Asthma Meds Side Effects and Asthma COPD Overlap

Asthma Meds

Side effects of beta-adrenoceptor agonists 

• Skeletal muscle tremor

• Cardiac tachycardia-tachyarrhythmias

• Modest prolongation of the QTc interval

• Tachyphylaxis

• Hypokalemia. 

• Nausea, vomiting, headache

Side effects of theophylline

• Positive chronotropic and inotropic effect. 

• Mild cortical arousal. 

• Stimulates secretion of gastric acid and digestive enzymes.

• Can cause hypokalemia, hyperglycemia, skeletal muscle tremors

• Can cause seizure- related to blood levels

• Can cause tachyarrhythmias

Side effects of glucocorticoids

• Linked to route and dosage

• Glucose intolerance, immunosuppression, bone demineralization, increase in weight, increased bp, decreased growth rate (children).

• Suppression of Adreno-pituitary axis (after 2 wks) with parenteral or oral. (use alternative day therapy)

• Throat thrush, oral hoarseness (inhaled preparations). can increase opportunistic infections

• Daily therapy for mild persistent asthma or short, intermittent courses of inhaled or oral corticosteroids 

Asthma COPD Overlap Syndrome (ACOS)

Figure 1. Hypothetical Course of Lung Function in Chronic Obstructive Pulmonary Disease (COPD) and Asthma.

COPD is an inflammatory disease of the small airways in particular and involves chronic bronchitis and tissue breakdown (emphysema). The disease may start with a low level of lung function as early as 25 years of age, followed by an accelerated decline in forced expiratory volume in 1 second (FEV₁) as compared with the normal decline. FEV₁ may decrease to 50% of the predicted (normal) value at 60 years of age and may go as low as 25% of the predicted value. During exacerbations, FEV₁ falls; the fall and recovery are more gradual than in asthma. In asthma, airway obstruction results predominantly from smooth-muscle spasm and hypersecretion of mucus. Exacerbations may accompany an accelerated decline in FEV₁ as well, with a rapid fall and more rapid recovery than in COPD. Progression of disease may occur in a subgroup of persons with asthma, leading to an FEV₁ of 50% of the predicted value at 60 years of age. FEV₁ seldom decreases to the low levels that occur more frequently in COPD. On the basis of an FEV₁ of 55% of the predicted value at 60 years of age, one cannot differentiate asthma from COPD. ACOS denotes asthma–COPD overlap syndrome.

Figure 1. Hypothetical Course of Lung Function in Chronic Obstructive Pulmonary Disease (COPD) and Asthma.

COPD is an inflammatory disease of the small airways in particular and involves chronic bronchitis and tissue breakdown (emphysema). The disease may start with a low level of lung function as early as 25 years of age, followed by an accelerated decline in forced expiratory volume in 1 second (FEV₁) as compared with the normal decline. FEV₁ may decrease to 50% of the predicted (normal) value at 60 years of age and may go as low as 25% of the predicted value. During exacerbations, FEV₁ falls; the fall and recovery are more gradual than in asthma. In asthma, airway obstruction results predominantly from smooth-muscle spasm and hypersecretion of mucus. Exacerbations may accompany an accelerated decline in FEV₁ as well, with a rapid fall and more rapid recovery than in COPD. Progression of disease may occur in a subgroup of persons with asthma, leading to an FEV₁ of 50% of the predicted value at 60 years of age. FEV₁ seldom decreases to the low levels that occur more frequently in COPD. On the basis of an FEV₁ of 55% of the predicted value at 60 years of age, one cannot differentiate asthma from COPD. ACOS denotes asthma–COPD overlap syndrome.

http://www.nejm.org/doi/full/10.1056/NEJMra1411863

How Doctors Think - Podcast

How Doctors Think - Podcast

Cause of arterial hypoxemia in asthma

From West, JB, Pulmonary Pathophysiology

First, let's look at the V/Q distribution in a normal lung in a young person:

The figure shows a typical pattern found in young normal volunteers. It can be seen that almost all the ventilation and blood flow go to lung units with ventilation–perfusion ratios near the normal value of 1.

Now, let's look at V/Q in patients with lung disease. The mechanism of arterial hypoxemia (low arterial PO2) is asthma and type B COPD (blue bloaters) is V/Q inequality as shown by inert gas analysis.

This shows about 25% of total blood flow going to regions of the lung with V/Q ratios of about 0.1.

Interesting that bronchodilators, while improving airflow in this patient, made the hypoxemia worse (PO2 decreased from 81 to 70), probably by reducing hypoxic vasoconstriction via beta 2 receptors in pulmonary arterioles.

Typically, in COPD the type A patient has only moderate hypoxemia (PO2 often in the high 60s or 70s), and the arterial PCO2 is normal. By contrast, the type B patient often has severe hypoxemia (PO2 often in the 50s or 40s) with an increased PCO2, especially in advanced disease. 

Type A (pink puffer) patient:

The distribution shows that a large amount of ventilation went to lung units with high ventilation–perfusion ratios (A/) (compare Figure 2-8). This would be shown as physiologic dead space in the ideal point analysis, and the excessive ventilation is largely wasted from the point of view of gas exchange. By contrast, there is little blood flow to units with an abnormally low A/. This explains the relatively mild degree of hypoxemia in the patient and the fact that the calculated physiologic shunt was only slightly increased. 

Type B (blue bloater) patient:

This patient was a heavy smoker and had had a productive cough for many years. The arterial PO2 and PCO2 were 47 and 50 mm Hg, respectively. Note that there was some increase in ventilation to high A/ units (physiologic dead space). However, the distribution chiefly shows large amounts of blood flow to low A/ units (physiologic shunt), accounting for his severe hypoxemia. It is remarkable that there was no blood flow to unventilated alveoli (true shunt). Indeed, true shunts of more than a few percent are uncommon in COPD.