Dornase/Pulmozyme Essay Example for Everyone

Introduction

Dornase alfa, a recombinant of human deoxyribonuclease I (rhDNase), is an enzyme that selectively cleaves the DNA. The protein is produced by the use of genetically engineered Chinese Hamster Ovary cells which contain DNA encoding for the native deoxyribonuclease I (DNase) protein (Allen, Panitch, & Rubenstein, 2016). Dornase alfa, as the main active ingredient in Pulmozyme, is mainly used to improve the functioning of the lung and also in preventing infections in patients suffering from cystic fibrosis. It breaks down the DNA causing the build-up of sputum in the lungs, to make breathing easier (Yang, Chilvers, Montgomery, & Nolan 2017). It is also used in treating lung-related complications caused by the buildup of mucus. Most organs use mucus to maintain their moisture and prevent drying out or being infected. However, due to the action of an abnormal gene, the mucus may become sticky and build up in the lungs thus blocking the airways; this leads to the growth of bacteria which cause cystic fibrosis. Dornase alfa breaks down extra DNA to hydrolyze the sputum thus decreasing the risk of lung infection and improving the functioning of the lungs (VanDevanter, Craib, Pasta, Millar, Morgan, & Konstan 2018). Observational studies, however, indicate that the drug is often reserved for patients with severe cases. According to Allen, Panitch, & Rubenstein, (2016), inhalation of dornase alfa has shown the ability to alter the effects of Cystic Fibrosis decreasing lung function decline in the patient. The encouraging results, which are indirectly linked to inflammation effects, encourage the use of dornase alfa therapy for the early treatment of Cystic Fibrosis, which assist in extending survival by preserving lung function (Yang, Chilvers, Montgomery, & Nolan 2017). This essay thoroughly examines dornase alfa by analyzing the general information on the drug class in which it is most effective, Pharmacodynamics, Pharmacokinetics, its indications, its contraindications and the side effects.

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Pharmadynamics

Cystic Fibrosis is a life-shortening hereditary disease in which the dominant cause of mortality is the progressive decline in pulmonary function (Allen, Panitch, & Rubenstein, 2016). The exaggerated inflammation responses and a vicious cycle of infections or obstruction in the airway are the main causes of lung destruction occurring in Cystic Fibrosis. Moreover, neutrophils accumulation and breakdown in the patient's infected lungs which lead to the release of large amounts of DNA which decrease ciliary transport and increase the infected sputum's viscosity (Shah, Keyzer, Russell, & Halderman 2018). Dornase alfa directly relieves obstruction in lungs by reducing DNA viscosity on the sputum; thus translating to a significant improvement in the functioning of the patient's lungs (Allen, Panitch, & Rubenstein, 2016). Besides that, the drug also reduces exacerbations risk or infections that require intravenous antibiotics; this may be linked to reduced bacterial infection as a result of improved mucociliary clearance and broader effects on host defenses against infection.

Observed benefits of the drug on both infection and obstruction has made it recommendable for treating patients with fair to serious lung disease to reduce exacerbations and increase the functioning of the lung. And although most people believe that it is only a lung disease, Cystic fibrosis also affects sex organs, sinuses, intestines, liver and the pancreas (VanDevanter, Craib, Pasta, Millar, Morgan, & Konstan 2018. Dornase alfa is also used in pediatric patients, experiencing a minimal reduction in spirometry, to improve ventilation inhomogeneity. Therefore, it is recommended for Cystic Fibrosis patients in all ranges of disease severity (Allen, Panitch, & Rubenstein, 2016).The drug is most beneficial if it is initiated earlier since it slows down the rate of lung function. According to, the drug's ability to modify lung function may be related to its indirect effects on inflammation.

Pharmacokinetics

Pulmozyme (dornase alfa) is a sterile, clear, colorless, highly purified, solution contained in single-use ampoules. It is administered by inhalation of an aerosol mist produced by a compressed air driven nebulizer (Yang, Chilvers, Montgomery, & Nolan 2017). Each ampule delivers 2.5 mL of the solution to the nebulizer bowl. Each mL of 8 aqueous solutions contains 0.15 mg of calcium chloride dehydrate, 1 mg dornase alfa, and 8.77mg of sodium chloride. Inhalation of dornase alfa in patients with cystic fibrosis results in measurable DNAse activity in sputum within 15 minutes (Allen, Panitch, & Rubenstein, 2016). According to (Yang, Chilvers, Montgomery, & Nolan 2017), inhaling 10 mg of the drug for three times a day would not raise levels of serum DNAse, above endogenous levels. Dornase alfa dissolves excess DNA debris accumulated due to mucus stasis, bacterial infection and the considerable influx of neutrophils found in the airway lumen. The optimal activity of Dornase alfa depends on the availability of divalent cations like magnesium and calcium, and it does not affect intracellular DNA (VanDevanter, Craib, Pasta, Millar, Morgan, & Konstan 2018.

The drug is absorbed in negligible amounts after inhalation. It is also associated with minimum accumulation with less than 10ng/mL serum concentration, regardless the administered dose. The distribution is primarily local, and there is a rapid decline in sputum concentration after inhalation. Studies on monkeys and rats indicate that the initial distribution volume is similar to that of serum (Shah, Keyzer, Russell, & Halderman 2018). The drug is metabolized by a protease that is commonly present in biological fluids. Also, according to its bioavailability, dornase alfa sputum concentrations can be measured after every 15 minutes. The onset is reached within 3 to 7 days (Mogayzel Jr, Naureckas, Robinson, Mueller, Hadjiliadis, and Hoag). However, dornase alfa may not fully cure cystic fibrosis; instead, it works together with other medicines like steroids, bronchodilators, and antibiotics to control the condition. The patient's quality of life and dyspnea vary indifferent trials, with some indicating that there is not statistically significant improvement after administering the drug (VanDevanter, Craib, Pasta, Millar, Morgan, & Konstan 2018.

Indications

According to the indications, Pulmozyme should be administered daily accompanied with therapies for cystic fibrosis (CF) patients to manage the condition and improve the pulmonary function. According to Pulmonary Clinical Practice Guidelines Committee (2013) daily administration also reduces the chances of a respiratory tract infection and does not affect the sputum of healthy individuals nor does it affect non-purulent sputum. Each amplule should only be used once and once opened; the remaining content must be discarded. The Pulmozyme solution does not contain any preservatives, and it has a nominal pH of 6.3. The solution should not be mixed or diluted with other drugs in the nebulizer because it can lead to changes in its action (Shah, Keyzer, Russell & Halderman, 2018). Patients with other respiratory medications should also seek further advice on the order of taking the drugs.

Contraindications

The drug is contradicted in patients who are hypersensitive to Chinese Hamster Ovary cell or its products and dornase alfa. If used in children the drug may increase incidences of rash, rhinitis, and cough (Yang, Chilvers, Montgomery, & Nolan 2017). Although, the drug is considered a pregnancy Category B medication, its full risk on pregnancy is not known, and whether or not it is passed through breast milk.

Side effects

Along with its needed effects, dornase alfa may cause some unwanted effects. The most common side effects of Pulmozyme include an allergic reaction which causes a difficulty in breathing, swelling of the hives, face, tongue, and lips. Other side effects include voice alteration, sore throat, fever; a Runny nose, Voice changes, Indigestion, heartburn, mild skin rash, and urticaria have also been observed. Adverse reactions include; nasal congestion, Laryngitis, conjunctivitis, rhinitis (Allen, Panitch, & Rubenstein, 2016). Nasal congestion is the obstruction of air flow which occurs due to the swelling of the lining tissues in nasal passages. Nasal congestions are worsened by prolonged use of decongestant sprays or in rare cases; it might be due to a tumor in the nasal passages. Laryngitis is an inflammation of voice cords found in the larynx. It is usually caused by common cold, exposure to polluted air or an upper respiratory infection. Conjunctivitis is another side effect of dornase alfa caused by swelling or inflammation of the conjunctiva (Shah, Keyzer, Russell & Halderman, 2018). The patient would start experiencing a burning sensation in the eyes, swollen eyelids, a pink discoloration of the eyes, and high sensitivity to light and discharge from the eyes.

Conclusion

Production of sticky respiratory secretion is the main feature of cystic fibrosis which leads to the various symptoms of the desease. Dornase alfa works on these symptoms by decreasing the secretions' viscosity to produce sustained improvements in the patient's lung functioning. It also slows down the progression of pulmonary disease and reduces the infection rates thus indicating that it has a long-term consequence on the disease. Although it is reasonable to conduct a trial of the drug on patients with cystic fibrosis and lung disease, continued treatment is exclusively based on clinical response. And, even though the benefits may not be as cost-effective, effects of disease progression justifies the use of the drug.

The medication is administered through a nebulizer which converts it to a fine mist that can be inhaled to decrease a thickness of pulmonary secretions for it to be cleared from the lung (VanDevanter, Craib, Pasta, Millar, Morgan, & Konstan 2018s. It is absorbed in negligible amounts, and it ensures a rapid decline in the concentration of sputum, after inhalation. Use of other medication such as steroids together with the inhalation of dornase alfa solution assists in controlling symptoms of cystic fibrosis. Besides, it also assists in reducing risks of infections that might require intravenous antibiotics (VanDevanter, Craib, Pasta, Millar, Morgan, & Konstan 2018. And like any other medication, it has side effects on the patient. These effects are mainly caused by Dornasealfa, the active component of Pulmozyme. Although it does not cure the disease, Pulmozyme solution plays a significant role in easing breathing and reducing lung infections, if used daily.

References

Allen, J. L., Panitch, H. B., & Rubenstein, R. C. (2016). Cystic Fibrosis. Boca Raton: CRC Press.

Yang, C. L., Chilvers, M., Montgomery, M., & Nolan, S. J. (2017). Dornase alfa for cystic fibrosis. Pediatric respiratory reviews, 21, 65-67.

Mogayzel Jr, P. J., Naureckas, E. T., Robinson, K. A., Mueller, G., Hadjiliadis, D., Hoag, J. B., ... & Pulmonary Clinical Practice Guidelines Committee. (2013). Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. American journal of respiratory and critical care medicine, 187(7), 680-689.

VanDevanter, D. R., Craib, M. L., Pasta, D. J., Millar, S. J., Morgan, W. J., & Konstan, M. W. (2018). Cystic fibrosis clinical characteristics associated with dornase alfa treatment regimen change. Pediatric pulmonology, 53(1), 43-49.

Shah, G. B., Keyzer, L., Russell, J. A., & Halderman, A. (2018, January). Treatment of chronic rhino sinusitis with dornase alfa in patients with cystic fibrosis: a systematic review. In International forum o...