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CHRONIC OBSTRUCTIVE PULMONARY DISEASE
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Chronic obstructive pulmonary disease (COPD) is defined as a disease state
characterized by airflow limitation that is not fully reversible
COPD includes emphysema- an anatomically defined condition characterized by
destruction and enlargement of lung alveoli and chronic bronchitis- a clinically
defined condition with chronic cough and phlegm
CLINICAL SIGNS
CRITERIA FOR SEVERITY OF AIRFLOW OBSTRUCTION IN COPD:
Patient Group A, Low Risk, Less Symptoms:
GOLD 1 or GOLD 2 and/or
0-1 exacerbation per year and
No hospitalization for exacerbation; and
CAT score < 10 or mMRC grade 0-1
Patient Group B, Low Risk, More Symptoms:
GOLD 1 or GOLD 2 and/or
0-1 exacerbation per year and
No hospitalization for exacerbation and
CAT score ≥ 10 or mMRC grade ≥ 2
Patient Group C , High Risk, Less Symptoms:
GOLD 3 or GOLD 4 and/or
≥ 2 exacerbations per year or
≥ 1 with hospitalization for exacerbation and
CAT score < 10 or mMRC grade 0-1
Patient Group D, High Risk, More Symptoms:
GOLD 3 or GOLD 4 and/or
≥ 2 exacerbations per year or
≥ 1 with hospitalization for exacerbation and
CAT score ≥ 10 or mMRC grade ≥ 2
PHARMACOLOGIC TREATMENT (STABLE COPD):
BRONCHODILATORS:
Increase the FEV1 or change other spirometric variables, usually by altering airway
smooth muscle tone
Improve emptying of the lungs, tend to reduce dynamic hyperinflation at rest and
during exercise and improve exercise performance
Long-acting Inhaled Bronchodilators are convenient and more effective at producing
maintained symptom relief than Short-Acting Bronchodilators
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Treatment with a Long-Acting Inhaled Anticholinergic drug reduces the rate of COPD
exacerbations and improves the effectiveness of pulmonary rehabilitation
Combining bronchodilators may improve efficacy and decrease the risk of side effects
compared to increasing the dose of a single bronchodilator
BETA2-AGONISTS
The principal action of Beta2-Agonists is to relax airway smooth muscle by
stimulating Beta2-Adrenergic receptors, which increases cyclic AMP and produces
functional antagonism to bronchoconstriction
Regular and an as-needed use of Short-Acting Beta2-Agonists improve FEV1 and
symptoms
Long-Acting Inhaled Beta2-Agonists, such as Salmeterol and Formoterol, show a
duration of effect of 12 hours or more
Indacaterol is a once daily Beta2-Agonist with a duration of action of 24 hours
Indacaterol has significant effects on breathlessness, health status and exacerbation
rate
Short- Acting: SALBUTAMOL, FENOTEROL Duration of Action (hours) 6-8 h
Long-Acting: FORMOTEROL, SALMETEROL, INDACATEROL ( ultra LONG)
BETA2-AGONISTS adverse effects:
Resting sinus tachycardia
Cardiac rhythm disturbances in very susceptible patients
Hypokalemia (when treatment is combined with Thiazide Diuretics)
ANTICHOLINERGICS:
The most important effect of anticholinergic medications is blockage of
acetylcholine’s effect on muscarinic receptors
Short-Acting drugs block M2 and M3 receptors and modify transmission at the preganglionic junction
The Long-Acting Anticholinergic Tiotropium has a pharmacokinetic selectivity for the
M3 and M1 receptors
The bronchodilating effect of Short-Acting Inhaled Anticholinergics lasts 8 hours
Acclidinium has a duration of at least 12 hours
Tiotropium and Glycopyrronium have a duration of action of more than 24 hours
ANTICHOLINERGICS adverse effects:
The main side effect is dryness of the mouth
A bitter, metallic taste ( after using Ipratropium)
Acute urinary retention (in patients with prostatic hypertrophy)
Acute glaucoma has been precipitated when nebulized doses are given via a face
mask (probably by a direct effect of the solution on the eye)
Paradoxical bronchoconstriction due to sensitivity to Benzalkonium chloride, which is
the preservative in the nebulizer solution
Short-Acting: IPRATROPIUM BROMIDE
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Long-Acting: TIOTROPIUM , GLYCOPYRRONIUM BROMIDE , ACLIDINIUM
METHYLXANTHINES:
Theophylline is effective in COPD but, due to its potential toxicity, inhaled
bronchodilators are preferred when available
METHYLXANTHINES, mechanism of action:
Relaxation of airway smooth muscle and inhibition of mediator release
Theophylline raises intracellular cAMP by inhibiting Phosphodiesterase
Antagonism of Adenosine
Anti-inflammatory activity on T-lymphocytes
METHYLXANTHINES, adverse effects:
Toxicity is dose related
Gastro-intestinal: nausea, vomiting
Cardiovascular: dilatation of vascular smooth muscle –headache, flushing and
hypotension; tachycardia and cardiac dysrhythmias (atrial and ventricular)
Central nervous system: insomnia, anxiety, agitation, hyperventilation, headache
COMBINATION BRONCHODILATOR THERAPY: Fenoterol+Ipratropium
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INHALED GLUCOCORTICOSTEROIDS
Long-term monotherapy with inhaled and systemic glucocorticosteroids is not
recommended in COPD
Long-term, regular use of inhaled glucocorticosteroids brings benefits for patients in
heavy and very heavy stage obstruction, who suffer from frequent exacerbations (>=
twice a year)
INHALED CORTICOSTEROIDS: Beclomethasone , Budesonide , Fluticasone
ORAL CORTICOSTEROIDS:
An important side effect of long-term treatment is steroid myopathy
Systemic corticosteroids for treating acute exacerbations have been shown to
improve symptoms, lung function, reduce rate of treatment failure, and shorten
length of hospital stay
COMBINATION LONG-ACTING BETA2-AGONISTS PLUS CORTICOSTEROIDS IN ONE
INHALER:
• Salmeterol+Fluticasone
• Formoterol+Beclometasone
• Formoterol+Budesonide
ADVERSE EFFECTS OF INHALED STEROIDS:
Candidiasis of the pharynx or larynx ( Using the minimum effective dose, or a ‘spacer
device’, or gargling/using mouthwashes after dosing, minimizes this problem)
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A hoarse voice may develop due to a laryngeal myopathy at high doses
Bruising and skin atrophy occur at high doses
Inhibition of long bone growth during prolonged highdose treatment in children
Posterior subcapsular cataracts may develop following prolonged use
PHOSPHODIESTERASE-4 INHIBITORS:
Reduce inflammation by inhibiting of the breakdown of intracellular cyclic AMP
Roflumilast has no direct bronchodilator activity,
Improve FEV1 in patients treated with Salmeterol or Tiotropium
PHOSPHODIESTERASE-4 INHIBITORS, adverse effects:
Nausea,
Reduced appetite,
Abdominal pain,
Diarrhea,
Sleep disturbances, headache
Patient group A:
• Recommended first choice: SABA as needed or SAMA as needed
• You can use a combination of short-acting drugs ( SABA and SAMA) or one of the
Long-acting agents ( LAMA or LABA)
• Other Possible Treatments: Theophylline
Patient group B:
• From this group symptomatic treatment should be regular
• Recommended first choice: LAMA (long-acting muscarinic antagonis) or LABA
( long-acting Beta2-Agonist)
• Alternative Choice: LAMA and LABA
• Other Possible Treatments: SABA or/and SAMA, Theophylline
Patient group C:
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Recommended First Choice: LABA + ICS or LAMA
Alternative Choice: LABA and LAMA or LAMA and inh-PDE4 or LABA and inhPDE4
Other Possible Treatments: SABA Or/and SAMA, Theophylline
Patient group D:
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Recommended First Choice: LABA + ICS Or/and LAMA
Alternative Choice: LABA + ICS and LAMA or LABA + ICS and inh-PDE4 or
LABA and LAMA or LAMA and inh-PDE4
Other Possible Treatments: Carbocysteine, SABA Or/and SAMA, Theophylline
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EXACERBATION of COPD, pharmacologic treatment:
The three classes of medications most commonly used for exacerbations of COPD
are: Bronchodilators , Corticosteroids, Antibiotics
Treatment of patients with mild exacerbation COPD includes increasing the daily
dose Inhaled Short-acting bronchodilators (Muscarinic Antagonist or/and Beta2agonist)
Antibiotics and Oral Corticosteroids used for exacerbations of COPD lengthen the
next exacerbation of the disease and reduce the risk of death
Modification of treatment Long-acting bronchodilators (formoterol, indacaterol) or
orally (Theophylline) by using the maximum dose or adding drugs from the other
treatment groups, which were not used as maintenance therapy
In the case of hospitalization use of glucocorticoids orally and intravenously allows
for a significant reduction in the number of failures and shorter hospital stay
SHORT-ACTING BRONCHODILATORS:
Short-Acting inhaled Beta2-Agonists with or without Short-Acting Anticholinergics are
usually the preferred bronchodilators for treatment of an exacerbation
Intravenous Methylxanthines (Theophylline) is considered second-line therapy, only
to be used in selected cases when there is an insufficient response to Short-Acting
Bronchodilators
Increase doses and/or frequency of Short-Acting Bronchodilators
Combine Short-Acting Beta2-Agonists and Anticholinergics
Use spacers or air-driven nebulizers
CORTICOSTEROIDS:
systemic corticosteroids shorten recovery time, improve lung function (FEV1) reduce
the risk of early relapse, treatment failure, and length of hospital stay
Prednisone p.o 40 mg/daily, or i.v: Metyloprednisolone 40 mg/daily or
Hydrocortisone 100 mg every 6-8 h
The latest randomized studies suggest: a dose of 40 mg Prednisone per day for 5 days
ANTIBIOTICS:
Antibiotics should be given to patients with exacerbations of COPD who have three
cardinal symptoms:
Increase in dyspnea
Increase in sputum volume
Increase in sputum purulence
Have two of the cardinal symptoms, if increased purulence of sputum is one of the
two symptoms or require mechanical ventilation (invasive or noninvasive)
ANTIBIOTICS:
The recommended length of antibiotic therapy is usually 5-10 days
The choice of the antibiotic should be based on the local bacterial resistance pattern
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First- choice:
Amoxicillin or
Amoxicillin with Clavulanic Acid
Second-choice or in case of failure of initial treatment:
Second-generation Cephalosporins or
Macrolide (Clarithromycin, Azithromycin) or
Moxifloxacin, Levofloxacin
In exacerbations caused by Pseudomonas Aeruginosa the first choice antibiotic is
Ciprofloxacin
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RESPIRATORY SUPPORT: OXYGEN THERAPY, VENTILATORY SUPPORT