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Overview of Anatomy and Physiology The respiratory system is composed of the upper and lower respiratory tracts. Together, the two tracts are responsible for ventilation (movement of air in and out of the airway). The upper tract, known as the upper airways, warms and filters the inspired air so that the lower respiratory tract (the lungs) can accomplish gas exchange. Upper Respiratory Tract Nose Paranasal Sinuses Turbinate Bones Pharynx Tonsils Adenoids Larynx Trachea Lower Respiratory Tract Lungs: Pleura Bronchi and Bronchioles Alveoli Upper Respiratory Tract Upper Respiratory Tract Infections A. Rhinitis Rhinitis is a group of disorders characterized by inflammation and irritation of the mucous membranes of the nose. It may be acute or chronic, nonallergic or allergic. Pharmacologic Therapy 1. Antihistamines H1 receptor antagonists, inhibit smooth muscle constriction in blood vessels & respiratory & GI tracts. Decrease capillary permeability. Decrease salivation & tear formation. Used for variety of allergic disorders to prevent or reverse target organ inflammation. i. First-generation H1-receptor Antagonists Non-selective/sedating Bind to both central & peripheral H1 receptors
Usually cause CNS depression (drowsiness, sedation) but may cause CNS stimulation (anxiety, agitation), especially in children Also have substantial anticholinergic effects Chlorpheniramine maleate (Aller-Chlor, Allergy, Chlo-Amine, Chlor-Trimeton Allergy 4 hour/8 hour/12 hour, Chlor-Tripolon) Clemastine fumarate (Dayhist-1, Tavist Allergy) Brompheniramine Diphenhydramine hydrochloride (Allerdryl, AllerMax Allergy and Cough Formula, Allermax Caplets, Aller-med, Banophen, Benadryl, Benadryl Allergy, Benylin Cough, Bydramine Cough, Compoz, Diphen Cough, Diphenhist, Diphenhist Captabs, Dormarex 2, Genahist, Hydramine, Hydramine Cough, Nervine Nighttime Sleep-Aid, Nordryl Cough, Sleep-Eze 3, Sominex, Tusstat, Twilite Caplets, Uni-Bent Cough) Hydroxyzine Promethazine hydrochloride(Phenadoz, Phenergan)/ Promethazine theoclate (Avomine) Azatadine Azelastine Buclizine Mechanism of Action: Competes with histamine for H1-receptor sites on effector cells. Drug prevents, but doesnt reverse, histamine-mediated responses. Adverse Effects: Sedation Dry mouth Blurred vision GI disturbances Headache Urinary retention Hydroxyzine is not recommended for pregnancy & breast-feeding Second-generation H1-receptor Antagonist Selective/non-sedating Cause less CNS depression because they are selective for peripheral H1 receptors & do not cross blood-brain barrier Longer-acting compared to first-generation antihistamines Cetirizine hydrochloride (Zyrtec) Deslortadine (Clarinex, Clarinex Reditabs) Fexofenadine hydrochloride (Allegra, Telfast) Loratadine (Alavert, Claratyne, Clarinase, Claritin, Claritin Reditabs, Claritin Syrup, Tavist ND, Allergy) Acrivastine (Semprex) Mechanism of Action: ii.
A long-acting non-sedating antihistamine that selectively inhibits peripheral H1 receptors. Adverse effects: May cause slight sedation Some antihistamines may interact with antifungal, e.g. ketoconazole; antibiotics, e.g. erythromycin; prokinetic drug-- cisapride or grapefruit juice, leading to potentially serious ECG changes e.g. Terfenadine Several antihistamine nasal sprays (for example, azelastine [Astelin]) are also available to treat symptoms such as runny nose, sneezing, and itchy nose.
First-line: i. Penicillins Amoxicillin and clavulanate potassium (Augmentin, Augmentin ES-600, Augmentin XR, Clavulin) Amoxicillin trihydrate (Alphmox, Amoxil, Apo-Amoxi, Cilamox, DisperMox, Moxacin, Novamoxin, Nu-Amoxi, Trimox) Ampicillin (Apo-Ampi, Novo Ampicillin, Nu-Ampi)/ Ampicillin sodium (Ampicin, Ampicyn, Penbritin)/ Ampicillin trihydrate (Penbritin, Principen) Mechanism of Action: Inhibits cell-wall synthesis during bacterial multiplication. Second-line: i. Cephalosporins Cefaclor (Ceclor, Ceclor CD, Raniclor) Cefazolin sodium (Ancef) Cefnidir (Omnicef) Mechanism of Action: Inhibits cell-wall synthesis, promoting osmotic instability; usually bactericidal.
ii.
Mechanism of Action: iii. Fluoroquinolones Ciprofloxacin (Cipro, Cipro I.V., Cipro XR, Ciproxin) Gatifloxacin (Tequin) Levofloxacin (Levaquin) Moxifloxacin hydrochloride (Avelox, Avelox I.V)
Mechanism of Action:
2. Nasal decongestants Ephedrine sulphate (Kondons Nasal) Phenylephrine hydrochloride (Neo-Synephrine) 3. Antihistamine
wall of the nasopharynx. Infection of the adenoids frequently accompanies acute tonsillitis. Pharmacologic Therapy 1. Antibiotic Therapy (same as in pharyngitis)
E. Peritonsillar abscess
Peritonsillar abcess is the collection of purulent exudate between the tonsillar capsule and the surrounding tissues, including the soft palate.
F. Laryngitis
Laryngitis is the inflammation of the larynx, often occurs as a result of voice abuse or exposure to dust, chemical, smoke, and other pollutants, or as a part of URI. Pharmacologic Therapy 1. Cortecosteroids Suppressing inflammation Decrease synthesis & release of inflammatory mediators Decrease infiltration & activity of inflammatory cells Decrease edema of the airway mucosa Decrease airway mucus production Increase the number of bronchial beta2 receptors & their responsiveness to beta2 agonists i. Inhaled Beclomethasone (Beclo-vent, Vanceril, Qvar) Budesonide (Pulmicort Respules, Pulmicort Turbuhaler) Mometasone furoate (Asmanex Twisthaler) Fluticasone (Flovent) Triamcinolone (Azmcort) Lower Respiratory Tract
A. Pneumonia
Pneumonia is an inflammation of the lung parynchema caused by various microorganisms, including bacteria, mycobacteria, chlamydiae, mycoplasma, fungi, parasites, and viruses. Pharmacologic Therapy 1. 2. Antibiotic Therapy Antiviral Therapy
B. Pulmonary Tuberculosis
Tuberculosis is an infectious disease that primarily affects the lung parenchyma. Pharmacologic Therapy 1. Antitubercular Drugs Group 1: First Line Oral Agents Isoniazid/ INH/ Isonicotinic Acid Hydrazide (Isotamine, Nydrazid, PMSIsoniazid) Mechanism of Action: Unknown. May inhibit cell-wall biosynthesis by interfering with lipid and DNA synthesis; bactericidal. Adverse Effects: Peripheral neuropathy Seizures Toxic Encephalopathy Memory impairment Toxic psychosis Nausea, vomiting, epigastric distress Optic neuritis and atrophy Agranulocytosis, haemolytic anemia, aplastic anemia, eosinophilia, thrombocytopenia Hepatitis, jaundice, bilirubinemia Pyridoxine deficiency Gynecomastia Rifampicin/ Rifampin (Rifadin, Rimactane, Rimycin, Rofact) Mechanism of Action: Inhibits DNA-dependent RNA polemyrase, which impairs RNA synthesis; bactericidal. Adverse Effects: Reddish discoloration of body fluids Headache, fatigue, drowsiness, behviral changes, dizziness, mental confusion, generalized numbness, ataxia Visual disturbances, exudative conjunctivitis Vomiting, anorexia, nausea, diarrhea, abdominal distress/pain. Pseudomembranous colitis, pancreatitis Hepatotoxicity, acute renal failure Hyperuricemia, osteomalacia Shortness of breath, wheezes Flu-like syndrome Ethambutol hydrochloride (Etibi, Myambutol) Mechanism of Action:
Unknown. May inhibit synthesis of one or more metabolites of susceptible bacteria, changing cell metabolism during cell division; bacteriostatic. Adverse Effects: Headache, dizziness, fever, mental confusion, hallucinations, malaise, peripheral neuritis. Optic neuritis Vomiting, anorexia, nausea, diarrhea, abdominal pain Thrombocytopenia Hyperuricemia, precipitation of gout Joint pain Toxic epidermal necrolysis Dermatitis, pruritus Group 2: Injectable Agents/ Aminoglycosides Streptomycin sulfate Kanamycin Amikacin sulfate Capreomycin Mechanism of Action: Inhibits protein synthesis by binding directly to the 30S ribosomal subunit; bactericidal Adverse Effects: Ototoxicity, tinnitus Blurred vision Confusion Nephrotoxicity Anemia, leukopenia, thrombocytopenia, agranulocytosis Muscle twitching, myasthenia gravis-like syndrome. Group 3: Fluoroquinolones Levofloxacin Ofloxacin Moxifloxacin hydrochloride (Avelox, Avelox I.V.) Group 4: Oral Bacteriostatic Second Line Agents Ethionamide Protionamide Cycloserine (Seromycin) Terizidone p-aminosalicylic acid Group 5: consists of agents with unclear efficacy Clofazimine Linezolid Thioacetazone Imipenem/cilostatin High-dose Isoniazid Clarithromycin
2.
Vaccination: BCG
Used for maintenance therapy of bronchoconstriction associated with chronic bronchitis & emphysema Ipratropium bromide (Atrovent) Tiotropium bromide (Spiriva) Oxitropium bromide (Oxivent) b. Cortecosteroids Suppressing inflammation Decrease synthesis & release of inflammatory mediators Decrease infiltration & activity of inflammatory cells Decrease edema of the airway mucosa Decrease airway mucus production Increase the number of bronchial beta2 receptors & their responsiveness to beta2 agonists Long-term treatment with oral corticosteroids is not recommended in COPD and can cause steroid myopathy i. Inhaled Beclomethasone (Beclo-vent, Vanceril, Qvar) Budesonide (Pulmicort Respules, Pulmicort Turbuhaler) Mometasone furoate (Asmanex Twisthaler) Fluticasone (Flovent) Triamcinolone (Azmcort) c. Other Medications: i. Alpha1-antitrypsin augmentation therapy ii. Antibiotic Agents iii. Mucolytic Acetylcysteine (Acetadote, Mucomyst, Mucosil-10, Mucosil-20) Mechanism of Action: Reduces the viscosity of pulmonary secretions by splitting disulphide linkages between mucoprotein molecular complexes. Also, restores liver stores of glutathione to treat acetaminophen toxicity. iv. Expectorants Render the cough more productive by stimulating the flow of respiratory tract secretions Guaifenesin is most commonly used Available alone & as an ingredient in many combination cough & cold remedies Guaifenesin/gyceryl guaiacolate (Allfen Jr. Anti-Tuss, Ganidin NR, Guiatuss, Hytuss, Hytuss 2x, Mucinex, Naldecon Senior EX, Robitussin, Scot-Tussin Expectorant)
v. Antitussive Drugs that suppress cough Some act within the CNS, some act peripherally Indicated in dry, hacking, nonproductive cough that interfere with rest & sleep Codeine phosphate 25mg/5ml syrup Pholcodine 5mg/5ml Elixir Dextromethorphan 10mg/5ml in Promethazine Compound Linctus Dextromethorphan hydrobromide (Balminil DM, Benilyn DM, Broncho-Grippol-DM, Buckleys DM, Childrens Hold, Delsym, Hold, Koffex DM, Pertussin CS, Robitussin Pediatric, St. Josepph Cough Suppressant for Children, Trocal, Vicks Formul 44e Pediatric) Diphenhydramine 10 mg/ 5ml Benzonatate (Tessalon, Tessalon Perles)
D. Asthma
Asthma is a chronic inflammatory disease of the airways that causes airway hyperresponsiveness, mucosal edema, and mucus production. a. Bronchodilators i. Beta2-Adrenergic Agonist Agent Stimulate beta2 receptors in smooth muscle of the lung, promoting bronchodilation, and thereby relieving bronchospasms They are divided into short-acting & long acting types Short-Acting Beta2 Agonists (SABAs) Albuterol (Proventil, Ventolin, Volmax) Metaproterenol (Alupent) Salbutamol Terbutaline sulfate (Brethine) Long-Acting Beta2 Agonists (LABAs) Bitolterol (Tornalate) Formoterol (Foradil) Salmetrol (Serevent Diskus) ii. Leukotriene Modifiers Act by suppressing the effects of leukotrienes, compounds that promote bronchoconstriction as well as eosinophil infiltration, mucus productions, & airway edema Help to prevent acute asthma attacks induced by allergens & other stimuli Indicated for long-term treatment of asthma Montelukast (Singulair) Zafirlukast (Accolate) Zileuton (Zyflo, Zyflo CR) iii. Methylxanthines Aminophylline (Phyllocontin)
Theophylline (Slo-bid, Theo-Dur) iv. Mast Cell Stabilizers b. Combined Medications i. Muscarinic antagonist+2 agonist Combivent (20mcg Ipratropium & 100mcg salbutamol /dose, MDI) ii. Corticosteroid+2 agonist Symbicort (160mcg Budesonide+4.5mcg Formoterol / dose, Turbuhaler) Seretide (Salmeterol+Fluticasone: MDi in Lite, Medium, Forte preparation & Accuhaler) c. Corticosteroids i. Inhaled Beclomethasone (Beclo-vent, Vanceril, Qvar) Budesonide (Pulmicort Respules, Pulmicort Turbuhaler) Mometasone furoate (Asmanex Twisthaler) Fluticasone (Flovent) Triamcinolone (Azmcort) ii. Systemic
E. Lung Abcess
A lung abscess is a localized necrotic lesion of the lung parenchyma containing purulent material that collapses and forms a cavity. Pharmacologic Therapy a. Antibiotic Therapy
Pulmonary arterial hypertension exists when the systolic pulmonary artery pressure exceeds 30 mmHg or the men pulmonary artery pressure exceeds 25 mmHg at rest or 30 mmHg with activities. Pharmacologic Therapy a. Endothelin Receptor Antagonist Bosentan b. Diuretics c. Inotropic Agents d. Anticoagulant Therapy e. Calcium Channel Blockers f. Prostaglandin
H. Cystic Fibrosis
Cystic fibrosis is the most common fatal autosomal recessive disease among the Caucasians. A person must inherit a defective copy of the gene to have CF. This is caused by a mutations in the CF transmembrane conductance regulator protein, which is a chloride channel found in all exocrine tissues. Pharmacologic Therapy 1. Mucolytic Agents Dornase alfa (Pulmozyme) Mechanism of Action: Hydrolyzes DNA in sputum of cystic fibrosis patients, causing decreased viscosity and elasticity of pulmonary secretions. Adverse Reactions: Chest pain Acetylcysteine (Acetadote, Mucomyst, Mucosil-10, Mucosil-20) Mechanism of Action: Reduces the viscosity of pulmonary secretions by splitting disulphide linkages between mucoprotein molecular complexes. Also, restores liver stores of glutathione to treat acetaminophen toxicity.