1. a.

Explain etiopathogenesis and pharmacotherapy of osteoporosis

Osteoporosis is a progressive disease characterised by low bone mass and microarchitectural deterioration of bone tissue resulting in increased bone fragility and
susceptibility to fracture. It is an important cause of morbidity in postmenopausal
women. The most important complication of osteoporosis is fracture of the hip.
PHARMACOTHERAPY OF OSTEOPOROSIS:
Vitamin D and calcium: Vitamin D deficiency is common in elderly people.
Treatment for 1218 months with 800 IU of vitamin D plus 1.2 g of calcium given
daily has been shown to reduce hip and non-vertebral fractures in elderly women
Calcitriol and alfacalcidol: Calcitriol (1,25-dihydroxyvitamin D), the active
metabolite of vitamin D, and alfacalcidol, a synthetic analogue of calcitriol, reduce
bone loss and have been shown to reduce vertebral fractures, but not consistently.
Serum calcium should be monitored regularly in patients receiving these drugs.
Bisphosphonates: Bisphosphonates, synthetic analogues of pyrophosphate, bind
strongly to the bone surface and inhibit bone resorption. Currently, three oral
bisphosphonates are available for the treatment of osteoporosis: alendronate,
etidronate and risedronate. Alendronate can be given either daily (10 mg) or weekly
(70 mg) with equal efficacy. It is effective in reducing vertebral, wrist and hip
fractures. Etidronate is given cyclically with calcium supplements to reduce the risk
of bone mineralisation defects. It reduces the risk of vertebral fractures.
Alendronate and risedronate are currently used as first-line drugs in older women
with osteoporosis.
Strontium ranelate: It increases both bone formation and reduces bone
resorption, reduces vertebral and non-Vertebral (including hip) fractures in
postmenopausal women with osteoporosis.
Hormone replacement therapy (HRT): Oestrogens increase bone formation and
reduce bone resorption. They also increase calcium absorption and decrease renal
calcium loss. HRT, if started soon after the menopause, is effective in preventing
vertebral fractures but has to be continued lifelong if protection against fractures is
to be maintained.
Raloxifene: Raloxifene, an oral selective oestrogen receptor modulator (SERM) that
has oestrogenic actions on bone and anti-oestrogenic actions on the uterus and
breast. It reduces the risk of vertebral fractures, but not those at other sites.
Adverse effects include hot flushes, leg cramps, and risk of venous
thromboembolism. It also protects against breast cancer.
Parathyroid hormone peptides: Teriparatide is the recombinant portion of
human parathyroid hormone, amino acid sequence 134, of the complete molecule
(which has 84 amino acids). It reduces vertebral and non-vertebral fractures in
postmenopausal women. It does not reduce hip fractures. It is given subcutaneously
at a dose of 20 cg daily.
Calcitonin: Calcitonin inhibits osteoclasts and decreases the rate of bone
resorption, reduces bone blood flow and may have central analgesic actions. It is
effective in all age groups in preventing vertebral bone loss. It is costly and has to
be given parenterally or intranasally. Antibodies do develop against calcitonin, but

they do not affect its efficacy. Calcitonin is useful in treating acute pain associated
with osteoporotic vertebral fractures.

2. Write short notes on Diagnosis test of COPD

Breathing, Exercise, and Oxygen Tests
Pulmonary function testing measures how well you are breathing. There are
different types of breathing tests that can be done during pulmonary function
testing.

Spirometry: A spirometry test measures airflow into and out of the

lungs. This indicates whether or not there is airway obstruction.
Spirometry test results are useful in making the diagnosis of a
specific lung disorder. Even more important, yearly spirometry
measurements help to detect lung disease at an early stage when
lifestyle changes and treatment may help forestall future problems.

Arterial Blood Gas Testing: Arterial blood gas is a blood sample test
ordered by your physician to evaluate measurements of oxygen
level, carbon dioxide (effectiveness of respiration), and several other
parameters..

Bronchial Provocation Test: The bronchial provocation test evaluates

how sensitive the airways in your lungs are. A spirometry breathing
test is done before and after you inhale a spray such as
methacholine. The spirometry results are compared before and after
you inhale the spray to see what changes there are in your
breathing.

Exercise Tolerance Testing: The exercise tolerance test evaluates the

ability of your heart and lungs to provide oxygen and remove carbon
dioxide from the bloodstream before, during and after you exercise.

Exercise for Desaturation Testing: The exercise for de-saturation test

evaluates your oxygen needs at rest and during exercise.

X-Rays and CT (CAT) Scans

X-rays: X-rays can show irregularities or damage in the lungs caused by

COPD and other chronic lung diseases.

CT Scan of the Chest : A CT or CAT scan is a shortened name for

computerized tomography. During a CT scan of the chest pictures are taken
of cross sections or slices of the thoracic structures in your body. Thoracic
structures include your lungs, heart and the bones around these areas.

CT Scan of the Sinuses : During a CT scan of the sinuses pictures are taken of
cross sections or slices of the sinuses. The sinuses are air-filled cavities in
your head. CT scans can identify problems with sinuses.

Other Tests

Bronchoscopy: A bronchoscopy allows the doctor to look inside the airways

in the lungs. The bronchoscopy can be videotaped to look at later. Your doctor
may also do a lavage, which involves putting a small amount of fluid into the
airways, and the fluid is then pulled out with cells from the airways of your
lungs. A biopsy of the airway may also be done, where a small amount of the
tissue is taken from the lining of the lung.

Mucus Culture: Some kinds of bacteria like to live in the mucus produced in
the sinuses and airways of the lungs. A culture of this mucus can help identify
an infection. Lung and/or sinus infections can complicate and/or mimic some
symptoms of COPD.

Bone Scan: A bone scan is a test that can identify bone that is diseased or
injured. Normally, bone absorbs nutrients that are the building blocks of bone
formation. If bone is diseased or injured nutrients are absorbed differently.
The bone scan takes pictures of this process. A bone scan can pick up on
bone disease or injury that may not be seen with a traditional x-ray.

pH Probe Study: A pH probe study measures the amount of

gastroesophageal reflux you child has. Gastroesophageal reflux is the
backward flow or reflux of food and acid from the stomach into the
esophagus. The esophagus is the tube that takes food from your mouth into
your stomach. A pH probe will help identify if you have increased amounts of
reflux and if it is causing you to have trouble breathing or other symptoms.

3. Explain the etiology and Pharmacotherapy of chronic obstructive airways

disease
Aetiology :
Tobacco smoking is the most important and dominant risk factor in the
development of COPD but other noxious particles also contribute, such as
occupational exposure to chemical fumes, irritants, dust and gases. A person's
exposure can be thought of in terms of the total burden of inhaled
particles.These cause a (normal) inflammatory response in the lungs. Smokers,
however, seem to have an exaggerated responsewhich eventually causes tissue
destruction and impaired repair mechanisms. In addition to inflammation, the
othermain processes involved in the pathogenesis of COPD arean imbalance of
proteinases and antiproteinases in the lungs,and oxidative stress.
Not all smokers go on to develop clinically significant COPD; genetic factors
seem to modify each individual's risk.
The age at which an individual begins smoking, total pack-years smoked and
current smoking status are predictive of COPD mortality. Passive exposure to
cigarette smoke may also contribute to respiratory symptoms and COPD by
increasing the lungs' total burden of inhaled particles and gases (GOLD, 2009).

Tobacco exposure is quantified in pack-years: Additional risk factors include the

natural ageing process of the lungs. Males are currently more at risk of
developing chronic bronchitis, but as the number of women who smoke
increases, the incidence of chronic bronchitis in females will also rise. The major
risk factors are summarized
RISK FACTOR
Smoking

Age

Gender

Occupation

Genetic factors

Air pollution

Socio economic status

Airway hyper-responsiveness and
allergy

EFFECTS
Risk increases with increasing
consumption but there is also large
interindividual variation in susceptibility
Increasing age results in ventilatory
impairment; most frequently related to
cumulative smoking
Male gender was previously thought to be
a risk factor but this may be due to a
higher incidence of
The development of COPD has been
implicated with occupations such as coal
and gold mining, farming,grain handling
and the cement and cotton industries
1-Antitrypsin deficiency is the strongest
single genetic risk factor, accounting for
12% of COPD. Other genetic disorders
involving tissue necrosis factor and
epoxide hydrolase may also be risk
factors
Death rates are higher in urban areas
than in rural areas. Indoor air pollution
from burning biomass fuel is also
implicated as a risk factor, particularly in
underdeveloped areas of the world
More common in individuals of low socio
Smokers show increased levels of IgE,
eosinophils and airway hyperresponsiveness but how these
influence the development of COPD is
unknown

Inflammation
COPD is characterised by chronic inflammation throughout the airways, parenchyma
and pulmonary vasculature. This is a different pattern of inflammation from that of
asthma, with an increase in neutrophils, macrophages and T-lymphocytes
(particularly CD8+); increased eosinophils occur in some patients during
exacerbations. These inflammatory cells cause the release of inflammatory
mediators and cytokines such as leukotriene B4, interleukin-8 and tumour necrosis

factor- (TNF-). Over time the actions of these mediators damages the lungs and
leads to the characteristic pathological changes
observed.
Proteinase and antiproteinase imbalance
The observation that 1-antitrypsin-deficient individuals are at increased risk of
developing emphysema has led to the theory that an imbalance between
proteinases and antiproteinases leads to lung destruction. In COPD, there is either
an increased production/activity of proteinases or a decreased production/activity of
antiproteinases. The main proteinases, proteolytic enzymes such as neutrophil
elastin are released by macrophages or neutrophils. The antiproteinases inhibit the
damage caused by the proteolytic enzymes. The main antiproteinase is 1antitrypsin, also known as 1-proteinase
inhibitor. Cigarette smoke has been shown to inactivate this protein. Oxidative
stress also decreases the activity of antiproteinases.
Oxidative stress
An imbalance of oxidants and antioxidants exists in COPD with the balance in favour
of the oxidants. This state of oxidative stress contributes to the development of the
disease by damaging the intracellular matrix, oxidising biological molecules which
cause cell destruction and promoting histone acetylation. There also seems to be a
link between oxidative stress and the poor response to corticosteroids seen in
COPD. To work, corticosteroids must recruit histone deacetylase to switch off the
transcription of inflammatory genes. In COPD,the activity of histone deacetylase is
impaired by the oxidative stress, thereby reducing the responsiveness to
corticosteroids. Cigarette smoke also impairs the function of histone deacetylase.
PHARMACOTHERAPY:
The primary goals of pharmacotherapy are to control symptoms (including
dyspnea), reduce exacerbations, and improve exercise tolerance and health status.
According to the guidelines, patients with intermittent symptoms should be treated
with short-acting bronchodilators. When symptoms become more persistent, longacting bronchodilators should be initiated. For patients with an FEV1 less than 50%
and who experience frequent exacerbations, inhaled corticosteroids should be
considered. Short-acting bronchodilators relieve symptoms and increase exercise
tolerance. Long-acting bronchodilators relieve symptoms,reduce exacerbation
frequency, and improve quality of life and health status. Patients have a variety of
choices in using inhalational
therapies, including metered dose inhalers (MDIs), dry powder inhalers (DPIs), or
nebulizers.
Bronchodilators: Bronchodilator classes available for the treatment of COPD
include 2-agonists, anticholinergics, and methylxanthines. Bronchodilators
generally work by reducing the tone of airway smooth muscle (relaxation), thus
minimizing airflow limitation. In patients with COPD, the clinical benefits of
bronchodilators include increased exercise capacity, decreased air trapping in the
lungs, and
relief of symptoms such as dyspnea.
Short-Acting Bronchodilators: The initial therapy for COPD patients who
experience symptoms intermittently are short-acting bronchodilators. Among these
agents, the choices are a shortacting
2-agonist or an anticholinergic. Either class of agents has a relatively rapid onset
on action, relieves symptoms, and improves exercise tolerance and lung function.

Short-Acting Sympathomimetics (2-Agonists) : 2-Agonists cause

bronchodilation by stimulating the enzyme adenyl cyclase to increase the formation
of cyclic adenosine monophosphate. Cyclic adenosine monophosphate is
responsible for mediating relaxation of bronchial smooth muscle, leading to
bronchodilation. In addition, it may improve mucociliary clearance. Although
shorter-acting and
less-selective -agonists are still used widely (e.g., metaproterenol,isoetharine,
isoproterenol, and epinephrine), they should not be used owing to their shorter
duration of action and increased cardiostimulatory effects. Short-acting, selective
2-agonists such as albuterol, levalbuterol, and pirbuterol, are preferred for therapy.
The preferred route of administration is by inhalation.
The use of oral and parenteral -agonists in COPD is discouraged because they are
no more effective than a properly used MDI or DPI, and the incidence of systemic
adverse effects such as tachycardia and hand tremor is greater.
Albuterol is the most frequently used 2-agonist. It is available as an oral and
inhaled preparation. Albuterol is a racemic mixture of (R)-albuterol that is
responsible for the bronchodilator effect and
(S)-albuterol that has no therapeutic effect. Levalbuterol is a single-isomer
formulation of
(R)-albuterol. The duration of action of short-acting 2agonists is 4 to 6 hours.
Short-Acting Anticholinergics: When given by inhalation, anticholinergics such
as ipratropium or atropine produce bronchodilation by competitively inhibiting
cholinergic receptors in bronchial smooth muscle. This activity blocks acetylcholine,
with the neteffect being a reduction in cyclic guanosine monophosphate, which
normally acts to constrict bronchial smooth muscle. Muscarinic receptors on airway
smooth muscle include M1, M2, and M3 subtypes. Activation of M1 and M3
receptors by acetylcholine results
in bronchoconstriction; however, activation of M2 receptors inhibits further
acetylcholine release.
Ipratropium is the primary short-acting anticholinergic agent used for COPD .It
provides a peak effect in 1.5 to 2 hours and has a duration of effect of 4 to 6 hours.
Ipratropium has a slower onset of action and a more prolonged bronchodilator effect
compared with standard 2-agonists.
Long-Acting Bronchodilators: For patients with moderate to severe COPD who
experience symptoms on a regular and consistent basis, or in whom short-acting
therapies do not provide adequate relief, long-acting bronchodilator therapies are
the recommended treatment. Long-acting, inhaled bronchodilator therapy can be
administered as a 2-agonist or an anticholinergic. Long-acting bronchodilators
provide similar benefits to short-acting agents. In addition, they reduce
exacerbation frequency and improve quality of life.
Long-Acting, Inhaled 2-Agonists: Long-acting, inhaled 2-agonists offer the
convenience and benefit of a long duration of action for patients with persistent
symptoms. Both salmeterol and formoterol are dosed every 12 hours and provide
sustained bronchodilation. Formoterol has an onset of action similar to albuterol
(less than 5 minutes), whereas salmeterol has a slower onset (15 to 20 minutes)
Long-acting -agonists are also useful to reduce nocturnal symptoms and improve
quality of life. When compared to short-acting bronchodilators or theophylline, both
salmeterol and formoterol improve lung function, symptoms, exacerbation
frequency and quality of life

Long-Acting Anticholinergics : Tiotropium bromide, a long acting quaternary

anticholinergic agent This agent blocks the effects of acetylcholine by binding to
muscarinic receptors in airway smooth muscle
and mucus glands, blocking the cholinergic effects of bronchoconstriction and
mucus secretion. When inhaled, tiotropium is minimally absorbed into the systemic
circulation and results in bronchodilation within 30 minutes, with a peak effect in 3
hours.
Corticosteroids : The antiinflammatory mechanisms whereby corticosteroids exert
their beneficial effect in COPD include (a) reduction in capillary permeability to
decrease mucus, (b) inhibition of release of proteolytic enzymes from leukocytes,
and (c) inhibition of prostaglandins.
1-Antitrypsin Replacement Therapy : In patients with inherited AAT deficiencyassociated emphysema,treatment focuses on reduction of risk factors such as
smoking, symptomatic treatment with bronchodilators, and augmentation therapy
with replacement AAT. Augmentation therapy consists of weekly infusions of pooled
human AAT to maintain AAT plasma levels greater than 10 micromolars.
4. Write about the rational use of drugs in following disorders
a) Osteoporosis
b) Diabetes mellitus