INTRODUCTION:

Chronic obstructive pulmonary disease (COPD) is a debilitating disorder that has become a major public health concern worldwide.^[1] Salbutamol is a short- acting Beta- 2 agonists, which is more often prescribed as bronchodilators for COPD and Asthma worldwide. Salbutamol stimulates the β-2 receptors in airway smooth muscle which induces the cyclic AMP (c-AMP) pathway. Activation of beta 2-adrenergic receptors on airway smooth muscle results in the activation of adenyl cyclase and to an increase in the intracellular concentration of cyclic-3′,5′-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP results in the activation of protein kinase A, which inhibits the phosphorylation of myosin and also lowers the intracellular ionic calcium concentrations, resulting in relaxation. Salbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles.

Increased cyclic AMP concentrations are also related with the inhibition of release of mediators from mast cells in the airway. Salbutamol is capable of producing unintended effects in Cardiovascular system and also causes disturbances in Metabolic functions. Adrenoreceptors are found in various organs and tissues, therefore β-2 agonists can cause extrapulmonary adverse effects. The elimination half-life of salbutamol is 4–6 hour and it is excreted through kidney. The Therapeutic range for bronchodilatory effects of salbutamol is between 5 and 20ng/mL and higher concentrations may results in greater risk of toxicity and undesired effects.^{[2, 3]} Inhaled salbutamol has a profound short- term effect in increasing Random Blood Sugar level and Heart rate. Beta adrenergic stimulants can produce hyperglycaemia. This is due to muscle and hepatic glycogenolysis and gluconeogenesis resulting from stimulation of the beta-2 receptor.^[4] Inhaled Salbutamol induced tachycardia is due to the direct stimulation of cardiac beta 2-adrenoceptors as well as indirect activation of peripheral receptors, inducing vasodilatation and consequent reflex vagal withdrawal.^[5]

MATERIALS AND METHODS:

Study design:

A prospective, observational study.

Study duration:

6 Months (October 2018 to March 2019).

Study instruments:

case report form.

Complete study procedure:

· Approval of study procedure by the Institutional Ethical Committee of Vels University was obtained prior to commencement.

· The study protocol was explained to all subjects in their Native Language prior to enrollment.

· Written informed consents was obtained from subjects willing to participate in the study.

· Enrolled both the gender with COPD patients (based on inclusion and exclusion criteria) in the study.

· Data is collected in the approved case report form.

· Analyzed the short-term effects of nebulized salbutamol in COPD patients.

· Assessed the incidence of Hyperglycemia and Tachycardia in COPD patients due to salbutamol.

Study Site:

Department of General Medicine, ESIC Hospital, Ayanavaram.

Study Population:

136 COPD patients of ESIC Hospital, Ayanavaram.

Study Criteria:

Inclusion criteria:

1. Both Gender (Male and Female)

2. Age >18 years

3. Salbutamol dose- 5 mg

4. Salbutamol dose frequency- Every 6^th hourly.

5. Salbutamol Route of administration- Inhalation route.

6. Salbutamol Duration of Drug Therapy- more than 1 day.

7. COPD Patients (Inpatients).

Exclusion criteria:

1. Hypoxemia

2. Known case of systemic hypertension

3. Known case of diabetes mellitus

4. Known case of arrthymias and other cardiovascular disorders.

5. Patient on anti-arrthymias drugs, oral hypoglycaemic drugs, Insulin, antihypertensive drug medications, Methyl Xanthine Derivatives.

6. Personal history of smoker and alcoholic

7. Known case of polycystic ovary diseases

8. Hemodynamic instability

9. Past medication history of Chronic treatment or long-term use of corticosteroids.

10. Caffeine intake are excluded.

Statistical analysis:

The statistical analysis is carried out using SPSS software. Results were expressed as the mean±SD. Comparison between two independent mean groups was done using student’s t test. P values reported were two-tailed.

Expected outcome:

Helps in analyzing the short-term effects of salbutamol induced Hyperglycemia and Tachycardia in COPD patients.

RESULTS:

Table 1. Sex distribution of the patients with COPD:

S. No.	Sex	Number of patient	Percentage (%)
1.	MALE	77	56.62 %
2	FEMALE	59	43.38 %

As per study protocol we enrolled 136 patients. Among the 136 patients 77 (56.2 %) were Male population and 59 (43.38 %) were Female population. This is shown in Table no. 1.

Table 2: Age distribution of patients with COPD:

S. No.	Age group (in years)	Number of patient	Percentage (%)
1.	20-25	13	9.5%
2.	26-30	25	18.3%
3.	31-35	15	11.02%
4.	36-40	22	16.1%
5.	41-45	8	5.88%
6.	46-50	30	22.05%
7.	51-55	12	8.82%
8.	>56	11	8.08%

Compared with age wise distribution, COPD Patients are predominant in above 36 years. This is shown in Table no.2

Table 3. Adverse drug reaction observed with the drug salbutamol:

S. No.	Adverse drug reaction	Number of patient	Percentage (%)
1.	Hyperglycemia	46	33.8%
2	Tachycardia	37	27.2%
3.	Both Hyperglycemia and Tachycardia	23	16.9%

Among 136 COPD patients, 46 (33.8%) patients developed Hyperglycemia, 37 (27.2%) patients developed Tachycardia and 23 (16.9%) patients developed both Hyperglycemia and Tachycardia. This is shown in the Table no. 3.

Table 4. Baseline Characteristics:

Baseline characteristics
Characteristics	Before salbutamol treatment	After salbutamol treatment
Age	17 ± 7.745	17 ± 7.745
Male	77 (56.6 %)	77 (56.6 %)
Female	59 (43.4 %)	59 (43.4 %)
Heart Rate	79.66 ± 7.24	-
Random Blood Sugar (RBS)	96.80 ± 15.12	-

Table 5. Comparison of Baseline and After Salbutamol Treatment:

Laboratory findings
Characters	Baseline (MEAN± SD)	After 24 Hours (MEAN± SD)	P Value
Random Blood Sugar (RBS)	96.80 ± 15.12	142.86 ± 49.69	< 0.0001
Heart Rate	79.66 ± 7.24	94.91 ± 16.30	< 0.0001

In the present study, the mean Random Blood Sugar level of patients with COPD was significantly increased after 24 hour of nebuliser salbutamol administration (p = <0.0001). Also, the mean heart rate was significantly increased after 24 hour of nebulised salbutamol (p = <0.0001). which is shown in Table no.5 and Figure no. 1 and 2.

Fig No. 1 Bar diagram of Random Blood Sugar Variations before and after treatment of salbutamol

Fig No. 2 Bar diagram of Heart Rate Variations before and after treatment of salbutamol

DISCUSSION:

In the study of 136 patients with COPD, the number of male patients was found to be 77 which were followed by female patients with count of 59. In this study, 46 patients was identified to have elevated Random Blood Sugar level (Hyperglycemia), 37 patients developed Tachycardia and 23 patients was found to have both Hyperglycemia and Tachycardia due to nebulised salbutamol in COPD patients. In the present study, the mean Random Blood Sugar level of patients with COPD was significantly increased after 24 hour of nebuliser salbutamol administration (p = <0.0001). Also, the mean heart rate was significantly increased after 24 hour of nebulised salbutamol (p = <0.0001).

CONCLUSION:

The study was an active pharmacovigilance study that was designed to evaluate the Salbutamol induced Hyperglycemia and Tachycardia in Indian COPD patients. In this study, it was concluded that salbutamol cause adverse reaction on cardiovascular and metabolic functions. The study concludes that the Nebulised salbutamol causes Hyperglycemia and Tachycardia in COPD patients which leads to unintended disturbance in the cardiovascular and metabolic functions. So, proper monitoring should be done on the patients with salbutamol based regimen.

CONFLICTS OF INTEREST:

The author declares no conflicts of interest.

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Received on 30.04.2019 Modified on 14.06.2019

Research J. Pharm. and Tech. 2020; 13(10):4621-4624.

DOI: 10.5958/0974-360X.2020.00813.6