1. The respiratory system
Weeks 3
Chapters 31 & 32

2. Antihistaminic Drugs and Mast Cell Release Inhibitors
Chapter 31

3. Action of Histamine Learning Outcomes
31.1 Explain the reactions produced by histamine released in response to allergic reactions.
Histamine is found throughout the body in the mast cells and basophilic white blood cells. Mast cells usually found alongside blood vessels contain granules of bioactive substances. The largest concentrations of mast cells are in the lungs, the gastrointestinal (GI) tract, and the skin.
The first time a person comes into contact with tree pollen, dust mites, or other allergens (antigens), white blood cells produce antibodies, specifically IgE immunoglobulin. On the repeated exposure, the allergen binds to the IgE and triggers a release of mast cell contents.
Among the substances immediately released into the blood are histamine, heparin, serotonin, prostaglandins, leukotrienes, platelets, and eosinophil activating factors.
Histamine interacts with the membrane receptors in certain tissues to produce the symptoms of allergy (itching, redness, urticaria, stuffy nose). This is a Type I (acute) hypersensitivity reaction because the response is immediate (not delayed).
Histamine is found throughout the body:
It is released into the blood when the body comes in contact with an allergen.
Histamine interacts with membrane receptors.
There are four types of histamine receptors:
H1, H2, H3, H4.
H1-receptors medicate allergic reactions.

4. Action of Histamine Learning Outcomes
31.1 Explain the reactions produced by histamine released in response to allergic reactions.
The erythema and edema produced by histamine in the skin are known as the Response of Lewis. When the edema and swelling are beneath the skin rather than on the surface, it is angioedema. Histamine also increases the production of nasal and bronchial mucus.
Histamine produces contraction of the smooth muscle of the intestine and bronchioles by stimulating H1- receptors. Contraction of intestinal smooth muscle results in disturbances of intestinal activity like increased peristalsis and diarrhea. Contraction of the bronchiolar smooth muscle results in
bronchoconstriction, which makes breathing difficult.
People who have pulmonary diseases (asthma and emphysema) may be 1000 times more sensitive to the respiratory actions of histamine. Antihistamines are not therapeutically useful in asthmatics because the intensity and nature of the allergic response requires an antiallergy approach.
Histamine usually produces rapid heartbeat. However, at high levels of histamine (histamine shock), cardiac conduction is impaired. Such impairment may lead to the development of arrhythmias and cardiovascular collapse.
Histamine can also cause increased peristalsis and diarrhea.
Histamine usually causes a rapid heartbeat.
High levels of histamine can lead to histamine shock.

5. Blocking Allergic Reactions
Allergic reactions can be blocked in two ways:
Preventing mast cells from releasing their contents –MOA for Mast Cell Inhibitors
Blocking the H1 receptors –MOA for H1 Antagonist
Learning Outcomes
31.2 Describe the difference in action between an antihistaminic and a mast cell release inhibitor.
31.6 Explain terminology associated with allergy and these drugs.
Allergic reactions can be blocked in two ways. Mast cells can be prevented from releasing their contents or the postsynaptic H 1 -receptors can be blocked from interacting with histamine.

6. Mast Cell Release Inhibiters
MOA -They block the mast cell from releasing its contents. MOA: interferes with antigen-antibody reaction of mast cells
cromolyn sodium (Crolom, Intal)
USE: There are four other mast cell release inhibitors that are all used as ophthalmics
USE: prophylactic control of chronic asthma
Learning Outcomes
31.2 Describe the difference in action between an antihistaminic and a mast cell release inhibitor.
31.6 Explain terminology associated with allergy and these drugs.
Cromolyn sodium is not a bronchodilator, a smooth muscle relaxant, or a histamine- receptor antagonist. It is one of the drugs known as mast cell release inhibitors. Since this drug has no effect on histamine receptors, cromolyn sodium must be administered before histamine release has begun.
Drugs like cromolyn sodium, which prevent the onset of symptoms or disease as a result of exposure before the reactive process can take place, are called prophylactic drugs.
There are four drugs in addition to cromolyn that inhibit the release of histamine and other mediators of inflammation from mast cells. Bepotastine (Bepreve), cromolyn (Crolom), lodoxamide (Almomide), nedocromil (Alocril), and pemirolast (Alamast) are only available by prescription as ophthalmic solutions.
Conjuctivitis is an inflammation of the conjunctiva, the thin, clear, outermost membrane that lies over the white part of the eye and lines the inside of the eyelid as well as the exposed parts of the eye, except the cornea.
When an infectious virus or bacteria are the cause, it is called “pink eye.” Most often it is due to an allergic response to pollen or some other antigen in sensitized individuals or contact lens wearers.

7. Mast Cell Release Inhibiters
Effective in reducing (USE):
Itching
Hyperemia
Mucous discharge
Adverse effects include:
Wheezing
Nasal itching and burning
Nausea
Drowsiness HA
Bad taste
Learning Outcomes
31.2 Describe the difference in action between an antihistaminic and a mast cell release inhibitor.
31.6 Explain terminology associated with allergy and these drugs.
Mast cell release stabilizers are effective in reducing itching, hyperemia (red-looking eye), and mucous discharge. In severe cases, they may be used concurrently with mild corticosteroids.
Cromolyn is currently used as a prophylactic adjunct in the management of chronic allergic rhinitis to prevent bronchospasms and ocular allergy. All of the ophthalmic drugs are indicated for the treatment of allergic conjunctivitis and keratoconjunctivitis. Oral cromolyn improves diarrhea, flushing, headaches, urticaria, abdominal pain, and nausea in some patients with mastocytosis.
Adverse effects to mast cell release inhibitors are minimal and include wheezing, nasal itching, nasal burning, nausea, drowsiness, and headache with cromolyn nebulization.
The usual side effects for the ophthalmic solutions include stinging or burning of the eyes, which resolves; hypersensitivity; nausea; and dryness in the nose.

8. Antihistamine H1 Antagonists
MOA -Block histamine from binding to the H1 receptors
Used to relieve the symptoms of allergic reactions after histamine has already been released
Separated into first-generation and second-generation categories
Learning Outcomes
31.2 Describe the difference in action between an antihistaminic and a mast cell release inhibitor.
31.3 Describe two specific therapeutic uses of antihistaminics that result from an action on the central nervous system (CNS) yet are not associated with allergic responses.
Antihistaminic drugs are used to relieve the signs and symptoms of acute reactions in which histamine has already been released. All of the antihistamines discussed in this chapter, block histamine from interfacing with its H1-receptors.

9. Antihistamine H1 Antagonists
Bromphiramine
Chlorphenirmaine
diphenhydramine (Benadryl)
First generation
cetirizine (Zyrtec)
fexofenadine (Allegra)
loratadine (Claritin)
Levocetirizine
Second generation
Learning Outcomes
31.4 Describe three side effects of antihistaminics.
31.5 Describe three examples of first- and second generation antihistamines and the characteristic difference between the two groups.
31.6 Explain terminology associated with allergy and these drugs.
First-generation antihistamines include bromphiramine, chloropheniramine (Chlor-Trimeton), clemastine (Tavist), diphenhydramine (Benadryl), dimenhydrinate, meclizine, and promethazine (Phenergan). These characterstically have a nonselective interaction with peripheral and central (CNS) histamine receptors.These drugs can be used interchangeably and frequently cause sedation (CNS) along with relief of allergy symptoms.
The second generation of antihistaminesincludes cetirizine (Zyrtec, now OTC only), fexofenadine (Allegra), desloratidine(Clarine ), levocetirizine (Xyzal), and loratadine (Alavert, now OTC only), appears to be more selective for peripheral H1-receptors.
These agents are not as sedating or drying and demonstrate equal antiallergic activity to the first-generation drugs. These drugs have much less anticholinergic activity than the first-generation antihistamines.

10. Antihistamine H1 Antagonists
Clinical indications (USES):
Itching
Local surface pain from insect bites
Urticaria
Hay fever
Rhinitis
Dermatitis
Motion sickness
Sleeplessness/insomnia
Learning Outcomes
31.4 Describe three side effects of antihistaminics.
31.5 Describe three examples of first- and second generation antihistamines and the characteristic difference between the two groups.
31.6 Explain terminology associated with allergy and these drugs.
Antihistamines can relieve itching and local surface pain of bites, stings, and excoriations. Diphenhydramine (Benadryl) is still considered an antihistamine of choice.
Dimenhydrinate (Dramamine) and meclizine (Antivert) exert a unique action in the brain to relieve vertigo and motion sickness and the nausea that accompanies it.
These drugs are usually taken orally, whether as single agents or combined with other drugs in cough-cold and allergy preparations. Only a few antihistamines are available for parenteral administration: dimenhydrinate (Dramamine), diphenhydramine (Benadryl), and promethazine.
Antihistaminics are frequently used in acute allergic reactions including urticaria, hay fever, insect bites, rhinitis, and dermatitis. Because of the inherent sedation, antihistaminics may be used to induce sleep in OTC sleeping aids (for example, Nytol) or to relieve motion sickness (Dramamine) or vertigo (Antivert).

11. Antihistamine H1 Antagonists
Side effects:
Drowsiness
Xerostomia
Adverse effects:
Hypertension
Rapid heartbeat
Anorexia
Epigastric distress
Urinary retention
Learning Outcomes
31.4 Describe three side effects of antihistaminics.
31.5 Describe three examples of first- and second generation antihistamines and the characteristic difference between the two groups.
31.6 Explain terminology associated with allergy and these drugs.
The most common side effects produced by the antihistaminics are drowsiness and sedation. Another frequently occurring side effect is dry mouth (xerostomia). This side effect is therapeutically useful in treating a runny nose in the common cold.
Other adverse effects include hypotension, rapid heartbeat, anorexia, epigastric distress, and urinary retention.
Because of their anticholinergic activity, antihistaminic drugs should be used with caution in patients with cardiovascular disease, hypertension, prostate enlargement, or urinary retention.
Antihistaminics also may produce drug fever, which will subside only when the drug is stopped. The mechanism of this drug-induced fever is not known.
Medications that affect the CNS (sedation) and cardiovascular system (alter blood flow to the brain) predispose patients to develop mental confusion.

12. Antihistamine H1 Antagonists (NC):
Contraindications—should be used with caution in patients with:
Cardiovascular disease
Hypertension
Prostate enlargement
Best to take minutes prior to exposure to allergen
Learning Outcomes
31.4 Describe three side effects of antihistaminics.
31.6 Explain terminology associated with allergy and these drugs.
Two second-generation antihistamines, astemazole and terfenadine, were removed from the market because they produced serious cardiovascular and hepatic effects that were fatal in some patients.
Four antihistamines still on the market prolong the QTc interval but have not been associated with fatalities: desloratadine, diphydramine, fexofenadine, and hydroxyzine.
Antihistamines should not be used by patients with a known hypersensitivity to antihistamines or patients with narrow-angle glaucoma, stenosing peptic ulcer, or prostatic hypertrophy.
Hydroxyzine is contraindicated for use in early pregnancy. Antihistamines are not recommended for use during pregnancy because safe use during pregnancy has not been established. Animal studies have demonstrated abnormalities in the offspring with certain antihistamines.
Antihistamines should not be used in newborn or premature infants because these patients are more susceptible to the adverse effects. Convulsions in newborns after exposure to antihistamines in the third trimester have been reported. These drugs should not be used by nursing mothers, since they are excreted into breast milk and thus passed into the newborn.

13. Respiratory Pharmacology, Treatment of Asthma, and COPD
Chapter 32

17. Chemical Mediators Prostaglandins and leukotrienes: Leukotrienes:
Bronchoconstriction
Edema
Mucus production
Leukotrienes:
Potent bronchoconstrictors
Long durations of action
Learning Outcomes
32.1 Describe the effects of chronic obstructive pulmonary disease (COPD) and asthma on respiratory function.
32.2 List the chemical mediators involved in asthma.
Prostaglandins and leukotrienes (LT) are two different chemical mediators that are both derived from arachidonic acid. Both prostaglandins and leukotrienes are formed and released in inflammatory conditions, such as asthma. Both mediators can cause bronchoconstriction, edema, and mucus production.
Prostaglandins are involved in a variety of physiological functions and also in inflammation and generation of pain.
The leukotrienes are potent bronchoconstrictors with long durations of action and considered to be one of the more important chemical mediators in asthma.
The different leukotrienes are designated as LTB4, LTC4, LTD4, and LTE4.
LTC4, LTD4, and LTE4 each stimulates a common leukotriene receptor, designated the cysteinyl leukotriene-receptor (LT-1). Activation of this receptor is responsible for causing the bronchoconstriction, edema, and other inflammatory actions.

18. Classes to Treat COPD and Asthma
Bronchodilators
Beta-Adrenergic Drugs
Anticholinergics
Anti-inflammatory Drugs
Corticosteroids
Leukotriene Inhibitors
Mast Cell Inhibiters

19. Bronchodilators Beta-Adrenergic Drugs: Albuterol “Rescue Inhaler”
MOA: stimulate beta-2 receptors in lungs, which causes bronchodilation
Profile Drugs:
Albuterol “Rescue Inhaler”
salmeterol (Serevent)
IND:
Prevention of bronchospasm
Treatment of acute bronchospasm—rescue treatment
Prevention of exercise-induced asthma
Learning Outcomes
32.4 Describe the mechanism of action and main pharmacological effects of the three types of bronchodilators.
Bronchiolar smooth muscle tone and secretion of mucus are normally Epinephrine (normally released from the adrenal gland) and isoproterenol are two potent beta-adrenergic drugs. These two drugs are nonselective and stimulate both beta-1 (heart) and beta-2 (relax smooth muscle) adrenergic receptors. When used as bronchodilators, they increase heart rate and may cause tachycardia and cardiac arrhythmias.
The selective beta-2 adrenergic drugs are the bronchodilators of choice for the chronic control of asthma and COPD. At therapeutic concentrations, these drugs produce little or no cardiac stimulation and few systemic drug effects. However, at increased dosages, these drugs can begin to cause cardiac stimulation.
The bronchodilating effects of these drugs begin almost immediately after inhalation and they are considered “rescue” drugs. Salmeterol and formoterol are two long-acting beta-2 drugs with increased beta-2 receptor selectivity.
The selective beta-2 drugs are generally well tolerated and, since they are usually administered by inhalation directly into the lungs, they cause few systemic adverse effects. Nervousness, skeletal muscle tremors, and increased heart rate, especially with oral administration, are effects most frequently reported.

20. Bronchodilators Beta-Adrenergic Drugs: Side effects: Nervousness
Skeletal muscle tremors
Increased heart rate
Learning Outcomes
32.4 Describe the mechanism of action and main pharmacological effects of the three types of bronchodilators.
Bronchiolar smooth muscle tone and secretion of mucus are normally Epinephrine (normally released from the adrenal gland) and isoproterenol are two potent beta-adrenergic drugs. These two drugs are nonselective and stimulate both beta-1 (heart) and beta-2 (relax smooth muscle) adrenergic receptors. When used as bronchodilators, they increase heart rate and may cause tachycardia and cardiac arrhythmias.
The selective beta-2 adrenergic drugs are the bronchodilators of choice for the chronic control of asthma and COPD. At therapeutic concentrations, these drugs produce little or no cardiac stimulation and few systemic drug effects. However, at increased dosages, these drugs can begin to cause cardiac stimulation.
The bronchodilating effects of these drugs begin almost immediately after inhalation and they are considered “rescue” drugs. Salmeterol and formoterol are two long-acting beta-2 drugs with increased beta-2 receptor selectivity.
The selective beta-2 drugs are generally well tolerated and, since they are usually administered by inhalation directly into the lungs, they cause few systemic adverse effects. Nervousness, skeletal muscle tremors, and increased heart rate, especially with oral administration, are effects most frequently reported.

21. Bronchodilators Anticholinergic Drugs:
MOA: block the action of acetylcholine, leading to bronchodilation
IND: treatment of COPD and Asthma
Administered by oral inhalation, as little drug is absorbed systemically
Learning Outcomes
32.4 Describe the mechanism of action and main pharmacological effects of the three types of bronchodilators.
By blocking the actions of acetylcholine, anticholinergic drugs produce bronchodilation and also reduce the volume of respiratory secretions.
Anticholinergic drugs are not as potent bronchodilators as the beta adrenergic drugs and in asthma are primarily indicated when other bronchodilators are contraindicated or additional bronchodilation is needed.
In COPD and especially chronic bronchitis, there appears to be increased cholinergic activity. Consequently, anticholinergic actions are useful in the treatment of COPD and these drugs are considered first-line drugs.

22. Bronchodilators ipratropium bromide (Atrovent):
A quaternary derivative of atropine
IND: asthma and COPD
tiotropium bromide (Spiriva):
Similar to ipratropium but longer duration of action
Side effects (for both):
excessive drying of mouth and upper respiratory system, and tachycardia
Learning Outcomes
32.4 Describe the mechanism of action and main pharmacological effects of the three types of bronchodilators.
Ipratropium is a quarternary derivative of atropine and is indicated for the treatment of both asthma and COPD. Excessive drying of the mouth and upper respiratory passages may cause discomfort and is the most common side effect. Tiotropium (Spiriva) is another anticholinergic bronchodilator that is similar to ipratropium but produces a longer duration of action.

23. What about combination drugs? Why are they effective?
They work on both sides of the lungs to aid with bronchodilation

24. Inhalation Medications
Aerosol- suspension of very small liquid droplets or fine solid particles in a gas
Nebulizers are machines that vaporize a liquid drug into a fine mist
Dry powder inhaler (DPI) allows a solid drug to be inhaled
Metered dose inhaler (MDI) uses a propellant to deliver a metered dose of drug

25. MDI- Important to remember
MDI use needs to be timed with inhalation
Allow 1 minute to pass between puffs
When using more than 1 resp med, take bronchodilator first
Take glucocorticoid on regular basis-not as needed
Rinse mouth after inhaler use
To prevent absorption from GI tract and decrease side effects
Also prevents development of thrush and other infections
Using bronchodilator first opens airway and increases effectiveness of 2nd med

26. Anti-inflammatory Drugs
Corticosteroids:
MOA: interfere with all stages of the inflammatory and allergic response
Potent antiinflammatory actions
IND: control of chronic asthma and COPD
Main route of administration is inhalation, but may be used systemically (orally) to treat initial acute phase of inflammation
Adverse effects:
oral infections, hoarseness, and vocal cord disturbances; if taken orally may have many more…
Learning Outcomes
32.5 Explain the therapeutic actions of the corticosteroids and leukotriene inhibitors in the treatment of asthma.
The antiinflammatory steroids and other drugs with antiinflammatory actions are referred to as “controller” drugs because they reduce and control the inflammatory response.
The corticosteroid drugs are considered the most potent antiinflammatory and antiallergic drugs available. They interfere with all stages of the inflammatory and allergic response. Corticosteroids inhibit the activity of inflammatory cells, the release of inflammatory mediators from mast cells, the production of allergic antibodies, edema, and many other antiinflammatory actions.
One of the main uses of these drugs is for treatment of inflammatory and allergic conditions such as asthma. The major effect of steroids in the treatment of asthma is to inhibit the inflammatory response that occurs in the respiratory airways.
Adverse effects associated with systemic steroid use include fluid retention, muscle wasting, metabolic disturbances, and increased susceptibility to infection. These effects are not usually observed with aerosol therapy. However, steroids increase the incidence of oral infections (usually fungal infections) and they can cause hoarseness and other vocal cord disturbances.

27. Corticosteroids for Inhilation
Nursing Considerations:
Not effective in stopping an asthma attack in progress
Monitor for adrenal insufficiency/Cushing’s, especially with long term oral use
Use shortest dose for the shortest time possible
Profile Drugs:
beclomethasone (Beclovent)
fluticasone (Flovent)

28. Anti-inflammatory Drugs
Leukotriene Inhibitor Drugs:
Profile drug: montelukast (Singular)
MOA: prevent synthesis of leukotriene or block the leukotriene receptor
IND: control of chronic asthma and COPD
Adverse effects:
Nausea
Diarrhea
Rash
Headache
Increased liver enzymes
Learning Outcomes
32.5 Explain the therapeutic actions of the corticosteroids and leukotriene inhibitors in the treatment of asthma.
A major focus of asthma research has been to discover drugs that inhibit the actions of the arachidonic acid derivatives known as leukotrienes. These chemical mediators cause bronchoconstriction, mucus production, and inflammation. Drugs known as leukotriene inhibitors or antileukotrienes have been developed and are indicated for the chronic control of asthma.
Adverse effects include nausea, diarrhea, rash, and headache. One of the more serious adverse effects involves the liver. An abnormal increase in liver enzymes and the development of fever, dark urine, clay-colored stools, or jaundice are signs of liver toxicity and should be reported to the physician.
Zafirlukast (Accolate) and montelukast (Singulair) are leukotriene receptor antagonists that block the leukotriene receptor, referred to as the cysteinyl leukotriene-1 receptor

29. Mucolytics, Expectorants, and Antitussives
Liquefy bronchial mucus
Enable mucus to be removed by coughing or suction apparatus
acetylcysteine (Mucomyst)
Expectorants:
Facilitate removal of thickened mucus from the lungs
Guaifenesin
Too many trade names, know this generic!
Antitussives:
Control cough by decreasing frequency and intensity
Dextromethrophan –most frequently used OTC
Opioids –most effective class
Learning Outcomes
32.7 Explain the use of mucolytic and expectorant drugs.
Omalizumab is an anti-IgE monoclonal antibody indicated for the treatment of asthma. The anti-IgE monoclonal antibody binds to and inactivates the immunoglobulin IgE. Omalizumab binds up the IgE antibody and decreases the circulating levels of IgE. This reduces the severity and frequency of asthmatic attacks.
Both expectorants and and antitussives raise the threshold of the cough center which decreases the frequency and intensity of cough.

30. Preferred Therapy for Asthma and COPD
Mild Intermittent
Beta-2 bronchodilator
Mild Persistent
Corticosteroid
Cromolyn
Anti-leukotriene
Moderate Persistent
Severe Persistent
Beta adrenergic bronchodilator
Learning Outcomes
32.8 Identify the preferred therapy for asthma and COPD.
Patients who experience less than two asthmatic episodes per week often do not require daily medication. Selective beta-2 adrenergic bronchodilators for oral inhalation that provide immediate onset of action, such as albuterol, can be carried by the patient and used for any sudden onset of symptoms.
Patients who experience more than two asthmatic episodes per week but less than one per day are usually prescribed daily treatment with low-dose inhaled anti-inflammatory corticosteroids. Alternate therapies include inhaled cromolyn and oral administration of antileukotriene drugs.
Patients who experience daily asthmatic episodes require daily treatment with low-to-moderate-dose inhaled antiinflammatory corticosteroids and inhaled selective beta-2 adrenergic bronchodilators. The selective beta-2 adrenergic drugs, such as albuterol or pirbuterol, or the longer-acting drugs like salmeterol are usually preferred for chronic therapy.
These patients require high-dose inhaled corticosteroids and long-acting beta adrenergic bronchodilators. Oral or parenteral steroids may be required when symptoms intensify. Additional bronchodilators and antileukotrienes may be added depending on the clinical situation and patient response.

31. Question #1
Your patient has been on a beta adrenergic bronchodilator for several years. You should instruct this patient that if tolerance develops to the drug he/she should:
A. Seek medical attention
B. Take a higher dose of the drug
C. Use the inhaler more frequently
D. Know that this is normal and no action is necessary A

32. Question #2
Pseudoephedrine (Sudafed) should be used cautiously in patients who have:
A. Asthma
B. Hypertension
C. Rhinitis
D. Diabetes mellitus B

33. Question #3
A nurse has an order to give a client salmeterol (Serevent), two puffs, and beclomethasone (Beclovent), two puffs, by metered dose inhaler. The nurse administers the medication by giving the:
A. Beclomethesone first and then the salmeterol
B. Salmeterol first and then the beclomethasone
C. Alternating a single puff of each, beginning with the salmeterol
D. Alternating a single puff of each, beginning with the beclomethesone

34. Question #4
A client has an order to take guaifenesin (Humibid). A nurse concludes that the client understands the most effective use of this medication if the client states that he or she will:
A. Watch for irritability as a side effect
B. Take the tablet with a full glass of water
C. Take an extra dose if the cough is accompanied by fever
D. Crush the extended release tablet if immediate relief is needed B