secretion by competitive inhibition of histamine at the H 2 - receptors of parietal cells cimetidine (Tagamet) is the prototype

8 Uses of Cimetidine Adverse Reactions of Cimetidine Haveles (pp ) Indicated for treatment of ulcers and management of symptoms of ulcers and GERD Antacids inhibit absorption and should not be administered within 1 hour of H 2 -blockers Cimetidine is also used as an adjunct in management of urticaria Haveles (p. 285) Side effects include CNS effects such as slurred speech, delusions, confusion, and headache Cimetidine binds with androgen receptors; ranitidine and famotidine have not been found to possess antiandrogenic activity Cimetidine inhibits liver microsomal enzymes responsible for hepatic metabolism of some drugs (cytochrome P-450 oxidase system), resulting in a delay in elimination and an increase in serum levels of some drugs Dental Drug Interactions of Cimetidine Haveles (p. 285) Metabolism of these may be reduced by cimetidine Ketoconazole and itraconazole: concurrent administration with H 2 -receptor antagonists may result in a marked reduction of absorption Alcohol: cimetidine may raise blood alcohol level if the person has ingested alcoholic beverages Benzodiazepines: metabolism may be slower Other H 2 -receptor antagonists Other H 2 -blockers are unlikely to produce important dental drug interactions Drugs Used to Treat Peptic Ulcer Disease and Gastroesophageal Reflux Disease Acid reducers H 2 -blockers cimetidine (Tagamet) famotidine (Pepcid) ranitidine (Zantac) nizatidine (Axid) Proton-Pump Inhibitors Haveles (p. 285) omeprazole (Prilosec) was the first PPI marketed and is the prototype Inhibitor of gastric acid secretion, heals both gastric and duodenal ulcers, and is approved for GERD Inhibits the H + /K + ATPase enzyme system at the surface of the gastric parietal cell Side effects of omeprazole include headache and abdominal pain Mucosal atrophy of the tongue and dry mouth have been reported Drugs Used to Treat Peptic Ulcer Disease and Gastroesophageal Reflux Disease Acid reducers PPIs omeprazole (Prilosec) lansoprazole (Prevacid) esomeprazole (Nexium) pantoprazole (Protonix) rabeprazole (AcipHex)

9 Mixed Antiinfective Therapy for Ulcer Treatment Haveles (p. 285) To treat ulcers, a combination of two or three antiinfective agents, an acid reducer, an H 2 - blocker or a PPI, and bismuth subsalicylate (Pepto-Bismol) may be used Newer combinations often use one antibiotic and a PPI, such as esomeprazole and clarithromycin Haveles (pp ) Antacids Acute gastritis (heartburn) and symptoms of ulcers are sometimes managed with antacids Partially neutralize hydrochloric acid in the stomach By raising the ph to 3 or 4, the erosive effect of the acid is decreased and pepsin activity is reduced Antacids Classified as systemic or nonsystemic, depending on the amount of absorption from the GI tract Sodium bicarbonate is the only systemic antacid Alkalosis can occur It also contains sodium and is contraindicated in cardiovascular patients who are to minimize sodium intake Active ingredients in nonsystemic antacids include calcium carbonate, aluminum and magnesium salts, and magnesium-aluminum hydroxide gels Drugs Used to Treat Peptic Ulcer Disease and Gastroesophageal Reflux Disease Antacids Sodium bicarbonate Magnesium hydroxide Aluminum hydroxide Calcium carbonate Miscellaneous Gastrointestinal Drugs Miscellaneous Gastrointestinal Drugs Haveles (p. 286) Haveles (p. 286) metoclopramide (Reglan): a dopaminergic antagonist Facilitates cholinergic effects in the GI tract Stimulates motility of upper GI tract without stimulating secretions Increases motility in the duodenum and results in accelerated gastric emptying time simethicone (Mylicon, Gas-X): used to relieve flatulence misoprostol (Cytotec) is prostaglandin PGE 2α and is indicated for NSAID-induced ulcers Increases gastric mucus and inhibits gastric acid secretion sucralfate (Carafate): used to treat duodenal ulcers Combines with proteins, forming a complex that binds preferentially with the ulcer site

10 Laxatives and Antidiarrheals Haveles (pp ) Laxatives: indicated for short-term, occasional use for constipation and before diagnostic procedures (barium enema) Bulk laxatives: contain polysaccharides or cellulose derivatives that combine with intestinal fluids to form gels Lubricants: mineral oil is no longer recommended; can be absorbed and interfere with absorption of fat-soluble vitamins Stimulants: produce local irritation of intestinal mucosa Stool softeners (emollients): wets and softens stool by accumulating water in the intestine Osmotic (saline) laxatives: osmotically hold water Drugs Used to Treat Peptic Ulcer Disease and Gastroesophageal Reflux Disease Laxatives Bulk psyllium seed (Metamucil) carboxymethylcellulose methylcellulose (Citrucel) polycarbophil (FiberCon) Stool softeners, emollient docusate (dioctyl sodium sulfosuccinate, DSS, Colace) Drugs Used to Treat Peptic Ulcer Disease and Gastroesophageal Reflux Disease Laxatives Stimulants magnesium hydroxide (Milk of magnesia [MOM]) bisacodyl (Dulcolax) cascara sagrada senna casanthranol castor oil phenolphthalein Drugs Used to Treat Peptic Ulcer Disease and Gastroesophageal Reflux Disease Laxatives Hyperosmotic glycerin lactulose salts (magnesium citrate, hydroxide, oxide, or sulfate; sodium phosphate) Laxatives and Antidiarrheals Drugs Used to Treat Other Gastrointestinal Disorders Haveles (p. 287) Antidiarrheals: either adsorbents or opioidlike drugs, used to minimize fluid and electrolyte imbalances The most common absorbent is kaolin and pectin (Kaopectate) Opioids, such as diphenoxylate with atropine (Lomotil) and loperamide (OTC Imodium), are the most effective antidiarrheal agents Decrease peristalsis by acting directly on smooth muscle of the GI tract Haveles (p. 286) (Table 22-4) Antidiarrheals Opioid-like agents loperamide (Imodium) diphenoxylate (in Lomotil) Adsorbents kaolin and pectin (Kaopectate)

11 Antiemetics Antiemetics Haveles (p. 287) (Fig. 22-6) Haveles (p. 287) Drugs used to induce vomiting and to prevent vomiting are used for certain GI tract problems Ipecac is used to induce vomiting after ingestion of a harmful substance Has been abused by individuals with bulimia Over time, with chronic use, the body becomes resistant to the emetic effect and the ipecac is absorbed Cardiac toxicity produced by retained ipecac has been fatal to patients with bulimia Haveles (p. 287) Antiemetics Vomiting may occur due to a variety of situations such as motion sickness, pregnancy, drugs, infections, or radiation therapy Phenothiazines: used to control severe nausea Side effects include sedation and extrapyramidal symptoms, including tardive dyskinesia Used in dentistry to treat nausea and vomiting associated with surgery and anesthesia Anticholinergics: can be used for nausea and vomiting associated with motion sickness and labyrinthitis 63 Antiemetics Antihistamines: diphenhydramine (Benadryl), an antihistamine with antiemetic properties, commonly produces sedation hydroxyzine (Atarax) is used as an antiemetic or antianxiety agent trimethobenzamide (Tigan): has an antiemetic effect mediated through the chemoreceptor trigger zone Produces sedation, agitation, headache, and dry mouth metoclopramide (Reglan): can control nausea and vomiting of patients receiving cancer chemotherapeutic agents Also indicated for gastric motility disorders such as diabetic gastric stasis benzquinamide (Emete-Con): has antiemetic, antihistaminic, anticholinergic, and sedative effects Used to treat nausea associated with anesthesia during surgery Cannabinoids: dronabinol (Marinol) and nabilone (Cesamet) are indicated to treat nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond to conventional antiemetic therapy 64 Drugs Used to Treat Other Gastrointestinal Disorders Haveles (p. 286) (Table 22-4) Antiemetics Phenothiazines prochlorperazine (Compazine) Antihistamines meclizine (Bonine) dimenhydrinate (Dramamine) trimethobenzamide (Tigan) Cannabinoids dronabinol (Marinol) nabilone (Cesamet) Agents Used to Manage Chronic Inflammatory Bowel Disease (IBD) Haveles (p. 288) Divided into ulcerative colitis and Crohn disease; an autoimmune response is thought to be associated with ulcerative colitis Crohn disease extends through all layers of the intestinal wall, whereas ulcerative colitis involves only the mucosa Crohn disease can involve the whole intestine, but the colon is most commonly affected Ulcerative colitis involves the rectum and may involve the distal part of the colon but does not involve the small intestine

12 Agents Used to Manage Chronic Inflammatory Bowel Disease Haveles (p. 288) Drugs used to treat IBD include laxatives, colonic stimulants, and osmotic agents; indicated for patients who do not respond to fiber supplementation Antidiarrheal agents: also used to treat IBD in patients with diarrhea-predominant irritable bowel syndrome Antispasmodics: best used for acute attacks of abdominal pain or before meals in patients with postprandial symptoms Serotonin 5-hydroxytryptamine modulators: play a major role in the regulation of intestinal motility, secretion, and visceral sensitivity Tricyclic antidepressants: used when diarrhea-persistent IBS is moderate to severe Drugs Used to Treat Other Gastrointestinal Disorders Haveles (p. 286) (Table 22-4) Agents in the treatment of IBD Nonaspirin salicylates sulfasalazine (Azulfidine) mesalamine (Rowasa, Pentasa, Asacol) olsalazine (Dipentum) Adrenocorticosteroids prednisone Immune modifiers cyclosporine azathioprine mercaptopurine (6-MP, Purinethol) Antibiotics metronidazole (Flagyl)

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