Part 5: Drugs Affecting the Respiratory System.
- Anti-histamines
Histamine is a bodily substance that performs many functions. It is involved in nerve impulse transmission in the central nervous system CNS, dilation of capillaries, contraction of smooth muscles, stimulation of gastric secretion, and acceleration of the heart rate.
There are two types of cellular receptors for histamine.Histamine 1 H1 receptors mediate smooth muscle contraction and dilation of capillaries, and histamine 2 H2 receptors mediate acceleration of heart rate and gastric acid secretion. This explains why the release of excessive amounts of histamine can lead to anaphylaxis and severe allergic symptoms and may result in any or all of the following physiologic changes:
- Constriction of smooth muscle, especially in the stomach and lungs.
- Increase in body secretions.
- Vasodilation and increased capillary permeability, which results in the movement of fluid out of the blood vessels and into the tissues and thus causes a drop in blood pressure and edema.
Antihistamines are drugs that directly compete with histamine for specific receptor sites. They also called histamine antagonists. Antihistamines that compete for the H2 receptors are called H2 antagonists and include such drugs as ranitidine and famotidine, they are discussed in detail in GIT. This chapter focuses on the H1 antagonists; these are the drugs more commonly known by the name antihistamines.
The clinical efficacy of the different antihistamines is very similar, although they have varying degrees of antihistaminic, anticholenergic, and sedating properties. The particular actions of particular antihistamines are determined by its specific chemical makeup. These drugs also differ from each other in their potency and their adverse effects, especially in the degree of drowsiness they produce.
Mechanism of action:
The binding of H1 blockers to the histamine receptors prevents the adverse consequences of histamine stimulation
More effective in preventing the actions of histamine rather than reversing them
Should be given early in treatment, before all the histamine binds to the receptors
Antihistamine effects:
Cardiovascular (small blood vessels)
Histamine effects:Dilation and increased permeability (allowing substances to leak into tissues)
Antihistamine effects:Reduce dilation of blood vessels and Reduce increased permeability of blood vessels
Smooth muscle (on exocrine glands)
Histamine effects :Stimulate salivary, gastric, lacrimal, and bronchial secretions
Antihistamine effects:Reduce salivary, gastric, lacrimal, and bronchial secretions
Immune system (release of substances commonly associated with allergic reactions)
Histamine effects: Mast cells release histamine and other substances, resulting in allergic reactions
Antihistamine effects: Binds to histamine receptors, thus preventing histamine from causing a response
Skin : Reduce capillary permeability, wheal-and-flare formation, itching
Anticholinergic : Drying effect that reduces nasal, salivary, and lacrimal gland secretions (runny nose, tearing, and itching eyes)
Sedative : Some antihistamines cause drowsiness
Indications:
Management of:
Nasal allergies
Seasonal or perennial allergic rhinitis (hay fever)
Allergic reactions
Motion sickness
Sleep disorders
Also used to relieve symptoms associated with the common cold
Sneezing, runny nose
Palliative treatment, not curative
Side effects:
Anticholinergic (drying) effects, most common: Dry mouth, Difficulty urinating, Constipation, and Changes in vision
Drowsiness: Mild drowsiness to deep sleep
Types of antihistamines:
1- Traditional antihistamines or First generation:
Older and Work both peripherally and centrally.
Have anticholinergic effects, making them more effective than nonsedating drugs in some cases
Chlorpheniramine.
Clemastine.
Diphenhydramine.
Promethazine.
Hydroxyzine.
2-Nonsedating or Second generation:
Developed to eliminate unwanted adverse effects, mainly sedation
Work peripherally to block the actions of histamine; thus, fewer CNS adverse effects
Longer duration of action (increases compliance)
Loratadine.
Cetrizine.
Desloratidine.
Levocetrizine.
Fexofenadine.
Nursing implications:
Gather data about the condition or allergic reaction that required treatment; also assess for drug allergies
Contraindicated in the presence of acute asthma attacks and lower respiratory diseases, such as pneumonia
Use with caution in increased intraocular pressure, cardiac or renal disease, hypertension, asthma, COPD, peptic ulcer disease, BPH, or pregnancy
Instruct patients to report excessive sedation, confusion, or hypotension
Instruct patients to avoid driving or operating heavy machinery; advise against consuming alcohol or other CNS depressants
Instruct patients not to take these medications with other prescribed or over-the-counter medications without checking with prescriber
Best tolerated when taken with meals—reduces GI upset
If dry mouth occurs, teach patient to perform frequent mouth care, chew gum, or suck on hard candy (preferably sugarless) to ease discomfort
Monitor for intended therapeutic effects
II: Bronchodilators and Other Respiratory Drugs.
Diseases of the lower respiratory system:
Asthma.
Emphysema.
Chronic bronchitis
Chronic obstructive pulmonary disease COPD is the name applied collectively to emphysema and chronic bronchitis. Asthma that is persistent and present most of the time despite treatment is also considered a COPD.
Asthma:
Bronchial asthma is defined as a recurrent and reversible shortness of breath and occurs when the airways of the lung become narrow as a result of bronchospasm, inflammation and edema of the bronchial mucosa, and the production of viscous mucus. Wheezing and difficulty breathing are symptoms. When an episode has a sudden and dramatic onset, it is referred to as an asthma attack.
Most asthma attacks are short, and normal breathing is subsequently recovered. However, an asthma attack may be prolonged for several minutes to hours and may not respond to typical drug therapy. This is a condition known as statusasthmaticus and often requires hospitalization.
Asthma is an inflammatory disease of the airways characterized by episodes of acute bronchoconstriction causing shortness of breath, Cough, Wheezing, and Chest tightness.
•The cause of the disease is unknown.
•Asthma is a chronic inflammatory disease.
The attacks are precipitated by trigger factors such as Infections, Exercise, Food, Strong odors, Smoking, Allergens, and Medications like aspirin and NSAIDs
Chronic bronchitis:
Chronic bronchitis is a continuous inflammation of the bronchi. The inflammation in the associated bronchioles is responsible for most airflow obstruction. Chronic bronchitis involves the excessive secretion of mucus and certain pathologic changes in the bronchial structure. The disease can arise as a result of repeated episodes of acute bronchitis or in the context of chronic generalized diseases. It is usually precipitated by prolonged exposure to bronchial irritants. One of the most common is cigarette smoke.
Emphysema:
Air spaces enlarge as a result of the destruction of alveolar walls
The surface area where gas exchange takes place is reduced
Effective respiration is impaired
Cigarette smoke appears to be the primary irritant responsible for precipitating the underlying inflammation that leads to the development of emphysema.
Treatment of diseases of the lower respiratory tract system:
Pharmacology overview:
- Bronchodilators:
They are able to relax bronchial smooth bans to dilate the bronchi and bronchioles that are narrowed as a result of the disease process. There are three classes of such drugs: beta agonists, anticholinergics, and xanthine derivatives.
1-Beta-Adrenergics Agonists:
Mechanism of action:
The beta agonists dilate airways by stimulating the beta2 adrenergic receptors located throughout the lungs. There are two types of these drugs:
1-Nonselective adrenergics drugs, which stimulating the beta1 and beta2 receptors, example: Epinephrine (given by subcutaneous).
2-Selective beta2 drugs, which primarily stimulate the beta2 receptors, example: salbutamol, terbutalin, salmetrol, and formetrol.
Activation of beta2 receptors activates adenylate cyclase, which is an enzyme needed to make cyclic adenosine monophosphate (cAMP), this results in produce more cAMP which relaxes smooth muscle in the airway and results in bronchial dilation and increased airflow
Short acting: Salbutamol: Oral or by inhalation. Terbutalin: Oral.
Long acting: Formetrol and salmetrol: inhalation.
Indications:
Relief of bronchospasm related to asthma, bronchitis, and other pulmonary diseases
Used in treatment and prevention of acute attacks (inhaled salbutamol).
Used in hypotension and shock (epinephrine)
Used to produce uterine relaxation to prevent premature labor (oral salbutamol and oral terbutalin)
Adverse effects:
Alpha and beta (epinephrine): Insomnia, Restlessness, Anorexia, Vascular headache, Hyperglycemia, Tremor, Cardiac stimulation
Beta 2agonists: Hypotension OR hypertension, Vascular headache, Tremor, and tachycardia.
Drug profile:
Salbutamol:
At large doses lose their selectivity, this lead to adverse effects like nausea and palpitation.
Used in acute attack by inhalation because the rapid onset of action (immediate), half-life up to 3-4 hours.
Salmetrol:
Used for maintenance treatment of asthma and COPD.
Given twice daily (half-life 12 hours).
2-Anticholenergics:
Ipratropium and tiotropium.
Mechanism of action:
Acetylcholine (ACh) causes bronchial constriction and narrowing of the airways
Anticholinergics bind to the ACh receptors, preventing ACh from binding
Result: bronchoconstriction is prevented, airways dilate
Indications:
Because their actions are slow and prolonged, anticholinergics are used for prevention of the bronchospasm associated with chronic bronchitis or emphysema and not for the management of acute symptoms.
Adverse effects:
Dry mouth or throat
Heart palpitations
Gastrointestinal distress
Headache
Coughing
Anxiety
Drug profile:
•These drugs can’t be taken by mouth, but taken by inhalation.
•Ipratropium (Atrovent):
Onset of action: 15 min
Duration: 4 hours.
Dosage form: aerosol, solution for inhalation.
•Tiotropium (Spiriva):
Long acting up to 20 hours.
Given once daily.
Dosage form: powder for inhalation.
3-Xanthine derivatives (Aminophylline (given parentrally) and theophylline (given orally).)
Mechanism of action:
Increase levels of energy-producing cAMP, this is done competitively inhibiting phosphodiesterase (PDE), the enzyme that breaks down cAMP.
Result: decreased cAMP levels, smooth muscle relaxation, bronchodilation, and increased airflow
Also cause cardiovascular stimulation: increased force of contraction and increased heart rate, resulting in increased cardiac output and increased blood flow to the kidneys (diuretic effect)
Also cause CNS stimulation.
Indications:
Xanthines may be used in mild to moderate cases of acute asthma and as an adjunct drug in the management of COPD. However, xanthines are now deemphasized as treatment for milder asthma because of their greater potential for drug interactions and narrow therapeutic index. They are often used for the prevention of asthmatic symptoms than for relief of acute asthma attacks.
Adverse effects:
Nausea, vomiting, anorexia
Tachycardia.
- Nonbronchodilating respiratory drugs:
1-Leukotriene respiratory antagonists (LRAs):
Montelukast (Singulair), zafirlukast (Accolate), zileuton (Zyflo). Montelukast is the only one found in the market.
Mechanism of action:
Leukotrienes are substances released when a trigger, such as cat hair or dust, starts a series of chemical reactions in the body. Leukotrienes cause inflammation, bronchoconstriction, and mucus production this result in coughing, wheezing, and shortnessof breath
LRAs As prevent leukotrienes from attaching to receptors on cells in the lungs and in circulationInflammation in the lungs is blocked, and asthma symptoms are relieved
By blocking leukotrienes:
Prevent smooth muscle contraction of the bronchial airways
Decrease mucus secretion
Prevent vascular permeability
Decrease neutrophil and leukocyte infiltrationto the lungs, preventing inflammation
Indications of montelukast:
Prophylaxis and chronic treatment of asthma in adults and children ages 2 and older, and for treatment of allergic rhinitis. NOT meant for management of acute asthmatic attacks
Adverse effects:
Zileuton: Headache, dyspepsia, nausea, dizziness, insomnia, liver dysfunction
Zafirlukast: Headache, nausea, diarrhea, liver dysfunction
Montelukast has fewer adverse effects
2-Corticosteroids:
They also had known as glucocorticoidsand used in the treatment of pulmonary diseases for their anti-inflammatory effects. They can be given by inhalation, orally, or even intravenously in severe cases of asthma. Inhalation prevents systemic adverse effects of corticosteiods. Corticosteroids may take several weeks before full effect can be seen.
Corticosteroids given by inhalation:
Beclomathasone.
Budesonise.
Flunisolide.
Fluticasone.
Systemic effects:
Dexamethasone: oral or parenteral.
Prednisone: oral.
Methylprednisonlone I.V or oral.
Mechanism of action:
The exact mechanism of action of the corticosteroids has not been determined. They have the dual effect of both reducing inflammation and enhancing the activity of beta agonists. They work by stabilizing the membranes ofleukocyte cells that normally release very harmful bronchoconstricting substances. They also have been shown to increase the responsiveness of bronchial smooth muscle to beta-adrenergic receptor stimulation, which results in more pronounced stimulation of the beta2 receptors by beta agonist drugs.
Indications:
They are used concurrently with bronchodilators, primarily beta-adrenergic agonists. Systemic corticosteroids are generally used only to treat acute exacerbations, or severe asthma.
Adverse effects:
Pharyngeal irritation, Coughing, Oral fungal infections.
Systemic effects are rare because low doses are used for inhalation therapy
Inhalers:
First-line drugs for treatment of asthma:
Beta-Agonists, and corticosteroids.
Alternative drugs to treat asthma:
Leukotriene antagonists, anticholinergics, xanthine derivaties, omalizumab (monoclonal antibody antiasthmatic, given by injection)
Drugs used to treat COPD:
Anticholinergics and beta-Agonists (can be used as combination)
Nursing implications:
Encourage patients to take measures that promote a generally good state of health so as to prevent, relieve, or decrease symptoms of COPD
Avoid exposure to conditions that precipitate bronchospasm (allergens, smoking, stress, air pollutants)
Adequate fluid intake
Compliance with medical treatment
Avoid excessive fatigue, heat, extremes in temperature, caffeine
Encourage patients to get prompt treatment for flu or other illnesses, and to get vaccinated against pneumonia or flu
Perform a thorough assessment before beginning therapy, including:
Skin color, Baseline vital signs, Respirations (should be between 12 and 24 breaths/min), Sputum production, Allergies, History of respiratory problems, Other medications
Teach patients to take bronchodilators exactly as prescribed
Ensure that patients know how to use inhalers and MDIs, and have patients demonstrate use of the devices
Monitor for adverse effects
Monitor for therapeutic effects
Decreased dyspnea
Decreased wheezing, restlessness, and anxiety
Improved respiratory patterns with return to normal rate and quality
Improved activity tolerance
Decreased symptoms and increased ease of breathing
Beta-agonist derivatives
salbutamol, if used too frequently, loses its beta2-specific actions at larger doses
As a result, beta1 receptors are stimulated, causing nausea, increased anxiety, palpitations, tremors, and increased heart rate
Ensure that patients take medications exactly as prescribed, with no omissions or double doses
Inform patients to report insomnia, restlessness, palpitations, chest pain, or
any change in symptoms
Xanthine derivatives:
Contraindications: history of PUD or GI disorders
Cautious use: cardiac disease
Timed-release preparations should not be crushed or chewed (cause gastric irritation)
Report to physician:Palpitations, Weakness, Convulsions, Nausea, Dizziness, Vomiting, and Chest pain
Be aware of drug interactions with cimetidine, oral contraceptives, allopurinol, certain antibiotics, others
Leukotrien receptor antagonists LRAs:
Ensure that the drug is being used for chronic management of asthma, not acute asthma
Improvement should be seen in about 1 week
Advise patients to check with physician before taking over-the-counter or prescribed medications—there are many drug interactions
Assess liver function before beginning therapy
Teach patient to take medications every night on a continuous schedule, even if symptoms improve
Inhaled corticosteroids:
Contraindicated in patients with psychosis, fungal infections, AIDS, TB
Teach patients to gargle and rinse the mouth with lukewarm water afterward to prevent the development of oral fungal infections
If a beta-agonist bronchodilator and corticosteroid inhaler are both ordered, the bronchodilator should be used several minutes before the corticosteroid to provide bronchodilation before administration of the corticosteroid
Encourage use of a spacer device to ensure successful inhalations
Teach patient how to keep inhalers and nebulizer equipment clean after uses
Inhalers: Patient Education
For any inhaler prescribed, ensure that the patient is able to self-administer the medication
Provide demonstration and return demonstration
Ensure that the patient knows the correct time intervals for inhalers
Provide a spacer if the patient has difficulty coordinating breathing with inhaler activation
Ensure that the patient knows how to keep track of the number of doses in the inhaler device