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ASTHMA & COPD *Asthma- excessive mucous inflammation Pathophysiology Clinical triad of Asthma 1.

Wheezing- abnormal breath sound 2. Cough- too much production to be expectorated 3. Dyspnea- difficulty of breathing, air trapping decrease airway Characteristics: 1. Inflammation- swelling, diameter, increase mucous secretion 2. Airway hyper reactivity-sensitivity 3. Bronchoconstriction- smooth muscle line, the airway would be contracting 4. Allergic Reaction 5. IgE antibodies- exposure an allergen reacts with mast cell- attached antibodies release of substance leads the ff: y localized edema in the walls of the small bronchioles (corticosteroids) y secretion of thick mucous into the bronchiolar lumens y spasm of the bronchiolar smooth muscle (relaxant to dilate airway ) *inflammation- mucous production decrease airway, expiration Asthma classification 1. Mild intermittent- occasional, mild symptoms 2. Mild persistent- once a week, night symptoms 3. Moderate persistent maintenance 4. Severe persistent- daily COPD- irreversible, damage have been done, damage can t be cure Classification 1. Chronic Bronchitis bluish, blue bloater. productive cough for at least 3 mos. for 2 consecutive years 2. emphysema- destruction of parenchyma,alveolar sac/ damage of alveoli, pink, It results from ff: *Chronic infection of the cilia of the respiratory epithelium by the effects of nicotine *excessive mucous secretion *inhibition of alveolar macrophages 3. Obstruction leads to entrapment of air in the alveoli and overstretching them Drugs used in Asthma Classification 1. C ontrollers/Preventers y Corticosteroids y Long Acting Bronchodilators- long acting beta agonist and theophylline y Stimulate Muscarinic Receptor y Combined Corticosteroid and Long Acting Bronchodilators Formeterol + Budenoside (Symbicort turbuhaler); Salmeterol+ Fluticasone (Seretide diskus) y Leukotriene Receptor Agonist Montelukast+ Zafirlukast 2. Relievers y Short-acting bronchodilators- short acting beta agonist and short acting theophylline y Anti-cholinergic drugs- Ipratropium bromide (Atrovent) y Combined anti-cholinergic & Short acting beta agonist- Ipratropium bromide + Salbutamol (Combivent & short acting beta agonist) y Sympathomimetic Agent

COPD NOTES treatment 1. Short actingF2 agonist and anticholinergic drugs- for acute symptoms 2. Long acting F2 agonist (Salmeterol) or long acting anticholinergic (Tiotropium) for persistent symptoms 3. Theophylline- improves contractile function of diaphragm primary respiratory muscle, contraction increase space thoracic space to allow air to come in 4. Nasal Oxygen- 100% of oxygen is not given prolong the survival increase high amount Oxygen- decrease respiratory drive. oxygen toxicity 5. Antibiotics- routine, infections MOA Sympathomimetic Agents Example 1.Epinephrine USES A/E CI DI OTHERS Effects of Sympathomometic Agent: *Relax airways smooth muscle *Inhibit release of bronchoconstricting from mast cells *Inhibit microvascular leakage(prevent edema) *edema- too much leakage in the capillary *increase mucociliary transport increase ciliary activity (Flush out the mucous) * Activate adenylyl cyclase increase cAMP relaxation of Smooth muscle

*Rapid acting *Non-selective agonist E1,F1,F2 *Stimulates E1,F1,F2 receptors Cardiovascular effects(tachycardia, increase blood pressure, increase heart rate) *Longer duration

*Anaphylactic shock *microaerosol

2. Ephedrine

*oral *less potent than epinephrine *maximal bronchodilation in 5 mins *rarely used *Increase in mortality due to cardiac arrhythmias

3.Isoproterenol

*Rapid Acting *non-selective

F2 selective Drugs

*Skeletal muscle tremor F2, stimulate contraction, increase glycogenolysis *nervousness, weakness

Example *Short Acting 1.Albuterol(Salbutamol/ Ventolin) 2.Terbutaline (Bricanyl/ Turbuhaler) 3.Metaproterenol

*inhaled/Oral *inhaled/Oral

4.Pirbuterol *Long Acting 1. Salmeterol 2.Formeterol Methylxanthines *Inhibit several members of the phosphodiesterase enzyme (esp. PDE4) family increase cAMP (bronchoconstriction) - stimulate cardiac functionpalpitation - smooth muscle relaxation -reduction of inflammation *inhibit adenosine receptor *anorexia, nausea, vomiting (too much acid secretion), abdominal discomfort, headache, anxiety Effects *CNS- mild cortical arousal, increase alertness & deferral of fatigue *CV- +chonotropy & inotropy(force of contraction) *GIT- stimulate gastric acid & digestive enzyme secretion *Kidney weak dieresis (theophylline) *SM- bronchodilation: inhibit antigen- induced release histamine *Skeletal muscle- improve contractility & reverse fatigue of the diaphragm in COPD pxs

Example 1.Theophylline

*most selective; narrow therapeutic window; improves long-term control of asthma, inexpensive,

*can be taken orally *emergency situation are not given, should check on plasma level/blood level

2. Theobromine 3.Caffeine 4.Aminophylline Antimuscarinic Agent *competitively inhibit the effect of the acetylcholne at muscarinic receptor *stops constriction, promote bronchodilation --blocks the contraction of airway Smooth muscle promote bronchoconstriction -- blocks the increase in mucus

Example 1.Atropine prototype 2. Ipratropium bromide 3.Tiotropium Spiriva

*enhance bronchodilation produced by nebulized albuterol *longer acting; for COPD; alternate to long acting F2 treatment of asthma *inhibit inflammatory cytokines *oropharyngeal candidiasis Leads to:

Corticosteroid

*hoarseness *increase risk of osteoporosis and cataracts Example 1.Prednisone 2.Beclomethasone 3.Budenoside 4.Ciclesonide 5.Fluniconide 6.Ciclesonide 7.Fluticasone 8.Mometasone 9.Triamcilone

*prodrug, highly bound protein *nasal spray, allergic rhinitis

Mast Cell Stabilizer

*Alters the function of delayed Cl channels and inhibits inflammatory cell activation *Inhibit mast cell degranulation

*Prophylaxis exercise induced asthma *Allergic rhinoconcjuctivitis/allergic rhinitis

*throat irritation, cough, dry mouth

*Reduce bronchial activity * Inhibit infiltration of asthmatic airways by lymphocyte, eosinophil (allergic rxn)and mast cell (release of inflammatory mediator) *can have severe S/E when given chronically; reserved for patients who require urgent treatment *refractory to treatment *adrenal suppression- adrenal cortex glands secretes aldosterone, cortisols, sex hormone

Example 1.Cromolyn 2.Nedocromil Leukotriene Pathway Inhibitors Example 1. Zilueton

2.Zafirlukast (Accolate) & Montelukast (Singulair) Anti- IgE monoclonal antibodies

*Inhibit of 5- lipoxygenase, prevenet leukotriene synthesis *least prescribed because of hepatotoxicity *inhibit binding of LTD4 to its receptor in target tissue *inhibit the binding of IgE to mast cells; does not provoke mast cell degranulation *IgE- release inflammatory mediation Benefits: *lower IgE to undetectable Levels *reduces the magnitude of early and late bronchospastic responses to antigen challenge

Example 1.Omalizumab

*lessen asthma severity night time symptom * reduces corticosteroid requirement

DRUGS USED IN ACID PEPTIC DISEASES HISTOLOGY 1. chief cells pepsin (enzyme), important in digestion 2. parietal cell- secreting HCl 3. Antral G cell- Gastrin 4. Antral D cell- Somatostatin 5. Enterochromaffin like cell (ECL)- Histamine Gastric Physiology Stimulated by: 1. Gastrin 2. Acetylcholine 3. Histamine Control of Acid Secretion 1. Somatostatin increase luminal pH concentration send signal, inhibits gastrin release 2. CCK (Cholecystokinin)- presence of protein and fats in the duodenum release of CCK to stop acid secretion Protective Barriers of the Stomach 1. Mucus- goblet 2. Mucosal Lining- simple columnar, prostaglandin will stimulate lining Acid Peptic Diseases 1. Peptic ulcer Disease 2. Gastroesophageal Disease 3. Gastritis- Acute & Chronic Approach Treatment 1. reduce the intragastric acidity y Antacid & H2 antagonist (Histamine 2 Receptor), y PPI- release HCl in parietal cell 2. Promote mucosal defense y Sucralfate protective barrier y Prostaglandin- allow regeneration of mucosal lining 3. Kill offending organism- associated with Helicobater pylori y antibiotic MOA USES A/E Antacid *neutralizes gastric acid Example 1.Sodium bicarbonate *produce sodium chloride and *belching& gastric carbon dioxide distention *potential cause of metabolic acidosis (milk alkali syndrome)

CI

DI

OTHERS

2.Calcium Carbonate

*produce Calcium Chloride & Carbon dioxide

3.Magnesium Hydroxide 4.Aluminum Hydroxide

*Produce magnesium chloride and water *produces Aluminum choride and water *competitively inhibit parietal cell H2 receptor *diminish gastrin & acetylcholine effect on gastric secretion *can cross placenta *GERD * PUD- promote healing *Gastritis *Comatose, critically ill

*hypercalcemia, renal insufficiency, metabolic acidosis (milk alkali syndrome) *osmotic diarrhea, tend to pull water *constipation Effect 1.Reduce nocturnal acid secretion (at night when sleeping since food is already digested) 2.Reduce meal- stimulated acid secretion

H2 receptor Antagonist

*secreted in breast milk

Example 1. Cimetidine- Tagamet (prototype)

*inhibits binding of dihydrotestosterone to androgen receptor Gynecomastia *Inhibit metabolism of estradiol, increase prolactin level gynecomastia, impotence, galactorrhea

*major inhibitor of cP450increase effects of quinidine, phenytoin, TCA & warfarin

2.Ranitidine- Zantac 3.Famotidine 4.Nizatidine Proton Pump Inhibitor

*irreversible direct inhibition of the proton- pump (K/H antiporter) in the gastric parietal cell * Longer duration of action

*GERD *PUD- rapid symptom relief and ulcer healing - for H.pylori associated ulcer - NSAID- associated ulcer - prevention of rebleeding *Non-ulcer dyspepsia *Stress- related Mucosal bleeding *Gastrinomas- Zollinger Ellison Syndrome

*Mild: diarrhea, decrease the absorption Vit.B12

*Ketoconazole/ItraconazoleAntifungal *Digoxin(Lanoxin)- Cardiac glycoside *Atazanavir- antiviral *decrease elimination of diazepam, warfarin & phenytoin

Characteristic *Administered as prodrugs *Formulation acid resistant, enteric- coated capsules/ tablets *Bioavailability decrease 50take on an empty stomach *Inhibits both fasting and meal-stimulated acid secretion

Example 1.Omeprazole 2.Esomeprazole 3.Lansoprazole 4.Pantoprazole Mucosal Prote

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