Insulin Utmost Care Needed.rtf

Not all side effects for insulin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

Applies to insulin: injectable liquid, injectable solution, subcutaneous suspension

Endocrine Hypoglycemia is the most common and serious side effect of insulin, occurring in approximately 16% of type 1 and 10% of type II diabetic patients (the incidence varies greatly depending on the populations studied, types of insulin therapy, etc). Although there are counterregulatory endocrinologic responses to hypoglycemia, some responses are decreased, inefficient, or absent in some patients. Severe hypoglycemia usually presents first as confusion, sweating, or tachycardia, and can result in coma, seizures, cardiac arrhythmias, neurological deficits, and death. Blood or urine glucose monitoring is recommended in patients who are at risk of hypoglycemia or who do not recognize the signs and symptoms of hypoglycemia. The risk for developing hypoglycemia is higher in patients receiving intensive or continuous infusion insulin therapy. The association between insulin and dyslipidemia is currently being evaluated.[Ref]

Permanent neuropsychological impairment has been associated with recurrent episodes of severe hypoglycemia. In one retrospective study of 600 randomly selected patients with insulin-treated diabetes mellitus, the

only reliable predictors of severe hypoglycemia were a history of hypoglycemia, a history of hypoglycemia-related injury or convulsion, and the duration of insulin therapy. Those with a history of hypoglycemia had been treated with insulin for 17.4 years, which was significantly longer than the 14.3 years in the insulin-treated patients without a history of hypoglycemia.

Human insulin does not appear to be associated with hypoglycemic episodes more often than animal insulin. Caution is recommended when switching from animal (either bovine or pork) to purified porcine insulin or biosynthetic human insulin, however, because of increased potency or bioavailability.[Ref]

Ocular An unusual ocular disturbance during the beginning of therapy is bilateral presyopia (blurry vision). This is thought to be due to changes in the osmotic equilibrium between the lens and the ocular fluids, and is usually self-limited. Dermatologic Dermatologic reactions to insulin can result in lipohypertrophy (insulin is lipogenic) or lipoatrophy (probably immunologically-mediated). The incidence of lipoatrophy is markedly decreased with the use of purer forms of pork insulin or biosynthetic human insulin and when injection sites are alternated. Without proper hygiene, subcutaneous insulin injections may be complicated by infection.[Ref] Hypersensitivity Hypersensitivity reactions--either local or systemic--are becoming rare (less than 1% of patients) due to the use of purer forms of pork insulin or biosynthetic human insulin. Local reactions may present as erythema, swelling, heat, or subcutaneous nodules. They usually occur within the first two weeks of therapy, then disappear. True allergy to insulin is rare, and sensitization is usually associated with specific animal proteins in bovine and less pure forms of porcine insulins.[Ref] A diabetic patient with true allergy to insulin can undergo desensitization. Desensitization kits and protocols are available from some insulin manufacturers.[Ref] Immunologic Immunologic responses to insulin, particularly animal insulin formulations, include the formation of antiinsulin antibodies. The presence of these antibodies causes the elimination half-life of insulin to increase. Immunologic analysis of anaphylaxis to some insulin preparations in some cases has revealed markedly elevated serum levels of lgE and lgG to protamine, but not to regular insulin.[Ref] Cardiovascular

The cardiovascular consequences of hyperinsulinemia are being evaluated. Given the high frequency of both microvascular and macrovascular diseases in patients with diabetes, some experts are evaluating insulin as a possible atherogenic agent. Controversy and continued study surround the role of hyperinsulinemia as the precursor of hypertension.

Other cardiovascular risk factors that are accentuated in persons with carbohydrate intolerance and hypertension include abnormalities in platelet function, clotting factors, the fibrinolytic system, and dyslipidemia. The relationship between diabetes, insulin, and these disorders is currently under investigation. Insulin may contribute to the pathogenesis of hypertension by stimulating the sympathetic nervous system, promoting renal sodium retention, and/or stimulating vascular smooth muscle hypertrophy. It may induce dyslipidemia by promoting hepatic synthesis of very low density lipoproteins (VLDLs). Insulin may stimulate heart rate in the absence of hypoglycemia.[Ref] General General weight gain is associated with insulin use, sometimes presenting as edema associated with abrupt restoration of glucose control in a patient whose control was previously poor. Weight gain may be due to more efficient use of calories during insulin therapy, suggesting additional benefits of dietary and exercise modifications. Patients on intensive insulin therapy may be more likely to experience weight gain.[Ref] Intensive insulin therapy causes an increase in body fat as a result of the elimination of glycosuria and reduction in 24-hour energy expenditure. The reduction in 24-h energy expenditure is the result of an insulin-associated decrease in triglyceride/free fatty acid cycling and nonoxidative glucose and protein metabolism.[Ref] Metabolic The metabolic side effects of insulin therapy may be particularly important in patients who are being treated for diabetic ketoacidosis (DKA). Insulin increases the intracellular transport of phosphate, which often results in hypophosphatemia during treatment of DKA. Hypokalemia and hypomagnesemia have been associated with DKA, and may be due to insulin.[Ref] Rare cases of hypophosphatemia have been associated with the use of glucose, insulin, and potassium infusions during the treatment of myocardial infarction.[Ref] Renal The renal effects from insulin-induced hypoglycemia include significantly decreased renal plasma flow, glomerular filtration rate, and significantly increased urinary albumin excretion rate. These changes are reversible upon resolution of hypoglycemia.

Hypoglycemia is associated with increased plasma dopamine, epinephrine, and plasma renin activity. Acute changes in renal function during insulin-induced hypoglycemia, therefore, may result from direct stimulation of the efferent sympathetic nerves to the kidney and hormonal counterregulatory mechanisms. Hematologic The effects of insulin-induced hypoglycemia on hemostasis may explain some of the clinical observations of embolic phenomenon during treatment of diabetic ketoacidosis.

Limited data show that diabetics have a significantly lower basal concentration of tissue plasminogen activator.[Ref]

The hematologic effects from insulin-induced hypoglycemia include an enhanced increase in the concentration of von Willebrand factor. Increased von Willebrand factor, combined with hypoglycemiaassociated decreased plasma volume and increased plasma viscosity, may predispose patients to reduced peripheral perfusion or embolic phenomenon. A single case of insulin-induced hemolytic anemia has been reported.[Ref]

Gastrointestinal Rare cases of gastrointestinal distress have been associated with insulin. GI distress tends to resolve with dose reduction.[Ref]

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The Pharmaceutical industry in India is valued at Rs. 90,000 Crore and is growing at the rate of 12 – 14 % per annum. Exports are growing at 25 % Compound Annual Growth Rate (CAGR) every year. The total export of Pharma products is to the extent of Rs. 40,000 Crore. India is now being recognized as the ‘Global pharmacy of Generic Drugs’ & has distinction of providing generic quality drugs at affordable

cost. India is also emerging rapidly as a hub of Global Clinical trials & a destination for Drug Discovery & Development.

Further, more & more new drugs are being introduced into the country which include New Chemical Entities (NCE), high tech pharma products, vaccines as well as new dosage forms, new routes of drug administrations and new therapeutic claims of existing drugs. This is reflected in the fact that total number of applications received & processed have more than doubled from around 10,000 in the Year 2005 to 22,806 in Year 2009 at CDSCO, HQ, New Delhi.This includes increase in New Drug Applications, Global Clinical Trials , Market Authorization of Vaccine & Biotech products from 1200 ,100 ,10 in Year 2005 to 1753, 262 & 137 in the Year 2009 respectively.

Such rapid induction of NCEs and high tech Pharma products in the market throw up the challenges of monitoring Adverse Drug Reactions (ADRs) over large population base.

All medicines (pharmaceuticals and vaccines) have side effects. Some of these side effects are known, while many are still unknown even though that medicine has been in clinical use for several years. It is important to monitor both the known and hitherto unknown side effects of medicines in order to determine any new information available in relation to their safety profile. In a vast country like India with a population of over 1.2 Billion with vast ethnic variability, different disease prevalence patterns, practice of different systems of medicines, different socioeconomic status, it is important to have a standardized and robust pharmacovigilance and drug safety monitoring programme for the nation. Collecting this information in a systematic manner and analyzing the data to reach a meaningful conclusion on the continued use of these medicines is the rationale to institute this program for India.

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Prescription Drug Deaths Increase Dramatically A growing number of overdoses of legal opioids, sedatives and tranquilizers led to a 65 percent increase in hospitalizations over seven years By Katherine Harmon | April 6, 2010 prescription drugs painkillers deaths overdose ISTOCKPHOTO/ZUZLIK The number of deaths and hospitalizations caused by prescription drugs has risen precipitously in the past decade, with overdoses of pain medications, in particular opioids, sedatives and tranquilizers, more than doubling between 1999 and 2006, according to a new study.

In fact, by 2006, overdoses of opioid analgesics alone (a class of pain relievers that includes morphine and methadone) were already causing more deaths than overdoses of cocaine and heroin combined.

"Teens and others have different attitudes in using these drugs," often presuming the prescription substances are safer and less addictive than illegal drugs such as cocaine or heroin, says Jeffrey Coben, a professor of emergency and community medicine at the West Virginia University School of Medicine in Morgantown and lead author of the new study. "I think that's a false assumption. Aside from the fact they can be taken orally rather than injected…[many prescription drugs] really are every bit as powerful,

addictive and dangerous as heroin," he notes, adding that, "when you combine them with other sedatives, that mix can become particularly lethal."

Using data collected by the Nationwide Inpatient Sample, which gathers hospital patient information for about 8 million people every year, Coben and his colleagues were able to assess what drugs were implicated in the majority of poisonings—and in many cases whether the poisonings were intentional or not. The team selected opioids, sedatives and tranquilizers as the focus of the analysis because these substances are "contributing the majority of prescription drug overdose deaths," Coben says. These categories of prescription drugs can kill and injure people by suppressing breathing, depriving the body of oxygen.

For prescription opioids, sedatives and tranquilizers—commonly prescribed for pain management—the number of hospitalizations for poisonings increased 65 percent between 1999 and 2006 (the first and last years, respectively, for which data were comparable and collected). The number of hospitalizations for all poisonings, including illegal drugs, other prescription medications and miscellaneous substances, increased during this time period as well, but that jump (33 percent) was about half the rate of those for the prescription pain drugs.

Unintentional poisonings from these drugs climbed 37 percent during the seven-year period, the researchers found. Intentional overdoses, in which people meant to inflict self-harm or death, jumped 130 percent (a far cry more than the 53 percent increase of intentional poisoning from other substances in the same time period). Intent was not listed in all cases and can be subject to reporting error. The results are detailed online April 6 in the American Journal of Preventive Medicine.

No accident Poisonings, from prescription drugs and other substances, are classified in medical records as injurious or accidental deaths. But regardless of whether the incidents are listed as unintentional or intentional, they are rarely true mistakes, noted Leonard Paulozzi, a medical epidemiologist with the U.S. Centers for Disease Control and Prevention, in congressional testimony in 2007. "Most unintentional drug poisoning deaths are not 'accidents' caused by toddlers or the elderly taking too much medication," he noted. "These deaths are largely due to the misuse and abuse of prescription drugs."

Accidents overall were the fifth most common cause of death in the U.S. as of 2005 (accounting for 117,809 deaths—4.8 percent—that year), according to the National Vital Statistics Report [pdf]. Of injury

deaths, poisoning is the second most common cause of death in the U.S., having doubled between 1985 and 2004, according to a 2007 Department of Health and Human Services analysis [pdf]. Among people 35 to 54 years old, poisoning is the most common accidental death—even more so than auto-related deaths.

Many experts think that the sheer prevalence of many of these drugs recently has contributed to the drastic increase in poisonings. Although growing illegal markets and distribution of these drugs might be a driving factor in their increasingly large role in poisonings and deaths, perfectly legal prescriptions are probably playing a role as well, Coben says.

"I think the whole issue of the availability of these drugs and whether they're being over-prescribed" should be investigated, says Susan Baker, a professor at Johns Hopkins Center for Injury Research and Policy, who was not involved in the new study but coauthored a 2009 report in the same journal about recent trends in injury mortality.

Many people do rely on pharmacological treatment for withdrawal, anxiety or chronic pain, but when communities have access to an overabundance of these medications, abuse appears to become more likely. If doctors prescribe too much medication or too many refills, excess drugs "are going to be sitting in people's medicine cabinets for someone else to take advantage of," Baker explains. For example, methadone poisonings were four times as frequent in 2006 as they were in 1999, a time period during which retail sales grew more than 1,000 percent, Coben and his team found.

Antidote unknown Although the new report details the stark increase in the reported poisoning data, the true number of deaths and hospitalizations in which prescription drugs have played a role might be even higher, the researchers pointed out. The new analysis assessed cases only in which prescription drug overdose was listed as the primary diagnosis. Some prescription drug–related hospitalizations might be classified under other primary categories, and those who abuse the drugs were not always labeled as having been poisoned. Additionally, the researchers explained, many common terms such as overdose, misuse and abuse are not well standardized in hospitals.

"I don't have any sense that it's getting any better," Coben says. With drug companies reporting strong overall sales (including a 5.1 percent increase in U.S. sales in 2009 to $300.3 billion for 3.9 billion individual retail prescriptions), in fact, the problem might be getting worse.

The researchers noted that the details surrounding these hundreds of thousands of overdoses are unknown. The medical data used for the analysis did not include full toxicology reports that would reveal drug-drug interactions. And although the researchers found that the majority of the people hospitalized for poisoning with these prescription drugs were women, they did not have enough other demographic data to propose possible reasons for the overdose increases.

"What we really need is something other than the coded data," Baker says. She notes that researchers need to know more about the circumstances in which people are overdosing before effective prevention measures can be put into place.

"There's a need to have informational interviews with people who have had overdoses and survived them," Coben says. He hopes that future research will "raise some opportunities for interventions with these people."

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Comments

LindaSW April 6, 2010, 6:22 AM Great article. Given the 2006 ONDCP mandate to reduce prescription drug 'abuse' by 15% by 2008, I would say we, as a s asociety, have failed. Indeed, poisonings are one horrible consequence, but there are so many others -- addiction, trauma, DUI, loss of productivity, medical and social costs -- yet we as a society spend much of our resources on the lesser used substances of use -- cocaine, heroin, meth. There's no one solution, but perhaps reducing the sheer availability at the point of the prescriber -- are a month's worth of CII opioids really necessary for a tooth extraction? what IS the evidence for prescribing opioids for arthritis? lower back pain?

Of course, at the other end, treatment for addictions of all kinds is inadequate, and even more so in the new economy. Linda Simoni-Wastila Report as Abuse | Link to This Richieo April 6, 2010, 8:54 AM Reducing the availability of legal drugs will not cure the problem, it will only send it to the black market... Report as Abuse | Link to This candide April 6, 2010, 10:08 AM Education is the answer. For example, APAP (acetaminophen - Tylenol, most of Vicodin) can easily be taken to overdose levels (destroys the liver), yet most people do not know this. Report as Abuse | Link to This jgrosay April 6, 2010, 6:56 PM Drugs do produce harm sometimes as they are active products, not inert dummys such a placebo, and this is the reason why you have to work long and hard to obtain a permit to write prescriptions from Health Regulatory Authorities. If you endorse a situation as in Spain, where pharmacists do openly sell almost all prescription only drugs under the sole buyer request; who has the moral strenght to discourage people from bought and use of addiction drugs, and end as in the China under british rule, when they were several million opium dependents? Report as Abuse | Link to This Hermit April 6, 2010, 8:38 PM 1) How many OD's included alcohol? "DO NOT USE WITH ALCOHOL" is printed under,"Warnings." 2) How many doctors who know their patients can't tell hypochondriacs and recreational users from real sufferers of pain? My doctor says he can see it in my face. 3) How many severe pain sufferers have lived in agony after being denied pain relief because some stranger misintrepreted their desperate plea for relief as drug withdrawel (which may have also been included?) 4) How many OD's would occurr if realistic drug education included how to use drugs (alcohol too, if you're going to use it) more safely and sanely rather than the archaic religious message of, "Just Say No." When an unaccountable military government agency gets to make it's own rules and set it's own budget

and keep confiscated property of the disobedient, it is a rogue agency. Without health or safety data they are selling fear of substances in replacement of a system where adults make those decisions and learn to handle or avoid problems. Report as Abuse | Link to This Hermit April 6, 2010, 8:50 PM 1) How many OD's included alcohol? "DO NOT USE WITH ALCOHOL" is printed under,"Warnings." 2) How many doctors who know their patients can't tell hypochondriacs and recreational users from real sufferers of pain? My doctor says he can see it in my face. 3) How many severe pain sufferers have lived in agony after being denied pain relief because some stranger misinterpreted their desperate plea for pain relief as drug withdrawal (which may have also been included?) 4) How many OD's would occur if realistic drug education included how to use drugs (alcohol too, if you're going to use it) more safely and sanely rather than the archaic religious message of, "Just Say No?" When an unaccountable military government agency gets to make it's own rules and set it's own budget and keep confiscated property of the disobedient, it is a rogue agency. Without health or safety data they are selling fear of substances in replacement of a system where adults make those decisions and learn to handle or avoid their own problems. Prohibition creates the problems and then milks us for money to "solve" them by assaulting our own citizens. What a racket. Report as Abuse | Link to This Wizard April 7, 2010, 1:39 AM When we will realize that the "science" of medicine defined efficacy of treatment by the elimination or reduction in specific symptoms, even if these symptoms are themselves defenses of the body. This "efficacy" is akin to unscrewing a warning light in your car and asserted that you've a "scientifically proven" method of treating cars that are sick. "Side effects" are not really "side effects." They are the result of the effective suppression of a symptom and of the disease, creating a more serious illness. An increase in death rates is totally predictable...and will be getting worse as a result of an increase in polypharmacy. Report as Abuse | Link to This l.kost April 7, 2010, 5:07 AM

around the ansyogen break in your life, regressive's effect of cannabis use can delivery in the time, ecocerebral time-defect or progressive delucidation... Report as Abuse | Link to This jack.123 April 7, 2010, 7:13 AM Did any body notice if the ones that overdosed were the ones prescribed the medication?People lIke myself who have cronic pain don't abuse ,because when you over use there isn't enough left for when you need it,being given just enough to subdue the pain is is the usual treatment,the pain isn't gone just reduced so it becomes bearable,people stealing these kind of drugs don't understand that the pain doesn't stop completely and keep taking more untill an overdose happens.You must keep theses kind of drugs under lock and key to protect freinds and family who don't unerstand the dangers!!! Report as Abuse | Link to This pyramus33 April 7, 2010, 8:20 AM Many people who suffer from chronic pain do not "abuse" the prescription drugs but they are at very high risk of becoming dependant on these pain killers. What I don't understand is how the government can continue to label marijuana users as criminals and the dealers that supply these users as scumbags when studies such as this show how extremely harmful the drugs the government is selling can be. Even today many senior politicians in the U.S still refuse to agree with the legalization of medicinal marijuana because they say we have "less harmful alternatives". Really? These drugs are less harmful or habit forming then marijuana? If so, why are many people going through rapid detoxification processes just to get off these "safe" drugs? The most recent example of this arrogance in the media was senator John McKain during the 2008 election. I think it's time we looked at some of these prescription drugs and decided what should be classified as truly harmful. I can still remember a number of years ago when pharmacies were being broken into almost every week by oxycontin addicts. Report as Abuse | Link to This

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