About Authors:
*Rohit Kumar, Mr. Vijay Sharma, Mr. Sunil Kumar
KNGD Modi Institute of Pharmaceutical Education and Research
Modinagar, Ghaziabad
*rohitkmr884@gmail.com
Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, airflow obstruction, and bronchospasm. Symptoms include wheezing, cough, chest tightness, and shortness of breath.
Medicines such as inhaled short-acting beta-2 agonists may be used to treat acute attacks. Attacks can also be prevented by avoiding triggering factors such as allergens or rapid temperature changes and through drug treatment such as inhaled corticosteroids. Leukotriene antagonists are less effective than corticosteroids, but have fewer side effects. Monoclonal antibodies, such as mepolizumab and omalizumab, are sometimes effective.
Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease as this term refers specifically to combinations of bronchiectasis, chronic bronchitis, and emphysema. Unlike these diseases, the airway obstruction in asthma is usually reversible; however, if left untreated, asthma can result in chronic inflammation of the lungs and irreversible obstruction. In contrast to emphysema, asthma affects the bronchi, not the alveoli. Public attention in the developed world has increased recently because of its rapidly increasing prevalence, affecting up to one quarter of urban children.
Reference ID: PHARMATUTOR-ART-1954
CLASSIFICATION
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Clinical classification of severity |
||||
|
Severity |
Symptom |
Nighttime |
%FEV1 |
FEV |
|
Intermittent |
<1 per week |
<2 per month |
>80% |
<20% |
|
Mild persistent |
>1 per week |
>2 per month |
>80% |
20–30% |
|
Moderate persistent |
Daily |
>1 per week |
60–80% |
>30% |
|
Severe persistent |
Daily |
Frequent |
<60% |
>30% |
Asthma is clinically classified according to the frequency of symptoms, FEV1 and peak expiratory flow rate. Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic), based on whether symptoms are precipitated by allergens (atopic) or not (non-atopic).
BRITTLE ASTHMA
Brittle asthma is a term used to describe two rare phenotypes of asthma distinguishable by recurrent, severe attacks. The subtypes are divided by symptoms into either Type 1 or Type 2, depending on the stability of the patient's maximum speed of expiration, or peak expiratory flow rate (PEFR). Type 1 is characterized by sustained, chronic variability of PEFR, while type 2 is distinguished by sudden unpredictable drops in PEFR where asthma symptoms are otherwise well controlled and the function of the lungs is not substantially impaired.
Brittle asthma is one of the "unstable" subtypes of "difficult asthma", a term used to characterize the less than 5% of asthma cases that do not respond to maximal inhaled treatment, including high doses of corticosteroids combined with additional therapies such as long-acting beta-2 agonists.
SIGNS AND SYMPTOMS
|
Severity of asthma attack |
||||
|
Sign/Symptom |
Mild |
Moderate |
Severe |
Pending arrest |
|
Alertness |
May show agitation |
Agitated |
Agitated |
Confused/Drowsy |
|
Breathlessness |
On walking |
On talking |
Even at rest |
|
|
Talks in |
Sentences |
Phrases |
Words |
|
|
Wheeze |
Moderate |
Loud |
Loud |
Absent |
|
Accessory muscle |
Usually not used |
Used |
Used |
|
|
Respiratory rate (/min) |
Increased |
Increased |
Often >30 |
|
|
Pulse rate (/min) |
100 |
100-120 |
>120 |
<60 (Bradycardia) |
|
PaO2 |
Normal |
>60 |
<60 ,possible cyanosis |
|
|
PaCO2 |
<45 |
<45 |
>45 |
|
Because of the spectrum of severity within the asthma, some people with asthma only rarely experience symptoms, usually in response to triggers, where as other more severe cases may have marked airflow obstruction at all times.
Asthma exists in two states: the steady-state of chronic asthma, and the acute state of an acute asthma exacerbation. The symptoms are different depending on what state the patient is in.
Common symptoms of asthma in a steady-state include: nighttime coughing, shortness of breath with exertion but no dyspnea at rest, a chronic 'throat-clearing' type cough, and complaints of a tight feeling in the chest. Severity often correlates to an increase in symptoms. Symptoms can worsen gradually and rather insidiously, up to the point of an acute exacerbation of asthma. It is a common misconception that all people with asthma wheeze—some never wheeze, and their disease may be confused with another chronic obstructive pulmonary disease such as emphysema or chronic bronchitis.
ASTHMA ATTACK
An acute exacerbation of asthma is commonly referred to as an asthma attack. The cardinal symptoms of an attack are shortness of breath (dyspnea), wheezing, and chest tightness. Although the former is often regarded as the primary symptom of asthma, some people present primarily with coughing, and in the late stages of an attack, air motion may be so impaired that no wheezing is heard. When present the cough may sometimes produce clear sputum. The onset may be sudden, with a sense of constriction in the chest, as breathing becomes difficult and wheezing occurs (primarily upon expiration, but sometimes in both respiratory phases). It is important to note inspiratory stridor without expiratory wheeze however, as an upper airway obstruction may manifest with symptoms similar to an acute exacerbation of asthma, with stridor instead of wheezing, and will remain unresponsive to bronchodilators.
Signs of an asthmatic episode include wheezing, prolonged expiration, a rapid heart rate (tachycardia), and rhonchous lung sounds (audible through a stethoscope). During a serious asthma attack, the accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck) may be used, shown as in-drawing of tissues between the ribs and above the sternum and clavicles, and there may be the presence of a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest.
During very severe attacks, an asthma sufferer can turn blue from lack of oxygen and can experience chest pain or even loss of consciousness. Just before loss of consciousness, there is a chance that the patient will feel numbness in the limbs and palms may start to sweat. The person's feet may become cold. Severe asthma attacks which are not responsive to standard treatments, called status asthmaticus, are life-threatening and may lead to respiratory arrest and death.
Though symptoms may be very severe during an acute exacerbation, between attacks a patient may show few or even no signs of the disease.
CAUSES
Asthma is caused by environmental and genetic factors, which can influence how severe asthma is and how well it responds to medication. Some environmental and genetic factors have been confirmed by further research, while others have not been. Underlying both environmental and genetic factors is the role of the upper airway in recognizing the perceived dangers and protecting the more vulnerable lungs by shutting down the airway. Margie Profit has argued that allergens look to our immune systems like significant threats. Asthma, in this view, is seen as an evolutionary defense. This view also suggests that removing or reducing airborne pollutants should be successful at reducing the problem.
ENVIRONMENTAL
Many environmental risk factors have been associated with asthma development and morbidity in children.
Environmental tobacco smoke, especially maternal cigarette smoking, is associated with high risk of asthma prevalence and asthma morbidity, wheeze, and respiratory infections. Low air quality, from traffic pollution or high ozone levels, has been repeatedly associated with increased asthma morbidity and has a suggested association with asthma development that needs further research.
Recent studies show a relationship between exposure to air pollutants (e.g. from traffic) and childhood asthma. This research finds that both the occurrence of the disease and exacerbation of childhood asthma are affected by outdoor air pollutants.
Viral respiratory infections are not only one of the leading triggers of an exacerbation but may increase one's risk of developing asthma.
Caesarean sections have been associated with inal birth, which modifies the immune system (as described by the hygiene hypothesis).
Psychological stress has long been suspected of being an asthma trigger, but only in recent decades has convincing scientific evidence substantiated this hypothesis. Rather than stress directly causing the asthma symptoms, it is thought that stress modulates the immune system to increase the magnitude of the airway inflammatory response to allergens and irritants.
Antibiotic use early in life has been linked to development of asthma in several examples; it is thought that antibiotics make one susceptible to development of asthma because they modify gut flora, and thus the immune system (as described by the hygiene hypothesis). The hygiene hypothesis is a hypothesis about the cause of asthma and other allergic disease, and is supported by epidemiologic data for asthma. For example, asthma prevalence has been increasing in developed countries along with increased use of antibiotics, c-sections, and cleaning products. All of these things may negatively affect exposure to beneficial bacteria and other immune system modulators that are important during development, and thus may cause increased risk for asthma and allergy.
Recently scientists connected the rise in prevalence of asthma, to the rise in use of paracetamol, suggesting the possibility that paracetamol can cause asthma.
It has been suggested that viral infections such as HSV, VSV and CSV are correlated to asthma episodes.
GENETIC
Over 100 genes have been associated with asthma in at least one genetic association study. However, such studies must be repeated to ensure the findings are not due to chance. Through the end of 2005, 25 genes had been associated with asthma in six or more separate populations:
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Many of these genes are related to the immune system or to modulating inflammation. However, even among this list of highly replicated genes associated with asthma, the results have not been consistent among all of the populations that have been tested. This indicates that these genes are not associated with asthma under every condition, and that researchers need to do further investigation to figure out the complex interactions that cause asthma. One theory is that asthma is a collection of several diseases, and that genes might have a role in only subsets of asthma. For example, one group of genetic differences was associated with asthma that develops in childhood.
GENE–ENVIRONMENT INTERACTIONS
|
CD14-endotoxin interaction based on CD14 SNP C-159T |
||
|
Endotoxin levels |
CC genotype |
TT genotype |
|
High exposure |
Low risk |
High risk |
|
Low exposure |
High risk |
Low risk |
Research suggests that some genetic variants may only cause asthma when they are combined with specific environmental exposures, and otherwise may not be risk factors for asthma.
The genetic trait, CD14 single nucleotide polymorphism (SNP) C-159T and exposure to endotoxin (a bacterial product) are a well-replicated example of a gene-environment interaction that is associated with asthma. Endotoxin exposure varies from person to person and can come from several environmental sources, including environmental tobacco smoke, dogs, and farms. Researchers have found that risk for asthma changes based on a person’s genotype at CD14 C-159T and level of endotoxin exposure.
EXACERBATION
Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different asthmatic individuals react differently to various factors. However, most individuals can develop severe exacerbation of asthma from several triggering agents.
Home factors that can lead to exacerbation include dust, house mites, animal dander (especially cat and dog hair), cockroach allergens and molds at any given home. Perfumes are a common cause of acute attacks in females and children. Both virus and bacterial infections of the upper respiratory tract infection can worsen asthma.
RISK FACTORS
Studying the prevalence of asthma and related diseases such as eczema and hay fever have yielded important clues about some key risk factors. The strongest risk factor for developing asthma is a history of atopic disease; this increases one's risk of hay fever by up to 5x and the risk of asthma by 3-4x. In children between the ages of 3-14, a positive skin test for allergies and an increase in immunoglobulin E increases the chance of having asthma. In adults, the more allergens one reacts positively to in a skin test, the higher the odds of having asthma.
Because much allergic asthma is associated with sensitivity to indoor allergens and because Western styles of housing favor greater exposure to indoor allergens, much attention has focused on increased exposure to these allergens in infancy and early childhood as a primary cause of the rise in asthma. Primary prevention studies aimed at the aggressive reduction of airborne allergens in a home with infants have shown mixed findings. Strict reduction of dust mite allergens, for example, reduces the risk of allergic sensitization to dust mites, and modestly reduces the risk of developing asthma up until the age of 8 years old. However, studies also showed that the effects of exposure to cat and dog allergens worked in the converse fashion; exposure during the first year of life was found to reduce the risk of allergic sensitization and of developing asthma later in life.
The inconsistency of this data has inspired research into other facets of Western society and their impact upon the prevalence of asthma. One subject that appears to show a strong correlation is the development of asthma and obesity. In the United Kingdom and United States, the rise in asthma prevalence has echoed an almost epidemic rise in the prevalence of obesity. In Taiwan, symptoms of allergies and airway hyper-reactivity increased in correlation with each 20% increase in body-mass index.
HYGIENE HYPOTHESIS
One theory for the cause of the increase in asthma prevalence worldwide is the so-called "hygiene hypothesis"—that the rise in the prevalence of allergies and asthma is a direct and unintended result of the success of modern hygienic practices in preventing childhood infections. Studies have shown repeatedly that children coming from environments one would expect to be less hygienic (East Germany vs. West Germany, families with many children, day care environments) tended to have lower incidences of asthma and allergic diseases. This seems to run counter to the logic that viruses are often causative agents in exacerbation of asthma. Additionally, other studies have shown that viral infections of the lower airway may in some cases induce asthma, as a history of bronchiolitis or croup in early childhood is a predictor of asthma risk in later life. Studies which show that upper respiratory tract infections are protective against asthma risk also tend to show that lower respiratory tract infections conversely tend to increase the risk of asthma.
ATHLETICS
Asthma appears to be more prevalent in athletes than in the general population. One survey of participants in the 1996 Summer Olympic Games, in Atlanta, Georgia, U.S., showed that 15% had been diagnosed with asthma, and that 10% were on asthma medication.
There appears to be a relatively high incidence of asthma in sports such as cycling, mountain biking, and long-distance running, and a relatively lower incidence in weightlifting and diving. It is unclear how much of these disparities are from the effects of training in the sport.
OCCUPATION
Asthma as a result of (or worsened by) workplace exposures is the world's most commonly reported occupational respiratory disease. Still most cases of occupational asthma are not reported or are not recognized as such. Estimates by the American Thoracic Society (2004) suggest that 15–23% of new-onset asthma cases in adults are work related. In one study monitoring workplace asthma by occupation, the highest percentage of cases occurred among operators, fabricators, and laborers (32.9%), followed by managerial and professional specialists (20.2%), and in technical, sales, and administrative support jobs (19.2%). Most cases were associated with the manufacturing (41.4%) and services (34.2%) industries. Animal proteins, enzymes, flour, natural rubber latex, and certain reactive chemicals are commonly associated with work-related asthma. When recognized, these hazards can be mitigated, dropping the risk of disease.
PATHOPHYSIOLOGY
Inflamed airways and bronchoconstriction in asthma results in airways narrowing and thus wheezing.
Asthma is an airway disease that can be classified physiologically as a variable and partially reversible obstruction to air flow, and pathologically with overdeveloped mucus glands, airway thickening due to scarring and inflammation, and bronchoconstriction, the narrowing of the airways in the lungs due to the tightening of surrounding smooth muscle. Bronchial inflammation also causes narrowing due to edema and swelling caused by an immune response to allergens.
MEDICATIONS
Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms and long-term control medications used to prevent further exacerbation.
Fast acting
- Short-acting, selective beta2-adrenoceptor agonists, such as salbutamol (albuterol USAN), levalbuterol, terbutaline and bitolterol.
- Tremors, the major side effect, have been greatly reduced by inhaled delivery, which allows the drug to target the lungs specifically; oral and injected medications are delivered throughout the body. There may also be cardiac side effects at higher doses (due to Beta-1 agonist activity), such as elevated heart rate or blood pressure. However, levalbuterol has been shown to have less cardiac side effects and significantly more anti-inflammatory effects on bronchial smooth muscle than its racemic counterpart albuterol.
- Older, less selective adrenergic agonists, such as inhaled epinephrine and ephedrine tablets, have also been used. Cardiac side effects occur with these agents at either similar or lesser rates to albuterol. When used solely as a relief medication, inhaled epinephrine has been shown to be an effective agent to terminate an acute asthmatic exacerbation. In emergencies, these drugs were sometimes administered by injection. Their use via injection has declined due to related adverse effects.
- Anticholinergic medications, such as ipratropium bromide may be used instead. They have no cardiac side effects and thus can be used in patients with heart disease; however, they take up to an hour to achieve their full effect and are not as powerful as the β2-adrenoreceptor agonists.
Long term control
- Inhaled glucocorticoids are usually considered preventive medications while oral glucocorticoids are often used to supplement treatment of a severe attack. They should be used twice daily in children with mild to moderate persistent asthma. A randomized controlled trial has demonstrated the benefit of 250 microg beclomethasone when taken as an as-needed combination inhaler with 100 microg of albuterol.
SALBUTAMOL
Salbutamol(INN) or albuterol (USAN) is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed by GlaxoSmithKline as Ventolin, Aerolin or Ventorlin depending on the market; by Cipla as Asthalin; by Schering-Plough as Proventil and by Teva as ProAir.
Salbutamol was the first selective Β2-receptor agonist to be marketed — in 1968. It was first sold by Allen & Hanburys under the brand name Ventolin. The drug was an instant success, and has been used for the treatment of asthma ever since.
Salbutamol sulfate is usually given by the inhaled route for direct effect on bronchial smooth muscle. This is usually achieved through a metered dose inhaler (MDI), nebulizer or other proprietary delivery devices. In these forms of delivery, the maximal effect of Salbutamol can take place within five to twenty minutes of dosing, though some relief is immediately seen. Salbutamol can also be given orally as an inhalant or intravenously.
CLINICAL USE
Salbutamol is specifically indicated in the following conditions:
- Acute asthma
- Symptom relief during maintenance therapy of asthma and other conditions with reversible or irreversible airways obstruction (including COPD and bronchitis)
- Protection against exercise-induced asthma
- Can be aerosolized with a nebulizer for patients with cystic fibrosis, along with ipratropium bromide, acetylcysteine, and pulmozyme.
As a β2-agonist, salbutamol also finds use in obstetrics. Intravenous salbutamol can be used as a tocolytic to relax the uterine smooth muscle to delay premature labour. While preferred over agents such as atosiban and ritodrine, its role has largely been replaced by the calcium-channel blocker nifedipine which is more effective, better tolerated and orally administered.
SIDE EFFECTS / HEALTH CONSEQUENCES
The most common side effects are of fine tremor, nervousness, headache, muscle cramps, dry mouth, and palpitation. Other symptoms may be tachycardia (rapid heart rate), arrhythmias, flushing, myocardial ischaemia, and disturbances of sleep and behaviour. Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse, whilst high doses may cause hypokalaemia (low potassium levels), especially in patients with renal failure and those on certain diuretics and xanthine derivaties.
DIET AND BODYBUILDING USE
Salbutamol is taken by some as an alternative to clenbuterol for purposes of fat burning. Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically in the 10-500 µg/L range.
DOPING
Clinical studies show no compelling evidence that Salbutamol and other beta 2 antagonists can increase performance in healthy athletes. In spite of this, Salbutamol remains on WADAs prohibited list and many athletes have been banned for use of salbutamol.
According to two small and limited studies, performed on 8 and 16 subjects respectively, Salbutamol increases the performance even for a person without asthma.
BAN OF CFC-CONTAINING INHALERS
The U.S. Food and Drug Administration (FDA) in April 2005 mandated that all (including salbutamol) inhalers containing chlorofluorocarbons (CFCs) will be prohibited in the United States as of December 31, 2008. CFC inhalers had previously been given "essential use" status, exempting it from a CFC-production ban, however in accordance with the Montreal Protocol they will be phased out; in many other countries patients have been transitioned to non-CFC based inhalers using hydrofluoroalkane (HFA) propellant. Pharmaceutical manufacturers are expected to produce adequate supplies of alternative (HFA) inhalers by 2009.
One drawback of this transition to HFA inhalers is that, due to patent restrictions, all HFA salbutamol inhalers are "brand-name" (ProAir, Proventil, and Ventolin). They cost approximately $20 more per inhaler than existing generic CFC salbutamol inhalers. These new formulations are patented. An industry consortium was formed to spread the costs of the FDA safety studies to get propellants such as 134a and 227 approved.
Generic HFA salbutamol inhalers are not expected to reach the United States market until after 2012 due to existing patents.
Salbutamol is widely used, and accounts for anywhere from 78% of all bronchodilator prescriptions in 2005 to 85% in 2008. However, patients in the United States who cannot tolerate the HFA salbutamol inhalers will not have a single salbutamol alternative available to them domestically after December 31, 2008. The FDA did not approve any alternatives to HFA and there are few standard inhaled lung medications in the United States that come in Dry Powder Inhaler (DPI) versions. Noticeably missing is salbutamol in DPI form in the United States, although it is available in most of the rest of the world in salbutamol DPIs.
CHEM
METHODOLOGY
Following are the essential steps involve in the present study.
1. Observational and survey method: This methodology involves the use of questionnaire distributed to the medical store in order to serve the purpose.
2. Necessary information has bee collected from both primary and secondary sources of information including market reports, related publication, literature available on net etc.
3. Beside this physician views and preference regarding the same through direct interaction as well as telephonically serve the purpose of study.
4. The study was aimed on exploring the current pharmaceutical marketing scenario of anti hypertensive drugs in India context.
To collect relevant and meaningful data medical store was selected randomly and their number was restricted to 20’ (twenty) The questionnaire prepared included simple question specifying and well destining the area of study undertaken.
The language of questionnaire was English the chemist were explained the question if demanded by them in complete responses were excluded from the study in order to increase the effectiveness of the study. Considerable time was provided to the chemist to fill the questionnaire suitable statistical tools were employed on the result whenever found appropriate the result were tabulated and efforts were directed to subject the result to an exhaustive interpretational analysis to make out an appropriate conclusion.
A questionnaire was prepared and distributed to them for furnishing the response.
QUESTIONNAIRE
1. How many prescriptions are received by you daily?
Less than 5 ( ) 5-10 ( ) 10-15 ( ) More than 15 ( )
2. Which are the leading physicians of whom, you receive the maximum prescriptions?
________________________
________________________
________________________
3. What is the average number of prescriptions of anti hypertensive drugs you receive weekly?
Less than 10 ( ) 10-20 ( ) 20-30 ( ) More than 30 ( )
4. Which are the brands of anti hypertensive drugs you sale?
|
S.No. |
Brand Name |
Combination |
Price/Strip |
Name of Manufacture |
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5. Which of the Above brands you sell the most?
|
Brand Name |
Name of Manufacture |
Sales/Week |
|
|
6. If, Yes what is the percentage of total sales?
7. Are the “NDDS” in this category are also prescribed by the physicians?
Yes ( ) No ( )
8. Are the patients counseled by you?
Yes ( ) No ( )
9. Do the patients complain you of the adverse effects?
Yes ( ) No ( )
10. If yes what is the No.? & type of adverse effects reported?
RESULT & DISCUSSION
MODIPON
|
S. No.
|
DRUG (ACTIVE CONSTITUENT) |
BRAND NAME |
MANUFACTURER |
SALE ( % ) |
|
1.
|
SALBUTAMOL SULPHAT+THEO-PHYLLIN |
THEO-ATHALLIN |
CIPLA |
46 |
|
2.
|
SALBUTAMOL |
ASTHALLIN |
CIPLA |
29 |
|
3.
|
SALBUTAMOL |
SOLBETOL |
FDC |
14 |
|
4.
|
SALBUTAMOL |
SOLBUTAMOL |
GSK |
11 |
Graphical representation of comparison of sale of Theo-asthallin drug at Modipon.
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