Sudesh Samuel asked:


A drug-drug interaction involves one drug affecting the activity of another usually when both are concurrently administered. Such interactions can result in the reduced or enhanced activity of one or both drugs. While many forms of drug-drug interactions exist, most can be broadly classified into interactions that involve the travel of the drug once administered (pharmacokinetic) or the action of the drug on the body (pharmacodynamic).

 

Drug-drug interactions that affect the travel of drugs in the body can be further understood as those that affect absorption into the bloodstream, distribution within the body, breakdown into different products or removal from the body.

 

Absorption interactions can occur when one drug’s particles have a large enough surface area to cause another drug’s particles to stick to them, both drugs may also bind to each other, or one drug alters the acidity of the stomach contents or the rate at which the stomach moves it’s contents. These interactions can alter the ability of one or both drugs to get into the bloodstream. When a drug only reduces the rate of absorption of another, a patient on regular use of both drugs is usually unaffected. However, if one drug reduces the extent of absorption of the other, the patient can be exposed to lower levels of the second drug than required and the second drug may hence be ineffective in treatment.

 

Distribution interactions may occur when drugs reach the bloodstream and the tissues. Competition between two drugs can arise for binding to the same proteins in the blood or one drug may dislodge another from it’s connection with tissues. It is more common in the second instance when one drug displaces another from the tissues, to find that the displaced drug accumulates in the blood leading to a greater risk of an affected patient experiencing toxicity. An example is when the heart medications quinidine and Lanoxin® (digoxin) are taken concurrently, digoxin blood levels can rise and adversely affect the patient if not monitored appropriately.

 

While drugs can be broken down at many different sites in the body, the most common site is the liver. Here, a system of enzymes can be up-regulated or down-regulated by one drug to result in the quicker or slower breakdown of the other respectively. Examples of drugs that up-regulate specific enzymes in the liver, include the anti-epileptics Dilantin® (phenytoin) and Tegretol® (carbamazepine). The enzyme up-regulation effect usually takes place gradually with maximal effects observed in 7 to 10 days of starting the drug. It may also take an equal or longer time before normalcy is regained upon discontinuing the drug. Examples of drugs that down-regulate specific enzymes in the liver, include the antibiotics erythromycin and ciprofloxacin. The onset of enzyme down-regulation is usually faster than up-regulation.
 

The majority of broken down drug products as well as whole drugs are removed from the body through the passing of urine. When one drug affects the pH of the urine, this can affect another drug’s ability to get into the urine depending on how it’s form changes during the filtering process in the kidneys. Transporter molecules in the kidney that facilitate drug removal may also become more or less available to one drug as a result of the presence of another.

 

Drugs can also interact and exert a net effect by their direct actions on the body. Two drugs with similar effects when administered together can display synergism in action although acting at different sites or receptors in the body. An example is the drowsiness that can be experienced when a sedative like Valium® (diazepam) is taken concurrently with an antihistamine like Polaramine® (dexchlorpheniramine). Conversely when two drugs that have opposing effects are taken concurrently, the response to either or both can be reduced. An example is the opposing wakefulness and drowsiness that can result from consuming a caffeine-based anti-migraine preparation and a sedative.

 

Another set of action-related drug-drug interactions occurs when two drugs exert toxicity towards the same organ or tissue in the body. Concurrent administration of the two drugs can result in damage to the corresponding organ or tissue despite the individual dose of each drug alone not being enough to result in toxicity under normal circumstances. The common organs that are most often affected by such drug-drug toxicity interactions are the kidneys and the liver. Of note is also that one drug can increase the organ-toxic effect of another even though it does not exert any direct toxicity towards that organ by itself.

 

Because of the numerous drugs available and the many more that are constantly arriving, drug-drug interactions can be quite common. However, the adverse effects can be minimized through consultation with an experienced medication expert. When such interactions are anticipated early, the most appropriate countermeasures can be readied to maintain well being.



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Steve M Caldwell asked:


Everybody knows that economic recession is hitting the world badly and thus every one wants to save their money in whatever way possible. One most essential thing that every one needs is the medicine, whatever it may be to survive and fight back the disease, we always need medicines. But, nowadays ever medicines have become so expensive. So many people tend to avoid them and land up in a big problem than before. Right now the demand for the high quality, low costs drugs is very more. The good news is that we have an option of the generic drugs available that are high in quality and low in price. The only need is to understand and not to believe in myths like generic drugs are or inferior quality. Generic drugs are the cheapest available option of the branded drugs in the market and show the same effects like the generic drugs. The most important thing is that generic drugs are approved by the FDA and WHO.

The financial income of the people is greatly affected because of the financial crises. All the markets are sinking because they are suffering too much lose. But, humans can not live without the medications if they have the ill health. Thus, to all these men generic drugs could be a best option to save the money. Reasons for the cheap price of the generic drug are— the cost of production of generic drug is very less as compared with the original brand name companies, no investment is done for the research on generic drug as the research is already conducted by the brand name manufacturer, clinical trials are not conducted by the generic drug manufacturer because they are previously conducted by the brand name manufacturer, and no cost is involved in the advertising and marketing of the generic drug because they get the benefit of the advertising and marketing done by the original drug manufacturer. Thus, generic drug allows the manufacturer to earn lots of profits.

Generic drugs not only save the money of the customers but also save the investment of the government in the pharmaceutical sector. US govt. has saved about 1 Billion dollars because of the generic drugs in the year 2007-08. Insurers are also very beneficial due to the use of the generic drugs. Insurance companies are asking the doctors to follow the step therapy that means doctors should first prescribe the generic drugs and if these drugs fail to produce the required effect then they should prescribe the more expensive brand-name drugs. FDA is sending pamphlets to the big pharmacy chain in US to promote the generic drugs. FDA is even asking these pharmacies to promote the sale of generic drugs. FDA says that all drugs must work well and be safe. FDA makes sure that before approving that generic drugs are of high quality, strong, pure, and stable as their respective brand-name drugs.

Generic drugs are allowed to be sold in the market only after they satisfy the following criteria:



Generic drug should have the same ingredient as the original drug.

Generic drug must be identical or bioequivalent to the original drug.

The pharmacokinetic and pharmacodynamic properties of the generic drugs should be similar to the original drugs.

Generic drugs should be similar in strength in comparison with the original brand name drug.

The side-effects of the generic drug are less or more than the original brand name drug.



Generic drugs are manufactured in the world class units that are checked and then approved by the FDA. The safety of the generic drugs is not at all in doubt because no casualties till date are noted by the intake of the generic drugs. Thus even the pharmacy distributors believe in the generic drug manufacturer and thus the sale of generic drug increases. Customer is using generic drugs because of the cost benefits and he is enjoying the same effects that he used to get by the original branded drugs. Hence, we can conclude that generic drugs perfectly match the demand of time.



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Sudesh Samuel asked:


An adverse drug reaction (ADR) is any unintended, noxious or undesired effect that occurs when a drug is used at accepted doses for preventing, diagnosing or treating a condition.

 

By this definition from the World Health Organization, ADRs can be further categorized into those that are related to the known mechanisms of the drug (although some may not be) or those that are related to reactions with the immune system.

 

Most ADRs are considered predictable. One such type of predictable dose-dependent ADR that is due to the known action of a drug is a side effect. An example is the experience of dry mouth from taking an antihistamine. Another such ADR is drug toxicity as seen with the liver toxicity caused by taking the anticancer drug methotrexate. A predictable ADR may occur secondary to a drug’s intended effect as exemplified by diarrhea that is experienced when antibiotics change the gut’s content of microorganisms. A good proportion of drug-drug interactions also lead to predictable ADRs. An example is a seizure experienced due to excess levels of theophylline that result from concurrently taking the antibiotic erythromycin as it inhibits liver enzymes responsible for the breakdown of theophylline.

 

Unpredictable ADRs make up a smaller proportion and are still mostly not related to immune system reactions. Unpredictable ADRs not related to immune system reactions includes intolerance of aspirin that results in ear ringing after a single small dose. Of the ADRs caused by immune system reactions, these usually come in four types depending on the type of immune system factors involved in the reaction, it’s onset, severity and duration. These have sometimes been termed drug hypersensitivity, a specific subset of which is associated with the immune system’s IgE protein and termed drug allergy. The presence of asthma is often an important predictor of more susceptible individuals to such reactions.

 

Drug allergy often occurs as quickly as within minutes to hours of drug exposure. Such a reaction can include itching, rashes, airway swelling, vomiting, diarrhea and the experience of shock. This can occur when allergy is experienced with penicillin-based antibiotics in susceptible individuals. In the other types of immune system mediated reactions, the onset is variable and can take as long as 3 weeks from drug exposure to manifest in symptoms. Reactions to anticonvulsants and specific sulphur-based drugs have been known to result in severe and dangerous skin destruction.

 

When drug hypersensitivity occurs, it is important for the attending doctor or pharmacist to be informed of all medicines or supplements (even foods) that were taken within one month of the symptoms, when they were started and for how long they were taken. The chronology of symptoms also facilitates an accurate diagnosis. In virtually all cases of drug hypersensitivity, the offending drug has to be discontinued. With appropriate treatment and supportive measures based on an accurate diagnosis, symptoms in the majority of cases will usually resolve within 2 weeks.

 

It is important to keep a list of all the medicines that one is allergic to and to make this list available to all healthcare providers. Drug hypersensitivity relating to immune system reactions often leads to a predictable yet also more serious health risk upon re-exposure to an offending drug or one that shares properties with the previously offending drug. The risk of cross-reactivity between an offending drug and another also is best discussed with an experienced medication expert.

 

Of value in improving the safety of medication use is the voluntary ADR reporting schemes that are available in various countries. The Yellow Card scheme is used in the United Kingdom while the MedWatch program is available in the United States and the Blue Card reporting form is used in Australia. Such reporting systems constitute pharmacovigilance and this allows for the collection and subsequent publishing of ADR data that encourages greater safety of commercially available drugs.

 

The increasing presence of ADRs can often be correlated with older-aged adults, increasing numbers of new drugs and self-medication. Consult an experienced drug expert on the probability of ADRs before taking any new drug.



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John Smart asked:


Observing the ever increasing incidents of drug abusing and the deteriorations of the quality of the work output drug testing has been made mandatory at many corporations so that they can control or prevent any harmful effect that may occur to the employees and also to the other employees with strong hand thus keeping the environment safe and healthy.

Various types of drug test are followed according to the various levels and circumstances. To mention the various levels and circumstances of corporate drug testing they are pre-employment drug testing, post accident drug testing, random drug testing, return to duty/ follow-up testing, request to retest and reasonable suspicion test. All of which aims at keeping the corporate environment healthy.

1. Pre-Employment Drug Test- It is the most common type of drug test followed by almost all the corporations and it is followed at the time of recruitment to detect the whether the candidate consumes drugs like marijuana, cocaine, PCP, opiates and amphetamines.

2. Post Accident Drug Test- Post drug testing is conducted on any employee who meets with an accident during the job timings. If the employee is found to take drug then the company is not duty-bound to pay for the employee or it is neither compelled to any sort of cases which may affect the company’s concern. It is wrong to interpret post accident drug test to fire the employee but it aims at protecting the company from the legal responsibility in the event that the individual is the victim of drug that caused the accident.

3. Random drug test- This type of drug test act as a deterrent on the employees as they will think several times before taking drugs as these tests are conducted without any prior notice.

4. Return to duty/ Follow-up test- This test gives a second chance to any employee who could not pass the drug test. The employee is allowed to once again undergo the drug test within forty-five days from the last test. The person should get a clearance from the EAP to rejoin the job. It does not end here; the person will have to undergo unannounced and periodical drug testing for six times even in the following year.

5. Request to retest-‘Retest’ as the name suggest is to sit or undergo for the test if there is any doubt with the result of the already done test. If an employee who has undergone the drug test has any kind of doubt with the result then he/she has the right to apply for retest to confirm the result and it can be done only after seventy-two hours after the previous test is been done.

6. Reasonable Suspicion Test- If any of the employee’s behavior is found to be suspicious then the employers has the right to conduct both the drug test and alcohol test. And if the employee is identified for the reasonable suspects then he is liable to get suspended but when the results for the drug test are negative then he/she will be again taken in the job and will also be paid for the length of period he has been prevented to work.

All the above mentioned drug test solely aims at improving the working environment but it is also true that person identified to be using drug get a stain in their career. Again it is also true that drug test act as a prevention on the employees as they will think several times before taking drugs so that they are not fired as no wants to lose their job.



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jeff turner asked:


Everybody knows that economic recession is hitting the world badly and thus every one wants to save their money in whatever way possible. One most essential thing that every one needs is the medicine, whatever it may be to survive and fight back the disease, we always need medicines. But, nowadays ever medicines have become so expensive. So many people tend to avoid them and land up in a big problem than before. Right now the demand for the high quality, low costs drugs is very more. The good news is that we have an option of the generic drugs available that are high in quality and low in price. The only need is to understand and not to believe in myths like generic drugs are or inferior quality. Generic drugs are the cheapest available option of the branded drugs in the market and show the same effects like the generic drugs. The most important thing is that generic drugs are approved by the FDA and WHO.

The financial income of the people is greatly affected because of the financial crises. All the markets are sinking because they are suffering too much lose. But, humans can not live without the medications if they have the ill health. Thus, to all these men generic drugs could be a best option to save the money. Reasons for the cheap price of the generic drug are— the cost of production of generic drug is very less as compared with the original brand name companies, no investment is done for the research on generic drug as the research is already conducted by the brand name manufacturer, clinical trials are not conducted by the generic drug manufacturer because they are previously conducted by the brand name manufacturer, and no cost is involved in the advertising and marketing of the generic drug because they get the benefit of the advertising and marketing done by the original drug manufacturer. Thus, generic drug allows the manufacturer to earn lots of profits.

Generic drugs not only save the money of the customers but also save the investment of the government in the pharmaceutical sector. US govt. has saved about 1 Billion dollars because of the generic drugs in the year 2007-08. Insurers are also very beneficial due to the use of the generic drugs. Insurance companies are asking the doctors to follow the step therapy that means doctors should first prescribe the generic drugs and if these drugs fail to produce the required effect then they should prescribe the more expensive brand-name drugs. FDA is sending pamphlets to the big pharmacy chain in US to promote the generic drugs. FDA is even asking these pharmacies to promote the sale of generic drugs. FDA says that all drugs must work well and be safe. FDA makes sure that before approving that generic drugs are of high quality, strong, pure, and stable as their respective brand-name drugs.

Generic drugs are allowed to be sold in the market only after they satisfy the following criteria:

•    Generic drug should have the same ingredient as the original drug.

•    Generic drug must be identical or bioequivalent to the original drug.

•    The pharmacokinetic and pharmacodynamic properties of the generic drugs should be similar to the original drugs.

•    Generic drugs should be similar in strength in comparison with the original brand name drug.

•    The side-effects of the generic drug are less or more than the original brand name drug.

Generic drugs are manufactured in the world class units that are checked and then approved by the FDA. The safety of the generic drugs is not at all in doubt because no casualties till date are noted by the intake of the generic drugs. Thus even the pharmacy distributors believe in the generic drug manufacturer and thus the sale of generic drug increases. Customer is using generic drugs because of the cost benefits and he is enjoying the same effects that he used to get by the original branded drugs. Hence, we can conclude that generic drugs perfectly match the demand of time.



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Sudesh Samuel asked:


A drug-food interaction occurs most commonly when the consumption of a specific food or beverage affects the activity of a drug or consumption of the drug affects the activity of the food or overall nutritional status.

 

When a food alters a drug’s activity or vice versa, the affected compound is changed in aspects of how quickly or how much of it gets absorbed into the body, how much of it distributes to it’s site of action, and how quickly it gets broken down or passed out from the body. Such drug-food interactions may result in the individual experiencing side effects, toxicity or not getting full benefit from the drug or food.

 

In altering the absorption of drugs, foods may bind with the drug, change the acidity of the stomach, moderate the contractions of stomach muscles or change the speed at which stomach contents move through the body. Dietary fibre in the form of pectin and other soluble fibres can slow down the absorption of Tylenol® (acetaminophen). Almost half of a single dose of the antibiotic Zithromax® (azithromycin) does not get absorbed when it is taken with food. When another antibiotic ciprofloxacin is taken with iron, a complex is formed and about half of a single dose also becomes unavailable for absorption. One of the most significantly food-affected drugs is Fosamax® (alendronate) where up to 99.9% of an oral tablet can become unavailable for absorption if taken with food, coffee or orange juice. Sometimes increased benefit is derived from taking certain medicines with food. Taking the statin Mevacor® (lovastatin) with food enhances it’s absorption while taking non-steroidal anti-inflammatory drugs like aspirin with food can help to reduce stomach irritation.

 

Different drinks can alter the breakdown of a drug in the body. Components of grapefruit juice can inhibit enzymes in the liver from breaking down a variety of drugs. Taking grapefruit juice while on the heart drug felodipine results in much less of the drug broken down and this can cause lower blood pressure and faster heart rates than otherwise expected. The heart drug Inderal® (propranolol) can escape early breakdown in the liver when it is taken with food hence it’s effectiveness could be increased.

 

One important class of drugs known as monoamine oxidase inhibitors (MAOIs) can inhibit body enzymes from breaking down a compound known as tyramine. This compound can be found in aged cheese, pickled fish, yeast extracts, red wine, fava beans and fermented products, and can accumulate in the body if taken with MAOIs and the combination could result in critically high blood pressure.

 

Milk, vegetables and citrus fruits can reduce the acidity of urine while meats, fish, cheese and eggs often increase the acidity of urine. These different effects can affect the quantity and rate of expulsion of certain drugs. Other drugs may be more or less active in the urinary system depending on the urine acidity. The mood controlling drug known as lithium is affected by a high salt (sodium chloride) diet because it competes with sodium for absorption back into the body from the kidney. With a high salt diet, more lithium is passed out and lithium is consequently less active in the body. The converse occurs with a low salt diet.

 

Some foods can directly affect the action of drugs without affecting the drugs themselves. Taking a lot of green leafy vegetables or green tea can increase vitamin K levels in the body that counteract the effects of the anticoagulant drug warfarin. Taking a lot of bananas while on the potassium-sparing water pills Aldactone® (spironolactone) can result in excessive amounts of potassium in the body that can be toxic. Alcohol can increase the drowsiness and reduced concentration associated with sleeping pills, antidepressants and allergy medicines. Another potentiating effect can occur when the asthma drug theophylline is taken with coffee. The caffeine in coffee shares the same structure as theophylline and helps with expanding the airways but also can increase theophylline’s side effects of nervousness, tremor or insomnia.

 

While most drug-food interactions can be detrimental, some have been used under supervised treatment to reduce drug doses and associated costs. Oncologists recently found that taking the ****** cancer drug Tykerb® (lapatinib) with food instead of without food as suggested by the drug development trials almost doubled the absorption of the drug and taking it with a high-fat meal tripled the absorption. Grapefruit juice may even further prevent the drug from being broken down in the body so that more of the dose remains available to fight cancer cells. While this is a novel and potentially useful means of taking food and drugs together for better treatment, expert supervision is important in ensuring benefit and minimizing undesirable effects.

 

Even while much of the concern over drug-food interactions center around how foods affect the activity of drugs, many drugs also expected to exert significant effects on foods, body nutrients and byproducts. The weight loss drug Xenical® (orlistat) is taken specifically with meals to interact with the fat in food so that it is not absorbed and passes out in the stools. Colestid® (colestipol) and Questran® (cholestyramine) are taken orally to bind bile acids in the intestine preventing such acids from being recirculated in the body and thereby reducing cholesterol. Another drug acting on food is Fosrenol® (lanthanum carbonate) that is used to bind and prevent the absorption of phosphates in the diet.

 

Some drugs can also affect nutritional well being resulting in the need for food or nutrient supplementation. Examples include taking certain antacids and water pills that can lead to nutrient deficiencies resulting in muscle weakness and other related symptoms. Folic acid supplementation may be required if on the anticonvulsant Dilantin® (phenytoin). Zinc deficiency coupled with the loss of taste can occur when on the antirheumatic penicillamine.

 

Drug-food interactions are becoming increasingly common and can be detrimental if not well understood or properly managed. Pharmacists are the experts to turn to for a better understanding and are in the best position to advise on optimum management.



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Steve Marshal Caldwell asked:


Low cost drugs have captured the market of the branded drugs because of their best quality and the reasonable prices. In all over the world, low cost drugs are now holding the share of about 61% in the pharmacy market. Before a decade, Low Cost Drugs were having only a share of 10% in the pharmacy market. But, it was after the discovery of the low cost version of impotence drugs that revolutionized the pharmacy market and made the customer to believe in the Low Cost Drugs.

Many low cost drugs were there in the market but, they were not purchased by the customers because of the wrong publicity of the low cost drugs that was done by the branded drug companies. The myth that “low cost drugs are of inferior quality and may cause severe harm to the health” was spread by the branded drug companies for maintaining their position in the market. But, impotence drugs made a breakthrough and became a more selling drug than its original counterpart.

In United States, the sale of low cost drugs is now improved considerably in the last 2 years because of the consistent effort of the US govt. in promoting the use of the low cost drugs. The US govt. has even reduced the taxes on the low cost drugs so that the basic medicines are available to the people at the lowest possible costs. Even the campaigns are carried out throughout the US in order to promote the use of the low cost drugs. These all things have contributed considerably in increasing the sale of the low cost drugs. The most important reason why low cost drugs are able to capture the market is the low pricing of the low cost drugs. The main reason why the low cost drugs are available for the very low cost was that the no investment was done in the research of the low cost drugs as the low cost drug manufacturer has to follow the same formulation of the branded drug manufacturer. Thus, the considerable amount of money is saved here.

Low cost drugs because of the low price do the annual saving of 6 billion euros that accounts into the profits made by the low cost drug manufacturers and insurers. Customers also prefer low cost drugs because of very low prices in comparison to the original branded drug and same in effectiveness like the original drug. Even the government in the European nations and European Drug Agency, noted that the existence of a large market for low cost drugs is necessary because of the increasing customer demands. Previously, low cost drugs were not at all purchased by the customers in European nations. But, due to continuous efforts put by the European Unions and low cost drug manufacturer, last year there was tremendous change in the pharmacy market. Low cost drugs started selling more than the branded drugs. Low cost drugs have captured 54% of the market in the European pharmacy market.

Low cost drugs are the adaptation of the branded drugs that are manufactured following the same standard guidelines but are manufactured in developing countries so are very cheap and affordable for the individuals staying in developed countries. Low cost drugs are in demand all over the world. Low cost drugs are defined as the drugs, which has the similar properties and effects as their brand-name drugs whose patent is expired. Low cost drugs are the pharmacologically similar to the brand name drugs. The active constituent of the low cost drug and the original branded drug is same and in equal concentration.

The real turnover came in the low cost drug when the first low cost drug’s approval by the Food and Drug Administration in United States. This year has already recorded the buyouts of $25.1 billion of low cost drugs in the pharmaceutical industry. Low cost drug industry holds the 57% of the pharmaceutical market and is expected to capture the 76% of the pharmaceutical market by 2015. Thus, it is quite sure than in the next decade low cost drugs will be the only medicines available to the customers.



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Yogesh Murti asked:


Introduction

A drug that is structurally very similar to already known drugs, with only minor differences. The term “me-too” carries a negative connotation. However, me-too products may create competition and drive prices down1.

The majority of the new products the industry puts out, are “me-too” drugs, which are almost identical to current treatments but “no better than drugs already on the market to treat the same condition.” Around 75 percent of new drugs approved by the FDA are me-too drugs. They can be less effective than current drugs, but as long as they’re more effective than a placebo, they can get the regulatory green light2.

This isn’t surprising at all, as someone who works in the field, but these so-called “me-too” drugs, which are reportedly better than their forebears, is driving costs. A “me-too” drug is a drug that has its origins in another drug. Probably the most famous example of this is Prilosec (“The Purple Pill”) and Nexium (“Today’s Purple Pill”). Prilosec’s active ingredient is omeprazole. Nexium’s active ingredient is called esomeprazole. The difference is that Nexium is the left-handed version of omeprazole. In chemistry, S stands for sinister, which means the molecular conformation has a left-handed orientation. (D would be right handed.) So this S-omeprazole is one half of the mixture that comprises its predecessor. By specifically picking only the S conformation, the drug is made more potent. This sounds great, but its efficacy is only marginally better than Prilosec-, which has a generic version, and costs about a third less than Nexium. Some other “me-too” drugs are: Claritin (loratidine) and Clarinex (desloratidine), Celexa (citalopram) and Lexapro (escitalopram)3.

What are “Me-Too” drugs?

Ever since the advent of modern chemotherapy, when drugs were discovered and developed through the process of screening thousands of molecules for a variety of disease conditions, using animal models, there has been a growing criticism that too many molecules were developed with similar chemical structure and the same pharmacological profile, with very little to distinguish them from each other in terms of their therapeutic utility. In other words, once the first breakthrough discovery is made of a new pharmacological activity for a new molecule, subsequent years saw the emergence of a host of new molecules or “me-too” drugs from the same chemical class and possessing the same pharmacological profile.

Such follow-up drugs have been termed molecular modifications, molecular roulettes or copycats, the development of which are alleged to be motivated by purely commercial considerations. They are also deemed to involve lower levels of innovation, compared to the original molecule. It is important to analyze in a historical perspective the end results of such efforts in different therapeutic areas of developing new molecular entities, as later generation products, after an initial breakthrough discovery has been made and the technical, medical and commercial merits of developing such drugs.

Development of “Me-Too” drugs

The success rate in the discovery of new chemical entities with fundamentally new chemical and biological profiles of activity are very low. In fact, even chemical entities within the same structural class of an approved drug are becoming rare now, compared to the period of sixties to eighties. In 2001, $ 26 billion was spent on developing new drugs and the U.S. FDA approved only 9 new chemical entities. At the same time, two thirds of the drugs approved from 1989 to 2000 were modified versions of existing drugs or even identical to those, in newer forms and formulations4.

Of the 1,035 drugs approved by FDA during 1989 to 2000, only 361 or 35% contained new active ingredients. Of these, only fewer than half were granted priority review status by the FDA. One impression is that these drugs are slightly altered versions of existing drugs, with little to offer in terms of better activity or tolerance, let alone new pharmacological profiles. The implication is that such drugs are developed, as patents on top-selling original drugs run out and not many truly new medicines are discovered. The indication that many of these drugs do not offer any major advantages over existing drugs is given by FDA’s unwillingness to grant priority review for most of them.

On the other hand, conventionally, the Regulatory Agencies, including the FDA, are not obliged to consider better efficacy over existing drugs as a criterion for approval; rather, they require only the establishment of efficacy and safety of the new drug over a placebo.

How good are they?

Notwithstanding such perceptions, historically, many “me-too” drugs have proved to be considerably better than their original counterparts. Examples are a series of generations of beta-blockers, which came up after the original drug Propanalol was discovered by ICI, with most of them having merits in terms of better efficacy, cardio-selectivity and safety. Ranitidine, the first follow-up drug after the introduction of the first H-2 receptor antagonist, Cimetidine, was followed by Famotidine and in each case these “me-too” drugs had notable merits over the original drug.

Apart from the major breakthrough in the development of orally active beta lactam antibiotics of the Penicillin and Cephalosporin class, within the same oral derivatives, there have been considerable improvements brought about by change in the side chains incorporated by condensation of specific agents with 6-APA, 7-ADCA and 7-ACA. A whole new range of broad-spectrum antibiotics of these structural classes could thus be developed. In each of the major classes of antibiotics, classified according to the mechanisms of their action, namely inhibition of cell wall synthesis (Beta Lactams, Vancomycin), inhibition of bacterial protein synthesis (Erythromycin, Tetracycline, Streptomycin), inhibitors of DNA or RNA replication (Quinolones, Rifamycins), inhibition of Folate Coenzyme biosynthesis (Sulfa drugs, Trimethoprim), there have been several “me-too” drugs marketed.

An important recent example to show that ‘me-too” drugs need to be developed is the case of the oral hypoglycemic drug Troglitazone, approved as an anti-diabetic drug in 1997. The drug was withdrawn from the market following reports of unacceptable hepato-toxicity. The follow-up “me-too” drugs, Rosiglitazone and Pioglitazone are much less toxic and are today widely used. If these drugs were not developed, the withdrawal of Troglitazone would have left a major therapeutic gap in anti-diabetic therapy.

“Me-Too” drugs: Strategies for New Drug Research for Indian Companies

Breakthrough innovations in pharmaceutical industry, of new drugs, such as the first beta blocker, the first NSAID, the first of each class of Antibiotics, Calcium Channel blockers, ACE inhibitors, Sulfonyl Ureas, Biguanides, Insulin, Glitazones, Glinides, Tricyclic Anti Depressants,major and minor Traquillisers, Selective Serotonin Receptor inhibitors, H-1 and H-2 Receptor antagonists, Proton Pump inhibitors etc are relatively rare and even though a few of the original drugs under these classes are still very much in use, they have been superceded in most cases, by later generation products, many of them “me-too”. The newer drugs are discovered both through incremental innovations on the original drugs as well as through new research.

Generally the original discovery leads to feverish activity both within the innovator company as well as in Competitors’ laboratories, to develop better products in the same therapeutic category. The essential caveat for commercial success, however, is that the newly discovered molecules should meet the minimum standards of patentability. For example within three years of the discovery of the highly successful Sildinafil Citrate (Viagra), three more new versions for the same indications have been patented and developed5.

Me-too drugs also provide therapeutic advantage6. For the practicing physicians, there’s the benefit of established drug MoA with a “me-too” medication, coupled with clinical studies that – hopefully – show patient-centered benefits such as better adverse events profiles, less frequent dosing, less bothersome potential for drug/drug interactions, and so forth. A “me-too” drug is a helluva lot easier to incorporate in practice than a totally novel medication7.

“Me-Too” drugs: The hidden dynamics

The most common criticism of drug development centers on the so-called “me-too” drugs that employ the same biological mechanism as pioneer brands. This involves a lot more than such high-profile targets as the anti-ulcer drug Nexium. We should be thinking about antidepressants, cholesterol-reducing drugs, diabetes treatments, anti-psychotics, and other therapeutic categories that have seen both blockbuster sales and rapid innovation. There is quite a bit of evidence that follow-on drugs do a lot of patients a lot of good. The newer statins, for example, often out-perform the older ones in clinical trials where the endpoints are the number of heart attacks and deaths prevented.

Me-too drugs are also a powerful tool for cutting health care costs. We should be glad that our research industry does not target only brand new biological mechanisms. That would be a very expensive business model indeed. Fortunately, the industry also works on marginal improvements, exploiting opportunities to make drug therapy better and sometimes opening the door to really radical improvements that happen to lie more or less next-door, scientifically speaking. In the meantime, we get price competition as a by-product. Me-too’s almost always undercut the prices of the pioneer drugs.

Another part of the me-too story gets almost completely ignored even though it is extraordinary important. For me-too manufacturers, advancing the science is a way to gain a competitive advantage. The classic example is the statin class of cholesterol drugs. Research on one of the follow-on drugs (Pravachol) demonstrated for the first time that using a statin to reduce cholesterol would actually prevent deaths from heart attacks, something that had previously been assumed without proof. Additional trials for several statins, including Lipitor, the formidable challenger to Zocor and Pravachol, have demonstrated that serum cholesterol is far more important than almost anyone thought (for preventing strokes, for example).

There are lots of other stories about the benefits of new research from me-too drugs, but they are part of a larger story: new uses for old drugs. The data showing a slowdown in new drug approvals exclude essential information: discoveries of new uses for old drugs. This kind of discovery has become so common that it amounts to a “new-use” revolution. One of the scientific ironies of the new era of pharmaceutical research is that as drugs become more tightly targeted on biological mechanisms, their uses actually become more diverse. This is because the body typically uses specific mechanisms over and over again, sometimes in what appear to be completely unrelated ways.

Consider the SSRI antidepressants. A recent Science article on the diverse and unexpected applications of drugs that fiddle with serotonin reuptake which is what the SSRIs do concluded that the very term “antidepressant” is misleading because there is no scientific reason to think of this drug as being just for depression. Fighting depression just happened to be the first really useful condition that was explored for this very interesting class of drugs.

Another example is the Cox-2 inhibitors like Celebrex (and Vioxx, which is important in this story and may return to the market partly for this reason). These were invented to relieve arthritis pain. But the Cox-2 enzyme turns out to be important for lots of things including cancer and Alzheimer’s. Clinical trials to exploit these leads have been underway for years. Celebrex has already been approved for reducing the risk of colorectal cancer, and Vioxx has also achieved promising results. Of course, the big news recently has been that these drugs may cause heart attacks. But even here, me-too economics is of surpassing importance. The traditional NSAIDS (non-steroidal anti-inflammatory drugs) like Alleve and Advil may have the same heart attack risks. The potential risk has been there for decades, but only the new drugs-the Cox-2s-have been put through large-scale long-term clinical trials because those are the only ones still under patent. This is an example of how me-too drug development adds importantly to the research base. Thanks to the me-too’s, we are learning about NSAIDs, heart attacks, cancer and probably much more.

Also dominated by new uses are the new-targeted cancer drugs, which attack such specific biological mechanisms that they avoid killing every fast-growing cell in sight (as traditional chemotherapy tends to do).

The implications are clear. The annual count of new drug approvals will only show a tick when a new cancer drug or a new statin gets its very first approval. But a new use for an old drug can be as valuable as an entirely new drug, or even more valuable when you consider that we know more about the safety profile of old drugs and one drug will sometimes do the work of two (preventing both heart attacks and strokes, for example)8.

Me-too products can sometimes have important advantages on tolerability or dosing. It could help create more competition and lower the price. If you have five me-toos, possibly the sixth is something that is a little better. That is for the plans to decide on behalf of their patients. And even if it has the same mechanism of action, more competition could help drive down the price of the entire class. That’s an important influence, with potentially an improvement in health from greater access.

How bad are they?

Even though the major problem of antibiotic therapy, namely drug resistance cannot be addressed by the development of “me-too” drugs, due to the propensity of the same class to develop cross resistance; in most cases, the new semi-synthetic derivatives had distinct advantages over the earlier ones. Thus, for example, the first generation Cephalosporins are useful for gram-positive infections, while the second-generation drugs cover a broader spectrum including gram-negative organisms. The third generation drugs provide resistance against the beta lactamase enzyme, as well as acting against some of the most intractable infections, such as those caused by Pseudomonas and Klebsiella strains.

Even while the pharmaceutical industry turns out families of me-too drugs for relatively mild conditions in affluent people, it pays almost no attention to serious diseases, such as malaria, affecting impoverished people. It also gives short shrift to less profitable drugs, so there now are shortages of some vaccines and life-saving drugs9.

The big problem with me-too drugs is that they are chemically very similar to other drugs already available, yet they are marketed as if they were important new breakthroughs, with very high prices. Many new, expensive me-too drugs are not necessarily better than older and less expensive drugs. Most of the time they are compared with placebos and not older drug comparisons.

“Me-too” drugs are responsible for 80% of increased spending in recent years, and on average they are four times more expensive than the comparable, older alternatives10. By Patented Medicines Pricing Review Board’s (PMPRB) definitions, at the time of their introduction “me-too” drugs were judged to provide moderate, little or no improvement – in terms of effectiveness and safety – compared to older alternatives. However, on average, “me-too” drugs cost about 2.5 times as much per prescription as comparable older drugs. The question is whether the perceived or real differences justify the increased costs. New drugs do have a role in some situations and for some patients. However, it makes sense to use the older equally effective drugs whenever possible11.

Changing FDA rules to discourage me-too drug approvals would make R&D far more expensive, would discourage competition and therefore raise healthcare costs, and would forestall the wave of new research that has revolutionized our scientific understanding of the therapeutic categories where competition has been most intense.

Conclusion

New drugs are not required to improve on old ones, and there’s usually no way to know whether they do. Although the FDA must test drugs before they are marketed, they don’t need to be compared with similar drugs already on the market. The FDA only requires they be reasonably safe and better than nothing-a low standard indeed. This loophole in FDA regulations opens the door for an unlimited number of me-too drugs, which are easier to develop than innovative drugs.

Given everything, it should come as no surprise that these more expensive “me-too” drugs cost the medical industry money. The prevalence of the me-too’s really says an awful lot about the lack of innovation within the pharmaceutical industry. If you look at the new drugs marketed over the last six years, 78 percent weren’t even new chemical compounds. They were just new combinations or different formulations of old drugs. And 68 percent were classified by the F.D.A. as unlikely to be improvements over drugs already on pharmacy shelves.

At the same time, there are shortages of some important drugs that the pharmaceutical companies aren’t much interested in making because they are not as profitable as the me-too’s. But the companies don’t have to turn out needed drugs, if they are not lucrative. And they don’t.

References

1. http://www.medterms.com/script/main/art.asp?articlekey=33748

2. http://www.motherjones.com/news/qa/2004/09/09_401.html

3. http://polyscience.org/2005/09/me-too-drugs

4. http://www.shvoong.com/books/465475-me-too-drugs

5. http://www.pharmabiz.com/article/detnews.asp?SecArch=&articleid=14604&sectionid=46

6. http://direct.bl.uk/bld/PlaceOrder.do?UIN=162532605&ETOC=RN&from=searchengine

7. http://www.archivum.info/sci.med/2005-09/msg00257.html

8. http://www.aei.org/publications/filter.all,pubID.27443/pub_detail.asp

9. http://blogs.wsj.com/health/2007/05/17/in-praise-of-me-too-drugs

10. http://www.chepa.org/KnowledgeExchange/LabelleLectureship/tabid/84/Default.aspx

11. http://www.ti.ubc.ca/pages/letter59.html



Onetoo3

Mark M Morris asked:


Drug addiction is a rising menace which surfaced in the olden times. Ever since drug addiction started to rise, especially after the “hippie revolution”, the deterioration of physical as well as mental health saw no boundaries. This led to drug addiction being considered as an international health crisis. While drug addictions can be grouped into various categories, the main abuses which drug addicts are habitual of administering include smoke related drugs, alcohols and banned substances which can either be chewed or directly injected into the bloodstream of the individual. Let us now discuss 4 ways to cure these patients through drug addiction help.

Take Baby Steps While Curing A Patient

Drug addiction treatment is a methodical procedure which needs to be followed step by step. Whenever you happen to try and aid a drug addict, you need to ensure that you do not do so with haste. This is so as drug addiction treatment calls for slow steps towards success and it is therefore a steady procedure. For example, if a person is a known drug addict and he is used to smoking fifteen cigarettes a day, you need to ensure that he reduces the number to three cigarettes by the end of the month. Once again, the process needs to be slow and restructured at the end of each week. In case you ask the patient to quit smoking drugs from the first day itself, his/her body would not be able to bear the strain and this in turn would lead to serious complications.

Drug Addiction Rehab Is Not A Permanent Solution

While most people are under the impression that drug addiction can be treated through the means of a drug addiction rehab, the truth is that a rehab center can only provide a temporary relief to your problems. There is no doubt that the patient would never be allowed to either smoke or drink while he/she is inside the rehab center, the moment he/she steps out, he/she would be back to his/her normal habits. Drug addiction help through the means of a rehab center is not permanent. It is like a jail which keeps a convict under control for a specified time period. After the period is over, the convict is back doing what he does best-committing crimes.

Friends And Family Play An Important Role

Drug addiction help can be provided through the means of friends and family members. In case you happen to have a drug addiction case in your family, it is your responsibility to get the patient back on track. Addiction to drugs is a bad habit which needs to be dropped through an able councilor. While there are various councilors available in the market, most of them are very expensive and obviously, they do not have a lot of time to spare on a single case. This is when the role of a family comes into picture. If you wish to cure a patient of his addiction to drugs, you need to be able to make sure that you convince the patient’s friends and family to take an active interest in the process.

A Natural Therapy Is Always The Best Cure

Drug abuse addictions are a very serious problem and if you wish to permanently cure a patient, you need to pay adequate attention towards the choice of the de-addiction therapy. While there are many traditional therapies which do not work well as they are temporary in nature, there are others which are considered permanent. They are natural therapies which work on the mindset of the patient. Once the patient’s mindset is changed, he/she can take control of his life without any external assistance. If you wish to end drug abuse addictions permanently, you need to adopt a natural therapy.



Onetoo3

Linda Wieland asked:


Cyrus Brooks is the coordinator of the Drug Free Ambassadors Australia in Sydney. In this editorial he expresses his commitment to helping youth avoid the pitfalls of drug addiction.

While a fierce debate rages over the dramatic rise in prescriptions for “ADHD” for children as young as four, there is another side to the ADHD medication issue—street use of these drugs.

In fact, in Australia a street name for Ritalin is “poor man’s cocaine” and there are stories of kids who are prescribed these drugs, selling them to their friends and crushing and snorting the powder.

There was a ten-fold increase in these prescriptions from 1993 to 2003. This is a dangerous trend.

According to one Australian youth, “it’s surprisingly easy to get dexamphetamines (a substance that is primarily used for treatment of ADD/ADHD) by pretending you have ADD, especially if someone who has been through the interview process coaches you with the right things to say.”

But why would people cheat to get prescribed an ADHD drug? In 2000, the Deputy Director of the Office of Diversion Control of the U.S. Drug Enforcement Administration briefed the U.S. Congress on the results of studies on both animals and humans who were given cocaine and Ritalin, saying “neither animals nor humans can tell the difference between cocaine, amphetamine, or methylphenidate (Ritalin) when they are administered the same way at comparable doses. In short, they produce effects that are nearly identical.”

And Australian statistics show these drugs are used on the street for the same reason. Seventeen percent of young “serious offenders” currently use dexamphetamines and benzodiazepines (chemical compounds used as anti-anxiety agents and muscle relaxants) in addition to heroin, cocaine/crack, street methadone, and morphine, and seven percent of all 14 year olds have tried amphetamines or speed (this figure includes illicit use of Ritalin or dexamphetamines).

I work as the coordinator of the Drug Free Ambassadors in Sydney, a drug educational program that is co-sponsored by Scientology churches throughout Australia and New Zealand. Humanitarian L. Ron Hubbard pointed out “…drugs set you up to get into situations which are truly disastrous and keep you that way.” It is my hope that through my work, and that of other dedicated volunteers and like-minded organizations, more and more youths will get the truth about these drugs and consider a drug-free life.



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