CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease is a major global health problem. Cigarette smoking is the main cause, and is increasing in the developing world as a result of targeting by the tobacco industry. Air pollution, also aetiologically important, is also increasing, and there is a huge unmet need for effective drugs. Despite this, COPD has received relatively little attention compared with asthma.

Clinical features.  The clinical picture starts with attacks of morning cough during the winter, and progresses to chronic cough with intermittent exacerbations, often initiated by a cold, when the sputum becomes purulent ('chronic bronchitis'). There is progressive breathlessness. Some patients have a reversible component of airflow obstruction identifiable by an improved FEV1 following a dose of bronchodilator. Pulmonary hypertension is a late complication, causing symptoms of heart failure (cor pulmonale). Exacerbations may be complicated by type 1 or type 2 respiratory failure (i.e. reduced PAo2 alone or with increased PAco2, respectively) requiring hospitalisation and intensive care. Tracheostomy and artificial ventilation, while prolonging survival, may serve only to return the patient to a miserable life.

Pathogenesis.  There is small airways fibrosis, resulting in obstruction, and/or destruction of alveoli and of elastin fibres in the lung parenchyma. The latter features are hallmarks of emphysema, thought to be caused by proteases, including elastase, released during the inflammatory response. Small airways obstruction and emphysema vary independently of one another. The explanation for this variation is unknown. It is emphysema that causes respiratory failure, because it destroys the alveoli, impairing gas transfer. There is chronic inflammation, predominantly in small airways and lung parenchyma, characterised by increased numbers of macrophages, neutrophils, and T lymphocytes. The inflammatory mediators have not been as clearly defined as in asthma. Lipid mediators, inflammatory peptides, reactive oxygen and nitrogen species, chemokines, cytokines and growth factors are all implicated.

Principles of treatment.   Stopping smoking  slows the progress of COPD. Patients should be immunised against influenza and Pneumococcus, because superimposed infections with these organisms are potentially lethal. Glucocorticoids are generally ineffective, in contrast to asthma, but a trial of glucocorticoid treatment is worthwhile because asthma may coexist with COPD and have been overlooked. This contrast with asthma is puzzling, because in both diseases multiple inflammatory genes are activated, which might be expected to be turned off by glucocorticoids. Inflammatory gene activation results from acetylation of nuclear histones around which DNA is wound. Acetylation opens up the chromatin structure, allowing gene transcription and synthesis of inflammatory proteins to proceed. HDAC is a key molecule in suppressing production of proinflammatory cytokines. Corticosteroids recruit HDAC to activated genes, reversing acetylation and switching off inflammatory gene transcription. There is a link between the severity of COPD (but not of asthma) and reduced HDAC activity in lung tissue , furthermore, HDAC activity is inhibited by smoking-related oxidative stress, which may explain the lack of effectiveness of glucocorticoids in COPD.

Long-acting bronchodilators have been a worthwhile if modest advance in the treatment of COPD, but do not deal with the underlying inflammation. No currently licensed treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma. Several new treatments that target the inflammatory process are in clinical development (Barnes & Stockley, 2005). Some, such as chemokine antagonists, are directed against the influx of inflammatory cells into the airways and lung parenchyma, whereas others target inflammatory cytokines such as TNF-α. PDE IV inhibitors (e.g. roflumilast; Rabe et al., 2005) show some promise. Other drugs that inhibit cell signalling  include inhibitors of p38 mitogen-activated protein kinase, nuclear factor κB and phosphoinositide-3 kinase-γ. More specific approaches are to give antioxidants, inhibitors of inducible NO synthase and leukotriene B4 antagonists. Other treatments have the potential to combat mucus hypersecretion, and there is a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema.

Specific aspects of treatment.   Short- and long-acting inhaled bronchodilators can provide useful palliation in patients with a reversible component. The main short-acting drugs are ipratropium and salbutamol ; long-acting drugs include tiotropium  and salmeterol or formoterol . Theophylline can be given by mouth but is of uncertain benefit. Its respiratory stimulant effect may be useful for patients who tend to retain CO2. Other respiratory stimulants (e.g. doxapram; are sometimes used briefly in acute respiratory failure (e.g. postoperatively) but have largely been replaced by ventilatory support (intermittent positive-pressure ventilation).

Long-term oxygen therapy administered at home prolongs life in patients with severe disease and hypoxaemia (at least if they refrain from smoking-an oxygen fire is not a pleasant way to go, especially for one's neighbours!).

Acute exacerbations.  Acute exacerbations of COPD are treated with inhaled O2 in a concentration (initially, at least) of only 24% O2, i.e. only just above atmospheric O2 concentration (approximately 20%). The need for caution is because of the risk of precipitating CO2 retention as a consequence of terminating the hypoxic drive to respiration. Blood gases and tissue oxygen saturation are monitored, and inspired O2 subsequently adjusted accordingly. Broad-spectrum antibiotics (e.g. cefuroxime; including activity against Haemophilus influenzae are used if there is evidence of infection. Inhaled bronchodilators may provide some symptomatic improvement.

A systemically active glucocorticoid (intravenous hydrocortisone or oral prednisolone) is also administered routinely, although efficacy is modest. Inhaled steroids do not influence the progressive decline in lung function in patients with COPD, but do improve the quality of life, probably as a result of a modest reduction in hospital admissions.

FOREIGN DRUG MAKERS WON 77% OF ALL PATENTS IN LAST THREE YEARS IN INDIA

Well this may not seem alarming but I think it is alarming more than two third of the pharmaceutical patents awarded by India in the last three years were granted to foreign drug maker such as Pfizer Ins , Novartis AG and F Hoffman La Roche Ltd ,which have been critical of India's intellectual property rights regime. The country issued 1,001 drug patents between April 2010 and march 2013 , of which 771 were given to foreign drug makers,mainly from the US and Europe , according to data released last week by the Indian patent office .

US insulin maker and biotech researcher Eli Lilly and co. won the most number of those patents in  that period ,securing 36 of them ,mainly for biological products and compounds to treat diabetes and related diseases. Eli Lilly was followed by Pfizer, the worlds largest drug maker ,with 32 patents and Switzerland based F Hoffmann-La Roche and Novartis with 22 and 14 patents , respectively . French drug maker Sanofi SA and Germany's Bayer AG ,too were  granted atleast a dozen Indian patents in three years.

IPO data also reveal that from April 2005 to march 2010, the patent office granted 3,488 drug patents of which more than 3000  were granted to foreign pharma companies the patents , which cover inventions related to single molecules or groups of compounds or processes leading to development of various medicine typically allow these companies exclusive marketing rights for such products for at least 15-20 years in India. 

The IPO data for 2010-13 also showed  that local drug makers and research institution were granted 230 patents. the names include Cadila healthcare Ltd, Ranbaxy laboratories ltd , Glenmark Pharmaceutical Ltd, Wockhardt Ltd and the state -run council of scientific and Industrial Research . India , which follows a stricter patent regime than the US and European Union ,has been at receiving end of criticism for turning down several patent application and revoking existing patents following judicial challenges filed  by local as well as foreign rivals. The country's patent law , unlike that of the US  and Europe doesn't allow patent grants for drugs invented before 1995 the cut off year fixed when India reintroduced its products patent ... the reasoning was that previous invention are already in the public domain and do not deserve a patent grant 

well even after this success Pfizer , in a may testimony to the US congress , alleged that India lacks a conducive business environment mainly because of its poor IPR regime .................

This reports shows a mirror to Indian drug research and development we really lack a proper research facility and as for foreign companies the are making most of this...............................................

Chicken Pox

Chicken pox

Chickenpox or chicken pox is a  illness caused by primary infections  with varicella zoster virus (VZV)^. It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring.

Chickenpox is an airborne disease spread easily through coughing or sneezing of ill individuals or through direct contact with secretions from the rash. A person with chickenpox is infectious from one to five days before the rash appears. The contagious period continues for 4 to 5 days after the appearance of the rash, or until all lesions have crusted over. Immunocompromised patients are probably contagious during the entire period new lesions keep appearing. Crusted lesions are not contagious.

It takes from 10 to 21 days after contact with an infected person for someone to develop chickenpox.

Symptoms:-

 myalgia, nausea, fever, headache, sore throat, pain in both ears, complaints of pressure in head or swollen face, and malaise in adolescents and adults. In children, the first symptom is usually the development of a popular rash, followed by development of malaise, fever (a body temperature of 38 °C (100 °F), but may be as high as 42 °C (108 °F) in rare cases), and anorexia. 

Diagnosis:-

The diagnosis of varicella is primarily clinical, with typical early "prodromal" symptoms, and then the characteristic rash. Confirmation of the diagnosis can be sought through either examination of the fluid within the vesicles of the rash, or by testing blood for evidence of an acute immunologic response.

Vesicular fluid can be examined with a Tsanck smear, or better with examination for direct fluorescent antibody.

Prenatal diagnosis of fetal varicella infection can be performed using ultrasound, though a delay of 5 weeks following primary maternal infection is advised. A PCR (DNA) test of the mother's amniotic fluid can also be performed, though the risk of spontaneous abortion due to the amniocentesis procedure is higher than the risk of the baby developing foetal varicella syndrome

Epidemiology:-

Primary varicella is an endemic disease. Cases of varicella are seen throughout the year but more commonly in winter and early spring. Varicella is one of the classic diseases of childhood, with the highest prevalence in the 4–10 year old age group. Like rubella, it is uncommon in preschool children. Varicella is highly communicable, with an infection rate of 90% in close contacts. Most people become infected before adulthood but 10% of young adults remain susceptible.

Pathophysiology:-

Exposure to VZV in a healthy child initiates the production of host immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A(IgA) antibodies; IgG antibodies persist for life and confer immunity. Cell-mediated immune responses are also important in limiting the scope and the duration of primary varicella infection. After primary infection, VZV is hypothesized to spread from mucosal and epidermal lesions to local sensory nerves. VZV then remains latent in the dorsal ganglion cells of the sensory nerves. Reactivation of VZV results in the clinically distinct syndrome of herpes zoster (i.e., shingles), and sometimes Ramsay Hunt syndrome type II.

Infection in pregnancy and neonates

For pregnant women, antibodies produced as a result of immunization or previous infection are transferred via the placenta to the fetus.Women who are immune to chickenpox cannot become infected and do not need to be concerned about it for themselves or their infant during pregnancy.

Varicella infection in pregnant women could lead to viral transmission via the placenta and infection of the fetus. If infection occurs during the first 28 weeks of gestation, this can lead to fetal varicella syndrome (also known as congenital varicella syndrome). Effects on the fetus can range in severity from underdeveloped toes and fingers to severe anal and bladder malformation. Possible problems include:

§  Damage to brain: encephalitis, microcephaly, hydrocephaly, aplasia of brain

§  Damage to the eye: optic stalk, optic cup, and lens vesicles, microphthalmia, cataracts, chorioretinitis, optic atrophy

§  Other neurological disorder: damage to cervical and lumbosacral spinal cord, motor/sensory deficits, absent deep tendon reflexes,anisocoria/Horner's syndrome

§  Damage to body: hypoplasia of upper/lower extremities, anal and bladder sphincter dysfunction

§  Skin disorders: (cicatricial) skin lesions, hypopigmentation

Treatment:-

In most cases, it is enough to keep children comfortable while their own bodies fight the illness. Oatmeal baths in lukewarm water provide a crusty, comforting coating on the skin. An oral antihistamine can help to ease the itching, as can topical lotions. Trim the fingernails short to reduce secondary infections and scarring.

Safe antiviral medicines have been developed. To work well, they usually must be started within the first 24 hours of the rash.

·         For most otherwise healthy children without severe symptoms, antiviral medications are usually not used. Adults and teens, who are at risk for more severe symptoms, may benefit if the case is seen early in its course.

·         For those with skin conditions (such as eczema or recent sunburn), lung conditions (such as asthma), or those who have recently taken steroids, the antiviral medicines may be very important. The same is also true for adolescents and children who must take aspirin on an ongoing basis.

·         Some doctors also give antiviral medicines to people in the same household who subsequently come down with chickenpox. Because of their increased exposure, they would normally experience a more severe case of chickenpox.

DO NOT GIVE ASPIRIN to someone who may have chickenpox. Use of aspirin has been associated with a serious condition calledReyes Syndrome. Ibuprofen has been associated with more severe secondary infections. Acetaminophen may be used.

Until all chickenpox sores have crusted over or dried out, avoid playing with other children, going back to school, or returning to work.

Complication:-

·         Women who get chickenpox during pregnancy are at risk for congenital infection of the fetus.

·         Newborns are at risk for severe infection, if they are exposed and their mothers are not immune.

·         A secondary infection of the blisters may occur.

·         Encephalitis is a serious, but rare complication.

·         Reye's syndrome, pneumonia, myocarditis, and transient arthritis are other possible complications of chickenpox.

·         Cerebellar ataxia may appear during the recovery phase or later. This is characterized by a very unsteady walk.