Respiratory System

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Respiratory System

• Hmzeh Elayan. 2015.

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• 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.

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• 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).

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• 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.

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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 Ther
apy 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
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•  Anti-Asthma Drugs
• Direct-acting ß2-selective agonists
• Inhaled ß2 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 (gt12h)
• Salmeterol
• Eformoterol
• ( should not be used to relieve acute symptoms)
• Side effects of ß2 -agonists
• Tremor. Hypokalaemia, Tachycardia
• Generally worse with oral administration

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• Long-term control
• Long-acting ß2 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 ß2 agonists are considered to be useful
  adjunctive therapy for attaining asthma control.

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• 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 ß2 agonists in
  chronic asthma high vagal tone only in acute
  asthma

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• 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)

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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.

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• Zileuton
• 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
  ß2-agonists corticosteroids improve
  respiratory function.
• Montelukast is approved for prevention of
  exercise-induced bronchospam.
• They are orally active.

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• 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.

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• 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.

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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 ß2-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).
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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 drow
siness, dizziness, dry mouth, difficulty
urinating.  Non-sedating Antihistamine ( 2nd
generation) Work peripherally (do not cross the
blood brain barrier) Loratadine, cetirizine
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a- 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 a-adrenergic agonist provide longer
duration of action, but also increased systemic
effects. Combinations of these agents with
antihistamines are frequently used.
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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.
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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.
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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.