University Of Jordan Faculty Of Pharmacy. Pharmacotherapy 2. Sheet number: 9 Price:. 1 P a g e

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1 University Of Jordan Faculty Of Pharmacy Pharmacotherapy 2 Sheet number: 9 Price:. 1 P a g e

2 COPD, Last time we said that COPD patients are separated into four categories, depending on the severity of the disease. And the severity of the COPD condition depends on 3 things: 1- Air flow limitation expressed in GOLD classes. 2- Symptoms expressed in CAT and MRC tests. 3- Risk for mortality and poor outcome expressed in number of exacerbations or severity of exacerbations. (High risk: two or more exacerbations in the last year regardless of their severity or 1 severe exacerbation that required hospitalization). Remember that: -Categories A and B (low risk) GOLD 1/2, Exacerbations less or equal to 1. -Categories C and D (high risk) GOLD 3/4, Exacerbation 2 or more or 1 that required hospitalization. So if a patient s GOLD class is 1 or 2, then he s definitely in either category A or category B (low risk). BUT, if the patient s GOLD class is 1 or 2, and he had 2 or more exacerbations, in that case we depend on the worst factor, so here the patient would be considered a high risk case. Meaning that, if a patient s GOLD class puts him in a low risk, but his exacerbations put him in a high risk He s considered a high risk patient. -But before determining the category, you have to make sure that these exacerbations are (true): not caused by another reason, like non-adherence. Note: Always make sure that there are no direct factors attributing to the risk status, symptoms or the GOLD class. Treatment: (Check slide 52) -Again, treatment depends on the patient s category. -We have: 1-Recommended first choice. 2-Alternative choice. 3-Other possible treatments, which are mostly used as add-on therapies rather than monotherapies, so they could be added to the recommended first choice or to the alternative choice. Theophylline can be used as an add-on therapy, in all categories. SABA is used in all categories, but its place in the therapy differs (it could be a first choice or an add-on therapy). 2 P a g e

3 Now remember, in asthma, SABA was used prn. In COPD, it s used daily. (Except when it s used as a first choice in category A). ICS are only indicated in high risk patients (categories C and D). PDE4-inhibitors are also only indicated in high risk patients (categories C and D). The only treatment that has a survival benefit in COPD is: smoking cessation. It s the only treatment that could stop the progression of COPD. ICS and PDE4-inhibitors decrease: exacerbations, morbidity, hospitalization, but has no survival benefit (no effect on slowing down the progression of the disease). The use of ICS in COPD is not evidence-based, meaning that there is no prove that this is the correct place in therapy for it doesn t decrease mortality and has no survival benefit: doesn t affect the progression of the disease. It s used because of the benefits mentioned in the previous point. A combination between ICS and PDE4-inhibitors is only used in category D, and LABA should be used with them as well. Carbocysteine and N-acetylcysteine (antioxidants): weak bronchodilatory effect. They are given as a nebulizer therapy. But we can t only depend on them. Remember in asthma, we said that LABA increase the risk of death, but in COPD they don t. Please refer to slide 52, while reading these notes. Beta2-agonists (slide 62): Short acting beta2-agonists: -Salbutamol (albuterol) -Levalbuterol -Fenoterol: not FDA-approved for asthma, but it s used for COPD. Long acting beta2-agonists: -Formoterol, Salmetrol and Vilanterol Can be used in asthma. The rest of the long acting beta2-agonists are for COPD only: -Indacaterol: DPI, once daily when it s used alone. If it s in a combination, we might give it twice daily, but the dose will differ. -Olodaterol: SMI (soft mist inhaler) Respimat (remember it s a new inhaler device). -Tulobuterol: Transdermal instead of inhalation. 3 P a g e

4 -Anticholinergics: Short acting anticholinergics: -Ipratropium bromide -Oxitropium bromide Long acting anticholinergics: -Tiotropium: The only long acting anticholinergic that s approved for asthma is: tiotropium, SMI (Respimat). Dose: mcg. In COPD: tiotropium, Spiriva (DPI). Higher dose needed: 18 mcg. Note: Respimat can also be used in COPD but in an off-label way. -Umeclidinium: COPD only. -Aclidinium bromide: COPD only. -Glycopyrronium bromide: COPD only. Combination of long-acting beta2-agonist plus anticholinergic in one inhaler: (This combination doesn t exist in asthma treatment). -Indacaterol/glycopyrronium -Olodaterol/tiotropium Systemic corticosteroids: -Prednisone -Methyl-prednisolone Depending on the severity, they could be given: IV for the first 3 days then switch to oral or oral from the beginning if the exacerbations were mild to moderate. (not more than two weeks for the management of exacerbations). Phosphodiesterase-4 inhibitors: Roflumilast: Controller Given to reduce the inflammation and the risk of exacerbations. It s given orally. 4 P a g e

5 There s a problem in COPD: 70% of patients are prescribed ICS and 5% are prescribed oral CS, as maintenance. A lot of cases in COPD don t require ICS, but unfortunately most of the patients are prescribed ICS, though they should be only indicated in high risk patients. And oral CS should be reserved for exacerbations. Now, when they use them for maintenance, the patient will become steroid-dependent, and so when exacerbations do happen, they will be severe, because the patient is already taking oral CS yet exacerbations occurred. -Regular ICS treatment does not modify the long-term decline in FEV1, nor the mortality in COPD patients. From slide 78 to 83, the doctor only mentioned some points and commented on them: In patients treated with or without ICS, high doses of N-acetylcysteine reduced exacerbation rates, but only in GOLD 2 patients inconsistent benefit for N- acetylcysteine, so it s not a standard therapy in COPD, but it s used in practice. With the chronic bronchitis and the mucus that develops, the use of mucolytics and cough suppressants provides no benefit (will not alleviate the cough or the thick mucus produced in chronic bronchitis). Nedocromil and leukotriene modifiers have not been adequately studied in COPD, and cannot be recommended. Roflumilast: Reduce the exacerbations, and improve the symptoms in patients with chronic bronchitis. Clenbuterol: LABA, available orally. Not approved by the FDA. But it s used in some countries as a weight loss drug; due to its sympathomimetic activity. It may cause arrhythmias or hypertensive crisis, so it s really risky to take it for weight loss and it s not approved. Now, if drugs didn t work in emphysema, there are two types of non-pharmacologic interventions : (Note: in emphysema, there are areas with damaged parenchyma and inefficient gas exchange). 5 P a g e

6 1-Endobronchial valve placement: a valve is placed where behind it is the damaged/affected area. Upon inhalation, air will only be able to reach the unaffected alveoli as the affected alveoli are blocked by the valve. Upon exhalation, the air can leave the affected alveoli. So this is a unidirectional valve where the air can t reach the affected area but air can escape through the valve. This will improve the efficiency of breathing and improve the symptoms. 2-Nitinol coils: the alveoli that are about to collapse are supported by a mesh of coils (structural support). This will improve the efficiency of breathing and slow down the damage. Drawbacks: increase in the risk of pneumonia, because we re putting a foreign body in the alveoli. That s why they re a late option in treatment. New approvals: Combination glycopyrrolate-indacterol (DPI): given twice daily. (Note: glycopyrronium: once daily). Indacterol dose: 15.6 mcg-27.5 mcg, and it s given twice daily, so the maximum dose is 55, which is still lower than when indacterol is given alone (75-300) mcg. COPD exacerbations We must know how to 1-Determine the severity, to distinguish severe exacerbations which need ICU. 2-The discharge criteria. 3-When to give antibiotics. Slide 89 When making the assessment of COPD exacerbations: 1- Medical history: -Severity of COPD -Duration of worsening or new symptoms -Number of previous episodes -Comorbidities -Present treatment regimen -Previous use of mechanical ventilation If one or more of the following is present, then the exacerbation is considered severe. 6 P a g e

7 Remember, exacerbation: acute deterioration of symptoms that could not be relieved by the patient s current treatments. Signs of severity: -Use of accessory respiratory muscles -Paradoxical chest wall movements -Worsening or new onset central cyanosis -Development of peripheral edema -Hemodynamic instability -Deteriorated mental status One or more of these indicates severe exacerbation. The use of antibiotics (Slide 90). Exacerbations are separated into 3 types depending on the cardinal symptoms: (Cardinal symptoms: worsening of dyspnea, increase in sputum volume, and increase in sputum purulence). -Type 1 (Mild): one cardinal symptom plus at least one of the following: UTRI within 5 days, fever, increase wheezing, increased cough, increase in respiratory rate >20% above baseline. -Type 2 (Moderate): two cardinal symptoms. -Type 3 (Severe): three cardinal symptoms. However several reports have shown that starting the antibiotic treatment early regardless of the type has improved the outcome, reduced hospitalization and improved cure rate, so it s now general practice to start patients with COPD on prophylactic antibiotic therapy. Criteria for hospital admission: Slide 91. Criteria for ICU admission: Slide 93. Treatment of exacerbations: Slide 96. -Using antibiotics in the first 2 days of hospitalization improved the outcomes. -Systemic corticosteroids: IV up to 3 days then switch to oral or oral from the beginning, up to 2 weeks 7 P a g e

8 -Oxygen therapy: If a COPD patient with hypoxemia (O2<90%), was given a 100% oxygen, he will suffer from respiratory failure. Because of chronic CO2 retention, the patient s body reprogrammed its breathing rate depending on the partial pressure of CO2, meaning that the rate of breathing now depends on CO2 not on oxygen in these patients. So if we give them a 100% O2, and all of the CO2 disappeared suddenly, respiratory failure will occur, because the body has nothing to depend on while determining the breathing rate (no CO2). So never give 100% O2 to a COPD patient at once, you can give him O2 but gradually. 8 P a g e