Glycomet

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Mandisa-Maia Jones-Haywood, MD

• Assistant Professor
• Anesthesiology
• Wake Forest University School of Medicine
• Winston Salem, North Carolina

The insulin-like growth factors (also called somatomedins) are peptides that have structural and functional similarity to insulin and 102 mediate growth hormone action diabetes type 2 research buy glycomet 500mg online. The genes are subject to a variety of promoters metabolic disease icd 9 code buy glycomet american express, and thus differential regulation can govern ultimate actions diabete games generic glycomet 500mg with mastercard. The intracellular component of the b-subunit is a tyrosine kinase that is activated by autophosphorylation control diabetes home remedies purchase glycomet 500mg without prescription. It is a single chain glycoprotein diabetes type 2 algorithm purchase online glycomet, with 90% of its structure extending extracellularly managing diabetes 911 buy glycomet us. The story becomes confused when various growth factors and regulators are studied, because of their various stimulating and inhibiting effects. This suggests that –1, -2, and -3 play a role in growing follicles, -2, -4, and -5 in atretic and failing follicles. Even though these changes may play a role in anovulatory pathophysiology, they are consistent with failure in development and thus may not be etiologic factors. This mechanism is of special interest when considering the development of pituitary tumors, such as the prolactin secreting pituitary adenoma. The insulin-like growth factor story is at once complex, fascinating, and compelling. Epidermal growth factor is a mitogen for a variety of cells, and its action is potentiated by other growth factors. Granulosa cells, in particular, respond to this growth factor in a variety of ways related to gonadotropin stimulation, including proliferation. This factor is a mitogen for a variety of cells and is present in all steroid-producing tissues. Both platelet-derived growth factor and epidermal growth factor may also modify prostaglandin production within the follicle. Leukocytes are a prominent component of the ovarian follicle and a major source of interleukins. In the rat, interleukin-1 stimulates ovarian 132 prostaglandin synthesis and perhaps plays a role in ovulation. It very likely is a key player in the process of apoptosis, a feature of follicular atresia as well as luteolysis of the corpus luteum. A variety of hormones can be found in the follicular fluid, as well as enzymes and peptides, which play important roles in follicular growth and development, ovulation, and modulation of hormonal responses. These increases in prorenin from the ovary are not responsible for any significant changes in the plasma levels of the active form, renin. Possible roles for this ovarian prorenin-renin-angiotensin system include stimulation of steroidogenesis to provide androgen substrate for estrogen production, regulation of calcium and prostaglandin metabolism, and stimulation of angiogenesis. This system may affect vascular and tissue functions both within and outside the ovary. Antimüllerian hormone directly inhibits proliferation of granulosa and luteal cells, as well as epidermal growth factor-stimulated proliferation. Pregnancy-associated plasma protein A, found in the placenta, is also present in follicular fluid. Growth hormone-binding protein is present in follicular fluid and similar in characteristics to the same binding protein in serum. Follicular phase estrogen production is explained by the two-ell, two-gonadotropin mechanism. Follicular response to the gonadotropins is modulated by a variety of growth factors and autocrine/paracrine peptides. Follicular Growth and Development in the Primate Ovary Concern that the story for ovarian follicular growth and development might be different in the primate originated with the failure to find estrogen receptors in any of the 140 significant ovarian compartments in the monkey: follicles, stromal tissue, interstitial tissue, or corpora lutea. However, in further monkey experiments, no reduction in total number or size of follicles resulted when estradiol production was effectively suppressed by treatment with an inhibitor of the aromatase enzyme system or with an inhibitor of 142, 143 3b-hydroxysteroid dehydrogenase. Oocyte development was not altered, although the subsequent fertilization rate was reduced by this treatment. Another argument against a major role for estrogen in follicular growth and development is the successful stimulation with gonadotropins of normal follicular growth and 144, 145 development in women with 17a-hydroxylase deficiency (an inherited disorder that prevents the production of androgens and estrogens). Nevertheless, oocytes were retrieved, and with in vitro fertilization, pregnancy was achieved. As the follicle grows, activin production decreases and inhibin production 150, 151 152 increases. In addition, follistatin levels increase in follicular fluid with increasing growth of the follicle, a mechanism for decreasing activin activity. In the mature granulosa of the dominant preovulatory follicle, activin serves to prevent premature luteinization and progesterone production. The successful follicle is characterized by the highest estrogen (for central feedback action) and the greatest inhibin production (for both local and central actions). The highest level of gene activity encoding activin B is found in immature antral follicles and the lowest level in preovulatory follicles. It is not certain which form of inhibin plays a key role, but as with circulating levels of inhibin, inhibin B is 153 the predominant inhibin in the follicular fluid of growing follicles. The growth factors assume an important, but perhaps not essential, role as facilitating agents. The Preovulatory Follicle Granulosa cells in the preovulatory follicle enlarge and acquire lipid inclusions while the theca becomes vacuolated and richly vascular, giving the preovulatory follicle a hyperemic appearance. Approaching maturity, the preovulatory follicle produces increasing amounts of estrogen. During the late follicular phase, estrogens rise slowly at first, then rapidly, 154 155 reaching a peak approximately 24–36 hours prior to ovulation. An increase in progesterone can be 51 detected in the venous effluent of the ovary bearing the preovulatory follicle as early as day 10 of the cycle. This small but significant increase in the production of progesterone in the preovulatory period has immense physiologic importance. Prior to the emergence of this follicular progesterone, the circulating level of 157 progesterone was derived from the adrenal gland. The traditional view has been that progesterone receptors are expressed in response to estrogen through an estrogen-receptor mediated mechanism. Progesterone affects the positive feedback response to estrogen in both a time and dose dependent manner. Hence, the surprising onset of ovulation occasionally observed in an anovulatory, amenorrheic woman administered a prgestin challenge. Appropriately low levels of progesterone derived from the maturing follicle contribute to the precise synchronization of the midcycle surge. Nevertheless, blockade of midcycle progesterone synthesis or activity in the monkey impaired the ovulatory process and 163 luteinization. The preovulatory period is associated with a rise in plasma levels of 17a-hydroxyprogesterone. This steroid does not appear to have a role in cycle regulation, and its appearance in the blood simply represents the secretion of an intermediate product. After ovulation, some theca cells become luteinized as part of the corpus luteum and lose the ability to express P450c17. Other luteinized theca cells retain P450c17 activity and are believed to continue to produce androgens for aromatization to estrogens. Because the products of thecal tissue are androgens, the increase in stromal tissue in the late follicular phase is associated with a rise in androgen levels in the peripheral plasma at midcycle. There is a 15% increase in androstenedione and a 20% increase in 164 testosterone. Androgen production at this stage in the cycle may serve two purposes: 1) a local role within the ovary to enhance the process of atresia, and 2) a systemic effect to stimulate libido. Therefore, androgens may play a regulatory role in ensuring that only a dominant follicle reaches the point of ovulation. If the midcycle rise in androgens affects libido, then an increase in sexual activity should coincide with this rise. Early studies failed to demonstrate a consistent pattern in coital frequency in women because of the effect of male partner initiation. If only sexual behavior 165 initiated by women is studied, a peak in female-initiated sexual activity is seen during the ovulatory phase of the cycle. The coital frequency of married couples has 166 also been noted to increase at the time of ovulation. Therefore, the midcycle rise in androgens may serve to increase sexual activity at the time most likely to achieve pregnancy. A midcycle increase in local and peripheral androgens occurs, derived from the thecal tissue of lesser, unsuccessful follicles. Ovulation the preovulatory follicle, through the elaboration of estradiol, provides its own ovulatory stimulus. Considerable variation in timing exists from cycle to cycle, even in the same woman. Ovulation occurs primarily in the morning during Spring, and primarily in the evening during Autumn and Winter. From July to February in the Northern Hemisphere, about 90% of women ovulate between 4 and 7 P. The gonadotropin surge stimulates a large collection of events that ultimately leads to ovulation, the physical release of the oocyte and its cumulus mass of granulosa 171 cells. This is not an explosive event; therefore, a complex series of changes must occur which cause the final maturation of the oocyte and the decomposition of the 172 collagenous layer of the follicular wall. Activin also suppresses progesterone production by luteal cells, providing yet another means of preventing premature luteinization. The oocyte enables cumulus cells to respond to the gonadotropin-induced physical and biochemical changes just before ovulation. The local factors that prevent premature oocyte maturation and luteinization are probably under control of the oocyte. In addition to its central effects, progesterone increases the distensibility of the follicle wall. A change in the elastic properties of the follicular wall is necessary to explain the rapid increase in follicular fluid volume, which occurs just prior to ovulation, unaccompanied by any significant change in intrafollicular pressure. The escape of the ovum is associated with degenerative changes of the collagen in the follicular wall so that just prior to ovulation the follicular wall becomes thin and stretched. The gonadotropin surge also releases histamine, and histamine alone can induce ovulation in some experimental models. The granulosa and theca cells produce plasminogen activator in response to the gonadotropin surge. Plasminogen is activated by either of two plasminogen activators: tissue-type plasminogen activator and urokinase-type plasminogen activator. These activators are encoded by separate genes and are also regulated by inhibitors. Plasminogen activators produced by granulosa cells activate plasminogen in the follicular fluid to produce plasmin. Thus, before and after ovulation, the inhibitor activity is high, while just at ovulation, activator activity is high and the inhibitors are at a nadir. The molecular regulation of these factors is necessary for the coordination that leads to ovulation. The inhibitor system, which is very active in the thecal and interstitial cells, prevents inappropriate activation of plasminogen and disruption of growing follicles. The inhibitor system has been demonstrated to be present in human granulosa cells and preovulatory 177, 178 and 179 follicular fluid and to be responsive to paracrine substances, epidermal growth factor and interleukin-1b. Movement of the follicle destined to ovulate to the surface of the ovary is important in that the exposed surface of the follicle is now prone to rupture because it is separated from cells rich in the plasminogen inhibitor system. Ovulation is the result of proteolytic digestion of the follicular apex, a site called the stigma. Prostaglandin synthesis is stimulated by interleukin-1b, implicating this cytokine in ovulation. Prostaglandins may also contract smooth muscle cells that have been identified in the ovary, thereby aiding the extrusion of the oocyte-cumulus cell mass. This role of prostaglandins is so well demonstrated that infertility patients should be advised to avoid the use of drugs that 186, 187 inhibit prostaglandin synthesis. Neutrophils are a prominent feature in the theca compartment of both healthy and atretic antral 188 189 follicles. The accumulation of leukocytes is mediated by chemotactic mechanisms of the interleukin system. These immune cells probably contribute to the cellular changes associated with ovulation, corpus luteum function, and apoptosis. The low midcycle levels of progesterone exert an inhibitory action on further granulosa cell multiplication, and the drop in estrogen may also reflect this local follicular role for progesterone. Finally, estrogen can exert an inhibitory effect on P450c17, a direct action on the gene that is not receptor-mediated. The granulosa cells that are attached to the basement membrane and enclose the follicle become luteal cells. This hyaluronic acid response depends upon maintenance of the link with the oocyte, indicating the secretion of a supporting factor. The oocyte further 190 secretes factors that promote granulosa cell proliferation and maintain the structural organization of the follicle. Expansion and dispersion of the cumulus cells allows the oocyte-cumulus cell mass to become free-floating in the antral fluid just before follicle rupture. It is likely that a combination of all of these influences cause the rapid decline in gonadotropin secretion. The many contributions of progesterone to ovulation are highlighted by the results of experiments in the monkey.

Diseases

• Mental retardation hip luxation G6PD variant
• Microphthalmos, microcornea, and sclerocornea
• Rhabdomyosarcoma 2
• Mirhosseini Holmes Walton syndrome
• Cystin transport, protein defect of
• Glucose 6 phosphate dehydrogenase deficiency
• Acrofrontofacionasal dysostosis

Merosin is bound to the dystrophin-glycoprotein complex and anchors the basal lamina to the sarcolemma blood glucose 240 buy discount glycomet on line. Merosin-negative congenital muscular dystrophy can be diagnosed by immunostaining of muscle or skin diabetes mellitus type 2 description order glycomet 500 mg fast delivery. Fukuyama-type congenital muscular dystrophy diabetes mellitus type 2 prevalence 500mg glycomet overnight delivery, occurring primarily in Japan diabetes definition dictionary purchase glycomet 500mg overnight delivery, is associated with mutations in the gene encoding for a protein named fukutin diabetes symptoms ulcers cheap glycomet. The same genetic defect probably accounts for the Walker-Warburg cerebro-ocular dysplasia syndrome diabetes and your kidneys symptoms purchase online glycomet. Fukutin is not associated with the sarcolemma and appears to be a secreted protein, but its function is unknown. Facioscapulohumeral Dystrophy Epidemiology and Pathobiology Inheritance of facioscapulohumeral dystrophy is autosomal dominant with high penetrance and variable expression within families. Affected family members may be unaware of their mild deficits, thus making examination of relatives of suspected patients very important. Facioscapulohumeral dystrophy has been linked to the telomeric region of chromosome 4q35. Although the gene has not been isolated, a deletion in this region is present in virtually all patients with facioscapulohumeral dystrophy. Clinical Manifestations the disease is initially manifested in childhood or adult life. It involves the facial muscles early and then descends to the scapular stabilizers (serratus anterior, rhomboid, trapezius, latissimus dorsi), the muscles of the upper part of the arm (biceps, triceps), and the anterior leg muscles. Early physical signs include failure to bury the eyelashes on forced eye closure, an expressionless face, winging of the scapulas when the arms are raised, and prominent indentation of the anterior axillary folds. The deltoids are relatively spared when compared with the other proximal arm muscles. Distal muscle weakness occurs first in the tibialis anterior and may result in footdrop and lead to a scapuloperoneal pattern of weakness. Muscle biopsy shows moderate myopathic changes, but a prominent mononuclear inflammatory infiltrate can be confused with polymyositis. Differential Diagnosis Scapuloperoneal muscular dystrophy is an autosomal dominant disorder that can resemble facioscapulohumeral dystrophy, but without facial weakness. Prognosis the rate of progression and the extent to which the pelvic girdle and forearm muscles are eventually affected vary considerably between and within families. Some patients experience a late exacerbation of weakness after years of little or slow progression. Clinical Manifestations Typical patients exhibit facial weakness with temporalis muscle wasting, frontal balding, ptosis, and weakness of the neck flexor muscles. Weakness of the extremities usually begins distally and progresses slowly to affect the limb-girdle muscles proximally. Weakness is a more common symptom than muscle stiffness or myotonia, although patients may complain of an inability to relax the fingers after a handgrip. Associated manifestations include posterior subscapular cataracts, testicular atrophy and impotence, intellectual impairment, and hypersomnia from both central and obstructive sleep apnea. Elevated serum glucose levels occur as a result of end-organ unresponsiveness to insulin, but frank diabetes mellitus rarely develops. Involvement of smooth muscle in the gastrointestinal tract can produce dysphagia, reduced gut motility, and chronic pseudo-obstruction. Muscle biopsies show excessive number of central nuclei, type 1 atrophy, and other nonspecific myopathic changes. Phenytoin, usually 300 mg daily, is the safest drug for myotonia; quinine, tocainide, and mexiletine can exacerbate cardiac conduction abnormalities. Sedatives and opiates should be used with caution because they can depress the ventilatory drive. Patients with myotonic dystrophy are at risk for pulmonary and cardiac complications during general anesthesia. Patients with mild weakness and myotonia can have very little progression, whereas those with severe weakness, cardiac conduction defects, and progressive disease have a shortened life expectancy. Distal Dystrophies Although a number of myopathies can have prominent distal weakness as a feature, some genetically distinct entities are classified as distal muscular dystrophies. Disturbed glycosylation is therefore now recognized as a molecular genetic defect for the muscular dystrophies. Examination of muscle biopsy specimens shows variable degrees of dystrophic changes. All these disorders have progressive courses and over time can involve the proximal muscles and lead to loss of ambulation. Myofibrillar Myopathy Myofibrillar myopathy (also known as desmin myopathy) is a heterogeneous group of muscular dystrophies that can be manifested as either distal or limb-girdle patterns of weakness. In 21 most kindreds the disorder is inherited in an autosomal dominant fashion, but sporadic cases occur. Oculopharyngeal Muscular Dystrophy Oculopharyngeal muscular dystrophy is inherited as an autosomal dominant disorder. This disease is manifested in the fifth or sixth decade as progressive ptosis followed by dysphagia. Extremity weakness usually occurs in a limb-girdle pattern, but some variants have distal involvement. Patients may benefit from surgical correction (cricopharyngeal myotomy) for achalasia or a gastric feeding tube. Death can result from aspiration pneumonia or starvation if adequate nutrition is not addressed. Onset can occur later in childhood and even in early adulthood, and some congenital myopathies have a severe course and fatal outcome. Moreover, the molecular defect of some congenital myopathies can result in the phenotype of a muscular dystrophy. Most patients have limb-girdle weakness, although distal weakness occurs in some families. Central Core Myopathy Central core myopathy is autosomal dominant, but sporadic cases occur. Some patients with malignant hyperthermia also have mutations in this gene, and thus the disorders may be allelic. The mechanism by which defects in the ryanodine receptor gene lead to these disorders is unknown. Nemaline Myopathy the histologic characteristic of nemaline myopathy, a congenital myopathy, is the presence of rods, or nemaline (Greek nema = “thread”) bodies, within muscle fibers. In most autosomal recessive families the disorder has been linked to 2q; nebulin is the probable candidate gene. In some autosomal dominant families, however, nemaline myopathy has been linked to a mutation in the -tropomyosin gene on chromosome 1q. Clinically, the myopathy can be manifested as a severe neonatal form with respiratory (diaphragm) involvement that is generally fatal within the first year of life or as a mild static or slowly progressive condition present from birth or early childhood. Centronuclear (Myotubular) Myopathy the histologic hallmark of centronuclear (myotubular) myopathy is the presence of large central nuclei within many muscle fibers. Myotubularin is a phosphatase important in muscle cell growth and differentiation. As with nemaline myopathy, there are severe neonatal varieties and static or slowly progressive forms with onset from birth to adulthood. Ptosis and ophthalmoparesis commonly occur in all forms of centronuclear myopathy and may distinguish these patients from those with other congenital myopathies. The severe infantile form is usually X-linked recessive and is associated with respiratory insufficiency; most patients die in infancy, but a few survive into childhood, usually with major disabilities. Congenital Fiber-Type Disproportion the distinguishing morphologic finding in congenital fiber-type disproportion is an increased number of small type 1 muscle fibers. Most patients have an onset at birth with hypotonia, and the course of the disorder is nonprogressive and relatively benign. A fourth group involving the utilization of adenine nucleotides is more controversial (Table 5). Glucose/Glycogen Metabolism Disorders Glucose and its storage form glycogen are essential for the short-term, predominantly anaerobic energy requirements of muscle. Disorders of glucose and glycogen metabolism (grouped under the term glycogenoses) have two distinct clinical patterns. The glycogenoses that affect muscle are usually transmitted as autosomal recessive traits, except for phosphoglycerate kinase, which is X linked. Many patients note a “second-wind” phenomenon after a period of brief rest so that they can continue the exercise at the previous level of activity. Muscle biopsy shows scattered necrotic and regenerating fibers, especially after an episode of rhabdomyolysis. Oral sucrose ingestion improves exercise tolerance in patients with myophosphorylase deficiency. Otherwise, no specific treatment is available for these disorders, but aerobic exercise training and a high-protein diet have been proposed as sensible strategies. Glycogenoses with Fixed Weakness and No Exercise Intolerance -Glucosidase Deficiencies -Glucosidase, also known as acid maltase, is a lysosomal enzyme that breaks down glycogen to glucose; when its level is deficient, glycogen accumulates within lysosomes, as well as freely in the cytoplasm of cells. The childhood (juvenile) type is manifested in infancy or early childhood as a myopathy. Weakness is more proximal than distal, and there may be calf enlargement simulating muscular dystrophy. The adult type is manifested between the second and seventh decades of life either as slowly progressive limb muscle weakness that mimics limb-girdle dystrophy or in a scapuloperoneal pattern. These patients often experience insidious ventilatory muscle weakness leading to respiratory failure. Muscle biopsy demonstrates a vacuolar myopathy with high glycogen content and acid phosphatase reactivity in the vacuoles. The diagnosis is confirmed by demonstrating -glucosidase deficiency in either muscle, skin fibroblasts, or lymphocytes. Treatment and Prognosis Enzyme replacement therapy with intravenous recombinant -glucosidase (Myozyme) can be life-saving and was recently approved by the Food and Drug Administration for the infantile, childhood, and adult forms of the disease. Debranching Enzyme Deficiency Debranching enzyme deficiency is a rare disease that can affect the liver, heart, or skeletal muscle. The disease is most 27 commonly manifested in childhood as hepatomegaly with fasting hypoglycemia that spontaneously resolves by adulthood. Patients less frequently have a disabling myopathy that affects both proximal and distal muscles and can appear in childhood or (more commonly) in adult life. There may be a depressed lactate response on forearm testing, but myoglobinuria is rare. Branching Enzyme Deficiency Deficiency of the branching enzyme is manifested in infancy as progressive liver and cardiac dysfunction, which leads to death in the first years of life. Muscle weakness is variable; if weakness is present, the tongue is severely affected. Disorders of Fatty Acid Metabolism Lipids are essential for the aerobic energy needs of muscle during sustained exercise. Serum long-chain fatty acids, which are the primary lipid fuel for muscle metabolism, are transported into the mitochondria as carnitine esters and are metabolized via -oxidation. As with glycogen pathway defects, the myopathic manifestations of fatty acid metabolism can consist of dynamic exercise intolerance with myoglobinuria or static weakness with a lipid storage myopathy. A lipid storage myopathy can be caused by primary carnitine deficiency or by another defect in fatty acid oxidation with secondary carnitine deficiency. Most lipid disorders occur sporadically; they are believed to be autosomal recessive. It causes a Reye syndrome–like illness with hypoketotic hypoglycemia, encephalopathy, hyperammonemia, and liver dysfunction. These attacks are distinct from those associated with glycolytic defects in that they occur after prolonged exercise, fasting, febrile illness, or other provocations that may increase muscle dependence on free fatty acids. Findings on muscle biopsy are usually normal except for evidence of muscle myopathic injury after rhabdomyolysis. Although there is no specific treatment, increasing intake of carbohydrates and the frequency of meals prevents episodes of rhabdomyolysis. In the systemic form, the impaired transport of carnitine into multiple tissues results from nonfunctional high-affinity carnitine receptors. Patients have a myopathy with cardiac involvement, as well as episodes of hepatic dysfunction with hypoketotic hypoglycemia and altered mental status. There is no urinary excretion of organic acids to suggest a secondary metabolic illness. When the disease is limited to muscle, patients are usually seen in childhood with limb girdle myopathy. Patients have diminished muscle uptake of carnitine and a fixed lipid storage myopathy but a normal serum carnitine level. Secondary Carnitine Deficiency Most carnitine deficiencies are secondary to enzyme defects in -oxidation. Defects in lipid metabolism lead to accumulation of acyl-CoA molecules, which are converted to acylcarnitines, forms that are more readily excreted in urine. This process leads to negative carnitine balance and, ultimately, to carnitine deficiency. Impaired metabolism of valproic acid may similarly lead to excretion of valproylcarnitine and secondary carnitine deficiency. Most of these illnesses occur in early childhood or infancy and lead to Reye syndrome–like episodes. Some surviving adults experience a lipid storage myopathy with the clinical phenotype of a limb-girdle syndrome. The free carnitine level is diminished, but that of esterified carnitine may be increased, especially after oral supplementation of depleted carnitine stores. Abnormal urinary excretion of organic acids is a critical clue to differentiate these disorders from primary carnitine deficiency. Different metabolic blocks in fatty acid metabolism lead to the excretion of distinct urinary acylcarnitine species, which can be distinguished by mass spectroscopy.

Cheap glycomet generic. Addressing Pre-diabetes with Biotech.

This can often lead to a person taking multiple and possibly mechanism-overlapping medications diabetes symptoms sleep buy 500mg glycomet visa. The questions to discuss with a health care professional are: Are the medications actually making a difference? In other words type 2 diabetes juice fasting order cheapest glycomet, taking pain medications is a choice that each person must make by weighing the benefits vs diabetes type 1 4 year old order glycomet 500mg overnight delivery. When the risks appear to outweigh the benefits of taking a pain medication diabetes insipidus in older dogs buy glycomet 500 mg otc, reducing the dose and ultimately discontinuing the medication should be considered diabetes definition who 2013 cheap 500mg glycomet visa. This is called weaning or tapering particularly when the individual has become dependent on the medication diabetes type 1 diet plan buy glycomet 500mg lowest price. The term “detoxification” is sometimes used interchangeably but should be limited to cases with opioid addiction. The goal of tapering/weaning down the dose is to safely discontinue medications that do not seem helpful in reducing pain while allowing the body to adjust while monitoring for negative effects of withdrawal symptoms. Oftentimes, people discover they feel better taking lower doses, fewer medications, or not taking medications at all. It is best to check with the health care professional before altering the medication regimen by taking less of the medication or stopping it. It is dangerous to abruptly stop taking some medications (sometimes referred to as going “cold turkey”). Because the body develops physical dependence to some medications when they are taken regularly, abrupt withdrawal or too rapid a reduction in the dose of these medications can be very uncomfortable or even hazardous to one’s health. It depends on the type of medication, how much, and for how long the medication has been taken. A sound approach is to talk to a health care professional before making any medication changes or if you have any other questions or concerns. Answer the following questions about each medication, and the person with pain should write down the answers beside the name of each medication during the visit: o For what condition is this medication being prescribed? The health care professional determines the rate at which the dose is reduced, and adjustments can be made as necessary. For example, reasonable opioid weaning protocols suggest decreasing pill intake by 10 20 percent per week, as tolerated. Hydration (drinking water), relaxation, and emotional support are all important to enhance the likelihood of success. Sometimes weaning or discontinuing medication (especially opioids) is most safely accomplished under the close supervision of a specialist (such as a pain or addiction medicine specialist) in a medically-supervised program to prevent complications and severe withdrawal symptoms. Other drugs to manage withdrawal symptoms during detoxification o naltrexone (Vivitrol) – an extended release non-addictive, once-monthly injection to prevent relapse in opioid dependent patients when used with counseling following detoxification. Alcohol has no place in the treatment of chronic pain, although some individuals turn to alcohol forrelief of their pain. It is important to discuss the use of alcohol with your health care provider, including the amount, frequency, and type of alcohol consumed. Alcohol can enhance the effects of certain prescription drugs as well as markedly increase potential toxic side effects. The mixture of alcohol and opioids along with sedatives or anti-anxiety drugs can cause death. Short-term effects of an average amount of alcohol include relaxation, breakdown of inhibitions, euphoria, and decreased alertness. Short-term effects of large amounts of alcohol include nausea, stupor, hangover, unconsciousness, and even death. Alcohol also affects the heart and blood vessels by decreasing normal function, leading to heart disease. Bleeding from the esophagus and stomach frequently accompany liver disease caused by chronic alcoholism. Many medications cannot be given to patients with abnormal liver function, thus making it more difficult to treat chronic pain. The early signs of alcoholism include the prominent smell of alcohol on the breath and behavior changes such as aggressiveness, passivity, decreased inhibitions, poor judgment, depression, and outbursts of uncontrolled emotion such as rage or tearfulness. Signs of intoxication with alcohol include unsteady gait, slurred speech, and poor performance of any brain or muscle function. Signs of severe alcohol intoxication include stupor or coma with slow, noisy breathing, cold and clammy skin, and an increased heartbeat. The long-term effects of alcohol addiction (alcoholism) include craving, compulsive use and continued use despite harm to family, job, health, and safety. When alcohol is unavailable to persons who are severely addicted, withdrawal symptoms will occur and may be life threatening if not treated immediately. Even with successful treatment, individuals addicted to alcohol may at risk for relapse, suggesting the need for ongoing treatment (such as involvement in 12-step programs, counseling, and family support). Smoking not only reduces blood flow to your heart but also to other structures such as the skin, bones, and discs. Due to this, the individual may get accelerated aging leading to degenerative conditions. The lack of blood supply caused by cigarette smoke is also responsible for increased healing time after surgery. After back fusion surgery, smoking cigarettes can increase the risk of the fusion not healing properly. Cigarette smoke triggers the release of pro inflammatory cytokines, thus increasing inflammation and intensifying pain. Smoking makes the bones weak and increases the prevalence of osteoporosis, spinal degenerative disease, and impaired bone and wound healing. Cigarette smoking is also considered a risk factor for misuse of opioid medications and should be considered when prescribing opioids. Assess readiness to quit smoking and ask a health care professional or pharmacist for help. They will make recommendations, modifications, and develop a treatment plan to optimize success. Knowing these triggers can help replace smoking a cigarette with healthier habits. Smoker’s Log: Cigarettes per day Time of each cigarette What triggered the craving? Some medications can help with the craving of cigarettes that many people experience when they are trying to quit. Dopamine is a neurotransmitter, a chemical messenger that plays a prominent role in addiction. It is responsible for the reward pathway and the “feel good” phenomenon experienced when smoking. Norepinephrine is also a neurotransmitter that sends signals from one neuron to the next. Norepinephrine is similar to noradrenaline and adrenaline and is responsible for constricting and narrowing the blood vessels. American Chronic Pain Association Copyright 2018 144 fi) Bupropion is an antidepressant (Wellbutrin ; however, it is also used in the smoking cessation fi process (Zyban) – i. Bupropion inhibits the reuptake of both dopamine and norepinephrine, increasing their concentrations within the brain. By increasing dopamine, the frequency and severity of nicotine cravings and urges are reduced. Norepinephrine plays a role in alleviating symptoms associated with nicotine withdrawal. Therefore, it is important for patients to start this medication one to two weeks prior to their “quit-date”. Less severe, more common side effects include dry mouth, headache, nausea, dizziness, sweating, and insomnia. Varenicline (Chantixfi) mimics nicotine at the receptors in order to aid in smoking cessation. Varenicline is similar in structure to cytosine, a natural compound that has aided in smoking cessation since the 1960s. First, varenicline is effective because it provides partial nicotine effects to help with nicotine withdrawal symptoms. Second, varenicline also binds to nicotine receptors to block nicotine’s effect if the person relapses. Patients who respond to treatment may receive another 12 weeks of therapy to increase their success rate. Common side effects include nausea, vomiting, insomnia, headache, and abnormal dreams. These warnings include changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Some neuropsychiatric adverse events, including unusual and sometimes aggressive behavior directed to oneself or others, may have been worsened by concomitant use of alcohol. It is allowed by some states for medicinal and now recreational purposes, but overall it is banned for distribution by the United States federal government. However, medicinal use has been independently legalized by 44 states and the District of Columbia. All of this creates a dissonance between federal and state perspectives on the medicinal use of marijuana (cannabis). This dissonance has also created a conundrum for physicians who are trying to do the right thing for their patients but may find themselves in violation of federal regulation. There is evidence of some analgesic benefits from marijuana, but there is a great deal of research that needs to still be done and this classification impedes that research. That can be compared to a Gallup poll in 1969 where only 12% said that marijuana should be legal. Some health care professionals may recommend the use of medical marijuana, some will not provide a recommendation but will not object to a patient’s use of marijuana with other pain medicines, and some will refuse to prescribe other medications (especially opioids) to individuals who are using marijuana. Some health care professionals take a “don’t ask, don’t tell” philosophy and do not check for marijuana when doing urine drug testing. Individuals cannot say they are using marijuana recreationally to deal with a medical problem and expect that to comply with the law as specific medical conditions. Nevertheless, the use of any substances should be discussed openly and honestly between the person and his or her health care professional. If the individual is on opioids and/or pain treatment program, the concurrent use of marijuana should be clearly spelled out in the opioid/pain treatment contract. Although some states allow the legal use of marijuana for medicinal purposes, which may or may not include pain, there is no high-level scientific research supporting the long-term use of marijuana for chronic pain. In fact, there is good evidence that excessive smoking of marijuana can be harmful (especially in young people). American Chronic Pain Association Copyright 2018 146 However, in January 2017, the National Academies of Sciences, Engineering and Medicine published a paper that concluded after studying 10,000 scientific abstracts published since 1999 that “found evidence to support that patients who were treated with cannabis or cannabinoids were more likely to experience a significant reduction in pain symptoms” 8. That means there is now a disagreement within the federal government whether marijuana can help manage pain (or even be considered medicinal). More frequent marijuana smoking is associated with an increased risk of severe respiratory illnesses, especially chronic bronchitis. Other potential delivery methods include oils, tinctures, vaporizers, and edibles. Use also leads to reduced workplace productivity, as well as impaired judgment, even hours after use. Marijuana intoxication impairs cognitive and psychomotor performance with complex, demanding tasks. Individuals who have used marijuana over long periods of time demonstrate impaired performance on a variety of neuropsychological tests. A recent review of the existing medical literature concluded that the use of marijuana at a young age increased the risk of schizophrenia or a schizophrenia-like psychotic illness by approximately three-fold. Emerging evidence suggests a link between more frequent, or severe, marijuana use and anxiety symptoms and disorders. Patients using opioids need to be aware of all prescribed and non-prescribed medications that affect the central nervous system, including marijuana and alcohol, because there may be a synergistic effect that may cause respiratory depression and death. People who are self-medicating with marijuana may not recognize the presence of marijuana withdrawal symptoms. Marijuana causes physical dependence, and withdrawal symptoms can start as early as hours after smoking marijuana and last for up to a month and include sleep disturbances, substantial anxiety (which can worsen pain), discomfort, lack of appetite, and commonly trigger marijuana craving. Despite some states allowing medicinal marijuana, it is a federal crime for a health care professional to prescribe a scheduled drug to a person known to be using the drug illegally. It is also important to remember that possessing marijuana when traveling through a state where medicinal marijuana is not allowed could result in being charged with possession of an illegal substance, even if the person is using the drug under the supervision of a physician and has the proper home state documentation. Additionally, an individual can be denied employment or fired if the employer or prospective employer conducts drug screenings as a part of the hiring process or has a ‘no-drug tolerance’ policy. American Chronic Pain Association Copyright 2018 147 Illegal Drugs Regarding chronic pain treatment (excluding cancer and end-of-life care), health care professionals will not prescribe opioids and other medications to individuals who are known to use illegal “street” drugs (heroin, methamphetamines, cocaine, and others) or to be irresponsible with prescription pain medication. The American Chronic Pain Association website can be a great source of information theacpa. This and other pain management programs include ways to track daily pain and activity and can be a useful vehicle to easily summarize progress over time. They can be especially helpful when starting an exercise routine by tracking progress based on frequency and duration of the exercises. These programs can also suggest warm-up and cool-down stretching routines catered for each individual’s pain problem. They also can be useful for monitoring medication use and giving helpful reminders throughout the day. Smart phone applications (apps) are in development specifically for persons with chronic pain. These programs are useful in identifying important information about the pain, summarizing progress for the health care professional, and offering daily tips and recommendations for improving pain management. When you understand what makes your pain worse, you can begin to work on ways to reduce or deal with your pain “triggers.

Agnus-Castus (Chasteberry). Glycomet.

• Premenstrual syndrome (PMS).
• Is Vitex Agnus-castus effective?
• What other names is Vitex Agnus-castus known by?
• Premenstrual dysphoric disorder (PMDD).
• Dosing considerations for Vitex Agnus-castus.
• Are there safety concerns?
• How does Vitex Agnus-castus work?

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96930

References

• Hyattsville, MD: National Center for Health Statistics, 2007.
• Elleder M, Jirasek A, Smid F, et al. Niemann-Pick disease type C. Study on the nature of cerebral storage process. Acta Neuropathol (Berl) 1985;66:325.
• Gautam M, Noakes PG, Moscoso L, et al. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell. 1996;85(4):525-535.
• Simon D, Fischer S, Grossman A, et al. Left ventricular assist device-related infection: treatment and outcome. Clin Infect Dis. 2005;40:1108-1115.
• Dekker A, Bulley S, Beyene J, et al. Meta-analysis of randomized controlled trials of prophylactic granulocyte colony-stimulating factor and granulocyte- macrophage colony-stimulating factor after autologous and allogeneic stem cell transplantation. J Clin Oncol 2006;24(33):5207-5215.
• Mosley WJ, 2nd, Lloyd-Jones DM. Epidemiology of hypertension in the elderly. Clin Geriatr Med 2009;25(2):179-189.
• Zimmern P, Nager CW, Albo M, et al: Urinary Incontinence Treatment Network: inter-rater reliability of filling cystometrogram interpretation in a multicenter study, J Urol 175:2174n2177, 2006.