Transcript Chapter 22 outline

Chapter 22:
Respiratory and Gastrointestinal Drugs
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Chapter 22 Outline

Respiratory and gastrointestinal (GI) drugs




Respiratory drugs
Drugs used to treat respiratory diseases
GI drugs
Drugs used to treat GI diseases
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2
Respiratory and Gastrointestinal
Drugs



Haveles (pp. 276-277) (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
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3
Respiratory Drugs


Haveles (pp. 276-277) (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
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4
Respiratory Diseases


Noninfectious respiratory diseases are
divided into asthma and COPD


Haveles (pp. 276-277)
COPD is divided further into chronic bronchitis and
emphysema
Other respiratory problems are related to viral
or bacterial respiratory infections
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5
Asthma


Haveles (pp. 276-277)
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
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6
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
cont’d…
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7
Chronic Obstructive Pulmonary
Disease

For a normal person, breathing is stimulated
by elevated partial pressure of carbon dioxide
(PaCO2)


For a person with COPD, breathing is stimulated
by a decrease in partial pressure of oxygen (PaO2)
If this person is given oxygen, the stimulus to
breathing may be removed, and the possibility of
inducing apnea occurs
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8
Drugs Used to Treat Respiratory
Diseases










Haveles (pp. 279-283)
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
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9
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
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10
Sympathomimetic Agents


Produce bronchodilation by stimulation of βreceptors in the lungs


Haveles (p. 279)
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 β2-agonists produce bronchodilation
with fewer cardiac side effects
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11
Short-Acting β2-Agonists


Have specificity for the respiratory tree


Haveles (p. 279) (Fig. 22-3; Table 22-1)
Side effects include nervousness, tachycardia, and
insomnia
Short-acting β2-agonists such as albuterol, may
be administered by inhalation or orally


The first line of treatment for mild occasional asthma
is a short-acting β2-agonist
Short-acting β2-agonists are the drug of choice for the
emergency treatment of an acute asthma attack
cont’d…
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12
Short-Acting β2-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
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13
U.S. Food and Drug Administration
(FDA)-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
Adrenergic agonists (inhaler)


β2-Agonist
Short-acting; used for an acute attack
• albuterol (Proventil, Ventolin)
• metaproterenol (Alupent, Metaprel)
• levalbuterol (Xopenex HFA)
• pirbuterol (Maxair Autohaler)
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14
Long-Acting β2-Agonists


Haveles (pp. 279-280) (Fig. 22-1)
A newer long-acting β2-agonist is salmeterol
(Serevent)


Onset is delayed and duration of action is
sustained
Not used for management of an acute asthmatic
episode
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15
FDA-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
Adrenergic agonists (inhaler)


β2-Agonist
Long-acting
• salmeterol (Serevent Diskus)
• formoterol (Foradil Aerolizer)
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16
Corticosteroids


Typical side effects seen with corticosteroid
therapy do not occur with topical aerosol
administration



Haveles (p. 281)
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
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17
FDA-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
Adrenergic agonists (inhaler)


Corticosteroids
Corticosteroids, inhaled
• beclomethasone (QVAR)
• budesonide (Pulmicort)
• ciclesonide (Alvesco)
• flunisolide (AeroBid)
• fluticasone (Flovent HFA)
• mometasone furoate (Asmanex Twisthaler)
• triamcinolone (Azmacort)
cont’d…
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18
FDA-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
Adrenergic agonists (inhaler)


Corticosteroids
Corticosteroids, oral
• prednisone (Deltasone, Meticorten)[PO]
cont’d…
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19
FDA-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
Adrenergic agonists (inhaler)


Inhaled corticosteroids/long-acting β2-agonists
Corticosteroid/β2-agonist
• fluticasone/salmeterol (Advair HFA)
• budesonide/formoterol (Symbicort HFA)
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20
Leukotriene Modifiers


Haveles (pp. 281-282)
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 β2-agonists
and corticosteroid inhalers
cont’d…
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21
Leukotriene Modifiers

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
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22
FDA-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
LT antagonists


LT pathway antagonist
• zafirlukast (Accolate) (PO)
• montelukast (Singulair)
LT pathway synthesis inhibitor (LPI)
• zileuton (Zyflo) (PO)
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23
Cromolyn


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
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24
FDA-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
Mast cell degranulation inhibitors

Mast cell stabilizers
• cromolyn (Intal) (Nasalcrom) IH
• nedocromil (Tilade)
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25
Methylxanthines


Consist of theophylline, caffeine, and
theobromine


Haveles (p. 282)
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)
cont’d…
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26
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
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27
FDA-Approved Drugs Used to
Manage Asthma


Haveles (p. 280) (Table 22-1)
Methylxanthines

Methylxanthines
• theophylline (Theo-Dur, Slo-Bid) (PO)
• aminophylline-theophylline ethylene diamine
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28
Anticholinergics


Haveles (p. 282)
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
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29
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
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30
Agents Used to Manage Upper
Respiratory Tract Infections




Haveles (pp. 282-283)
Nasal decongestants
Expectorants and mucolytics
Antitussives
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31
Nasal Decongestants


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
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32
Expectorants and Mucolytics




Haveles (pp. 282-283)
Expectorants promote removal of exudate or
mucus from respiratory passages
Liquefying expectorants decrease the
viscosity of mucus
Mucolytics destroy or dissolve mucus
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33
Antitussives


Haveles (p. 283)
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
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34
Dental Implications of the
Respiratory 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
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35
Gastrointestinal Drugs


Haveles (pp. 283-288)
Both over-the-counter and prescription drugs
are used for GI diseases

Some are used for specific diseases, others are
for symptomatic relief
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36
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
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37
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
cont’d…
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38
Gastroesophageal Reflux
Disease

Treated by decreasing the acid in the
stomach or by constricting the cardiac
sphincter



Histamine2 (H2)-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
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39
Ulcers


Haveles (pp. 283-284)
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 H2-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 (PGE2α) misoprostol (Cytotec)
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40
Drugs Used to Treat
Gastrointestinal Diseases









Haveles (pp. 284-288)
H2-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
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41
Histamine2-Blocking Agents



Haveles (p. 284) (Table 22-2)
Block and inhibit gastric acid secretion by
competitive inhibition of histamine at the H2receptors of parietal cells
cimetidine (Tagamet) is the prototype
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42
Uses of Cimetidine


Haveles (pp. 284-285)
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 H2-blockers
 Cimetidine is also used as an adjunct in
management of urticaria
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43
Adverse Reactions of Cimetidine


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
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44
Dental Drug Interactions of
Cimetidine


Metabolism of these may be reduced by
cimetidine




Haveles (p. 285)
Ketoconazole and itraconazole: concurrent
administration with H2-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 H2-receptor antagonists

Other H2-blockers are unlikely to produce
important dental drug interactions
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45
Drugs Used to Treat Peptic Ulcer
Disease and Gastroesophageal
Reflux Disease


Haveles (p. 284) (Table 22-2)
Acid reducers

H2-blockers
• cimetidine (Tagamet)
• famotidine (Pepcid)
• ranitidine (Zantac)
• nizatidine (Axid)
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46
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
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47
Drugs Used to Treat Peptic Ulcer
Disease and Gastroesophageal
Reflux Disease


Haveles (p. 284) (Table 22-2)
Acid reducers

PPIs
• omeprazole (Prilosec)
• lansoprazole (Prevacid)
• esomeprazole (Nexium)
• pantoprazole (Protonix)
• rabeprazole (AcipHex)
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48
Mixed Antiinfective Therapy for
Ulcer Treatment


Haveles (p. 285)
To treat ulcers, a combination of two or three
antiinfective agents, an acid reducer, an H2blocker 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
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49
Antacids


Haveles (pp. 285-286)
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
cont’d…
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50
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
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51
Drugs Used to Treat Peptic Ulcer
Disease and Gastroesophageal
Reflux Disease


Haveles (p. 284) (Table 22-2)
Antacids




Sodium bicarbonate
Magnesium hydroxide
Aluminum hydroxide
Calcium carbonate
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52
Miscellaneous Gastrointestinal
Drugs


misoprostol (Cytotec) is prostaglandin PGE2α
and is indicated for NSAID-induced ulcers


Haveles (p. 286)
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
cont’d…
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53
Miscellaneous Gastrointestinal
Drugs


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
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54
Laxatives and Antidiarrheals


Haveles (pp. 286-287)
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
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55
Drugs Used to Treat Peptic Ulcer
Disease and Gastroesophageal
Reflux Disease


Haveles (p. 284) (Table 22-2)
Laxatives


Bulk
• psyllium seed (Metamucil)
• carboxymethylcellulose
• methylcellulose (Citrucel)
• polycarbophil (FiberCon)
Stool softeners, emollient
• docusate (dioctyl sodium sulfosuccinate, DSS, Colace)
cont’d…
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56
Drugs Used to Treat Peptic Ulcer
Disease and Gastroesophageal
Reflux Disease


Haveles (p. 284) (Table 22-2)
Laxatives

Stimulants
• magnesium hydroxide (Milk of magnesia [MOM])
• bisacodyl (Dulcolax)
• cascara sagrada
• senna
• casanthranol
• castor oil
• phenolphthalein
cont’d…
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57
Drugs Used to Treat Peptic Ulcer
Disease and Gastroesophageal
Reflux Disease


Haveles (p. 284) (Table 22-2)
Laxatives

Hyperosmotic
• glycerin
• lactulose
• salts (magnesium citrate, hydroxide, oxide, or sulfate; sodium
phosphate)
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58
Laxatives and Antidiarrheals


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
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59
Drugs Used to Treat Other
Gastrointestinal Disorders


Haveles (p. 286) (Table 22-4)
Antidiarrheals


Opioid-like agents
• loperamide (Imodium)
• diphenoxylate (in Lomotil)
Adsorbents
• kaolin and pectin (Kaopectate)
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60
Antiemetics


Haveles (p. 287) (Fig. 22-6)
Drugs used to induce vomiting and to prevent
vomiting are used for certain GI tract
problems
cont’d…
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61
Antiemetics


Haveles (p. 287)
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
cont’d…
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62
Antiemetics


Haveles (p. 287)
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
cont’d…
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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
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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)
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65
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
cont’d…
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66
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
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67
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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68