Thursday, 27 June 2013

Popular drugs banned by Govt of India recently



The government has banned three popular medicines
1. Pioglitazone
2. Deanxit
3. Analgin

PIOGLITAZONE :
It is the widely prescribed anti-diabetes drug. Pioglitazone is a prescription drug of the class thiazolidinedione (TZD) with hypoglycemic (antihyperglycemic, antidiabetic) action to treat diabetes. It is used to improve glucose control in adults over the age of 18 with type 2 diabetes. 

MECHANISM OF ACTION:
Pioglitazone selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma. It modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver.
 As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues; increases the expense of insulin-dependent glucose; decreases withdrawal of glucose from the liver; reduces quantity of glucose, insulin and glycated hemoglobin in the bloodstream.

SIDE EFFECTS:
According to some experts, the use of pioglitazone can lead to fluid retention that precipitates or worsens congestive heart failure among patients. While it's believed that it can cause increases the risk of bladder cancer

2. DEANXIT
 Deanxit is a combination of two psychoactive agents (Flupenthixol and Melitracen ) which has antidepressant properties. It is designed for short term usage only. It is produced by Lundbeck.

MECHANISM OF ACTION:
Deanxit is a combination of Flupenthixol and Melitracen.
 Melitracen  is a tricyclic antidepressant for the treatment of depression and anxiety. The pharmacology of melitracen has not been properly investigated and is largely unknown, but it is likely to act in a similar manner to other Tricyclic antidepressants. Indeed, melitracen is reported to have imipramine and amitriptyline-like effects and efficacy against depression and anxiety, though with improved tolerability and a somewhat faster onset of action.
Flupentixol acts as an antagonist at various dopamine serotonin (5-HT2), adrenaline (α1), and histamine (H1) receptors, without affecting the muscarinic acetylcholine receptors.
Its antipsychotic effects are likely caused by D2 and/or 5-HT2A antagonism, whereas its antidepressant effects at lower doses may be mediated by preferential D2/D3 autoreceptor blockade, resulting in increased postsynaptic activation.


SIDE EFFECT:
 Deanxit, is a harmful combination, which has been long banned even in Denmark, its country of origin. anti-depressant deanxit—in the wake of health risks associated with them
This decision comes in the wake of a strong stand by the government on suspending marketing of all drugs prohibited for sale in other countries like the US, the UK, EU and Australia.

3. ANALGIN :
Analgin® is a brand name for Metamizole sodium, a medication used to treat a variety of pains. Analgin® is referred to as an analgesic and an antipyretic. This means that it is designed as a painkiller and a fever reducer. Besides fever, Analgin® is used to treat toothache and headache. Other ailments include arthralgia, which involves pain of the joints; neuralgia, which is pain in one or more nerves; and myositis, which concerns inflammation of the muscles.

SIDE EFFECT:
A side effect of the medication, however, caused major concern. Scientists discovered that the drug could heighten the risk of agranulocytosis, a medical condition that involves a lowered white blood cell count, thus weakening the immune system's ability to fight diseases. In 1974, Sweden was the first country in the world to ban the drug, analgin has been discarded the world over on grounds of patient safety.


THE CASE HISTORY:

The ministry of health and family welfare has suspended the manufacture and sale of all three drugs under Section 26A of the Drugs and Cosmetics Act, 1940 with immediate effect, While the ministry has been dilly-dallying on withdrawing analgin and deanxit for years now, despite pressure from a parliamentary panel, the decision on the diabetes drug pioglitazone has taken the industry completely by surprise.

The decision to ban pioglitazone and its combinations will hit the Rs 700-crore market for such drugs and adversely impact a clutch of companies including Abbott, Sun Pharma, USV, Lupin, Ranbaxy and Wockhardt.

Pioglitazone combination is a bigger market than plain pioglitazone itself which is has posted a strong double-digit growth, with over 30 companies marketing the drug. The top-selling brands of posiglitazone include Pioz MF G and Pioz (USV), Gemer P (Sun Pharma), Tribet (Abbott), Tripride (Micro Labs) and Gluconorm PG (Lupin).

Popular pain-reliever analgin is a relatively small market with brands like Baralgan and Novalgin (Sanofi Aventis), as most companies fearing a ban have already pulled out from the market, industry experts said. The third drug, a combination of Flupenthixol and Melitracen sold as Deanxit (Lundbeck), Placida (Mankind), Franxit (Intas) and Restfull (Lupin) is facing a ban because deanxit is prohibited for sale in Denmark, its country of origin, and also, the combination is not sold in major countries.

Under the Drugs and Cosmetic Rule 30-B, the import and marketing of any drug the use of which is prohibited in the country of origin, is banned in India. A parliamentary panel report on health earlier this year had rapped the government for dilly-dallying on withdrawing deanxit and analgin, which are not sold in markets globally.

The family of 'glitazones', used for blood glucose lowering properties, has been mired in controversy since the beginning, with many drugs under the class having already been banned globally, and in India. Three years back, another drug from this family, rosiglitazone, marketed by a host of companies including GSK India was banned, following a decision taken in Europe.

In the case of pioglitazone too, France has already taken it off the shelves, while in the US it is sold with a boxed warning. The warning emphasizes that it may cause or worsen heart failure, and its use for over a year may be associated with an increased risk of bladder cancer.

Doctors here in India had said in a study last year that more robust data on use of pioglitazone on Indian patients was needed. Till that time, the patient should be adequately informed about this adverse effect and the drug should be used in as small a dose as possible, with careful monitoring and follow up. Earlier this month, the ministry had suspended sale of dextropropoxyphene, sold as Wockhardt's Proxyvon, a widely-used pain-killer.

REFERENCES
Wikipedia
Drug bank
Times of India

Monday, 24 June 2013

TOP TEN DRUG DISCOVERIES

DRUG DISCOVERY
As till now we all know drug discovery is a procedure to develop new drugs . it is consist of various steps these steps are fully described in my post NEW DRUG DISCOVERY . The drug discovery  showed us various advancement ,there were failures also but we will discuss them later. As we talk about top ten drug discoveries they can be given as follows :
Penicillin  was discovered by Alexander Fleming .Penicillin was the first antibiotic to be used clinically in 1941 . It is a miracle that the' least toxic drug of its kind was the first to be discovered.It was originally obtained from the fungus Penicillium notatum, but the present source is ahigh yielding mutant of P. chrysogenum  When Alexander Fleming stumbled upon penicillin in the 1930s it was one of the biggest discoveries in the healthcare industry and at the time it was dubbed a ‘miracle drug.’ An antibiotic mould which could fight bacterial infections, penicillin is considered to be one of the most powerful antibiotics available and as soon as it reached the mass market it was saving lives. Previous to its discovery, deaths were caused from a simple graze or sore throat as doctors had no way to treat the infections. Penicillin meant that infections were no longer fatal and Fleming  along with Howard Florey and Ernst Chain who took penicillin to market, were awarded a Nobel Prize in 1945. It proved to be the starting point for a range of antibiotics and today remains as one of the most widely used. 
structure of penicillin

mechanism of action of penicillin

Lipitor  A product of global pharmaceutical company Pfizer, cholesterol-lowering drug Lipitor is the best selling treatment in the world. It is currently at the centre of fairly intense media coverage, as Pfizer will lose its exclusive patent rights to the drug in May 2012, seeing it face competition from drug makers who will be able to produce cheaper, unbranded versions of Lipitor.it is described in my previous post  LIPITOR :DRUG THAT MADE HISTORY

Anesthetics A key medical advance for surgical operations, when a number of doctors discovered it was possible to create a reversible loss of sensation surgeons were able to operate without patients feeling any pain. This allowed for more intricate procedures to take place and saved lives as previous to the discovery, many people chose death over the pain of surgery.anesthetics are of two types which can be given as :

  • general anesthetics
  • local anesthetics


General  Anaesthetics
Local Anaesthetics
Site of action
CNS
PNS
Area involved
Whole body
Restricted area
Consciousness
Lost
Unaltered
Poor health patient
Risky
Safer
Non cooperative patient
Possible
Not possible
Major surjery
Preferred
Cannot be used
Minor surgery
Not preferred
preferred

Oral contraceptives A massively popular drug discovery, it is estimated over 100 million women worldwide take oral contraceptive pills. It is one of the first drugs to be taken for an extensive period of time by ‘healthy’ people. This then paved the way for the development of drugs that prevented conditions rather than treating them . the oral contaceptive can be given as .
Combined pill It contains an estrogen and a progestin. With accumulated experience, it has  been possible to reduce the amount of estrogen and progestin in the 'second generation' OC pills without compromising efficacy, but reducing side effects and complications. 'Third generation' pills containing newer progestins like desogestrel with improved profile of action have been introduced in the 1990s. 
Phased regimens These have been introduced to permit reduction in total steroid dose without compromising efficacy. These are biphasic or triphasic. The estrogen dose is kept constant (or varied slightly between 30-40 pg), while the amount of progestin is low in the first phase and progressively higher in the second and third phases. Phasic pills are particularly recommended for women over 35 years of age or when other risk factors are present.
Mini Pill (progestin only pill) It has been devised to eliminate the estrogen, because many of the long-term risks have been ascribed to this component. A low-dose progestin only pill is taken daily continuously without any gap. The menstrual cycle tends to become irregular and ovulation occurs in 20-30% women

Insulin Before the development of insulin, diabetes was a feared illness and diagnosis came with a warning of almost certain death. The 1920’s discovery of the insulin hormone enabled diabetes sufferers to live relatively normal lives by balancing blood sugar levels. Dr Frederick Banting and Professor John Macleod were awarded a Nobel Peace Prize for their discovery and Banting was also awarded a knighthood.
structure of insulin
mechanism of action of insulin

Prozac  After being introduced to the US healthcare sector in 1988 it only took two years for Prozac to achieve its ‘most widely prescribed antidepressant  status, an accolade it still retains today.
It was also one of the first selective serotonin reuptake inhibitor antidepressants and by 1999 25 percent of Eli Lilly’s revenue, the manufacturer of Prozac, was coming from the drug’s sales.

Viagra Another product courtesy of Pfizer, the matter of who exactly invented Viagra is cloudy, with the company saying “hundreds” of people were involved in making the popular aphrodisiac.
In 2000 Viagra accounted for over 90 percent of erectile dysfunction treatments, but this has since dropped dramatically after reports of adverse side effects such as deafness and blindness.Sildenafil's popularity with young adults has increased over the years. Sildenafil's trade name "Viagra" is widely recognized in popular culture, and the drug's association with treating erectile dysfunction has led to its recreational use.The reasons behind such use include the belief that the drug increases libido, improves sexual performance, or permanently increases penis size. Studies on the effects of viagra when used recreationally are limited, but suggest that it has little effect when used by those not suffering from erectile dysfunction. In one study, a 25 mg dose was shown to cause no significant change in erectile quality, but did reduce the post-ejaculatory refractory time.

mechanism of action of  viagra
Aspirin Aspirin was patented in 1990, after a Bayer employee rediscovered a French Chemist’s pain relief formula.
structure of aspirin
It was sold as a powder until 1915 when aspirin tablets were manufactured. As well as now being one of the main ingredients in a number of pain relief remedies, it is thought aspirin can prevent heart attacks, certain types of cancer and lower blood pressure. Aspirin also has an antiplatelet effect by inhibiting the production of thromboxane, which under normal circumstances binds platelet molecules together to create a patch over damaged walls of blood vessels
mechanism of action of aspirin

Morphine Named after Morpheus the Greek god of dreams for its ability to cause drowsiness, the painkiller Morphine was first sold commercially by Merck in 1827.
structure of morphine
The use of morphine intensified after the introduction of the hypodermic syringe in the 1850s and today it is estimated approximately 230 tonnes of the drug are used every year.The euphoria, comprehensive alleviation of distress and therefore all aspects of suffering, promotion of sociability and empathy, "body high", and anxiolysis provided by narcotic drugs including the opioids can cause the use of high doses in the absence of pain for a protracted period, which can impart a morbid craving for the drug in the user. Being the prototype of the entire opioid class of drugs means that morphine has properties that may lend it to misuse. Morphine addiction is the model upon which the current perception of addiction is based.
mechanism of action

Botox Manufactured by Allergan, although Botox has been around for years it is only fairly recently been used on a mass scale.
structure of bacterium clostridium
Botox was first approved by the FDA in 1989 initially to treat muscle spasms in the eye. It has gone on to gain popularity across the world as a cosmetic surgery able to banish wrinkles as well as treating medical conditions such as extreme sweating.Botulinum toxin is a protein and neurotoxin produced by the bacterium Clostridium botulinum. It is the most acutely toxic substance known, with an estimated human median lethal dose of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13 ng/kg when inhaled.The cosmetic effect of BTX-A on wrinkles was originally documented by a plastic surgeon from Sacramento, California, Dr. Richard Clark, and published in the journal Plastic and Reconstructive Surgery in 1989.Canadian husband and wife ophthalmologist and dermatologist physicians, JD and JA Carruthers, were the first to publish a study on BTX-A for the treatment of glabellar frown lines in 1992.
mechanism of action of botox
Similar effects had reportedly been observed by a number of independent groups (Brin, and the Columbia University group under Dr. Monte Keen. After formal trials, on April 12, 2002, the FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows In cosmetic applications, a Botox injection, consisting of a small dose of botulinum toxin, can be used to prevent development of wrinkles by paralyzing facial muscles.

Wednesday, 19 June 2013

Stem cell


An advanced approach in Stem Cell Therapy
Pratikshita Mishra*
Department of Pharmacology
Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India

Abstract

Stem cell therapy is emerging as a potentially revolutionary new way to treat disease and injury, with wide-ranging medical benefits. It aims to repair damaged and diseased body-parts with healthy new cells provided by stem cell transplants. Disease and disorders with no therapies or at best, partially effective ones are the lure of the pursuit of stem cell research. Recently a plethora of work has been done in this field in world around including India. However, Stem cell research presents many ethical and scientific questions as well as future challenges. Nevertheless, stem cell therapy, a prologue to an era of medical discovery of cell-based therapies that will one day restore function to those whose lives are now challenged every day, is still at the beginning of the road.

Keywords- Stem cell, adult stem cell, stem cell therapy, embryonal stem cell, pluripotent stem cells.

INTRODUCTION:
Stem cell research has emerged as the most vibrant biological research activity. This is evidently a reflection of the fact that these cells have the capacity of self renewal and the potential to differentiate into one or more cell types depending on the signals in vivo. The applications of such cells clearly go beyond medical imagination, as they can possibly be used in the treatment of diseases like Parkinson’s, Alzheimer’s, diabetes, heart disorders, spinal cord injuries or for development of in vitro assay system for drug discovery and toxicity or for understanding basic developmental process.
Patients may have concerns about adverse reactions to the stem cell transplants. The most common reactions to the treatment are fever, headache, leg pain, diarrhoea, vomiting, and allergic reactions. Less than four percent of patients e xperience any of these symptoms.
 
 
Figure  Showing stem cell as a pluripotent cell

Stem cell cultivation
 
Growing cells in the laboratory is known as cell culture. Human embryonic stem cells are isolated by transferring the inner cell mass into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. Over the course of several days, the cells of the inner cell mass proliferate and begin to crowd the culture dish. When this occurs, they are removed gently and plated into several fresh culture dishes. Embryonic stem cells that have proliferated in cell culture for six or more months without differentiating, are pluripotent and appear genetically normal are referred to as embryonic stem cell line.

Stem cells and diabetes
Type 1 diabetes appears to be especially difficult to cure, because the cells are destroyed when the body’s own immune system attacks and destroys them. This autoimmunity must be overcome if researchers hope to use transplanted cells to replace damaged ones. The molecular mechanisms of cellular self-renewal must be understood more deeply that can efficiently maintain human stem cell lines in their pluripotent state. In addition, the culture methods should be improved to generate sufficient cells for clinical use. A strong potential for developing differentiated b-like cells from human ESCs, although much more work is needed to realize it.

 
Role of stem cell  in Bioartificial Liver Construction

The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been
developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular
therapies is the limited availability of human hepatocytes.



Induced pluripotent stem cells for retinal degenerative diseases