1. Respiratory System
Hmzeh Elayan

2. Respiratory Disorders
1- Asthma is characterized by:
- Episodes of acute bronchoconstriction.
- Inflammation of the bronchial wall.
- Increased secretion of mucus.
Causing:
shortness of breath, cough, chest tightness, wheezing, and rapid respiration.
It is a chronic disease with an underlying inflammatory pathophysiology that , if untreated, may incur airway remodeling, resulting in increased severity and incidence of exacerbations and/or death.

3. Asthma Triggers Allergen exposure e.g. pets, pollens etc.
Exercise/cold-air - drying airway mucosa.
Drugs - Beta blockers, NSAIDs
Food additives.
Upper respiratory tract
infections rhinovirus.
Gastro esophageal
reflux (GERD).

4. 2- Chronic obstructive pulmonary disease (COPD)
includes:
Emphysema which involves
damage to the lungs over time.
Chronic bronchitis which
Involves a long-term cough
with mucus. Smoking is the leading cause of COPD
3- Allergic rhinitis an inflammation of the mucous membranes of the nose ,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.

5. Asthma is State of bronchial hyperreactivity resulting from a persistent inflammatory process in response to a number of stimuli in a genetically susceptible individual
Key features of its pathophysiology
mucosal edema
secretion of mucus
epithelial damage
Bronchoconstriction
Therapy is aimed at
Symptomatic relief - relieving bronchoconstriction
Disease modification - reducing inflammation and lung damage
Drug Treatment of Asthma
Reflecting infiltration/activation of
eosinophils, mast cells & T h2 cells

6. Direct-acting β2-selective agonists
 Anti-Asthma Drugs:
Direct-acting β2-selective agonists
Inhaled β2 adrenergic agonists are the drugs of choice for mild asthma, that is, in patients showing only occasional, intermittent symptoms or exercise-induced bronchospam.
Short-acting (2-3h)
Salbutamol
Terbutaline
Long-acting (>12h)
Salmeterol
Eformoterol
( should not be used to relieve acute symptoms)
Side effects of β2 -agonists
Tremor. Hypokalaemia, Tachycardia
Generally worse with oral administration

7. Long-term control: Long-acting β2 adrenergic agonists (LABA ):
provide bronchodilation for at least 12 hours.
have slower onsets of action.
and should not be used for quick relief of an acute asthma attack.
Use of a LABA alone is contraindicated, and should be used in combination with Inhaled corticosteroids
Inhaled corticosteroids remain the long-term control drugs of choice in asthma, and long acting β2 agonists are considered to be useful adjunctive therapy for attaining asthma control.

8. Antimuscarinics. Ipratropium bromide (aerosol or nebulized) Mechanism
Competitive inhibition of M3 receptors of bronchial SM cells.
Prevents high vagal tone-induced bronchoconstriction in acute asthma.
Side-effects Limited absorption but atropine-like effects at high doses e.g. dry mouth, mydriasis, urinary retention
Generally less effective than β2 agonists in chronic asthma – high vagal tone only in acute asthma

9. Theophylline Weak bronchodilator Oral dosing Problems with its use
Poorly tolerated (GI side-effects especially) in up to 1/3rd of patients
Narrow therapeutic range (10-20mg/L)
Bioavailability varies widely between preparations
Extensive P450 metabolism - source of many interactions
Current Status
Probably 4th line following introduction of Leukotriene receptor antagonists (LTRAs)

10. Leukotriene antagonists
Leukotriene (LT) B4 and the cysteinyl leukotrienes, LTC4, LTD4, & LTE4, are products of the 5-lipoxygenase pathway of arachidonic acid metabolism and part of the inflammatory cascade. 5-Lipoxygenase is found in mast cells, basophils, eosinophils, & neutrophils. LTB4 is a potent chemoattractant for neutrophils and eosinophils, whereas the cysteinyl leukotrienes constrict bronchiolar smooth muscle, increase endothelial permeability, and promote mucus secretion.

11. Zileuton Zafirlukast &Montelukast inhibitor of 5-lipoxygenase,
preventing formation of both
LTB4 & the cysteinyl leukotrienes.
Zafirlukast &Montelukast
Block cysteinyl leukotriene-1 receptor.
Block effects of cysteinyl leukotrienes.
All three drugs are approved for the prophylaxis of asthma
not effective in acute attack of asthma.
Produce modest reductions in the doses of β2-agonists & corticosteroids & improve respiratory function.
Montelukast is approved for prevention of exercise-induced bronchospam.
They are orally active.

12. Corticosteroids Inhaled corticosteroids:
Beclomethasone, fluticasone, triamcinolone
Inhaled corticosteroids are the drugs of first choice in patients with asthma (mild, moderate, or severe).
No direct effect on the airway smooth muscle.
Decrease the inflammatory cascade (eosinophils, macrophages, and T lymphocytes), reversing mucosal edema, decrease the permeability of capillaries, and inhibit the release of leukotrienes.
Adverse effects: oropharyngeal candidiasis and Hoarseness.
Severe asthma or Status asthmaticus may require IV administration of methylprednisolone or oral prednisone.

13. Cromolyn Prophylactic agent, not useful in acute asthma attack.
inhibits mast cell degranulation and release of histamine &block the initiation of
immediate and delayed
asthmatic reactions.
Poorly absorbed.
Available as a nebulized solution.
Has only minor adverse effects.
Pretreatment with cromolyn
blocks allergen- and exercise-
induced bronchoconstriction.
Recommended, particularly in
children & pregnant women.

14. Drugs Used To Treat Chronic obstructive pulmonary disease (COPD)
COPD is a chronic, irreversible obstruction of airflow. Smoking is the greatest risk factor for COPD.
Inhaled bronchodilators, such as anticholinergic and β2-agonists, are the foundation of therapy for COPD.
These drugs increase airflow, alleviate symptoms, and decrease exacerbation of disease.
Combination of salbutamol and ipratropium
provides greater effect than with either drug alone.
Longer acting drugs, such as salmeterol have the advantage of less frequent dosing.
Inhaled corticosteroids are known to increase the risk of pneumonia in patients with (COPD).

15. DRUGS USED TO TREAT ALLERGIC RHINITIS
Combinations of oral antihistamines with decongestants are the first-line therapies for allergic rhinitis.
Antihistamines ( H1-Blockers)
decreased symptoms of allergic reactions (nasal stuffiness, red swollen eyes)
Sedating Antihistamines (1st generation)
Chlorphenramine diphenhydramine
drowsiness, dizziness, dry mouth, difficulty urinating.
 Non-sedating Antihistamine ( 2nd generation)
Work peripherally (do not cross the blood brain barrier) Loratadine, cetirizine

16. α- Adrenergic agonists
Phenylephrine
Short-acting nasal decongestant.
Oxymetazoline
Longer-acting.
As an aerosol, these drugs have a rapid onset of action and few systemic effects.
Should be used no longer than 3 days due to the risk of rebound nasal congestion .
Not useful in the long-term treatment of allergic rhinitis.
oral α-adrenergic agonist provide longer duration of action, but also increased systemic effects.
Combinations of these agents with antihistamines are frequently used.

17. Corticosteroids
Beclomethasone, budesonide, fluticasone, are effective when administered as nasal sprays.
They may cause nasal irritation, nose bleed, sore throat, and, rarely, candidiasis.
Topical steroids may be more effective than systemic antihistamines in relieving the nasal symptoms of both allergic and nonallergic rhinitis.

18. Leukotriene antagonists
Cromolyn
Intranasal cromolyn may be useful, particularly when administered before contact with an allergen.
Due to a short duration of action, cromolyn requires multiple daily dosing.
Leukotriene antagonists
The leukotriene antagonist montelukast is indicated for treatment of both seasonal and perennial allergic rhinitis.

19. DRUGS USED TO TREAT COUGH
Codeine
Decreases the sensitivity of cough centers in the CNS to peripheral stimuli & decreases mucosal secretion.
common side Effects:
constipation, dysphoria, fatigue & addictive potential.
Dextromethorphan
Synthetic derivative of morphine that suppresses the response of the central cough center.
low addictive profile, but may cause dysphoria at high doses
Dextromethorphan has better side effect profile than codeine and has been demonstrated to be equally effective for cough suppression.