Natural Solution for Diabetes

The Big Diabetes Lie

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The Big Diabetes Lie Summary

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Inhaled Insulin System Safety

All reports published regarding pulmonary function with inhaled insulin, regardless of the system, have shown a small decline from baseline and was comparable to SC insulin delivery (39,42,43,47,51-53). In studies investigating Exubera, patients with T1DM who received inhaled insulin experienced a statistically significant decline in DLCO and a non-significant decrease in FEV1 compared to those patients randomized to SC insulin (Fig. 9) (42,43,60). Although there was a statistically significant decrease in DLCO there were no clinical manifestations and was deemed not clinically significant (42,43). This decline occurred within 2 weeks after insulin initiation and did not progress any further (60). Moreover, patients who did not receive inhaled insulin had a small decline in lung function over time (60). Studies with Exubera, AERx, and AIR systems agree that changes in lung function are not clinically significant and reversible upon treatment discontinuation (42,51-53). Thoracic high...

Patient Satisfaction And Insulin Resistance

Insulin therapy continues to be the cornerstone of treatment in T1DM, but is underutilized in the treatment of T2DM. Some investigators believe that multiple daily injections of insulin are disliked by patients and are partly responsible for patients not reaching goal (15,16). This demonstrated resistance to the implementation or administration of insulin therapy has been well documented. Often the reasons cited by clinicians to delay insulin therapy include fear of patient loss from practice, lack of time to implement, and clinical inertia, or the wait and see approach. Patient's reasons for delaying insulin therapy include the frequent asymptomatic course of diabetes, patient refusal to follow directions, and importantly, injections and hypoglycemia (15,16,693). Thus, inhaled insulin may help to overcome some of these concerns. In a study of theoretical treatment choices in inadequately controlled T2DM individuals, subjects were more likely to choose insulin therapy when the insulin...

Antidiabetic Activity

Noninsulin-dependent diabetes mellitus is one of the most common disorders worldwide 42 . It is a group of metabolic disorders characterized by hyperglycemia. The metabolic disorders include alterations in the carbohydrate, fat, and protein metabolism associated with absolute or relative deficiencies in insulin secretion and or insulin action. Along with hyperglycemia and abnormalities in serum lipids 43 , diabetes is associated with microvascular and macrovascular complications, which constitute the main cause of morbidity and mortality of diabetic patients 44 . The prevention of diabetes is an urgent worldwide public health concern. Obesity and insulin resistance induced by overeating and physical inactivity typically characterizes the period preceding onset of type 2 diabetes. Shigeta et al. 62 have shown that caloric restriction and physical exercise have obvious importance. They stress that actively promoting healthy eating and sleeping habits should be considered for the...

Summary Drug Table Insulin Preparations

TYPES OF INSULIN Rapid-Acting Insulins insulin injection (regular) insulin lispro (insulin analog) insulin aspart solution (insulin analog) Intermediate-Acting Insulin isophane insulin suspension (NPH) insulin zinc suspension (Lente) Long-Acting Insulins Insulin glargine solution extended insulin zinc suspension (Ultralente) Mixed Insulins isophane insulin suspension and insulin injections (NPH) isophane insulin suspension and insulin injection High-Potency Insulin insulin injection concentrated insulin injection concentrated

Oral Antidiabetic Drugs

The oral antidiabetic drugs are used to treat patients with type 2 diabetes that is not controlled by diet and exercise alone. These drugs are not effective for treating type 1 diabetes. Five types of oral antidiabetic drugs are currently in use Additional drugs are listed in the Summary Drug Table Antidiabetic Drugs.

Uses Of The Antidiabetic Drugs

The oral antidiabetic drugs are of value only in the treatment of patients with type 2 (NIDDM) diabetes mellitus whose condition cannot be controlled by diet alone. These drugs may also be used with insulin in the management of some patients with diabetes mellitus. Use of an oral antidiabetic drug with insulin may decrease the insulin dosage in some individuals. Two oral antidiabetic drugs (eg, a sulfonylurea and metformin) may also be used together when one antidiabetic drug and diet do not control blood glucose levels in type 2 diabetes melli-tus. Figure 49-3 is a pharmacological algorithm indicating the appropriate medication regimen for type 2 diabetes mellitus.

Summary Drug Table Antidiabetic Drugs Continued

Type 2 diabetes with a sulfonylurea or insulin to improve glycemic control Type 2 diabetes in combination with metformin to improve glycemic control Type 2 diabetes in combination with metformin to improve glycemic control Type 2 diabetes with sulfonylurea, metformin, or insulin to improve glycemic control Type 2 diabetes in combination with metformin to improve glycemic control Headache, pain, myalgia, aggravated diabetes, infections, fatigue Antidiabetic Combination Drugs Type 2 diabetes Other initial monotherapy options Acarbose Miglitol Pioglitazone Rosiglitazone Repaglinide Insulin Other combination options Metformin or a Sulfonylurea plus Acarbose Miglitol, or Pioglitazone Rosiglitazone or Repaglinide (with metformin), or Insulin Add intermediate bedtime insulin or add third oral agent or switch to insulin monotherapy or refer to specialist *If initial presentation with fasting glucose > 260 mg dL is a symptomatic patient, consider insulin as initial intervention. Preferred in...

See also Insulin General Information

Insulin aspart is a rapid-acting synthetic insulin in which proline is replaced by aspartate at position 28 in the B chain. Insulin aspart has been reviewed (1). Its adverse effects do not differ from those of soluble human insulin and it has a similar effect on the blood glucose concentration (2). A new development is the binding of two 9-fluorenylmethoxy-carbonyl moieties to two amino acids in the structure of aspart insulin, phenylalanine and lysine (3). This compound has no biological activity but gradually releases its groups and keeps diabetic animals in a good metabolic state over 2-3 days. Experiments in humans have not yet been reported. Aspart insulin and biphasic insulin aspart (30 soluble rapid-acting insulin and 70 protamine-bound aspart insulin) have been reviewed (4).

Insulinlike growth factor IGFI

Griffin ME, Feder A, Tamborlane WV. Lipoatrophy associated with lispro insulin in insulin pump therapy an old complication, a new cause Diabetes Care 2001 24(1) 174. 29. Ampudia-Blasco FJ, Hasbum B, Carmena R. A new case of lipoatrophy with lispro insulin in insulin pump therapy is there any insulin preparation free of complications Diabetes Care 2003 26(3) 953-4. 30. Fineberg SE, Huang J, Brunelle R, Gulliya KS, Anderson JH Jr. Effect of long-term exposure to insulin lispro on the induction of antibody response in patients with type 1 or type 2 diabetes. Diabetes Care 2003 26(1) 89-96. 31. Kitzmiller JL, Main E, Ward B, Theiss T, Peterson DL. Insulin lispro and the development of proliferative diabetic retinopathy during pregnancy. Diabetes Care 1999 22(5) 874-6. 32. Jovanovic L, Ilic S, Pettitt DJ, Hugo K, Gutierrez M, Bowsher RR, Bastyr EJ 3rd. Metabolic and immunologic effects of insulin lispro in gestational diabetes. Diabetes Care 1999 22(9) 1422-7. 33. Tupola S, Komulainen...

Modes of administration of insulin R

The American Diabetes Association has published revised guidelines on insulin administration, including storage of insulin, use and reuse of needles, alternatives to syringes, injection techniques, and patient management related to dosing of insulin, self-monitoring, and hypo-glycemia (34S). Developments in the administration of insulin through the skin, the mouth, the nose, and the lung have been reviewed (35R).

Insulin and Hypoglycemic Agents

Repaglinide Nateglinide

2.1 Insulin and Its Analogs, 4 2.2 Insulinotropic Agents, 11 2.3 Insulin-Sensitizing Agents, 20 Insulin is a 58-kDa polypeptide hormone produced by p-cellsin pancreatic islets of Langerhans regulating, in vivo, the storage, release, and utilization of nutrient energy, carbohydrate in the form of glucose, fat, and protein, in response to changing supply and demand. Pancreatic j3-cells respond to an increase in circulating levels of glucose as occurs after ingestion of a meal by increasing the rate of insulin release. The major metabolic actions of insulin include the following (1)promotion of uptake and storage of glucose in liver and muscle in the form of glycogen, (2) suppression of hepatic glycogenolysis and gluconeo-genesis, (3) increasing the rate of glucose oxidation in muscle, (4) suppression of lipolysis and release of fatty acid from adipose tissue, (5)enhancing triglyceride synthesis and storage and de novo lipogenesis from carbohydrate in liver and fat, and ( promotion of...

Experimental Antidiabetic Plants

Various studies have been undertaken in different regions of Morocco in order to select and classify the main medicinal plants used to treat diabetes. Ziyyat et al. 63 conducted an ethnomedical study in eastern Morocco on plants used for diabetes and hypertension and an inventory of 42 plants used has been established. For diabetes, 38 species have been reported the most used were Trigonella foenum-grae-cum (Leguminosae), Globularia alypum (Globulariacea), Artemisia herba-alba (Compositae), Citrullus colocynthis (Cucurbitaceae), and Tetraclinis articulata (Cu-pressaceae). Three of these species, namely Artemisia herba-alba, Tetraclinis articulata, and Trigonella foenum-graecum are also used for hypertension, which suggests a relationship between hypertension and diabetes. Bnouham et al. 64 examined antidiabetic effect of an aqueous extract of the aerial parts of Urtica dioica (nettle), a plant used in eastern Morocco for both diabetes and hypertension, on hyperglycemia induced by oral...

Ideal Pulmonary Delivery of Insulin

The concept of inhaled insulin was first introduced in 1925 where it was studied in five diabetic patients (18). Variability in bioavailability and system portability made pulmonary insulin delivery at the time unfeasible. Interest in pulmonary delivery resurfaced in the 1970s and 1980s in the clinical setting (19). With the advancements in drug delivery technology, the pulmonary delivery of insulin became more viable. Pulmonary delivery of insulin is ideal due to the large surface area of the lung available for absorption (up to 100 m2) having high permeability at the alveolar surface, and a vast circulation. However, the lung prohibits deep penetration Table 1 Available or Developing Inhaled Insulin Products

Insulin and Synthetic Hypoglycemic Agents

Drugs used for lowering the glucose level in the blood are called hypoglycemic agents. Likewise, substances that raise the level of glucose in the blood are called hyperglycemic agents. Changes in the level of glucose in the blood can be caused by various reasons, the primary cause being diabetes mellitus. Diabetes mellitus is a metabolic disease associated with a high level of blood sugar and as a rule, disturbance of carbohydrate, lipid, and protein metabolism. The most common biochemical condition in diabetes mellitus is ketoacidosis. Insulin and other hypoglycemic agents are used to treat diabetes mellitus. Depending on the condition of the organism, diabetes is classified into two types. Insulindependant (type I), in which there is suppression of endogenous insulin production by the organism itself, and insulin-independent (type II), which results either because of insufficient insulin production, or because of a breakdown of insulin receptors, which is usually a result of other...

Lente Insulin Is A Nursing Alert

Lente Insulin

Insulin requirements may change when the patient experiences any form of stress and with any illness, particularly illnesses resulting in nausea and vomiting. Insulin is ordered by the generic name (insulin zinc suspension, extended) or the trade (brand) name (Humulin U) (see the Summary Drug Table Insulin Preparations). The nurse must never substitute one brand of insulin for another unless the substitution is approved by the health care provider because some patients may be sensitive to changes in brands of insulin. In addition, it is important never to substitute one type of insulin for another. For example, do not use insulin zinc suspension instead of the prescribed prota-mine zinc insulin. Care must be taken when giving insulin to use the correct insulin. Names and packaging are similar and can easily be confused. The nurse carefully reads all drug labels before preparing any insulin preparation. For example, Humalog (insulin lispro) and Humulin R (regular human insulin) are...

Insulin thiazolidinediones

Insulin plus metformin (27 patients, 2000 mg day) or troglitazone (30 patients, 600 mg day) in patients with type 2 diabetes using at least 30 U day was compared with insulin alone (30 patients) for 4 months (42). Body weight increased in the insulin and the insulin plus trogli-tazone groups. In the insulin plus metformin group there were significantly more gastrointestinal adverse effects but less hypoglycemia than the other groups. The addition of rosiglitazone to insulin for 26 weeks in a double-blind study in 315 patients with inadequately controlled type 2 diabetes improved glycemic control and was well tolerated (43). There was a significant fall in hemoglobin, and some patients in both the rosiglita-zone and placebo groups developed edema.

Diabetes mellitus and pregnancy

Diabetes mellitus is the collective name for heterogeneous disturbances of metabolism which all are characterized by chronic hyperglycemia. In essence, there are three different types. While type I is caused by a disturbed secretion of insulin, type II and gestational diabetes are characterized by a disturbed action of insulin. Both causes can also occur simultaneously. A poor glyccmic control in prcgestational diabetes, as measured by glycosylated hemoglobin (HbAlc > 6.5 ), is correlated with an increased risk of major congenital malformations. HbAlc is a parameter for the blood glucose concentration of the last 120 days, the survival time of erythrocytes it can also be referred to as the blood sugar memory. The higher the concentration of HbAlc, the higher the statistically confirmed rate of malformations an HbAlc of 8.5 is correlated with a malformation rate of 4 an HbAlc of 10.5 has a risk for abnormalities of 6 . The most common birth defects are anomalies of the spine and...

Insulin and oral antidiabetics

Insulin as a proteohormone does not reach the mother's milk, and is not absorbed intestinally. Any effect on the infant can therefore be ruled out. There are no data on the other oral antidiabetics, acarbose, gli-bornuride, gliclazide, glimepiride, gliquidone, glisoxepide, miglitol, pioglitazone, repaglinide, and rosiglitazone. Recommendation, insulin and metformin are not problems during breastfeeding. Glibenclamide may also be taken however, the infant should be observed for symptoms of hypoglycemia after the start of therapy. Other oral antidiabetic should not be taken, but single doses do not require any limitation of breastfeeding.

A10Drugs Used in Diabetes

It has been well proven that there is a higher prevalence of erectile dysfunction in diabetic men than in non-diabetic men. The figures of the odds ratio vary between 1.04 and 6.97. In most studies the confidence interval does not include 1.0, i.e. there is a significant difference. Only one study has found no increase of the risk with medication of antidiabetics. The incidence of erectile dysfunction increases with the duration of the disease a 10 higher risk was calculated with each year of duration of diabetes, and it was even higher in combination with depression and cardiac disease. In a duration of diabetes > 5 years 56 of men had erectile dysfunction, and 72 of men with > 20 years of diabetes. On the other hand, the prevalence of diabetes mellitus in men with erectile dysfunction was significantly higher than in a control group of non-impotent men.

Insulin biguanides

Metformin was given as an adjunct to insulin in a double-blind, placebo-controlled study in 28 adolescents needing more than 1 U kg day (19). The dose of metformin was 1000mg day when body weight was under 50 kg, 1500 mg day when it was 50-75 kg, and 2000 mg day when it was over 75 kg. Metformin lowered insulin requirements. The number of episodes of hypoglycemia increased compared with placebo. There was gastrointestinal discomfort in six patients taking metformin and five taking placebo. A comparable placebo-controlled study was reported in 353 patients with type 2 diabetes for 48 weeks. All were taking insulin, and HbA1c fell in those who also took metformin. Body weight was reduced by 0.4 kg by metformin and increased by 1.2 kg by placebo. Symptomatic episodes of hypoglycemia were more common with met-formin. There were mild transient gastrointestinal complaints in 56 and 13 respectively (20). Insulin plus metformin (27 patients, 2000 mg day) or troglitazone (30 patients, 600 mg...

Inhaled Insulin

Insulin is a polypeptide that is denatured in the gastrointestinal tract when taken orally therefore, parenteral administration is necessary. Patients are required to receive multiple doses of insulin either subcutaneously or intravenously. Since the introduction of insulin therapy, alternative delivery routes and systems have been investigated. Pulmonary delivery is attractive because insulin is permeable at the level of the alveoli. In January 2006, an inhaled dry powder formulation of fast-acting insulin was approved in the United States and Europe for the treatment of type 1 and 2 diabetes in adults (17). There are several other insulin inhalational systems under various stages of development (Table 1). Differences between these systems include formulation, particle size, and delivery device. This chapter will review the ideal delivery, differing delivery systems, pharmacodynamic, pharmacokinetics, efficacy, and safety of inhaled insulin.

Insulin Antibodies

Delivery of insulin to the pulmonary mucosa could induce an immune or allergic reaction which may have safety implications. A large meta-analysis with the Exubera system showed higher insulin antibody levels with inhaled insulin versus comparator therapies (61). The same holds true with the AERx system in one clinical study (52). These increases in insulin antibodies had no significant effect on insulin pharmacokinetics, glucodynamics, glucose control, or safety profile (61). No insulin antibodies were observed with the Technosphere Insulin technology (62) and no data is available for the AIR system.

Insulin

Insulin is a hormone manufactured by the beta cells of the pancreas. It is the principal hormone required for the proper use of glucose (carbohydrate) by the body. Insulin also controls the storage and utilization of amino acids and fatty acids. Insulin lowers blood glucose levels by inhibiting glucose production by the liver. Insulin is available as purified extracts from beef and pork pancreas and is biologically similar to human insulin. However, these animal source insulins are used less frequently today than in years past. They are being replaced by synthetic insulins, including human insulin or insulin analogs. Human insulin is derived from a biosynthetic process using strains of Escherichia coli (recombinant DNA, rDNA). Human insulin appears to cause fewer allergic reactions than does insulin obtained from animal sources. Insulin analogs, insulin lispro, and insulin aspart are newer forms of human insulin made by using recombinant DNA technology and are structurally similar to...

Oral antidiabetics

Oral antidiabetics are not hormones and do not work in the way that insulin does they are not substitutes. The most commonly used sulfonylurea derivatives merely stimulate those ,i-cells in the pancreas that still have the ability to function. Among these medications arc the second-generation sulfonylureas glibenchamide (glyburide), glibor-nuride, gliclazide, glimepiride, glipizide, gliquidone, and glisoxepide. First-generation sulfonylureas are acetohexamide, chlorpropamide, tolazamide, and tolbutamide. Acarbose and miglitol, as glucosidase inhibitors, inhibit carbohydrate absorption in the intestine - a controversial therapy for diabetes. Nateglinide and repaglinide regulate postprandial blood sugar by a short increase in insulin secretion from the -cells. Pioglitazone and rosiglitazone increase the sensitivity to insulin. Muraglitazar belongs to the same group, but results of studies have shown an increased risk for serious cardiovascular adverse effects, so there is no approval by...

Insulin meglitinides

In 80 patients taking metformin 850 or 1000 mg tds plus NPH insulin at bedtime, metformin was withdrawn and repaglinide 4 mg tds added in half of the patients for 16 weeks (37). In the repaglinide group the dose of insulin increased slightly and weight gain was 1.8 kg more. Mild hypoglycemia occurred more often in the metformin group nightly episodes of hypoglycemia occurred only with repaglinide. One patient taking repaglinide had a myocardial infarction, and one had three separate hospitalizations for chest pain (myocardial infarction was excluded). No specific data were presented about gastrointestinal adverse effects or infections.

Drugs and Diabetes

Diabetes mellitus is a chronic disease whose characteristics include defects in the metabolism (or utilization) of insulin, carbohydrate, fat, and proteins. The structure and functions of blood vessels are also adversely affected as the disease progresses. To consider diabetes only as a pancreatic endocrine disease is an oversimplification. The pancreatic cells known as islets of Langerhans found throughout the gland produce at least four hormones. The largest proportion of islet cells are the beta cells that produce insulin (actually proinsulin and C-peptide see later). The alpha cells, representing about one-fifth of the islet cells, produce proglucagon and glucagon, which is a hyperglycemic factor. Its function is to mobilize glycogen stores. The delta cells produce the hormone somatostatin, which is sometimes referred to as the universal secretory cell inhibitor. It is also produced in and secreted by the hypothalamus. Finally, a small number of islet cells produce pancreatic...

Aspart insulin

The new short-acting insulin aspart has been reviewed (24M). Its adverse effects do not differ from those of human insulin. Immunologic When short-acting insulins are given to patients who are allergic to regular insulin the allergic reactions can disappear. Although the short-acting insulins often have the same immunogenic epitopes, rapid dissociation of the fast-acting insulins into monomers can reduce their antigenic effects. Lispro insulin is known to be beneficial, and now this has also been reported for aspart insulin (25A). A 45-year-old man with type 2 diabetes treated with glibenclamide and metformin received combined chemotherapy for non-Hodgkin lymphoma and was given premixed insulin. He developed local wheal-and-flare reactions immediately after the injections. Skin prick tests were positive for various types of insulin but weakly positive for lispro and negative for insulin aspart. He tolerated aspart insulin without any allergic reactions.

Glargine insulin

The new long-acting insulin analogue glargine insulin has been reviewed (26M ). In general one daily injection gives more constant insulin concentrations and fewer nightly attacks of hypoglycemia than NPH insulin. Treatment satisfaction appeared to be constantly better with glargine in 517 patients (27C). There was a consistent mean reduction in the perceived Glargine and NPH-insulin have been compared in 349 children and adolescents in a multicenter, open, randomized study (28C). Besides the usual thrice-daily regimen of regular insulin they used either glargine at bedtime or NPH at bedtime or twice daily. HbA1c did not differ. The target for fasting blood glucose was 4.4-8.8 mmol l, and 5 more patients who used glargine reached the target (44 compared with 39 of the patients who used NPH). Symptomatic hypoglycemia was similar with the two treatments. In contrast to most long-acting formulations, glargine is a clear solution. Confusion with lispro insulin has been reported. A...

Antidiabetic Drugs

Cannabis increases appetite and so when taken regularly it may appear to reduce the effectiveness of antidiabetic medication by increasing carbohydrate intake. By contrast, a case of diabetic ketoacidosis supposedly caused by oral administration of cannabis has been described (Hughes et al., 1970). The patient exhibited the classic signs and symptoms of diabetic coma within 24 hours of eating an unspecified quantity of cannabis. The link with cannabis is exceedingly tenuous for the following reasons he had a family history of diabetes he had smoked cannabis before on numerous occasions without problems and he was still frankly diabetic, requiring insulin, one month after this event. The temporal link between florid symptoms of diabetes and the ingestion of cannabis was undoubtedly coincidental.

Ritalin And Insulin

Although many pediatricians believe that depriving a hyperactive child of Ritalin is similar to, say, depriving a diabetic of insulin, others find this metaphor faulty. Diabetes, they argue, is a physiological disease, whereas ADHD is a collection of behaviors without a known biological cause. Although diabetes is caused in part by the lack of insulin, the brains of children with ADHD cannot suffer from a lack of Ritalin. Unlike insulin, a hormone that naturally is produced in the body, Ritalin is an artificial drug. Step 1 Rule out medical problems as the cause of the observed symptoms. A physical examination of the child must be performed first to rule out many conditions whose symptoms could mimic ADHD. Among these conditions are vision and hearing problems, lead poisoning, thyroid problems, allergies, neurological problems, parasites, diabetes, and hypoglycemia. Taking some medications, such as those for asthma, could make a child fidgety or distracted.

The Truth about the Accurate Diagnosis

Although we may all think that we know what a diagnosis is, the term is actually used in a variety of different ways. Sometimes a diagnostic term describes the main symptom in a word derived from Latin or Greek, such as asthma (Greek for panting) or diabetes (Greek for to go through, and applied to disorders of excessive urination). Sometimes it's a term that describes the part of the body that isn't working correctly, such as heart failure or broken leg. Sometimes the term describes the cause of the illness, such as the flu, referring to the influenza virus. No matter where it comes from, however, the purpose of a diagnosis is to communicate the essential aspect of whatever ails a person.

Passage of drugs to the unborn and fetal kinetics

Transfer of drugs to the fetus is inevitable. Most drugs have a lower molecular weight than 600-800, and will therefore be able to cross the placenta. The notable exceptions to this rule are the conjugated steroid and peptide hormones such as insulin and growth hormone. However, larger molecules (e.g. vitamin B 2 and immunoglobulins) do cross the placenta via specific receptor-mediated processes. It should be noted that modified immunoglobulins used therapeutically, e.g. abciximab, do not cross the placenta but are metabolized by the placenta because they are only Fab fragments and do not have Fc terminals (see also Chapter 2.12 Miller 2003).

Dry Powder Inhalation

In addition, recent technological developments in spray drying and particle engineering have resulted in co-processed single dose DPI formulations combining, for example, a mixture of excipients (12) in the commercial insulin product, Exubra (Pfizer Nektar) (13), or by the addition of excipients which promote aerosolization efficiency through altering the particle physical morphology (14,15).

Diagnoses in Psychiatric Disorders

The pathogenesis of schizophrenia is unclear as well. Although there are abnormalities in the size of different areas of the brain and the levels of some of the chemicals in brain cells of people with schizophrenia, it isn't known how these relate to the production of the syndrome. For almost a century the hallmark of people with schizophrenia was the deterioration of intellectual capacity and functioning throughout the course of their lives. It was believed that the illness itself caused progressive brain damage. This contributed to the hopelessness felt by patients, their families, and clinicians. This hopelessness led to extreme treatments such as insulin therapy, electroshock therapy, lobotomy, and long-term institutionaliza-tion of people with schizophrenia.

Risk communication prior to pharmacotherapeutic choice

Drug administration during pregnancy means that both the mother and unborn child are exposed. The drug or metabolite concentration may be even higher in the embryonic or fetal compartment than it is in the mother. The fetus as an additional patient therefore demands a strict pharmacotherapeutic approach, as it is imperative to try to restore maternal health without endangering the development of the child. In severe conditions, such as bronchial asthma, diabetes melli-tus, epilepsy or particular communicable diseases, treatment is obligatory regardless of pregnancy. In contrast, inessential products such as antitussive preparations, pregnancy-supporting substances, and high doses of vitamins and minerals should not be prescribed or used, as their potential risks outweigh their unproven benefits. The disease itself may be a greater fetotoxic risk than the appropriate drug therapy, as in diabetes mellitus. The same applies to severe psychic stress. An individual risk evaluation related...

General Information

They slow down food digestion in the gut, reducing peak blood glucose concentrations after meals. They also prevent reactive hypoglycemia, as can be seen after gastric operations, in dumping syndrome, and in idiopathic forms. When carbohydrates appear in the colon, bacterial fermentation can occur, leading to gastrointestinal adverse effects, of which flatulence and loose stools are the most frequent. During long-term treatment the colonic bacterial mass can increase. In elderly patients acarbose increases insulin sensitivity but not insulin release (1). Acarbose may reduce the incidence of colon cancer, the risk of which is 30 higher in people with diabetes than in the non-diabetic population (2).

See also Diuretics General Information

Patients with congenital nephrogenic diabetes insipidus are often treated with a combination of a thiazide and a potassium-sparing diuretic, without consensus on the preferred potassium-sparing diuretic. A Japanese adult was systematically studied to determine the renal effects of hydrochlorothiazide plus amiloride and hydrochloro-thiazide plus triamterene (1). The combination with amiloride was superior to that with triamterene in preventing excessive urinary potassium loss, hypokalemia, and metabolic alkalosis. These results suggest that amiloride is the preferred add-on therapy to hydrochlorothia-zide in nephrogenic diabetes insipidus.

Electrolyte balance

ACE inhibitors can cause hyperkalemia because they inhibit the release of aldosterone. The effect is usually not significant in patients with normal renal function. However, in patients with impaired kidney function and or in patients taking potassium supplements (including salt substitutes) or potassium-sparing diuretics, and especially aldosterone antagonists, hyperkalemia can occur. In two cases, hypoaldosteronism with diabetes was implicated (53,54).

Adverse Reactions

More than half of the patients receiving this drug by the parenteral route experience some adverse reaction. Severe and sometimes life-threatening reactions include leukopenia (low white blood cell count), hypoglycemia (low blood sugar), thrombocytopenia (low platelet count), and hypotension (low blood pressure). Moderate or less severe reactions include changes in some laboratory tests, such as the serum creatinine and liver function tests. Other adverse reactions include anxiety, headache, hypotension, chills, nausea, and anorexia. Aerosol administration may result in fatigue, a metallic taste in the mouth, shortness of breath, and anorexia.

Contraindications Precautions And Interactions

This drug is contraindicated in individuals who have had previous hypersensitivity reactions to pentamidine isethionate. Pentamidine isethionate is used cautiously in patients with hypertension, hypotension, hyper-glycemia, renal impairment, diabetes mellitus, liver impairment, bone marrow depression, pregnancy (Category C), or lactation.

Gene Targeting Of Pi3k Isoforms

Two deletions of the p85a regulatory subunit have been reported. A deletion of the first exon of p85a interrupts the expression of the full-length protein but does not affect the p55a and p50a splice variants (39). These animals develop a B-cell immunodeficiency and, surprisingly, increased insulin sensitivity and hypoglycemia. Deletion of all splice variants of p85a and leads to death of most of the animals within 4 d (40). Interpretation of this phenotype is hampered owing to upregulation of p85P and a reduction in the levels of p110a and p110P, supporting a role for p85a in protecting the catalytic subunits from proteolysis. P85P deletion also results in mice with improved insulin sensitivity and hypoglycemia (41).

Tardive Dyskinesia and Other Tardive Syndromes

Prevalence surveys indicate that mild forms of TD occur in approximately 20 of patients who receive chronic treatment with conventional antipsychotic medication. A major prospective research demonstrates that the cumulative incidence of TD is 5 in the first year, 10 the second year, 15 the third year, and 19 the fourth year in a patient who receives a typical neuroleptic. Prevalence rates of TD may exceed 50 in high-risk groups, such as the elderly. The reported prevalence of tardive dystonia is around 1.5 to 4 . Among the most significant predictors of TD are older age, female gender, presence of EPS, diabetes mellitus, affective disorders, and certain parameters of neuroleptic exposure such as dose and duration of therapy.

Observational studies

In a large American study in 3234 non-diabetic people with a raised fasting blood glucose and a raised blood glucose 2 hours after a glucose load, diabetes occurred in 7.8 cases per 100 participants per year after a mean treatment period of 2.8 years with metformin 850 mg bd there were 11 cases per 100 participants per year after placebo and 4.8 cases per 100 participants per year after a life-style intervention program (8). Gastrointestinal symptoms were most frequent in those who took met-formin. In a later study, glucose tolerance tests were performed after a 14-day washout period of metformin and placebo in the patients who had not developed diabetes (9). Diabetes was more frequently diagnosed in the metformin group, but when the diabetes conversions during treatment and washout were combined, diabetes was still significantly less common in the metformin group.

Comparative studies

Metformin and troglitazone have been compared in 21 patients with type 2 diabetes unresponsive to glibencla-mide 10 mg bd (10). Metformin stabilized weight and reduced adipocyte size, leptin concentrations, and glucose transport. GLUT1 and GLUT4 in isolated adipocytes were not changed. Insulin-stimulated whole-body glucose disposal rate increased by 20 . Troglitazone caused increases in body weight, adipocyte size, leptin concentrations, and basal and insulin-stimulated glucose transport. GLUT4 protein expression was increased two-fold and insulin-stimulated whole-body glucose disposal rate increased by 44 .

Placebocontrolled studies

In a placebo-controlled study in 40 patients with impaired glucose tolerance metformin 500 mg bd for 6 months increased insulin-stimulated glucose metabolism by 20 with minimal improvement in glucose tolerance this effect was maintained after 12 months (11). In 82 children aged 10-16 years with type 2 diabetes, metformin lowered HbA1c and fasting blood glucose compared with placebo (12). More patients who took placebo had to drop out because more medication was necessary. Most of the adverse events (abdominal pain, diarrhea, nausea, vomiting) occurred during metformin treatment.

Factors that alter measurements

Sports like hiking and skiing at moderate high altitude make glucose estimation mandatory for people with diabetes. Changes in temperature, PaO2, and humidity can result in errors in blood glucose determination. When tested at 3000 m (10000 feet) the glucose meter Elite (Bayer Diagnostics) had a tendency to overestimate glucose concentrations, while the Life Scan One Touch II had a tendency to underestimate them (2). The bias was not clinically meaningful, although some In patients with diabetes given a 75 g oral glucose load followed by a rapid-acting insulin, producing a wide range of blood glucose concentrations, of three different devices for blood glucose estimation, only finger-prick estimations followed the changes in blood glucose (5), although patients preferred other sites for testing (6).

Organs and Systems Immunologic

Finger sepsis aggressive enough to cause osteomyelitis has been reported in two women, one aged 61 years with Staphylococcus aureus, Staphylococcus agalactiae, and Enterococcus faecalis, and another aged 57 years with a beta-hemolytic staphylococcus, Candida non-albicans, and unidentified anaerobic bacteria. Antibiotic treatment and local drainage were unsuccessful and the third phalanx had to be amputated. Both patients had poorly controlled diabetes (HbA1c 14 and 12 respectively) they had estimated their blood glucose six times a week using an automatic lancet without changing their disposable needle (8).

R Valproateassociated polycystic ovary syndrome

In a prospective study of polycystic ovary syndrome in 52 controls and 72 women with epilepsy (37 taking valproate monotherapy and 35 carbamazepine monotherapy), the frequency of polycystic ovaries, hyperandrogenism, or both was significantly higher in those taking valproate than in the controls (70 vs. 19 ) (86C). They occurred in 20 of the patients taking carbamazepine. The obese women taking valproate who had polycystic ovaries or hy-perandrogenism or both had hyperinsulinemia and associated unfavorable changes in serum lipid concentrations consistent with insulin resistance. In both obese and lean women, polycystic ovaries and related hyperandrogenism were similarly found. Most of the abnormalities were reversed when valproate was withdrawn (87C).

Ginseng and Erectile Function

Erectile dysfunction is commonly associated with diabetes, a condition that has well-characterized effects on peripheral tissue innervation and vascularization 21 . Penile intracavernous pressure after nerve stimulation was significantly lower in long-term diabetic rats relative to age-matched controls 22 . In diabetic rats treated with Korean red ginseng (30 mg kg-1) for one month, however, erectile function was not different from nondiabetic age-matched controls 22 . Ginseng use has also been shown to produce beneficial effects in clinical studies (Table 4.1) that evalu-

Contraindications

These drugs are used cautiously in patients with coronary insufficiency, cardiac arrhythmias, angina pec-toris, diabetes, hyperthyroidism, occlusive vascular disease, or prostatic hypertrophy, and in those taking digoxin. Patients with diabetes may require an increased dosage of insulin. Epinephrine is used cautiously in patients with Parkinson's disease (may temporarily increase rigidity and tremor) or ventricular fibrillation and in the elderly. Ephedrine is used cautiously in patients with acute-closure glaucoma. Midodrine is used cautiously in patients with urinary problems or hepatic disease and during lactation. Adrenergic drugs are classified as Pregnancy Category C and are used with extreme caution during pregnancy.

Alphaglucosidase inhibitors

However, in a formal study of the pharmacokinetics of a single dose of digoxin 0.75 mg before and after the administration of acarbose 50 mg tds for 12 days in healthy volunteers, apart from a small increase in Cmax, the pharmacokinetics of digoxin were unaffected by acar-bose (219). It is not uncommon for anecdotal reports of a possible interaction to be unconfirmed by formal kinetic studies, and it is possible in such cases that there is a subset of patients who are susceptible to the interaction who have not been included in the formal study. In this case, for example, it may be that the interaction occurs in people with diabetes and not in healthy subjects. There may also be a difference in the effect of acarbose on a single dose of digoxin, compared with steady-state therapy. Advice that acarbose and digoxin should be administered 6 hours apart is still reasonable.

Tuberculosis and pregnancy

Untreated tuberculosis represents a greater hazard to the mother and her fetus than does the treatment of the disease (Bothamley 2001, Raju 1998, Brost 1997). There are slight differences in the recommendations of the different organizations in the world, such as the WHO, the International Union against Tuberculosis and Lung Disease (IUATLD), and several national organizations (Frieden 2003). Treatment considerations depend on disease status and drug resistance. Some treatment schedules recommend delaying preventive therapy until after delivery in pregnant women with only a positive tuberculin skin test (PPD) but a negative chest radiograph, unless they have a high risk of progressing to active disease (for example, HIV patients, diabetics, recent converters, and those who are close contacts of a person with an active disease). For the treatment of active tuberculosis, isoniazide (INH), rifampicin, and ethambutol arc considered to be the first-line antituberculous drugs during...

Epidemiology and Aetiopathology

Hypoglycaemia, defined as a blood glucose concentration < 2.2 mmol l, has been known for almost 80 years to be a complication of P. falciparum infection (Fitz-Hugh 1944 Peterson 1926). However, the first prospective assessment of the frequency and clinical course of malaria-associated hypoglycaemia was conducted only about 20 years ago, in Thai adults (White et al. 1983). In this study, 12 of 151 subjects with cerebral malaria had hypoglycaemia and the case fatality rate of these patients was significantly higher than of those who were normoglycaemic. Plasma insulin and C peptide levels were inappropriately high during episodes of hypoglycaemia. Measured quinine and insulin concentrations were positively correlated. Quinine infusions in normal volunteers also increased plasma insulin concentrations that resulted in falls in fasting blood glucose levels (White et al. 1983). Pregnant women in Thailand and Sudan are prone to hypoglycaemia without associated hyperinsulinaemia (White et...

IL12 Knockout and Transgenic Mice

The naturally occurring homodimer IL-12p40 subunit acts as an antagonist of bioac-tive IL-12 p35 p40 heterodimer. When IL-homodimer is given to diabetes-prone nonobese diabetic (NOD) mice, diabetes is suppressed (532). This result supports a role for IL-12 in driving Thl-driven autoimmune diabetes.

Pharmacokinetics And Glucodynamics

Several insulin delivery systems are in development or on the market. Each pulmonary insulin delivery system consists of three components an insulin formulation, a unique insulin delivery packaging, and a unique delivery device. Though they all may be characterized as inhaled insulin systems, these unique characteristics require us to individually scrutinize each product. The inhalers range from handheld breath actuated devices to meter dose inhalers similar to those used for asthma agents. Insulin delivery packaging ranges from dry-powder blister packs or capsules, to liquid blisters or liquid in asthma type canisters. Diverse particle technologies have also been investigated for the delivery of insulin. The Exubera and AERx systems were first technologies investigated in the 1990s.

Lung Function Parameters

Forced expiratory volume in 1 second (FEV1) and diffusing capacity of carbon monoxide (DLCO) are parameters utilized to evaluate lung function in studies testing inhaled insulin products. FEV1 measures the volume of air exhaled during the first second of a forced expiratory maneuver. Values are reported as a percentage of predicted normal values and are used to measure airway obstructions or changes in airway diameter. DLCO reveals oxygen-diffusing capacity influenced by lung surface area, speed of blood flow and thickness of the air-blood barrier. A reduction in DLCO is a hallmark finding in patients with emphysema and interstitial lung disease. Lung function can be affected by various factors. Lung diseases such as COPD (55), interstitial lung disease, or asthma and patient specific factors such as age, smoking, ethnicity, weight or height can have a marked impact on lung function (56,57). Patients with diabetes have an unexplained decrease in lung function compared to those...

Family Cucurbitaceae A L de Jussieu 1789 nom conserv the Cucumber family

And melanoma, and are therefore worth exploring further. Cucurbitacin E (ela-terin), the active principle of Ecballium elaterium (L.) A. Rich., annihilates efficiently the survival of prostate carcinoma cells cultured in vitro (IC50 7 nM-50 nM in 2-to 6-day exposures). The cytotoxicity of cucurbitacins is related to their ability to disrupt the F-actin cytoskeleton and thereby the division of cells. Note that Cucurbitaceae are also interesting for the proteins they contain in their roots and seeds. These proteins are abortifacient, antitumoral, ribosome inactivating, anti-HIV and immunomodulatory. It will be interesting to learn whether more intensive future research on Cucurbitaceae will disclose any molecules of chemotherapeutic interest. About 50 Cucurbitaceae plant species are medicinal in the Asia-Pacific, mostly on account of their steroidal and triterpenes contents. The fruits are mainly used to promote urination, soothe inflamed parts, check hemorrhages, counteract poisoning,...

Pharmaceutical interest

Antidiabetes properties In regard to the antidiabetic property of Benincasa hispida (Thunb.) Cogn., a number of experiments conducted in vivo tend to demonstrate that the plant is inactive. An ethanolic extract of Benin-casa hispida (Thunb.) administered at a dose of 250 mg Kg orally to rats failed to lower blood sugar or to depress the peak value, after glucose load (Chandrasekar B etal., 1989). Uses In China, the fruits of Benincasa hispida (Thunb.) Cogn. are eaten to treat diabetes, dropsy and kidney diseases. The seeds are eaten to promote urination, relieve the bowels of costiveness, treat fever, heal hemorrhoids, and soothe inflamed intestines. The rind is eaten to promote urination and to invigorate the spleen. The pulp is used to promote urination, treat fever and as a demulcent. In India, the fruits are eaten to relieve the bowels of costiveness, promote urination and libido, check hemorrhages, treat strangury and expel urinary stones. The oil expressed from the seeds is...

Second Generation Effects Pregnancy

There is growing evidence that desmopressin can be used safely in pregnant women and no adverse effects have been reported in either mothers with diabetes insipidus or their babies (57), or in women with clotting factor deficiencies (58). However, the manufacturers advise that it should be used with caution in women with bleeding disorders, who require high doses.

Treatment Options for Psychotic Disorders

All atypical antipsychotics can cause substantial weight gain (an increase of 10 to 20 of your current body weight in the first couple of months), diabetes, and elevations of cholesterol or triglycerides (another form of fat in the blood). People with a family history of diabetes are at a higher risk for developing these complications. These serious complications are associated with high blood pressure, heart attacks, strokes, and gallbladder problems. It's not clear if high doses are more likely to cause these problems than low doses. It's not clear if atypical antipsychotics cause these changes in metabolism directly or whether the changes result from weight gain. In either case, it is important to monitor your weight and be tested regularly for the presence of high cholesterol and diabetes. Careful dieting and exercise can minimize weight gain and even permit weight loss in people who have gained weight. There are significant differences among the six atypical antipsychotics....

Organs and Systems Cardiovascular

The major risk during dopamine treatment is that of severe peripheral ischemia, particularly in patients in whom the peripheral circulation is already impaired, since dopamine is converted to noradrenaline gangrene has repeatedly resulted. In some of the reported cases the error lay in extravasation of dopamine from a peripheral venous infusion site in others the dosage had been high and prolonged, or ergometrine had also been given. In cases of pre-existing vascular damage from arteriosclerosis, diabetes, Raynaud's disease, or frostbite, particular care must be taken. If discoloration appears, the infusion should be stopped and phentolamine 5-10 mg given intravenously. Nitroprusside may fail to prevent the onset of gangrene.

Federal Schedule Listing Unlisted

Although the substance has been available for hundreds of years it was not used as a drug until the nineteenth century began. The compound relaxes muscles and increases blood sugar levels. For decades it was a standard anesthetic but has been superseded by chemicals that work faster, that are better tolerated by patients, and that are less of a fire hazard. Nonetheless, knowledgeable medical personnel can use ether safely without complicated equipment, and the drug remains common where high-tech medical facilities are not common or nonexistent. In liquid form ether is used medically to clean skin surfaces before putting on adhesive tape and is used to help take off adhesive tape.

Biosynthesis Of Pgs And Leukotrienes

The stereospecific introduction of oxygen into the 5-position of arachidonic acid is catalyzed by the nonheme iron dioxygenase 5-lipoxygenase. This initiates a cascade of transformations that result in the synthesis of an array of potent mediators of cellular activities, some of which are illustrated in Figure 8.2. Simple reduction of the hydroperoxy group leads to 5-hydroxyeicosatrienoic acid (HETE), which is a potent chemotactic agent as well as a promoter of islet cell insulin release. Epoxide formation leads to leukotriene (LT)A4 which is a central precursor for a number of metabolites such as LTB4 and LTC4, which in turn lead to about two dozen known products (not shown).

Other Modes of Drug Delivery Including Some Which Are Experimental and Promising

Proteins and peptides used as drugs require special modes of delivery because of their molecular sizes and susceptiblity to digestion. They can be linked to endogenous carriers such as vitamin B12 or can form complexes such as an insulin-enzyme-albumin conjugate which will go wherever there are insulin receptors. d. Pumps can be used such as the Infusaid which is a device which designed for the steady infusion of insulin to diabetics. The ultimate in this delivery mode would be a glucose-sensitive self-modulating system.

Cannabinoid Receptors

And acetylcholine in slices of hippocampus, cerebellum, and neocortex has been reported either from direct observation or indirectly, through electrophysiological methods (25). Other key proteins are regulated through signal transduction from cannabinoid receptors. They include focal adhesion kinase, which is phosphorylated on tyrosine residues and plays a role in synaptic plasticity (26), and PI3K activation by Py-subunits of Gi, resulting in phosphorylation of Raf-1 and then phosphorylation of MAPK to activate it. In turn, MAPK can activate phospholipase A2 and trigger the arachidonic acid cascade and production of prostaglandins (27), and can decrease growth factor receptor synthesis in certain tissue, a basis for antiproliferative action of cannabinoids (28). PI3K is also biochemically associated with mediation of insulin-like effects with upregulation of glucose transporter 4 (insulin-dependent glucose uptake in skeletal muscle and adipose tissue), stimulation of glycogen...

Fibric Acid Derivatives

The fibric acid derivatives are contraindicated in patients with hypersensitivity to the drugs and those with significant hepatic or renal dysfunction or primary biliary cirrhosis because these drugs may increase the already elevated cholesterol. The drugs are used cautiously during pregnancy (Pregnancy Category C) and lactation and in patients with peptic ulcer disease or diabetes. Although it rarely occurs, when the fibric acid derivatives, particularly gemfibrozil, are administered with the HMG-CoA reductase inhibitors, there is an increased risk for rhabdomyolysis (see Nursing Alert). When clofibrate, fenofibrate, or gemfibrozil is administered with the anticoagulants, there is an increased risk for bleeding.

Atypical antipsychotic drugs

There are reports on more than 200 pregnancies exposed to olanzapine (McKenna 2005, Levinson 2003, Ernst 2002, Mendhekar 2002, Biswas 2001, Malek-Ahmadi 2001, Nagy 2001, Neumann 2001, Goldstein 2000, Kirchheiner 2000, registry data of the producer), none of which indicate teratogenicity. There were three retrospective reports with neonatal seizures after exposure until the end of pregnancy (Goldstein 2000, observations of the authors). Glucose intolerance and onset of gestational diabetes have also been reported after the use of olanzapine in pregnancy (Gentile 2004). Olanzapine has also been associated with pre-eclampsia (Yonkers 2004. Kirchheiner 2000).

Other Potential Targets

In addition to the kinases discussed above, many other types of kinases might be targeted with potential clinical benefit, and the list is growing ever longer due to the rapidly progressing work of molecular biologists in the cancer field. For example, attempts are being made to develop inhibitors for the insulin-like growth factor (IGF)-1R receptor pathway, which is triggered by the IGF-1 and IGF-2 growth factors and is important for many cellular functions, including transformation and proliferation (see Scheme 5.7). Mutant Flt-3 is also of interest and is known to be important in leukemic (AML and ALL) cells (see Scheme 5.8). Other areas of research include the MET and SRC kinases, and the flos ERK1-2, AKT and STAT pathways. The attraction of MET kinase is that it is important in the process of metastasis which, if controlled, could allow more focus on the treatment of primary tumors.

Saccharomyces Cerevisiae

Analgesic, anodyne, stimulant, sedative, anesthetic, inebriant. Specific reactions seem to vary with body type and psychology, perhaps also with blood sugar level and other hormonal balances. Mesomorphs tend to become boisterous and aggressive, endomorphs expansive, sentimental, or maudlin. Ectomorphs, it is said, just get depressed.

Potassium Sparing Diuretics

Hyperkalemia (increase in potassium in the blood), a serious event, may be seen with the administration of potassium-sparing diuretics. Hyperkalemia is most likely to occur in patients with an inadequate fluid intake and urine output, those with diabetes or renal disease, the elderly, and those who are severely ill. In patients taking spironolactone, gynecomastia (breast enlargement in the male) may occur. This reaction appears to be related to both dosage and duration of therapy. The gynecomastia is usually reversible when therapy is discontinued, but in rare instances, some breast enlargement may remain.

Hawthorn Leaves and Flowers in CHF

Yet, in that RCT Walker et al. 61 examined a different hawthorn extract than the one they have analysed in the pilot study. 79 hypertensive patients with type 2 diabetes (70 under hypotensive treatment) were treated (daily dosis 1200 mg extract duration 16 weeks). The study showed a small but significant decrease in diastolic blood pressure in the hawthorn group vs. placebo (-2.6mmHg p 0.035).

Organs and Systems Metabolism

In a double-blind, randomized, crossover study in 10 healthy subjects, subcutaneous glucagon-like peptide-1 after a 16-hour fast caused a near five-fold rise in plasma insulin concentration and circulating plasma glucose concentrations fell below the reference range in all subjects (6). One subject had symptoms of hypoglycemia. A rise in pulse rate correlated with the fall in plasma glucose concentration and there was an increase in blood pressure. In eight patients with type 2 diabetes and seven matched non-diabetics, subcutaneous glucagon-like pep-tide-1 and intravenous glucose caused reactive hypogly-cemia in five controls but not in the patients (7). Glucagon was suppressed.

Sympathomimetics Pharmacology and toxicology

The use of fenoterol and other -sympathomimetics, especially when combined with corticosteroids to enhance fetal lung maturity, can result in impaired carbohydrate tolerance, sometimes leading to an abrupt increase in insulin need in insulin-dependent diabetics. As in their mothers, -sympathomimetics can cause fetal and neonatal cardiovascular side effects, as well as impaired carbohydrate tolerance in the neonate.

Other Biological Activities

Beside antimicrobial and antidiabetic investigations in Moroccan plants, other bi-oassays have been carried out, consisting mainly of studies on molluscicidal, larvi-cidal, cardiovascular, diuretic, and hypotensive effects. Molluscicidal activity has been studied using Bulinus truncatus, the mollusc intermediate host of shistosomi-asis in Morocco. This disease affects more than 200 million people in 73 tropical and subtropical countries 77 and constitutes one of the major health problems in rural communities living near slow moving water. In our laboratory, we have initiated a program in which some selected plants have been evaluated for molluscicidal and larvicidal potential, such as the latex of Calotropis procera 31, 78 , some selected Solanaceous plants such as Solanum elaeagnifolium, S. sodomaeum 79 , and Quercus lusitania 80 . Our results showed that C. procera latex and extracts from S. elaeagnifolium were the most promising as molluscicide and larvicide.

Onset Peak and Duration of Action

Onset, peak, and duration are three properties of insulin that are of clinical importance. Onset when insulin first begins to act in the body Peak when the insulin is exerting maximum action Duration the length of time the insulin remains in effect To meet the needs of those with diabetes mellitus, various insulin preparations have been developed to delay the onset and prolong the duration of action of insulin. When insulin is combined with protamine (a protein), the absorption of insulin from the injection site is slowed and the duration of action is prolonged. The addition of zinc also modifies the onset and duration of action of insulin. Insulin preparations are classified as rapid-acting, intermediate-acting, or long-acting. The Summary Drug Table Insulin Preparations gives information concerning the onset, peak, and duration of various insulins.

Prolactin antagonists

Vasopressin influences the transamniotic water transfer from the mother to the fetus. Vasopressin is inactivated by vasopressinase. During pregnancy, subclinical diabetes insipidus may be aggravated as a result of increased levels of placental vasopressinase. Vasopressin deficiency results in diabetes insipidus, for which vasopressin or its analogs have been used as therapy. The peripheral anomalies of the extremities that have been induced by vasopressin in animal experiments (Love 1973, Davies 1970, Jost 1951), apparently caused by vasoconstriction, have not, as yet, been observed in human beings. Among the natural and synthetic analogs are argipressin, desmopressin (DDAVP), lypressin, ornipressin, and terlipressin. Desmopressin, which is not inactivated by vasopressinase, has been most frequently described in connection with the treatment of pregnancy-related diabetes insipidus. DDAVP, at therapeutic Recommendation. Oxytocin may be used obstetrically for the induction or...

Preadministration Assessment

If the patient has recently received a diagnosis of diabetes mellitus and has not received insulin or if the patient is known to have diabetes, the initial physical antidiabetic drugs, oral assessment before administering the first dose of insulin includes taking the blood pressure, pulse, and respiratory rate, and weighing the patient. The nurse makes a general assessment of the skin, mucous membranes, and extremities, with special attention given to any sores or cuts that appear to be infected or healing poorly, as well as any ulcerations or other skin or mucous membrane changes. The nurse obtains the following information and includes it in the patient's chart Family history of diabetes (if any) The nurse reviews the patient's chart for recent laboratory and diagnostic tests. If the patient has diabetes and has been receiving insulin, the nurse includes the type and dosage of insulin used, the type of diabetic diet, and the average results of glucose testing in the patient's chart....

Ongoing Assessment

The number and amount of daily insulin doses, times of administration, and diet and exercise requirements require continual assessment. Dosage adjustments may be necessary when changing types of insulin, particularly when changing from the single-peak to the more pure Humulin insulins. The nurse must assess the patient for signs and symptoms of hypoglycemia and hyperglycemia (see Table 49-1) throughout insulin therapy. The patient is particularly prone to hypoglycemic reactions at the time of peak insulin action (see the Summary Drug Table Insulin Preparations) or when the patient has not eaten for some time or has skipped a meal. In acute care settings, frequent blood glucose monitoring is routinely done to help detect abnormalities of blood glucose.

Promoting an Optimal Response to Therapy

There is no standard dose of insulin as there is for most other drugs. Insulin dosage is highly individualized. Sometimes the health care provider finds that the patient achieves best control with one injection of insulin per day sometimes the patient requires two or more injections per day. In addition, two different types of insulin may be combined, such as a rapid-acting and a long-acting preparation. The number of insulin injections, dosage, times of administration, and type of insulin are determined by the health care provider after careful evaluation of the patient's metabolic needs and response to therapy. The dosage prescribed for the patient may require changes until the dosage is found that best meets the patient's needs.

Relieving Anxiety and Fear

The patient with newly diagnosed diabetes often has many concerns regarding the diagnosis. For some, initially coping with diabetes and the methods required for controlling the disorder creates many problems. Some of the fears and concerns of these patients may include having to give themselves an injection, having to follow a diet, weight control, the complications associated with diabetes, and changes in eating times and habits. An effective teaching program helps relieve some of this anxiety. The patient in this situation needs time to talk about the disorder, express concerns, and ask questions.

Assisting the Patient With Impaired Adjustment Coping and Altered Health Maintenance

The patient with newly diagnosed diabetes may have difficulty accepting the diagnosis, and the complexity of the therapeutic regimen can seem overwhelming. Before patients can be expected to carry out treatment, they must accept that they have diabetes and deal with their feelings about having the disorder. The nurse has an important role in helping these patients gradually accept the diagnosis and begin to understand their feelings. Understanding diabetes may help patients work with health care providers and other medical personnel in managing their diabetes.

Cannabinoids as Immune Therapeutic Agents

Molina-Holgado et al. (1998) utilized Theiler's murine encephalomyelitis virus (TMEV) to produce persistent brain infection in mice with attendant chronic primary immune-mediated demyelination resembling MS. The effects of anan-damide on astrocytes infected with TMEV were examined, since these glial cells in the brain are potent producers of pro-inflammatory cytokines upon virus infection. Astrocytes from susceptible (SJL J) and resistant (BALB c) strains of mice infected with TMEV exhibited increased IL-6 release that was enhanced by anan-damide. Treatment of TMEV-infected astrocytes with arachidonyl trifluoromethyl ketone, a potent inhibitor of the amidase that degrades anandamide, potentiated this anandamide effect. SR141617A, the CBi antagonist, blocked the enhancing effects of anandamide on IL-6 release by TMEV-infected astrocytes, suggesting a cannabinoid receptor-mediated pathway. The investigators indicated that, while the physiological implications of these results were...

Gerontologie Alert

After the patient has been taking sulfonylureas for a period of time, a condition called secondary failure may occur. Secondary failure occurs when the sulfonylurea loses its effectiveness. When the nurse notes that a normally compliant patient has a gradual increase in blood sugar levels, secondary failure may be the cause. This increase in blood glucose levels can be caused by an increase in the severity of the diabetes or a decreased response to the drug. When secondary failure occurs, the health care provider may prescribe another sulfonylurea or add an oral antidiabetic drug such as metformin to the drug regimen. See the Summary Drug Table Antidiabetic Drugs for additional drugs that can be used in combination with the sulfonylureas.

Educating the Patient and Family

Failing to comply with the prescribed treatment regimen may be a problem with patients taking an oral antidiabetic drug because of the erroneous belief that not having to take insulin means that their disease is not serious and therefore does not require strict adherence to the recommended dietary plan. The nurse informs these patients that control of their diabetes is just as important as for patients requiring insulin and that control is achieved only when they adhere to the treatment regimen prescribed by the health care provider. If the diagnosis of diabetes mellitus is new, the nurse discusses the disease and methods of control with the patient and family after the health care provider has revealed the diagnosis to the patient. Although taking an oral antidiabetic drug is less complicated than self-administration of insulin, the patient with diabetes taking one of these drugs needs a thorough explanation of the management of the disease. The teaching plan is individualized...

See also Prostaglandins General Information

Most clinical experience with iloprost has been gained in patients with critical leg ischemia. An intermittent intravenous infusion of up to 2 nanograms kg minute for 2-4 weeks reduced rest pain and improved ulcer healing in roughly half of the patients with critical leg ischemia, including diabetics. Compared with placebo, the improvement obtained with iloprost was significant in most but not all individual clinical trials. In addition, a meta-analysis showed a 15 reduction in major amputation rate compared with placebo (2).

TABLE 501 Activity of Glucocorticoids in the Body

Action is decreased, and blood pressure falls. Facilitates the breakdown of protein in the muscle, leading to increased plasma amino acid levels. Increases activity of enzymes necessary for glucogenesis producing hyperglycemia, which can aggravate diabetes, precipitate latent diabetes, and cause insulin resistance A complex phenomena that promotes the use of fat for energy (a positive effect) and permits fat stores to accumulate in the body, causing buffalo hump and moon- or round-shaped face (a negative effect).

See also Vaccines General Information

In a randomized, double-blind study, trivalent, live, attenuated, cold-adapted intranasal influenza vaccine (FluMist) has been compared with intranasal placebo plus a trivalent injected inactivated influenza vaccine (5). The 200 patients were aged 65 years and over and had chronic cardiovascular or pulmonary conditions or diabetes mellitus. During the 7 days after immunization, sore throat was reported on at least one day by significantly more of the FluMist recipients (15 versus 2 ). The increased frequency of sore throat may have been attributable to direct or indirect effects of vaccine virus replication. No other symptom was associated with FluMist. These findings were consistent with evaluations of other live, attenuated, cold-adapted influenza vaccine formulations in older adults. However, further studies of the safety of FluMist are warranted.

Overall level of evidence for adverse effects B

22206 Grover SA, Lowensteyn I, Kaouache M, Marchand S, Coupal L, DeCarolis E, Zoccoli J, Defoy I. The prevalence of erectile dysfunction in the primary care setting importance of risk factors for diabetes and vascular disease. Arch Intern Med. 2006 Jan 23 166(2) 213-9. English Risk factors age smoking diabetes high cholesterol hypertension depression anxiety disorders No

Organs and Systems Nervous system

Susceptibility factors for cerebral edema during keto-acidosis in children have been investigated in 61 cases of cerebral edema during 6977 hospital admissions (7). They were matched with two types of controls for each case three children with ketoacidosis randomly selected and three children matched for age (within 2 years), onset of diabetes, blood pH, and serum glucose at entry. The results suggested that high initial serum urea concentrations and a low PaCO2 are associated with an increased probability of cerebral edema. Children with these abnormalities should be monitored for signs of neurological deterioration, and hyperosmolar therapy should be immediately available. Treatment with bicarbonate was associated with an increased risk and should be avoided. In an accompanying editorial it was stated that high doses of insulin, hypotonic fluids, and bicarbonate are often seen as culprits, but it is also possible that it is an idiosyncratic response to diabetic ketoacidosis there is...

Long Term Effects Drug tolerance

Insulin resistance has been reported with continuous subcutaneous infusion. Diabetes mellitus in a 36-year-old man with acute pancreatitis could not be controlled with continuous subcutaneous insulin infusion, even with doses up to 1800 U day, because of insulin resistance (134). Intravenous insulin by pump had to be stopped because of a catheter infection. The continuous subcutaneous infusion of freeze-dried insulin and the addition of aprotinin, a protease inhibitor, soluble dexamethasone or prednisolone, and intravenous immunoglobulin was ineffective. An implantable pump for intraperitoneal delivery established good regulation at a dosage of 30 U day. A 23-year-old diabetic woman had severe subcutaneous insulin resistance for 11 years (135). Continuous subcutaneous insulin infusion with regular or insulin lispro did not prevent periods of fluctuating responses to insulin. The addition of heparin to insulin lispro in the pump improved serum insulin concentrations and metabolic...

Drug contamination

A skin reaction to latex in rubber associated with an insulin formulation has been reported (142). In a 35-year-old woman, pruritic, erythematous, urti-cated plaques occurred at insulin injection sites, and persisted for 48 hours, after the use of a prefilled cartridge pen containing Humulin (Lilly) and Human Monotard (Novo Nordisk) aspirated from a punctured vial, but not when the insulin was taken directly from the vial. She had positive skin-prick tests to latex solutions. Both the cartridge bungs and the vial bungs contain butyl rubber with added natural rubber latex. Switching to latex-free vials alleviated the problem.

Drug administration route

The American Diabetes Association has published revised guidelines on insulin administration, including storage of insulin, use and reuse of needles, alternatives to syringes, injection techniques, and patient management related to dosing of insulin, self-monitoring, and hypoglycemia (143). Developments in the administration of insulin through the skin, the mouth, the nose, and the lung have been reviewed (144). Methods of absorption other than subcutaneous, such as nasal insulin, buccal insulin, rectal insulin, and insulin in enteric-coated capsules, are still experimental. A problem in nasal administration is still how to get a daily reproducible dose (145). The frequency of hypoglycemia is comparable to the frequency with subcutaneous insulin (146). Nasal irritation, sometimes with congestion, and dyspnea (147) can occur. Pulmonary insulin, delivered by aerosol inhalation, is another experimental method. No lung obstruction was reported, but the uptake varied considerably (148)....

Interference with Diagnostic Tests Blood glucose measurement

Three diabetic patients on chronic ambulatory peritoneal dialysis (CAPD) had symptoms of hypoglycemia when glucose readings on strips were higher than 4 mmol l (223). Venous testing showed glucose concentrations as low as 1.8 mmol l. Large amounts of glucose are used in CAPD, which not only affects the regulation of diabetes but can also affect the peritoneal wall. Since 1999, icodex-trin has been used in dialysis fluids. Icodextrin is glucose-free and reduces the need for insulin. However, it is also absorbed systematically and can be metabolized to maltose and maltotriose. Paper systems that use either glucose oxidase or glucose dehydrogenase overestimate glucose readings when icodextrin is used, and patients and their carers are not able to measure low blood glucose concentrations. Another factor is that during end-stage renal insufficiency, insulin catabolism is reduced. This contributes to the problems when CAPD is changed to automated (overnight) peritoneal dialysis, in which...

The Role of Reactive Oxygen Species

In cancers of the reproductive system, those regulating metabolism and weight, and those affecting disorders related to insulin. The immune system and its cytokines are also involved in the latter, particularly diabetes mellitus. EGCG also effects production of cytokines, including those which cause inflammatory responses, in ways that are only recently being explored.

Drug Administration Drug formulations

In contrast to most medium- and long-acting formulations, insulin glargine is a clear solution. In two cases, patients gave themselves rapid-acting insulin instead of glargine. A 25-year-old woman and a 52-year-old woman injected lispro instead of insulin glargine (25). The first realized her mistake and managed to prevent severe hypoglycemia by eating continuously, despite a fall in blood glucose to 3.7 mmol l. The other had a blood glucose of 3.1 mmol l and recovered after intravenous dextrose. Four other mistakes have been reported (26,27). The authors advised the use of pens for injection of short-acting insulins, as all the mistakes were made by patients who used vials and syringes to administer both types of insulin.

Novel Uses for RXRActive Compounds

In other heterodimeric contexts, known as permissive heterodirners, RXR is able to activate transcription. The most important of these in a clinical sense are probably RXRPPAR (237-239) and RXRLXR (240) heterodirners. The ability of RXR agonists to activate RXRPPARy heterodirners is extremely important in the treatment of type II diabetes (non-insulin dependent diabetes), a disease of epidemic proportions in the United States and worldwide. For example, thiazol-idinedione antidiabetic drugs are becoming increasingly used in the treatment of type II diabetes. These drugs are PPARy agonists that activate RXR-PPARy heterodimeric complexes that, in turn, regulate the expression cf genes encoding proteins that improve glucose tolerance by enhancing the cellular sensitivity to insulin. Administration of RXR agonists to diabetic and obese mice also improves glucose tolerance, and the co-administration of RXR agonists with a thiazolidinedione results in synergistic improvements in several...

Neuroendocrine Tumors Somatostatin Analogs

Somatostatin (also known as somatotropin release-inhibiting factor SRIF or SRIF-14 , growth hormone-release inhibiting factor, or hypothalamic release-inhibiting hormone) is a widely occurring cyclic tetradecapeptide with a molecular weight of 1637.91 kDa (Structure 6.24). Together with other peptides (e.g., somatoliberin), it mediates the neuroregulation of somatotropin secretion. In particular, it inhibits release of growth hormone, insulin, and the glucagons, and is also a potent inhibitor of a number of systems including central and peripheral neural, GI, and vascular smooth muscle. It was first isolated from ovine hypothalamic extracts and then structurally elucidated and synthesized in the early 1970s.

Monitoring and Managing Adverse Reactions

When the androgens are administered to a patient with diabetes, blood glucose measurements should be done frequently because glucose tolerance may be altered. Adjustments may need to be made in insulin dosage, oral antidiabetic drugs, or diet. The nurse monitors the patient for signs for hypoglycemia and hyper-glycemia (see Chap. 49).

Other features of the patient

Adverse effects due to drug-drug interactions are not expected in diabetic patients using insulin and oral hypo-glycemic drugs that are not metabolized by CYP3A4 (for example tolbutamide, gliclazide, glibenclamide, glipizide, and metformin). The pharmacokinetic and safety data from clinical trials and postmarketing surveillance have been reviewed to assess the safety of itraconazole in diabetic patients with onychomycosis or dermatomycosis (54). Postmarketing surveillance, including all adverse event reports in patients taking itraconazole concomi-tantly with insulin or an oral hypoglycemic drug, revealed 15 reports suggestive of hyperglycemia and nine reports suggestive of hypoglycemia. In most patients there was no change in antidiabetic effect. From clinical trials in 189 diabetic patients taking itraconazole for various infections, one itraconazole-related adverse event was recorded this was a case of aggravated diabetes in a renal transplant patient who was also taking...

Neurotrophic Factor Signaling Pathways

Other pathways that are activated by Trk include phospholipase C-y (PLC-y) and phosphatidylinositol-3'-OH-kinase (PI-3-K). As discussed for PLC, PLC-y also cleaves phosphatidylinositol into IP3 and DAG, resulting in release of intracellular Ca2+ and activation of PKC. The mechanisms underlying the regulation of PI-3-K are not as well characterized. PI-3-K is able to bind phos-phorylated Trk receptors, but it is more likely that it interacts with another family of proteins, insulin receptor substrate (IRS) proteins that bind to au-tophosphorylated Trk receptors. IRS proteins, including IRS1, IRS2, and IRS4

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