--Drugs Affecting on Respiratory System - Dental

Chapter II: Drugs affecting on respiratory system

Dr. Mahmoud H. Taleb

Assistant Professor of Pharmacology and ToxicologyDepartment of Pharmacology and Medical sciencesFaculty of Pharmacy- Al azhar University

*Dr. Mahmoud H. Taleb


Dr. Mahmoud H. Taleb*


Asthma:Bronchial asthma is a condition characterized by repeated attacks of paroxysmal dyspnea. It is now recognizes that chronic asthma involves a characteristic inflammatory response in the airways that is present in patients with very mild asthma. Bronchial hyperresponsiveness or an exaggerated bronchoconstrictor response to many different stimuli is characteristic of asthma. There is remains considerable debate about the types of inflammatory cells and mediators involved in asthma. Dr. Mahmoud H. Taleb*


Lymphokines may be important mediators in increasing the inflammatory response, and interleukin-5 release by lymphocytes also may be important in acting to prime the eosinophils in the mucusa.Dr. Mahmoud H. Taleb*


Dr. Mahmoud H. Taleb*Mechanisms of response to inhaled irritants


Drugs Used in Asthma: IntroductionThe clinical hallmarks of asthma are recurrent, episodic bouts of coughing, shortness of breath, chest tightness, and wheezing. In mild asthma, symptoms occur only occasionally, eg, on exposure to allergens or certain pollutants, on exercise, or after a viral upper respiratory infection. More severe forms of asthma are associated with frequent attacks of wheezing dyspnea, especially atnight, and even chronic limitation of activity. Asthma is the most common chronic disabling disease of childhood, but it affects all age groupsDr. Mahmoud H. Taleb


Asthma therapies are thus sometimes divided into two categories: "short-term relievers" and "long-term controllers."Short-term relief is most effectively achieved with bronchodilators, agents that increase airway caliber by relaxing airway smooth muscle, and of these the -adrenoceptor stimulants , a methylxanthine drug, and antimuscarinic agents are also used for reversal of airway constriction. Long-term control is most often achieved with an anti-inflammatory agent such as an inhaled corticosteroid, with a leukotriene antagonist, or with an inhibitor of mast cell degranulation, eg, cromolyn or Ketotifen.Dr. Mahmoud H. Taleb*


A. Goals of therapyA. Reducing impairment:B. Prevent chronic and a. troublesome symptoms.C. Require infrequent use of inhaled short-acting B2 agonist for quick relief of symptoms.D. Maintain normal pulmonary function.E. Maintain normal activity levels (including exercise and other physical activity and attendance at work orschool). Dr. Mahmoud H. Taleb*


Drugs Used to Treat Asthma 1-Bronchodilator drugs: Activation of 2-adrenoceptors on the smooth muscle of the airways causes activation of adenylyl cyclase with a subsequent increase in the intracellular concentration of cyclic AMP.

(A) Adrenergic agonistsInhaled adrenergic agonists with B-2 activity are the drugs of choice for mild asthma that is, in patients showingonly occasional, intermittent symptoms .Direct-acting B- agonists are potent bronchodilators thatrelax airway smooth muscle.Quick relief: Most clinically useful B2 agonists have a rapid onset of action (5-30 minutes) and provide relief for 4 to 6 hours. Dr. Mahmoud H. Taleb*


They are used for symptomatic treatment of bronchospasm, providing quick relief of acute bronchoconstriction. [Note: Epinephrine is the drug of choice for treatment of acute anaphylaxis.] 2 Agonistshave no anti-inflammatory effects, and they should never be used as the sole therapeutic agents for patients with persistent asthma.



Monotherapy with short-acting 2 agonists may be appropriate only for patientsidentified as having mild intermittent asthma, such as exercise-induced asthma. The direct-acting 2-selectiveagonists, such as terbutaline ,and albuterol offer the advantage of providing maximally attainable bronchodilation with little of the undesiredeffect of or 1 stimulation. Adverseeffects, such as tachycardia, hyperglycemia, hypokalemia, and hypomagnesemia are minimized with dosing viainhalation versus systemic routes.Dr. Mahmoud H. Taleb*


B-Anticholinergic drugs:Atropine is a competitive blocker of acetylcholine at muscarinic cholinergic receptors and thus can cause a variety of effects due to loss of parasympathetic activity, including blurring of vision, increase in heart rate, and drying of secretions in the salivary glands and respiratory tract. This limits its usefulness as a bronchodilator. Atropine is best used by inhalation, which reduces, but does not eliminate entirely, these unwanted side effects.Dr. Mahmoud H. Taleb*


Ipratropium bromide (Atrovent) is a quaternary isopropyl-substituted derivative of atropine that can not cross the blood-brain barrier and therefore has practically no central effect; it also shows some degree of bronchoselectivity. The actions of ipratropium bromide are otherwise similar to those of atropine, and its therapeutic use is confined to aerosol administration. The drug is administered by inhaler and each puff contains 20g, the exact place of ipratropium bromide in the treatment of asthma remains somewhat uncertain, and the drug appears to have little advantage over the selective 2-agonists.



C-MethylxanthinesThe 3 important are theopylline, theobromine, and caffeine. Their major source of intake by humans is beverages such as tea, cocoa, and coffee, respectively. Their effects are as follows:CNS effects: in low to moderate doses, the methylxanthines, especially caffeine, cause mild cortical arousal with increased alertness and deferral of fatigue, in unusually sensitive individuals, the caffeine contained in beverages (e.g., 100mg in a cup of coffee) is sufficient to cause nervousness and insomnia. Nervousness and tremor are primary side effects in patients taking large doses of aminophylline for asthma.Dr. Mahmoud H. Taleb*


Cardiovascular effects: the methylxanthines have direct positive chronotropic and inotropic effects on the heart. At low con., these effects appear to result from increased calcium influx, probably mediated by increased cyclic AMP. At higher con., sequestration of calcium by the sarcoplasmic reticulum is impaired, so intracellular calcium con. Is increased and myocardial contraction is strengthened. Methylxanthines have occasionally been used in the treatment of pulmonary edema associated with heart failure. These agents also relax vascular smooth muscle except in cerebral blood vessels, where they cause contraction.



GIT effects: they stimulate secretion of both gastric acid and digestive enzymes.Kidneys: they, especially theophylline, are weak diuretics. This effect may involve both increased glomerular filtration and reduced tubular sodium reabsorption. This effect is not sufficient therapeutically.



Smooth muscle: the bronchodilatation produced by the methylxanthines is the major therapeutic action. Tolerance does not develop, but side effects, especially in the CNS, may limit the dose. In addition to this direct effect on the airway smooth muscle, these agents inhibit antigen-induced release of histamine from lung tissue; their effect on mucociliary transport is unknown.agent.Dr. Mahmoud H. Taleb*


Skeletal muscle: the therapeutic actions of the methylxanthines may not be confined to the airways, for they also strengthen the contractions of isolated skeletal muscle in vitro and have potent effects in improving contractility and in reversing fatigue of the diaphragm in patients with chronic obstructive lung disease. Dr. Mahmoud H. Taleb*


2- Anti-inflammatory steroids:Glucocorticoid drugs such as prednisone, prednisolone, dexamethasone and Budesonide are known empirically to relieve airway obstruction in bronchial asthma, but the mechanism of their action is complex. The possible actions include:Anti-inflammatory activity.Reduction of tissue sensitivity to antigens.Inhibition of contraction of bronchial smooth muscle.Mucolytic action.Increased responsiveness of 2-adrenoceptors.



Dr. Mahmoud H. Taleb*Recently, glucocorticoid drugs such as beclomethasone dipropionate and beclomethasone valerate, budnoiside, predisone have been developed for administration by inhalation. Inhalation of these compounds is as effective as oral prednisone in patients starting on steroids. Only a small amount of the steroid administered in this manner is systemically absorbed. Therefore there is little or no systemic effect or adrenal suppression and the problem of growth suppression in children may be avoided. The major problem with this form of therapy to date has been the development of fungal infections (candidiasis) in the oropharynx in about 10% of patients because of suppression of phagocytic activity by the high local concentrations of corticosteroid.


3- Mast cell stabilizers Cromolyn sodium (sodium cromoglycate), and KetotifenIt inhibits the release of mediators such as histamine and leukotrienes from the secretory granules of mast cells following the challenge of antigen interacting with specific IgE antibodies. The exact mechanism underlying the action of cromolyn sodium is not clear, but the drug is active only against type I (immediate) allergic reactions and not against delayed or immune reactions. However, cromolyn sodium is also effective in asthma induced by exercise and by exposure to cold dry air. Therefore it is suggested that cromolyn sodium acts as a nonspecific stabilizer of the mast cell membrane and/or granules.



Cromolyn sodium is absorbed poorly from the gastrointestinal tract and therefore is effective only when deposited directly into the airways. Two methods of administration are currently used for asthma. In adults, the drug can be given by a "Spinhaler" apparatus that causes a capsule to be punctured so that its powdered contents are entrained into inspired air and deposited in the airways. The usual dose is 20 mg inhaled four times daily. In children, who may have difficulty in using this device, the drug may be given by aerosol.



4- Leukotriene Pathway InhibitorsEfficacy in blocking airway responses to exercise and to antigen challenge has been shown for drugs in both categories: zileuton, a 5-lipoxygenase inhibitor, and zafirlukast and montelukast, LTD4-receptor antagonists. All have been shown to be effective when taken regularly in outpatient clinical trials. Their effectsDr. Mahmoud H. Taleb*


5- Monoclonal antibodies eg. OmalizumabOmalizumab is a recombinant DNA derived monoclonal antibody that selectively binds tohuman immunoglobulin E (IgE). This leads to decreased binding of IgE to the high-affinity IgE receptor on the surface of mast cells and basophils. Reduction in surface-bound IgE limits the degree of release of mediators of the allergic response. Omalizumab may be particularly useful for treatment of moderate to severe allergic asthma in patients who are poorly controlled with conventional therapy. Due to the high cost of the drug (approximately $600 for a 150-mg vial), limitations on dosage, and available clinical trial data, it is not presently used as first-linetherapy.Dr. Mahmoud H. Taleb*


Drugs Used to Treat Chronic Obstructive Pulmonary DiseaseDr. Mahmoud H. Taleb*


DRUGS AFFECTING THE COUGH REFLEXThe cough reflex is mediated by receptors located in the mucosa or deeper structures of the larynx, trachea, and major bronchi, and by mechanoreceptors that detect changes in bronchial intramural tension. Stimuli are transmitted via the vagus to the cough center in the medulla. Efferent impulses originating from the cough center are transmitted through cholinergic pathways to the abdominal and intercostal muscles and to the diaphragm, producing sudden explosive expiratory movements. Dr. Mahmoud H. Taleb*


Antitussive Drugs:Opioid antitussive agents:Opioid analgesics are most effective in depressing the cough center. Codeine thus appears to be a more effective cough suppressant relative to its analgesic activity. The usual antitussive dose is 15-20 mg as required.Dr. Mahmoud H. Taleb*


Codeine also has significantly less respiratory depressant effect than morphine. The development of tolerance and physical dependence is a major drawback to morphine-like drugs, and for this reason, their long-term use as antitussive agents is discouraged. They can, however, be used for short-term cough suppression. Because of the low dose of codeine required, and its relatively low addiction liability, it may be more suitable than other opioid drugs for long-term antitussive useDr. Mahmoud H. Taleb*


Nonopioid antitussive agents:

Dextromethorphan is a synthetic opioid derivative that is an effective antitussive agent, suppressing the response of the cough center but lacking analgesic or habituating properties. It is the d-isomer of levomethorphan, which is a potent opioid analgesic. This demonstrates that the analgesic activity, as well as the addictive properties, are exerted through receptors with stereospecificity, while the antitussive receptor sites lack the opioid stereospecificity. Levopropoxyphene is similarly an antitussive that lacks the analgesic activity of its isomer dextropropoxyphene. Other nonopioid drugs that have some antitussive activity in addition to their other pharmacological actions include phenothiazines, antihistamines, and benzononatateDr. Mahmoud H. Taleb*


Mucolytic Agents:Mucolytic inhalants are mucokinetic substances that liquefy mucus and aid the elimination of excess solidified mucus in patients with respiratory disease. Excess mucus may be liquefied by proteolytic agents and disulfide bond cleaving agents. Acetylcysteine. It possesses a reactive sulfhydryl group that splits the disulfide bonds of the mucin molecule and thereby reduces the viscosity of mucus. This drug is an extremely effective mucokinetic agent, but it is little used because it causes many side effects such as stomatitis, nausea, vomiting, rhinorrhea, and especially bronchospasm. Bromohexine (Rx Bisolvon, Solvex ,, Mucocare) It stimulates lysosomal activity , leads to hydrolysis of mucopolysaccharides and decrease the viscosity of the mucus



Drugs Used to Treat Allergic RhinitisRhinitis is an inflammation of the mucous membranes of the nose and is characterized by sneezing, itchy nose/eyes, watery rhinorrhea, and nasal congestion. An attack may be precipitated by inhalation of an allergen (such as dust, pollen, or animal dander). The foreign material interacts with mast cells coated with IgE generated in response to a previous allergen exposure ,The mast cells release mediators, such as histamine, leukotrienes, and chemotactic factors, that promote bronchiolar spasm and mucosal thickening from edema and cellular infiltration. Dr. Mahmoud H. Taleb*


Combinations of oral antihistamines with decongestants are the first-line therapies for allergic rhinitis. Systemic effects associated with these oral preparations (sedation, insomnia, and, rarely, cardiac arrhythmias) have prompted interest in topical intranasal delivery of drugs.



Drugs used to treat allergic rhinitisA. Antihistamines (H1-receptor blockers) eg. Chlorophenermine malate,cyproheptadine, loratidine, cetrizine, and fexofenadineB. -Adrenergic agonists eg, phenylephrine. Ephedrine , oxymetazoline and naphazoline. C. Corticosteroids eg. fluticazone, BudesonideD. Cromolyn and ketotifenDr. Mahmoud H. Taleb*


Thank you!*Dr. Mahmoud H. Taleb


--Drugs Affecting on Respiratory System - Dental

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