It's Time to Quit

One would think that a diagnosis of cancer is all a smoker needs in order to be motivated to quit. Unfortunately, in many cases this logic would be wrong. Although smoking is responsible for one-third of all cancer deaths, one-half to four-fifths of cancer patients who smoke continue to do so after diagnosis.

In a recent study, cancer patients who smoke confront even more barriers to quitting than other smokers. “I think what surprised me when I did the review,” Duffy said, “was the multitude of issues that cancer patients face, and that there are so many variables affecting why they don't get treatment, and if they do get treatment, why they may not respond. Nicotine addiction, health issues, emotional issues, psychological issues and system level issues are all in the way.” Cancer patients who are unmarried, uninsured, or depressed are particularly likely not to quit. 

Unfortunately, cancer patients who smoke often do not get the push they need from their physicians: most oncologists provide no smoking interventions other than advising patients to quit. Oncology nurses, however, may be better positioned to help patients stop smoking. As Duffy et al point out, oncology nurses are skilled educators who have access to patients and considerably more time available than oncologists to offer psycho-social interventions. Additionally, a systematic review of clinical trials found that high-intensity interventions provided by nurses who are directly involved in patient care significantly increases the likelihood of a patient quitting. 

Targeting education on tobacco use to a cancer patient's immediate situation is more effective than providing general information about the health hazards of smoking. Everyone knows that smoking is bad for health, but many are unaware that smoking reduces the effectiveness of cancer treatment, increases the risk of cancer recurrence and secondary cancer, and shortens survival.

Hospitalization is an ideal time to provide smoking cessation intervention because patients may be more motivated while undergoing treatment, are monitored and less liable to skip intervention sessions, and may have temporarily quit because of hospital smoking policy. Intervention programs that begin in the hospital and follow patients for at least a month after discharge have been shown to improve rates of smoking cessation 1 year later. In-hospital stop-smoking programs may be particularly effective in surgical patients. 

Community-based programs have also shown some success in helping people who want to quit smoking. Many states have  1-800-QUIT-NOW helplines, which have been shown to significantlyimprove smoking cessation rates in a real-world setting for periods up to a year, and the American Cancer Society offers a web-based Guide to Quitting Smoking.

Duffy et al offer specific advice to providers to help patients stop smoking. The key educational moment for cancer patients is immediately after their diagnosis. Many patients may assume that because they have cancer, there is little point to their quitting. Teaching them about the improved treatment outcomes, especially improved survival, that they may achieve if they quit smoking can help provide the motivation they lack. Patients with little confidence of success in quitting, and patients who are overconfident that they can quit on their own, should be referred to smoking cessation programs. Interventions should focus on identifying smoking triggers, preparing for high-risk situations, managing withdrawal and quitting-related stress, and setting a quit date. All patients should be evaluated for drug therapy, including nicotine replacement, bupropion, and varenicline, although each drug has contraindications to consider. Regular follow-up, either with the patient's provider or through a telephone helpline, is essential. If possible, the patient's family should be part of the process, and encouraged to quit if they too smoke.

Source:CA 
by
Dr. Akshaya Srikanth
Pharm.D India

ASPIRIN: The Wonderful Pill

It's been 100 years since the Bayer Company introduced aspirin. It was greeted as a miracle drug then and a century later, continues to astound scientists with its many health benefits.

Although best known for its role in relieving headache and other kinds of pain, studies over the past several decades have shown aspirin can play a role in helping to prevent and treat heart attacks and may reduce risk of colon cancer.

1) How Aspirin Works

 - The use of salicylates, the chemical root of aspirin, goes back to the 5th century B.C., when Hippocrates used the bark of the willow tree to treat fevers and pain. It's come a long way since.

2) Potential Hazards

- Should you take one a day? Balance the benefits and risks.

3) Aspirin Timeline

- Great moments in the history of America's favorite remedy.

4) The Best Pain Reliever? 

- Aspirin, acetaminophen or ibuprofen? It all depends on what ails you.

The use of salicylates, the chemical root of aspirin, goes back to the 5th century B.C., when Hippocrates used the bark of the willow tree to treat fevers and pain. Despite widespread use of willow bark, its active ingredient, salicin, wasn't discovered until 1828. In the 1830s, salicin was refined into two similar medicinal compounds, salicylic acid and sodium salicylate. Unfortunately, these remedies had side effects that made them unattractive as pain relievers, including nausea, ringing in the ears and severe stomach irritation.

In 1897, in an attempt to ease his father's suffering from rheumatoid arthritis, Felix Hoffmann, a chemist working for Bayer, discovered a milder formulation called acetylsalicylic acid (ASA). This compound was called "Aspirin" —"A" from acetyl, "spir" from the spirea family of plants from which salicin was derived and "in" referring to a common ending in drug nomenclature.

Aspirin was immediately heralded as an excellent medication for controlling fever and reducing pain, especially from arthritis and headache. Plus, in the 1950s, some physicians began to prescribe aspirin for prevention of heart attacks because of its observed blood-thinning ability. Remarkably, no one knew how aspirin worked.

In 1971, the mystery was, for the most part, solved by British pharmacologist John Vane. Although many scientists believe that there is still much to discover about aspirin, careful experimentation has revealed that aspirin controls body compounds called prostaglandins.

Prostaglandins are hormone-like substances produced in small quantities throughout the body. There are many different types of prostaglandins, and each performs a different function. Some cause inflammation, redness and swelling in response to an injury or illness. Others are responsible for the general "housekeeping" of the body — keeping things running smoothly by protecting the gastrointestinal lining, for example.

Aspirin works by decreasing the production of prostaglandins. Because prostaglandins are involved in so many different body functions, aspirin can have many different types of effects on the body, both positive and negative. Aspirin can: 

• Reduce fever by inhibiting prostaglandins that work to raise body temperature.
• Relieve headache and other pain by inhibiting prostaglandins responsible for inflammation and by dampening pain sensations. Even with all the other treatments available, aspirin is still considered quite effective against migraine headaches and arthritis.
• Reduce swelling by inhibiting prostaglandins that respond to injury sites.
• Reduce risk of heart attack and ischemic stroke. Aspirin inhibits prostaglandins that are responsible for platelets sticking together to form blood clots. Aspirin or other types of platelet inhibitors are usually prescribed for patients who are known to have or are at risk of blockages in the blood vessels that supply blood to the heart (coronary artery disease). Patients who have had a stroke or transient ischemic attack (TIA, or "mini-stroke") will usually take aspirin or another anticlotting medicine to prevent future stroke.
• Treat heart attacks (myocardial infarctions). Heart attack patients who are treated immediately with aspirin have better outcomes and a reduced risk of second heart attacks and strokes.
• Potentially reduce the risk of colon cancer. Although the data are not conclusive, there is some evidence that regular use of aspirin reduces the risk of developing colon cancer and precancerous polyps. The optimal dosage required is not yet known, but at least one study has found that just 80 milligrams of aspirin a day, the equivalent of one "baby aspirin," is enough to reduce production of certain prostaglandins suspected to be involved in tumor formation.

One of the most confusing questions at the drug store is what pain reliever to use — aspirin, acetaminophen, ibuprofen or another type?

Each pain reliever is chemically distinct, and we all respond differently to them depending on our own body chemistry and the particular problem we are experiencing. An individual may respond to one pain reliever but not to another.

Work closely with your pharmacist or physician to determine which medication in which dosages might be best for you. Whichever pain reliever you choose, don't exceed the dosage recommended on the label without consulting your doctor.

Here are some basic differences:

Acetaminophen

·       Controls pain well and can bring down a fever.

·       Gentler on the stomach than aspirin.

·       Does not control inflammation.

·     Can cause liver damage if taken in high doses, especially in people who drink large amounts of alcohol regularly.

Aspirin (any brand)

·      Controls pain, inflammation and fever.

·    Should not be taken by people with nasal polyps and asthma or anyone taking a   blood-thinning medication without medical advice.

·       Should not be given to children who may have a viral illness.

·       Harshest on the stomach. Can cause gastric irritation, ulcers and bleeding.

Ibuprofen 

·       Controls pain, inflammation and fever.

·       Works well against menstrual cramps.

·       Can cause gastric irritation and bleeding.

·       Interferes with blood clotting but to a lesser degree than aspirin.

Great Moments in Aspirin's History

• 400 BC: Hippocrates uses willow bark on patients to reduce fevers and pain. Willow bark is later found to contain salicin, the same active component as aspirin.
• 1763: The Royal Society of London publishes an article by the Rev. Edward Stone, "Account of the success of the Bark of the Willow in the Cure of Agues," officially reporting what had been folklore for centuries.
• 1828: The active ingredient in willow bark, salicin, is chemically separated.
• 1839: French chemists synthesize salicylic acid from salicin, which is later used medically.
• 1853: French chemist Charles Frederic Gerhardt first creates a crude form of acetylsalicylic acid, but its medical uses are not yet recognized.
• 1897: German chemist Felix Hoffmann modifies salicylic acid to acetylsalicylic acid to make it less harsh on the stomach. Since he worked for Bayer, the company got the patent.
• 1899: Acetylsalicylic acid is named Aspirin by Bayer. By November of this year, Aspirin is in wide-spread use.
• 1917: Bayer's patent on Aspirin runs out, allowing other companies to sell acetylsalicylic acid. Bayer retains the trademarked name, "Aspirin."
• 1920: Bayer loses its trademark of the name "Aspirin" in court. This reduces "aspirin" to a generic word for any brand of acetylsalicylic acid.
• 1950: Dr. Lawrence L. Craven of California describes his observations about aspirin's action as a blood-thinner, and begins prescribing daily doses to his patients as a means of preventing heart attacks.
• 1971: British pharmacologist John R. Vane discovers aspirin's mechanism of action — that it inhibits the production of hormone-like substances in the body called prostaglandins.
• 1982: Sir John R. Vane is co-winner of the Nobel Prize in Medicine for his discoveries concerning prostaglandins.
• 1988: Results of the Physicians' Health Study show that aspirin significantly reduced risk of first heart attack.
• 1990s: Studies show regular use of aspirin may reduce risk of colon cancer.
• 2005: Research shows that aspirin reduces the risk of stroke in healthy women, although no clear benefit is seen for prevention of heart attack.

by

Dr.Akshaya Srikanth

Pharm.D

Hyderabad, India

Pharm.D India

Pharmacist Action on Awarness, Prevention and Counselling for HIV/AIDS

A pharmacist is a crucial and a focal point in the community. Practically everyone in the population comes in contact with him at some point of time, i.e. whenever any medicine or baby product is required. The outreach of this person is tremendous. We at this point of time are still facing the problem of lack of knowledge/ information on this issue with the general population. This is compounded by the fact that the information is laden with misconceptions on the subject. Pharmacists deal with people from all sections of society and largely those who are ignorant on the issue of HIV/AIDS and therefore they can be a powerful medium for spreading the message on awareness, prevention and counseling. 

Role of Pharmacist:

1. A center for exposing people to HIV/AIDS information through the display of Information Education and Communicating Posters (IECP) material as well as by keeping leaflets on the counter for the people to pick up for themselves.
2. When a syringe is sold, information on the safe use of a new needle and disposable syringe could be disseminated to the customer along with the information to destroy the same, to avoid recycling.
3. With every sale of a condom, educate the person on its correct use, as people mostly feel that they know how to use it but are not aware of the correct way along with the basics such as not reusing the condom, not to apply a lubricant, checking the expiry date as well as disposal of the same after use.
4. Condoms should not be hidden under the shelf; rather they should be kept prominently for people to get used to seeing them in the open. When the media can openly display advertisements of condoms, why can’t a pharmacy display the same? May be this will help people break mindsets and barriers for the same.
5. Information could be given when a drug related to STD is sold. Here a message for the complete course of medication along with treatment for spouse could be given. Further, the benefit of using a condom could be emphasised for the prevention of STDs.
6. The pharmacist, besides giving information and clearing doubts of those people who seek clarification on the disseminated information on a product related in some way to HIV/AIDS and its related issues, can also serve as a focal person for providing information on care of those infected as well as on how to take care of the affected family.
7. Living in the community, the pharmacist could initiate a social support group for those infected, reducing stigma related to the infection. Further, he/she could also be a trainer for people in the community for home-based care (hospice), which reduces the financial burden on the family.
8. The pharmacist is in a position to emphasise the availability of balanced and cheap nutrition, as drugs by themselves can’t help a person regain strength. It has been observed that people are generally unaware of nutrition facts. A poster regarding the same too could be displayed for people to read and understand.
9. People have faith in the pharmacist as he/she dispenses drugs for various ailments. This way we are targeting not just HIV/AIDS but all other infections, which often precipitate the onset of major illnesses. In such instances, documentation of any STD or HIV case should also be done. People generally go to the pharmacists, describe the symptoms and ask for the appropriate drug.
10. Once noted the case could be forwarded to the appropriate agency for further follow up. It should be so planned that the person comes back to the drug store every 3/5 days. This will help in seeing the progress of the person and could also be an avenue for counseling regarding the infection. Education input at this point could help reduce the number of recurring cases, new infection and increase of condom use, preventing spread as well as population control. 

All these will help in developing positive attitudes towards the people infected as well as affected. It should not be misunderstood that the pharmacist has to do each and every activity stated above. In a day, may be just one of the many may require his input. And some days may be all or a few. He/she should judge the situation and then provide the necessary input. 

Source: FIP-HIV/AIDS Care
by
Dr.Akshaya Srikanth,
Pharm.D

India

Patient Educating Points on Peptic Ulcer

Patient education regarding causes, risk factors, and therapy of peptic ulcer disease is very essential for peptic ulcer healing and for preventing ulcer recurrence. In this post, I’m focusing on 4 key points on peptic ulcer disease patient education. The aim of this post is to help healthcare professionals who deliver peptic ulcer disease patient education to be prepared with the required knowledge, and so to “be informative” for their patients.

1) Set treatment goals in participation with the patient: The main treatment goals for peptic ulcer diseases are:

• Relief of ulcer pain
• Healing of ulcer
• Preventing ulcer recurrence
• Preventing complication
• The patient should at least understand the importance of each of the previous goals.

2) Identify and modify risk factors:

This is achieved by: first, taking patient history regarding:

• Presence of other illnesses,
• Patient medication history; especially use of OTC drugs as non-steroidal anti-inflammatory drugs (NSAIDs) and use of corticosteroids,
• Lifestyle habits including diet, alcohol and cigarette smoking.
• Then, helping the patient to modify these risk factors. 
   For example, modifying NSAIDs administration for peptic ulcer disease patients who are in need for NSAIDs (ASPIRIN). Another example, offering advice regarding diet and foods to avoid by peptic ulcer patients.

3) Encourage proper medication use:

• Encourage compliance to the specified regimens (whether it is Helicobacter pylori eradication regimen, proton pump inhibitor PPI therapy, … etc.) and educate the patient about the potential peptic ulcer disease complications (bleeding ulcer – perforation of stomach or duodenum – gastric outlet obstruction) that might occur if these regimens are not followed properly. And make sure that the patient understands when to administer the medications. For example, PPIs should be administered 15-30 minutes before meals.
• Identify potential drug – drug interactions by referring topatient medication history. Among the important peptic ulcer medications that may cause drug interactions are proton pump inhibitors and H2-receptor blockers.
• Educate the patient about possible side effects that may make him/her stop taking the medications.

4) Always remember that good communication with the patient improves disease management.

Source: Zoomout-Ph

by

Dr.Akshaya Srikanth

Pharm.D

Hyderabad, India

Types of Pneumonia

Aspiration Pneumonia:
Aspiration Pneumonia results when food, drink, vomit, secretions or other foreign material is inhaled and causes an inflammatory response in the lungs and bronchial tubes.
Aspiration Pneumonia occurs predominantly in the right lung because its total capacity is greater than that of the left lung .

Atypical Pneumonia:
This term refers of Pneumonia caused by the following bacteria: Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Atypical pneumonia is caused by bacteria and does not respond to the normal antibiotics used for treatment.

Bacterial Pneumonia:
Bacterial Pneumonia occurs when pneumonia-causing bacteria masses and multiplies in the lungs. The alveoli become inflamed and pus is produced, which spreads around the lungs. The bacteria that caused Bacterial Pneumonia are: streptococcus pneumonia, hemophilus influenza, legionella pneumophilia and staphylococcus aureus.

Bronchial Pneumonia:
Bronchopneumonia is “a descending infection starting around the bronchi and bronchioles”. The terminal bronchioles become blocked with exudates and form consolidated patches. This results in atelectasis.

Community-acquired Pneumonia:
This means the infection was acquired at home. With this type of pneumonia the most common cause is 'Streptococcus Pneumonia' 

Hospital-acquired Pneumonia:
Patients develop features after being in hospital for 24 hours or longer. 

Infectious agent is often Gram-negative bacteria such as 'Escherichia coli or Klebsiella'

Mycoplasmal Pneumonia: (also known as 'walking pneumonia')
It is similar to bacterial pneumonia, whereby the mycoplasmas proliferate and spread - causing infection.

Pneumocystis carinii Pneumonia:
Pneumocystis carinii pneumonia is the result of a fungal infection in the lungs caused by the Pneumocystis carinii fungus.
This fungus does not cause illness in healthy individuals, but rather in those with a weakened immune system.

Ventilator Associated Pneumonia (VAP):
This type of pneumonia usually occurs two days after a hospitalised patient has been intubated and been receiving mechanical ventilation.
This is especially a life-threatening infection as patients who require mechanical support are already critically ill.

Viral Pneumonia:
Viral Pneumonia is believed to be the cause of half of all pneumonias. The viruses invade the lungs and then multiply- causing inflammation

by

Dr.Akshaya Srikanth,

Pharm.D India

Regulatory Framework for Medical Devices in India

India has emerged as one of the leading markets for pharmaceutical products. Increase in the private healthcare infrastructure, widening rural markets, and inclusion of newer technologies have placed healthcare as an independent sector in India. With privatization of healthcare, the medical devices sector is growing too.

In order to regulate the import, manufacture, distribution and sale of drugs and cosmetics, the Drugs and Cosmetics Act, 1940 (“D&C, Act”) was introduced in India in 1940. However, no separate legislation/regulation has been enacted for regulating the import, manufacture, distribution or sale of medical devices in India till date by the Government of India.

The Central Drugs Standard Control Organization (CDSCO) is the key medical regulatory organization in India. Since 2006, both the Indian Department of Science and Technology and the Ministry of Health and Family Welfare have sought to completely restructure the regulations for the medical devices. Till date, neither of these attempts has been successful. Medical device market is quite diverse which includes medical and diagnostic equipment; medical implants like heart valve and cardiac stents, pacemakers, cannulae, knee joints; and lower end plastic disposables, blood bags, IV sets, syringes etc. In light of its widespread applicability, overall medical device market is experiencing reasonable growth.
Historically, most Indians had very limited access to any type of modern medical service. Today, however, the situation is much improved. There is a growing awareness about health issues within India, an increasing demand for quality care at affordable prices, further the Indian Healthcare industry is in a steady growth trajectory and is expected to grow in the next few years.
The Indian economy is worth about US$1,243 billion and rapidly getting bigger. The GDP growth reached 9% in the year to March 2008. The 2010-11 budget extended the coverage to another 20% of the Indian population covered by the National Rural employment Guarantee Act (NREGA) programmes, who have worked for more than 15 days during the preceding financial year.Budget 2010-11 also allocated US$ 2,920 million under the National Rural Health Mission (NRHM), an increase of 15% over the previous year.

Regulations on Medical Devices in India
 Undoubtedly, the medical devices and surgical instruments are currently not covered under the regulatory framework in India. However, any device which is intended for internal or external use in the diagnosis, treatment, mitigation or prevention of disease or disorder in human beings or animals, as may be specified by the Central Government by notification in the Official Gazette would be considered as a drug under the D&C Act and provisions of D&C Act and Rules made therein would be applicable on such device. From time to time, Ministry of Health and Family Welfare, Government of India vide gazette notifications has notified certain medical devices as drugs under the D&C Act.
 Prior to 2005, only medical devices such as disposable hypodermic syringes, tubal rings, condoms, metered dose inhalers, were required to be registered in India. In 2005, the Ministry of Health and Family Welfare (MOHFW) vide gazette notification dated 6 October 2005 further notified 10 sterile devices (“Notified Medical Devices”) to be considered as drugs and consequently regulated their import, sale and manufacture under Section 3(b) (iv) (defined below) of the D&C Act.
Regulating Authority for Notified Medical devices
In India, the Central Drugs Standard Control Organization (‘CDSCO’) is the main regulatory body currently regulating import, sale and manufacture of medical devices which have been notified as drugs by virtue of Section 3(b) (iv) of the D&C Act.The CDSCO lays down standards of drugs, cosmetics, diagnostics and devices and issues licenses to drug manufacturers and importers. It also lays down regulatory measures, amendments to Acts and Rules and regulates market authorization of new drugs, clinical research in India and standards of imported drugs etc. The CDSCO has setup a separate division which is called Medical Device Division in order to facilitate mattes related to Notified Medical Devices.

New Proposed Medical Devices Regulation Bill
 In 2006, the Medical Devices Regulation Bill (MDRB) was proposed by the Ministry of Science and Technology. The MDRB was designed to consolidate laws related to medical devices and establish the Medical Device Regulatory Authority of India (MDRA). This proposal was aimed at establishing and maintaining a national system of controls for the quality, safety and availability of medical devices in India. If enacted, the MDRB will govern all medical devices throughout India. Companies wishing to import devices into India or manufacture products locally will have to comply with the design, manufacturing, packaging, labeling, import, sale, use, and disposal requirements of the MDRB. Also the bill will expand the list of products requiring registration.
 The Bill provides for the creation of a Medical Device Regulatory Authority which has been empowered with extensive powers relating to fining and imprisoning defaulters. Besides looking to harmonize the standards in accordance with the global norms to push the export potentials, the Bill also seeks to lay down concrete norms on import of devices and their conformity with the Indian standards. Standards notified by the Bureau of Indian Standards or other international standards making bodies like International Organization for Standardization (ISO), may be incorporated for harmonization. The Bill seeks to regulate the design, manufacture, packaging, labelling, import, sale, usage and disposal of medical devices in India.
 With a view to raise the level of control on Medical Devices, the Drug Technical Advisory Board (DTAB) in India has submitted the final draft of the guidelines on medical devices and has recommended strict implementation of Indian Conformity Assessment Certificate (ICAC) for the medical devices manufactured, imported and marketed on Indian market under Schedule M III of Drugs & Cosmetics Rules 1945. The Medical Devices have been classified into Class A, B, C & D as per their level and intended use. It is provided that all Medical Devices sold in India (except for custom made devices, meant for a particular patient use) should, as a general rule, bear the Indian Conformity Assessment Certificate mark (ICAC) to indicate their conformity with the provisions of this schedule.
Proposed New Clinical Trial Regulations 
Additionally, the MDRB discusses clinical trials and Clinical Research Organizations (CROs) in India. If the bill is approved, some high-risk medical devices will require local clinical trials in India in addition to foreign clinical data. In general, more-stringent regulations will apply to CROs and clinical trials.

My Comment:

The Indian medical devices and supplies market is at a nascent stage and was estimated at US$2.75 billion in 2008. This is about 1.25% of the global medical devices and supplies market of around US$220 billion in 2008. By 2012, India’s medical devices market is expected to nearly double to around US$5 billion.The production of low value medical supplies and disposables is dominated by domestic manufacturers, whereas the high end medical equipment is generally imported. In the future, due to the huge market opportunity in India, more and more foreign medical device companies are expected to explore Indian market for their products.

With an evolving regulatory situation, medical device companies are required to stay up-to-date in order to achieve success in India. The Indian government is working on a comprehensive regulatory framework for the medical device sector. India’s health authorities plan to issue a set of guidelines to define and regulate medical devices as a separate category.

 The growth of Indian medical devices industry is driven by a host of factors and is sure to see exponential growth in the coming years. Some market drivers for this industry are:

1. An increase in the Gross Domestic Product growth of the Indian economy
2. Increase in the Healthcare Expenditure
3. Improvement of overall health status
4. Changing of demand pattern for medical devices in India due to a rise of lifestyle-related diseases such as diabetes, cardiovascular disease etc.
5. Increasing of Medical Tourists
6. Increasing of medical infrastructures like hospitals, specialized diagnostic centers, laboratories

In a nutshell, continued flow of investment in private sector infrastructure has resulted in a steady increase in the market for medical equipments and supplies. It is estimated that the market will continue to grow. Further, the recent liberalization of trade and investment laws makes India one of the most promising markets for medical device manufacturers. It is predicted that India will be the most populous country in the world by 2050. India will make its mark as a growing market, potential partner in manufacturing and R&D, and as a preferred destination for clinical trials.

Source: CDSCO

by

Dr.Akshaya Srikanth,

Pharm.D India

Drug Induced Liver Injury (DILI)

The liver is the first stop on the path a drug takes after oral ingestion. From the liver’s “point of view”, drugs are like other exogenous agents and are handled by the liver for excretion. Absorption is largely into the portal system which brings intestinal blood to the liver where transformation and metabolism occur in preparation for elimination (e.g. in the urine, in bile etc.). Metabolism may occur in two phases: Phase I is preparation by oxidation, reduction, hydrolysis and other reactions of the compound for action in Phase II. The second phase occurs in the cytosol and involves reactions catalyzed by transferase enzymes. The cytochrome P-450 system plays a major role in this. The study of the P-450 system allows some degree of prediction of possible hepatotoxicity.
Liver toxicity is usually thought of as producing damage to the liver parenchymal cells (hepatocytes) but toxicity can also be produced affecting biliary cells, kupffer cells, fat storing cells etc.

Adverse events can be classified as Type A which represents pharmacologic effects and are often (but not always) predictable. There may be a dose response effect with worsening of the toxicity only after a particular blood level or threshold is reached of the drug or its metabolites. The classic example of this is acetaminophen (paracetamol) toxicity which is toxic only if more than about 6-8 grams a day are taken. Type B reactions are idiosyncratic and unpredictable. Many drugs can do this.
The toxicity produced by drugs can be of various types. Very common is inflammation (hepatitis) with cell necrosis and inflammation. Viruses can produce hepatitis also of course. Drug induced hepatitis may be acute (many drugs, alcohol) or chronic (e.g. methyldopa, alcohol). It may be catastrophic or mild. Drugs may cause bile flow impairment with or without inflammation and with or without bile duct damage. Oral contraceptives, allopurinol and chlorpromazine may produce cholestasis as can alcohol. Other drug toxicities include fatty liver (steatosis), granuloma production and injury to the blood vessels. Finally long exposure to some exogenous agents including drugs can produce malignancies of the liver.
Many drugs may produce mild elevations of transaminases (enzymes) such as aspartate transaminase (AST also known as SGOT), alanine aminotransferase (ALT also known as SGPT), GGTP, and alkaline phosphatase which are often called “liver enzymes” or “liver function tests”. This is something of a misnomer as other non-hepatic problems can raise these enzymes. Bilirubin can also be elevated with liver toxicity.
Mild reversible elevations of these lab tests are usually benign and reverse after the drug is stopped or sometimes decrease or return to normal even if the drug is continued. The real issue is to prevent severe, irreversible and sometimes fatal liver toxicity.
The clinical spectrum of liver toxicity can range from no signs or symptoms at all to mild, moderate, severe and fatal. There is no way to absolutely know that a drug induced liver toxicity. Even liver biopsy may not prove it.
There are some risk factors including the underlying medical condition, the very old or young, bad nutritional status, nutritional status, alcohol use (amount, chronic, acute) and concomitant medications. The frequency of severe liver toxicity may be less than one case per 10,000 which means that this will not be identified before marketing when only a few thousand patients at most are examined in clinical trials.
Unfortunately there is usually no way to predict which patients will get the severe or fatal types of liver injury. The incidence and amount of AST/ALT elevation, the time to onset or the type of injury do not always predict the risk and outcome of liver injury. Thus one cannot always take comfort from the fact that the liver enzymes were “only” twice normal.

by

Dr.Akshaya Srikanth

Pharm.D India

Fever of Unknown Origin and Cancer

A 62-year-old woman presents to the hospital with an almost 2-year history of intermittent fevers of up to 102°F. She reports that over that same time span, she has become progressively weak and has been experiencing darker urine. The family states that occasionally she is “not acting herself”, but they attribute it to old age. The patient is admitted to the hospital with acute kidney injury (AKI), elevated liver function tests (LFTs), and failure to thrive (FTT), presumably due to her decreased oral intake and poor diet. 
During her hospitalization, she continues to spike fevers up to 103°F, and she becomes increasingly altered to the point where she is minimally responsive. Blood cultures remain negative and a CT of her head shows no acute changes or intracranial bleed. Endocarditis, abscesses, and connective tissue diseases are all ruled out as potential causes of her fever. 
At this point, the patient can be described as having a fever of unknown origin (FUO). By definition, FUO is characterized by a temperature >100.9°F on multiple occasions for at least 3 weeks in addition to a negative workup in a hospital for at least one week. The differential diagnosis of FUO is extensive, although one important diagnosis includes cancer. 
Although the data varies between studies, up to 10% of all FUO cases can be attributed to an underlying cancer. The most likely cancers to present with FUO include the hematological malignancies such as lymphoma, leukemia, multiple myeloma, and myelodysplastic syndrome. Additional solid organ tumors that have been associated with FUO include hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The textbook triad of findings in RCC includes hematuria, flank pain, and a palpable abdominal mass, although these occur in less than 10% of all RCC patients. A persistent fever in combination with some of these findings could lead to further investigation into RCC. Metastases to the liver, especially those of adenocarcinoma origin, have also been implicated in FUO.
Depending on the patient presentation, history, and physical, the workup could vary. Further laboratory studies in addition to basic bloodwork include ESR, CRP, tumor markers, chromosomal studies, and bone marrow biopsies. Potentially helpful imaging studies include an abdominal ultrasound; CT of the chest, abdomen, and pelvis; and PET scans. All of these tests are not necessary in every patient with a diagnosis of FUO. Sound clinical judgment is necessary in order to evaluate which tests are the most beneficial to the patient and which will directly impact clinical decision making.

by
Dr.Akshaya Srikanth
Pharm.D, India

Risks of Hypoglycemic Drugs in Diabetics with CKD

According to the World Diabetic Association (WBA), approximately 40% of adults with diabetes have some degree of chronic kidney disease (CKD). That's a lot of patients more than one might think.They should be getting an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker(ARB) for renoprotection, and blood pressure and lipids should be aggressively managed, but how does our approach to managing their antidiabetic therapy change?

We might consider taking a more aggressive approach to their glycemic control. In some clinical trial reports, tight glycemic control has been shown to be the primary determinant of decreased microvascular complications. However, once we've decided how aggressively to manage glycemia, the choice of which antidiabetic to use and is especially important in these patients. Unfortunately, when the therapeutic strategy is to maximize glycemic control, the risk of hypoglycemia also increases - in both frequency and severity. Patients taking oral antidiabetics that are primarily eliminated by the kidneys are particularly susceptible. Furthermore, it should be noted that older patients are also at higher risk. 

Dosing errors are common in CKD patients and can cause poor outcomes. Drugs cleared renally should be dose-adjusted based on creatinine clearance or estimated glomerular filtration rate (eGFR). Dose reductions, lengthening of the dosing interval, or both may be required. 

As metformin is nearly 100% renally excreted, it is contraindicated in a number of patients: when serum creatinine is higher than 1.5 mg/dL in men or 1.4 mg/dL in women, in patients older than 80 years, or in patients with chronic heart failure. The primary concern here is that other hypoxic conditions (e.g., acute myocardial infarction, severe infection, respiratory disease, liver disease) may increase the risk of lactic acidosis. Because of this danger, and despite the fact that metformin is usually the recommended first-line treatment for type 2 diabetes, one should use caution when considering metformin in patients with renal impairment. Similarly, sulfonylureas should be used with care in diabetics with CKD. The clearance of both sulfonylureas and their metabolites is highly dependent on kidney function. As such, severe and sustained episodes of hypoglycemia due to sulfonylurea use have been described in dialysis patients. 

Regardless of which antidiabetic agent is selected, HbA1c and kidney function should be regularly monitored and the antidiabetic regimen appropriately adjusted. As patients with type 2 diabetes tend to progress over time, most will require a combination of agents to achieve desired glycemic control. These combinations should be chosen carefully in patients with CKD.

Finally, awareness of and screening for renal impairment in diabetics is a necessary precursor to successful intervention. In these patients, CKD is underdiagnosed and undertreated, and awareness of the disease is low among providers and patients alike. Early detection of disease via eGFR or urinary albumin excretion can lead to timely, evidence-based intervention and help prevent or delay progression of CKD. Check with the benefits in Improved kidney and cardiovascular outcomes, prevent emergencies, improving quality of life and lower associated costs.

by

Dr.Akshaya Srikanth

Pharm.D

DRUGS AND COSMETIC AMENDMENT 2007 REVIEW

The Central Drug Authority of India (CDAI) is the principle for the licensing for drugs and cosmetics. 

The Drugs and Cosmetics (Amendment) Bill, 2007 seeks to replace the Drugs Technical Advisory Boards for allopathic and Indian systems of medicine with the Central Drugs Authority (CDA). Drug consultative committees may be established to advise the CDA and central and state governments.

The CDA shall be the licensing authority for the manufacturing, distribution, sale, import and export of drugs and cosmetics. It shall also recommend to the central government standards for drugs and cosmetics, measures to regulate clinical trials, etc.

The 2007 Bill expands the definition of “drugs” to include medical devices. It also defines “clinical trial”, states that all clinical trials require the approval of the CDA, and prescribes penalties for any person violating this provision.

The Standing Committee has submitted its recommendations on the 2005 Bill. It recommended enhanced penalties for spurious and adulterated drugs that lead to prolonged illness. It also suggested separate courts for trying offences under the Act.

The CDA shall be the licensing authority for the manufacture, sale or stocking of drugs and cosmetics. Currently, these functions are delegated to state governments.

The 2007 Bill does not mandate medical and scientific experts in the CDA. A member can be any person with special knowledge of and a minimum of 15 years professional experience in the pharmaceutical industry, public administration, finance or law.

Based on the above Amendment, Recently on the RajSabha T.V had called for the panel discussion of the expert committee. Dr.Sunil Kumar Jain, Chief Pharmacist, AIIMS, Vice-President IPA, New Delhi and R.Narayaswamy, Former Deputy Drug Controller of India, President of IPA, Tamil Nadu.

Post-marketing surveillance of approved drugs not complied with by pharma companies

The post-marketing surveillance system in the country is in shambles, putting the patients at risk without effective monitoring of the side effects by some drugs, if the recent findings by the Parliamentary panel are to be believed.

There is a poor follow-up on the side effects in Indian patients both by doctors and manufacturers, as per the report by the Parliamentary Standing Committee attached to the Health Ministry which found that even some drugs which were not `officially launched’ were available in the market.

Once new drugs are approved, rules require that manufacturers submit post marketing Periodic Safety Update Reports (PSURs) listing side effects, fatalities, injuries etc. in Indian patients once every six months in the first two years and then annually in the following two years.

“In order to scrutinize the compliance of this rule, the Health Ministry was asked to furnish PSURs in respect of 42 randomly selected new drugs. Since files in respect of three drugs were reportedly missing, PSURs should have been supplied for the balance 39 drugs. The Committee is, however, constrained to note that PSURs in respect of only 8 drugs were submitted by the Ministry. The Committee was informed that 14 drugs though approved were not being marketed or were launched lately and hence PSURs would be expected later. There was no explanation for not submitting PSURs in respect of rest of 17 drugs,” the panel report said.

“Out of 14 drugs that were reported to be either not yet launched or lately launched, the Committee discovered that, at least, two products (FDC of glucosamine with ibuprofen; and moxonidine) were indeed in the market for some time and concerned manufacturers should have submitted PSURs. But the Committee has not been given any explanation for non-submission of PSURs for these two drugs,” it said.

The panel also found that the PSURs were not being submitted in time as per the rules. In the case of two drugs of MNCs (dronedarone of Sanofi Aventis and pemetrexid of Eli Lilly), the PSURs were neither India specific nor in the approved format as required by law. Some companies submitted PSURs for the products being marketed in the country but very few PSURs were India-specific, according to the panel.

“The Committee strongly recommends that the Ministry should direct CDSCO to send a stern warning to all manufacturers of new drugs to comply with mandatory rules on PSURs or face suspension of Marketing Approval. PSURs should be submitted in CDSCO-approved format which would help track adverse effects discovered in Indian ethnic groups,” the report said.
by
Dr.Akshaya Srkanth,
Hyderabad

Why To Choose Pharm.D

Careers in Pharmacy offers many benefits and opportunities. These include working in the community, a hospital, home health care, pharmaceutical research companies, nursing homes, government health agencies, and higher education. Pharmacists play a vital role in improving patient care through the medicine and information they provide. Pharmacy is a well-rounded career blending science, health care, direct patient contact, computer technology and business. In addition, pharmacy has excellent earning potential and is consistently ranked as one of the most highly trusted professions due to the care and service pharmacists provide.

A Pharm.D degree can be applied to diverse careers in

• Clinical pharmacists promote appropriate, effective and safe medication use for patients. By working as part of a health care team, pharmacists are able to closely monitor patient drug therapy and make recommendations on the selection of the best medication for a patient’s condition, the correct dose, and the duration of therapy.
• Some community pharmacists provide specialized services to help patients manage conditions such as diabetes, asthma, smoking cessation, or high blood pressure. Community pharmacists are the most visible branch of practice advising patients on the proper use of their prescription and non-prescription medication use, and keeping records of their patient’s health, illnesses, and medications.
• A hospital pharmacist advises other health professionals about the actions, interactions, and side effects of drugs, and counsels patients about medications. They advise physicians and other health practitioners on the selection, dosages, interactions, and side effects of medications.
• Graduates can work for the Drug Control Administration, the Drug Enforcement Administration, the Veterans Administration, the Public Health Service, the Armed Forces, the National Institutes of Health and biologicals and many other government agencies.
• Pharmacists in academia require a postgraduate degree and/or residency and are involved with teaching, research, public service, and patient care.
• Others serve as consultants for local, state, national, and international organizations.
• The Pharm.D program emphasizes problem solving and critical thinking and qualifies the graduate for national pharmacy and healthcare services. Pharm.D students learn to practice as patient-oriented healthcare professionals who will work as part of an interdisciplinary team. Pharm.D students can choose from many electives explore pathways that focus on areas of interest, and seize opportunities to work closely with members of any large and excellent faculty. To round out their education, students elect practice rotations from preceptors working in every imaginable setting in which pharmacy is the focus.

by

Akshaya Srikanth

Pharm.D Intern

RIMS, Kadapa

It's a Pain

Pain relief is one of the top reasons that people seek medical attention, and the abuse of prescription pain relievers is at an all-time high. This begs the question:what is causing all this pain? And, furthermore, is resorting to addictive and potentially dangerous narcotics the only answer?

We believe that the link between hormone imbalances and the prevalence of chronic pain deserves further exploration. Consider these findings:

Thyroid: A scientist, specialized in pain treatment, had issues with chronic pain himself, along with numerous symptoms of hypothyroidism, and he suspected the two might be related. Working with his mentors, they confirmed that his thyroid levels were indeed low, despite “normal” lab test results. He started thyroid hormone therapy and soon also became pain free. Upon further scrutiny of his patients seeking pain relief, he found that 98% of them also exhibited signs of hypothyroidism, which he determined needed to be addressed first. He also observed that many of his patients presented with a type of autoimmune hypothyroidism. These patients tended to be gluten intolerant and highly allergic, and had to be treated with bioidentical T3 (liothyronine) and T4 (levothyroxine) rather than whole thyroid gland to successfully address their pain and hypothyroid symptoms. 

Cortisol: One researcher suggests that the pain associated with rheumatoid arthritis may be very closely linked to hormone disturbances in his book, Safe Uses of Cortisol. As evidence, he points out that arthritis symptoms tend to disappear during pregnancy, when many hormone levels are high; that women with a history of infertility or a reduced menstrual timespan have a stronger likelihood of developing arthritis; and that women are more prone to arthritis after natural or surgical menopause.

Other scientist notes that, although high doses of synthetic cortisol derivatives such as prednisone have been effective for relieving pain, it is a poor choice for long-term treatment due to the side effects. Instead, he recommends using bioidentical cortisol or cortisone in small physiologic doses to achieve safer pain relief. 

Estrogens:  In Bioidentical Hormones 101, there are numerous citations regarding the treatment of osteoarthritis with estrogens. He points out that the conventional medical treatment for osteoarthritis is pretty grim, typically starting with Tylenol and non-steroidal anti-inflammatories such as ibuprofen and pain relief creams; followed by painful injections of steroids into the joints and physical therapy; and finally, when the pain becomes unbearable, joint replacement is proposed as the last option. Dich et.al cites studies that demonstrate osteoarthritis pain as a result of estrogen deprivation, as well as animal and human studies showing the benefits of restoring estrogen.

Progesterone:  Accompanying the decline of estrogens is a corresponding decline in the production of progesterone. Adequate progesterone levels encourage the normal production of collagen, which is needed for structural support and promotes the normal growth and maintenance of connective tissue, bone and soft tissue. According to Ross Hauser et al, this may explain why supplementing progesterone in postmenopausal women can help relieve chronic pain.

Testosterone: A study states that a testosterone deficiency is increasingly recognized as a concern in both men and women who suffer chronic pain. This finding is not too surprising given that adequate testosterone must be present to bind the body’s own pain-relieving compounds to their receptors, and also for the transport of hormones in the brain, including dopamine and norepinephrine. Testosterone is also necessary for the maintenance of muscles and bones, as well as for healing and controlling inflammation. A lack of testosterone results in poor pain control, depression, sleep loss and general loss of energy.

The stress of chronic pain can also create or exacerbate a testosterone deficiency by overworking the hypothalamus and pituitary glands so much that they stop signaling the body to produce more testosterone.  Ironically, narcotic type drugs can also suppress testosterone production by disrupting the hypothalamus, adrenal glands and sex organs, and diminishing the pain tolerance even as more pain medications are used.

It has also seen some success treating pain with human chorionic gonadotropin (HCG), another anabolic hormone that is most often associated with fertility and pregnancy. He believes the pain relief may be mediated through HCG’s ability to influence the thyroid gland, adrenal glands and sex organs to produce more hormones.

Vitamin D:  Non-specific neuromuscular pain may be linked to low levels of vitamin D, according to the Mayo Clinic, and therefore they recommend screening all people with such pain. This type of pain is not relieved by anything else except Vitamin D supplements. (Remember that Vitamin D, in spite of its name, is also a hormone related to the sex and adrenal hormones.) 

Oxytocin: Studies suggests that oxytocin, a hormone from the pituitary gland typically associated with orgasm and nursing, shows promise in treating the pain associated with fibromyalgia but that further studies are needed.

It is clear that many different hormones play various roles in keeping our bodies functioning well—and possibly pain free. So, when dealing with chronic pain, it makes sense to speak with your healthcare practitioner about the possibility that a hormone imbalance may be an underlying issue. Could a hormone imbalance be part of the problem? Or, better yet, could hormones be part of the solution?

by

Akshaya Srikanth

Pharm.D

Hyderabad, India