Home Remedies for Anorexia

Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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Bulimia Help Method

Endorsed by University Professors, Eating Disorders Specialists, Doctors and former bulimics, the Bulimia Help Method is a proven & trusted approach to lifelong recovery from bulimia. The Bulimia Help Method home treatment program gives you the insight, skills and tools needed to break free from bulimia and to make peace with food and your body. You are guided step-by-step along the way so you always know what to expect and what to do next. A powerful audio program will help to reprogram your old eating habits at a sub-conscious level, speed up your recovery and help you feel more calm and grounded.

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Perspectives For Pharmacogenetic Research Into Eating Disorders And Obesity

Eating disorder drugs The antidepressant drug Fluoxetine, a more selective serotonin reuptake inhibitor, is generally well tolerated and may be an effective treatment option for adolescents with bulimia nervosa. (Kotler et al., 2003). Treatment with fluoxetine in patients with bulimia nervosa improved outcome and decreased the likelihood of relapse. (Romano et al., 2002). Fluoxetine may also prevent relapse in AN. It dimishes associated symptoms of anorexia nervosa following adequate weight restoration (Kim, 2003). Thus, for the treatment response to fluoxetine, genes constituting the serotonin system may play a role. Since serotonin 2C receptors expressed on leptin-sensitive POMC cells mediate at least some of the effects of the reuptake inhibitor fenfluramine on eating behaviour, also the neuropeptidergic genes implicated in the leptin response, are candidate genes for the treatment responsiveness of this class of drugs. Olanzapine has been evaluated as drug therapy in anorexia...

Current Perspectives on Drug Therapies for Anorexia Nervosa and Bulimia Nervosa

Summary This article presents current perspectives on drug therapies for anorexia nervosa and bulimia nervosa. Topics include diagnostic considerations, drug treatment for anorexia nervosa, and drug treatment for bulimia nervosa. The authors maintain that there is little if any role for pharmacotherapy in anorexia nervosa. Drugs used to promote food intake and weight gain in bulimia nervosa have provided disappointing results. Newer antidepressants, anticonvulsants, benzodiazepines, lithium, fenfluramine, and opiate antagonists may prove useful, although all require further research. 1 table. 85 references.

Eating Disorders

Bulimia Nervosa 5-HT involvement in bulimia nervosa has been based on several observations (Jimerson et al. 1989 Kaye et al. 1988). Kaye et al. (1988) hypothesized that variations in the ratio of tryptophan to other amino acids, consequent to recurrent bingeing and vomiting, mediated both satiety and mood. Some patients with bulimia nervosa, independent of mood status, manifest a blunted prolactin response to m-chlorophenylpiperazine (m-CPP). This has been interpreted as evidence of postsynaptic 5-HT hypersensitivity within select hypothalamic pathways (Brewerton et al. 1990). Goldbloom et al. (1988) reported that the Vmax (maximum velocity) the maximum amount of substrate per unit of time that an enzyme can break down or synthesize at saturation (i.e., when all of the enzyme's active sites are filled) of platelet 5-HT uptake was increased among bulimic patients without depression. Jimerson et al. (1989) observed a significant inverse association between CSF 5 HIAA and symptom...

Alterations in Physiological Function Circardian Rhythms Sleep Pain Perception and Appetite

Depressed patients also frequently complain about altered appetite. Both the endocrine systems and neurotransmitters are involved in appetite control. The mono-amines that are often perturbed during depression also have effects on appetite. DA modulates sensory feedback and appetite (198, 199). NE in the hypothalamus increases meal size and stimulates carbohydrate intake through a2-adrenergic receptors (200). This effect shows rapid tolerance. Corticosterone upregulates a2-adrenoreceptors. 5-HT acts through the 5-HT2C receptor to affect eating rate and through the 5-HT1B receptor to affect meal size (198). CRF is a potent anorectic when injected in cerebral ventricles or paraventricular nucleus. Thus, when present, elevated CRF associated with depression may contribute to anorexia.

Immune Activation In Major Depression

The status of the immune system in major depression has been extensively studied over the last ten years and there is now some evidence that the acute episode of this illness may be accompanied by immune activation acute phase response (Maes., 1993 Sluzewska et al., 1996b). The acute phase response (apr) is a response of the organism to disturbances of its homeostasis due to factors such as, infection, tissue injury, neoplastic growth or immunological disorders (Heinrich et al., 1990). Within this systemic reaction, that involves the endocrine, immunologic and metabolic system (Kushner and Mackiewicz., 1993), there are also behavioural changes, which are expressed as sickness behaviour, characterised by psychomotor retardation, sleep disturbances, anorexia, anergy, and lethargy (Kent et al., 1992).

Attentiondeficithyperactivity Disorder

ADHD, usually first evident in childhood, is characterized by excessive motor activity, difficulty in sustaining attention, and impulsiveness. A variety of stimulant drugs have been utilized in the treatment of ADHD, and they are particularly indicated in moderate-to-severe cases. Methylphenidate is effective in children with ADHD and is the most common intervention treatment may start with a dose of 5 mg in the morning and at lunch, increasing gradually over a period of weeks depending on the response as judged by parents, teachers, and the clinician. The total daily dose generally should not exceed 60 mg. Methylphenidate has a short duration of action thus, most children require 2-3 doses day, with the timing individualized for effect. Methylphenidate, dextroamphetamine, and amphetamine probably have similar efficacy in ADHD. pemoline appears to be less effective, although like sustained release preparations of methylphenidate (ritalin sr, concerta, metadate) and amphetamine...

Specific Metabolic Features of Women with Bipolar Disorder

And a propensity towards higher waist circumferences 10 . Obese patients with either BD or schizophrenia are more likely to be women 30 , and weight gain has been shown to be associated with female sex 31 . An evaluation of data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) demonstrated greater rates of obesity in bipolar women (31 ), compared to bipolar men (21 ) in contrast, there were greater rates of overweight in bipolar men (38 ), compared to women (22 ) 32 , a finding consistent with previous studies 33 . Women with BD appear to have a higher likelihood of increased waist circumference than men with BD, suggesting a sex-specific vulnerability to IR in BD. Changes in weight and appetite are found more commonly in women than in men with BD 34, 35 . Higher rates of thyroid and eating disorders are seen in women with BD 36 . Factors that influence the onset and maintenance of obesity in BD include both gender and eating behavior 37 . Similarly,...

Herbal Remedies And Abnormal Liver Function Tests

Chaparral can be found in health food stores as capsules and tablets and is used as an antioxidant and anti-cancer herbal product. Leaves, stems and bark in bulk are also available for brewing tea. However, this product can cause severe hepatotoxicity. Several reports of chaparral-associated hepatitis have been reported. A 45-year-old woman who took 160 mg of chaparral per day for 10 weeks presented with jaundice, anorexia, fatigue, nausea and vomiting. Liver enzymes and other liver function tests showed abnormally high values (ALT 1611 U L 1, AST 957 U L 1, alkaline phosphatase 265 U L 1, GGT 993 U L 1 and bilirubin 11.6 mgdL 1). Hepatitis, CMV and EBV were ruled out. A liver biopsy showed acute inflammation with neutrophil and lymphoplasmocytic infiltration, hepatic disarray and necrosis. The diagnosis was drug-induced cholestatic hepatitis, which in this case was due to the use of chaparral.53 Gordon et al. reported a case where a 60-year-old woman took chaparral for 10 months and...

Use of Rivastigmine in the Treatment of Alzheimers Disease

Improvement across all measures in patients taking high dose rivastigmine (6-12 mg day) compared with the placebo group, and that the improvement was dose-dependent. There was no difference in cognition in subjects on low dose rivastigmine (1 -4 mg day) compared with placebo. In addition, there were no major adverse effects reported during the study. Rivastigmine was tolerated well with most side effects being transient, relating to gastrointestinal symptoms such as nausea, vomiting, anorexia, and diarrhea 40 .

Treatment Of Cytokineinduced Mood Disturbance

The recent explosion in the elucidation of the mechanisms of cytokine-induced CNS effects has encouraged innovative trials of pharmacologic interventions, including antidepressants (Goldman, 1994 Levenson & Fallon, 1993), opiate antagonists, (Valentine, Meyers, & Talpaz, 1995), stimulants (Valentine et al., 1998), and corticosteroids (Amato et al., 1995). The synthetic steroid megestrol acetate may be an effective treatment for the anorexia and cachexia caused by cytokine treatment (Plata-Salaman, 1998). In the future it may be possible to specifically inhibit certain induced cytokines responsible for adverse side effects but maintain the therapeutic efficacy of the given cytokine (Taylor & Grossberg, 1998). Finally, non-pharmacologic approaches, including exercise and time management strategies, may be of benefit (Dalakas, Mock, & Hawkins, 1998). From these early experiences it is becoming clear that appropriate interventions will allow patients to continue on effective doses of...

Pharmacological Properties

Response in the endocrine, autonomic, immune, and behavioral systems through the activation of the hypothalamic-pituitary-adrenal (HPA) axis and extrahypothalamic pathways. The peptide itself is highly conserved between species, and its evolutionary role is to mobilize energy stores and appropriate behavior(s) in response to a stressor. It has since evolved to regulate a variety of responses to stress. CRF was first isolated and characterized by Vale and colleagues in 1981. Due to the similarity in sizes of ACTH and CRF and limits on detection techniques, purification was performed on approximately 490,000 sheep (ovine) hypothalami in order to generate enough samples for isolation. This was part of an ongoing study elucidating a variety of hypotha-lamic peptides. In the majority of studies, the CRF system has consistently been shown to be dysregulated in many patients suffering from a variety of psychiatric illness including post-traumatic stress disorder (PTSD), early life trauma,...

Characterization Of Depressive And Anxiety Disorders

Clinical depression must be distinguished from normal grief, sadness, disappointment, and the dysphoria or demoralization often associated with medical illness. The condition is underdiagnosed and frequently undertreated. Major depression is characterized by feelings of intense sadness and despair, mental slowing and loss of concentration, pessimistic worry, lack of pleasure, self-deprecation, and variable agitation or hostility. Physical changes also occur, particularly in severe depression, including insomnia or hypersomnia altered eating patterns, with anorexia and weight loss or sometimes overeating decreased energy and libido and disruption of the normal circadian and ultradian rhythms of activity, body temperature, and many endocrine functions. As many as 10-15 of individuals with severe clinical depression, and up to 25 of those with bipolar disorder, display suicidal behavior at some time. Depressed patients usually respond to antidepressant drugs, or, in severe or...

Role of Pharmacotherapy Diagnostic Categories

Anorexia nervosa primarily affects adolescent females and young women, and only about 5-10 of people with the diagnosis are male. Two subtypes have been specified Anorexia nervosa is a serious and potentially life-threatening disorder with the highest standardized mortality rate among all psychiatric disorders, due to the chronic course, the associated medical complications, and the mental comorbidity. The cumulative lifetime prevalence is estimated to be 0.6 in the general population (Hudson et al. 2007) with an onset peak around 15-19 years. Anorexia nervosa is frequently associated with other psychological symptoms including depression, anxiety, and obsessive-compulsive features. Therapy typically includes nutritional rehabilitation and psychother-apeutic interventions, inpatient treatment is frequently required. There is no officially approved medication for the treatment of anorexia nervosa. A variety of agents have been examined with mostly discouraging results with regard to...

Current Concepts and State of Knowledge

Applicability of Current Models to Human Eating Disorders In addition to replicating the core symptoms defined in the DSM-IV (see Table 1), animal models of eating disorders should address three key elements gender bias, comorbidity with other psychiatric disorders, and adolescent onset. Anorexia and bulimia affect three times as many women as men (Hudson et al. 2007). The gender bias of binge-eating disorder is only slightly less pronounced, with 1.75 times as many women as men affected during their lives. Given this differential risk, animal models should incorporate the study of females whenever possible. Animal models should also address the high An ideal animal model would possess face, construct, and predictive validity, but eating disorders present significant challenges to the development of such a model. Because the causes of anorexia, bulimia, and binge-eating disorder in humans remain unclear, assessing the

Pharmacological Actions

Although slightly less selective than morphine, propoxyphene binds primarily to j opioid receptors and produces analgesia and other CNS effects that are similar to those seen with morphinelike opioids. It is likely that at equianalgesic doses the incidence of side effects such as nausea, anorexia, constipation, abdominal pain, and drowsiness are similar to those of codeine.

Hypothalamicpituitarygonadal Axis

Soules et al. 1984 Steele and Judd 1986). Gonadal steroids exert negative feedback effects on the amplitude and frequency of GnRH pulses and through this mechanism (in addition to direct actions on the pituitary) inhibit the secretion of LH and FSH. Likewise, central opioids, particularly ( -endorphin, exert a tonic inhibition on GnRH secretion (Ferin and Vande 1984). Circadian changes in LH secretion are not as prominent as those of the HPA axis (Jaffe et al. 1990). During puberty and following recovery from anorexia- or exercise-induced amenorrhea, nighttime secretion of LH becomes particularly prominent. Furthermore, nighttime slowing of LH pulses during the early follicular phase also occurs in normal women (Soules et al. 1985).

Neuroimmunoendo Crine Actions During Longterm Elevation Of Brain Corticotropinreleasing Hormone

Disturbances of the brain CRH system are thought to be implicated in several stress-related disorders such as major depression and anorexia bulimia, but also in Alzheimer's disease. There is evidence that major depression is associated with an increased central CRH drive. Patients suffering from major depression have elevated levels of CRH in the cerebrospinal fluid (Nemeroff, Widerlov, Bissette, Walleus, Karls-son, Eklund, Kilts, Loosen, & Vale, 1984), increased numbers of CRH expressing neurons and CRH mRNA levels in their PVN (Raadsheer, Hoogendijk, Stam,Tilders, & Swaab, 1994 Raadsheer, Van Heerikhuize, Lucassen, Hoogendijk, Tilders, & Swaab, 1995) and reduced CRH receptor density in the frontal cortex (Owens & Nemeroff, 1993). In addition, these patients present many symptoms reminiscent of the effects of centrally administered CRH in experimental animals, such as an activated HPA axis, increased sympathetic outflow, anxiety, increased emotionality, and loss of appetite and...

Neurotransmitter Transporters

Plasma membrane transporters have long been recognized as important components of the machinery for neural signaling. Reuptake inhibitors increase the levels of neuro-transmitter in the synapse, thus enhancing synaptic transmission, and provide important targets for therapeutic intervention. Indeed, the importance of neurotransmitter transporters is highlighted by the broad spectrum of drugs targeting these proteins, including those used to treat depression, anxiety, obesity and epilepsy, in addition to drugs of abuse, such as cocaine, amphetamine, and ecstasy (2). Furthermore, it is well established that neurotransmitter transporters have roles in several neurological and psychiatric diseases, including amyotrophic lateral sclerosis, severe orthostatic hypotension, obsessive-compulsive disorder, Asperger's syndrome, anorexia, and autism (3).

Evaluation and treatment

Anorexia, weight loss, fatigue, nausea and other nonspecific symptoms are common. Further investigation is prompted by the presence of anemia, hematemesis, melena, hematuria, and palpable masses on physical exam. Referral to an oncologist for a definitive diagnostic work-up and possible surgical exploration biopsy is always appropriate though initial diagnostic imaging may need to be performed so that referral can be facilitated.

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A review of evidence supported the use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite (Voth and Schwartz 1997). In patients with anorexia due to advanced cancer, THC (2.5 mg PO tid) was effective in stimulating appetite and was well tolerated at low doses (Nelson et al. 1994). Cannabinoids produced positive results for treatment of AIDS-related anorexia. Positive results of open trials were later confirmed with methodologically controlled studies. Dronabinol (2.5 mg PO twice daily) produced consistent and substantial improvement in appetite in patients with AIDS (Beal et al. 1995, 1997). Patients also reported improved

Molecular and Functional Imaging of the Histaminergic Nervous System

Psychosocial stress has been associated with increased rates of various psychiatric disorders, such as major depression, schizophrenia, anxiety, and eating disorders in our daily lives. The incidence of cognitive disorders is also increasing. We have recently conducted a variety of studies to elucidate the pathophysiological mechanisms of psychiatric disorders mentioned above 35-39 , putting emphasis on alterations in neural transmission in the histaminergic neuronal system 35 . For this purpose, 11C doxepin is the tracer of choice for imaging histamine H1 receptors (H1Rs). Using PET and nC doxepin, a large amount of evidence has been accumulated regarding the role of the histaminergic neuronal system in the patho-physiology of these disorders. In our recent studies, histamine H1 receptor binding was measured, by PET and nC doxepin, in 10 normal male subjects and 10 patients with schizophrenia 36 , 10 patients with major depression 37 , and 10 patients with AD 39 , respectively, as...

Other visceral cancers

Neoplasms can arise in all abdominal and pelvic structures. Symptomatology related to these neoplasms is similar for all sites with dull constant pain a common early symptom. Pain is generally localized to the chest or upper abdomen for upper gastrointestinal tract lesions and organs located in the upper abdomen. It is generally localized to lower abdomen perineum for lower gastrointestinal tract lesions and pelvic organs. The key statement is generally since no symptomatology or location is pathognomonic for any specific disease site due to the frequent presence of metastatic extension prior to diagnosis. Visceral cancers are frequently asymptomatic until obstruction or invasion of other structures occurs. Anorexia, weight loss, fatigue, nausea, and virtually every other nonspecific symptom can be noted at presentation. Anemia, hematemesis, melena, hematuria, and palpable masses on physical exam may direct further investigation. Appropriate imaging and surgical exploration biopsy are...

Indications And Efficacy

Food and Drug Administration (FDA)-labeled indications for fluoxetine are major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, bulimia nervosa, and premenstrual dysphoric disorder (PMDD). We will review these as well as some other disorders for which fluoxetine is commonly used.

Psychological Effects Of Immune Activation In Humans

Acute infectious illness, such as influenza, upper respiratory tract infections, gastroenteritis, Epstein-Barr virus, and cytomegalovirus, are associated with a range of depressive symptoms, including fatigue, psychomotor retardation, anorexia, somnolence, lethargy, muscle aches, cognitive disturbances, and depressed mood (Hickie & Lloyd, 1995). The evidence for these alterations is mainly anecdotal and only few studies examined these symptoms systematically. Experimentally-induced viral infections (e.g., common cold, influenza) are associated with decreased psychomotor performance of simple reaction-time tasks and memory impairments (Smith, Thomas, Brockman, Kent, & Nicholson 1993 Smith,Tyrrell, Al-Nakib, Coyle, Donovan, Higgins, & Wiliman, 1987 Smith,Tyrrell, Al-Nakib, Coyle, Donovan, Higgins, & Willman, 1988). In addition, they are often associated with long term psychiatric effects, particularly depression. Experimentally-induced influenza (but not infections with coronavirus or...

Adaptive And Maladaptive Aspects Of Immunologic Allyinduced Depression

Adaptive febrile response (Hart, 1988) Anorexia reduces the motivation of the organism to look for food, which may involve expenditure of energy. It also reduces the consumption of nutrients that are essential for the growth and proliferation of many pathogens (e.g., iron) (Hart, 1988) Anhedonia may further ensure the lack of motivation to engage in goal-directed behaviors, including social activity and sexual behavior Finally, the inhibition of female sexual behavior following activation of the immune system may be adaptive in preventing conception when the animal is sick, thus reducing the risk of spontaneous abortion, prenatal infection and abnormal development (Avitsur et al., 1997 Avitsur et al., 1998 Yirmiya, Avitsur, Donchin, Cohen, 1995). A depressive-like response to infection in the same way that pain is adaptive in response to tissue injury. Whereas pain serves to protect and attend to a specific tissue or organ, which usually displays local inflammation, depression due to...

Coordination of GCMediated Control of the Neuroimmune Response and Energy Homeostasis Control

Leptin is released by adipose tissue in response to AA or PGE2, and circulating leptin is involved as a mediator for the LPS-induced anorexia and fever in rats (Fain et al., 2001 Sachot et al., 2004), which supports a key role of this peptide in the peripheral coordination between energy homeo-stasis and the adaptation to stress and inflammation. Additionally, in the CNS, this peptide acts as an indirect inflammatory signal by causing IL-1b release from microglial cells, by inducing IL-1b expression in macrophages located in the meninges and perivascular space, and by inducing COX2 expression in endothelial cells (Inoue et al., 2006 Pinteaux et al., 2007). Moreover, leptin has been shown to stimulate cPLA2 activity in bone marrow stromal cells, in alveolar macrophages and in muscle cells, leading, in the later two cases, to increased AA release (Bendinelli et al., 2005 Kim et al., 2003 Mancuso et al., 2004). Accordingly, leptin was shown to cause the release of PGE2 and PGF2a in the...

Behavioral Effects Of Infectious Diseases And Cytokine Administration In Animals

Anorexia and Body Weight Loss Anorexia and body weight loss are among the most robust effects of acute as well as chronic illness (Plata-Salaman, 1996). Such effects have been recently demonstrated in experimental models of disease, including influenza virus in-fection (Swiergiel, Smagin, & Dunn, 1996 Swiergiel, Smagin, Johnson, & Dunn, 1997), local inflammation induced by subcutaneous injection of turpentine (Kozac, Poli, Soszynski, Conn, Leon, & Kluger, 1996 Kozac, Soszynski, Rudolph, Conn, & Kluger, 1997), and exogenous administration of pathogen products, including LPS (Kozac et al., 1997 Yirmiya, 1996), and heat-inactivated Mycoplasma fermentans (Yirmiya, Barak, Avitsur, Galilly, & Weidenfeld, 1997). Several lines of evidence suggest that anorexia and body weight loss are mediated by cytokines 1) Similar effects were observed following exogenous administration of cytokines, particularly IL-ip, TNFa, and IL-8, which act centrally and synergistically to suppress feeding...

Effects Of Antidepressants On Depression Induced By Immune Activation

Bendsen Signs

Chronic administration of imipramine (daily injection for 5 weeks) attenuated many other behavioral effects of LPS. Imipramine-treated rats exhibited facilitated recovery from LPS-induced anorexia, body-weight loss, and reduced social activity. In addition, they did not demonstrate LPS-induced suppression of locomotor and exploratory behavior in the open field test. In another experiment, we showed that acute administration of imipramine did not have such effects, i.e., there was no effect of acute imipramine on LPS-induced reduction in food consumption, body weight, social exploration, and open-field activity. The dissociation between the effects of acute and chronic imipramine treatment is important, since in clinical settings, imipramine is also effective in alleviating depression only following chronic, but not acute administration (Montgomery, 1994).

Toxic Side Effects of As2O3

Instead, As2O3 induces leukocytosis in about 50 of patients.11,13,36 The leuko-cytosis can resolve in all cases without chemotherapy.87 The APL patients on As2O3 can also develop retinoic acid syndrome (RAS)-like symptoms such as fever, skin rash and edema, which can be readily relieved by steroid administra-tion.88 Other mild effects were reported in about 40-50 of relapsed patients, including fatigue, fever, edema, nausea, anorexia, diarrhea, emesis, headache, insomnia, cough, dyspnea, dermatitis, tachycardia, pain, hypokalemia, hypo-magnesemia and hyperglycemia. The most common ( 10 ) Grade 3 and 4 adverse events were abdominal pain, epistaxis, dyspnea, hypoxia, bone pain, thrombocytopenia, neutropenia, hypokalemia and hyperglycemia.11,36,89 In a clinical trial, prolonged QT intervals (the time intervals for the contraction of the ventricle from the beginning of the Q wave to the end of T wave a prolonged QT interval indicates cardiac toxicity) were observed in all patients during...

Chronic Arsenic Poisoning

The most common early signs of chronic arsenic poisoning are muscle weakness and aching, skin pigmentation (especially of the neck, eyelids, nipples, and axillae), hyperkeratosis, and edema. GI involvement is less prominent in long-term exposures. Other signs and symptoms that should arouse suspicion of arsenic poisoning include garlic odor of the breath and perspiration, excessive salivation and sweating, stomatitis, generalized itching, sore throat, coryza, lacrimation, numbness, burning or tingling of the extremities, dermatitis, vitiligo, and alopecia. Poisoning may begin insidiously with symptoms of weakness, languor, anorexia, occasional nausea and vomiting, and diarrhea or constipation. Subsequent symptoms may simulate acute coryza. Dermatitis and keratosis of the palms and soles are common features. Mee's lines are found characteristically in the fingernails (white transverse lines of deposited arsenic that usually appear 6 weeks after exposure). Desquamation and scaling of...

HT Receptors Feeding Behavior and Body Weight in Rodents

5ht2c Receptor Alzheimer

Fig. 17.1 Functional divergence in 5-HT2C receptor pathway. Serotonin (5-HT) inhibits feeding-stimulatory NPY AgRP neurons through 5-HT1B receptor, while activating feeding-inhibitory POMC CART neurons through 5-HT2C receptors. The primary effect by 5-HT receptor on energy metabolism requires downstream activation of MC4R. A novel 5-HT2C receptor pathway that regulates physiologic gastrointestinal (GI) motility, requiring sympathetic activity and leading to inhibition of ghrelin but not MC4R. 5-HT indirect agonist-selective serotonin reuptake inhibitors activate both 5-HT2C receptor pathways, but not the 5-HT1B pathway, for the anorexia and GI motor effects produced. AgRP agouti-related peptide, CART cocaine- and amphetamine-regulated transcript, DVC dorsal vagal complex, IML intermediolateral nucleus of the spinal cord, NPY neuropeptide Y, POMC pro-opiomelanocortin, SNS sympathetic nervous system (Reproduced from Fujitsuka et al. 2009. With permission) Fig. 17.1 Functional divergence...

O Diseases Of Bone Tissue Utilizing Approved Drug Therapies

Bisphosphonate Binding

There are controllable risk factors that reduce the risk and severity of the disease. These include anorexia in the age span when humans are accumulating dietary calcium, a diet low in calcium and vitamin D (cholecalciferol), inactive lifestyle, cigarette smoking, and excessive use of alcohol. Staying as physically active as possible throughout one's life span is important, particularly focusing on activities that include working against gravity (walking, hiking, jogging, stair climbing, and dancing). It is important for all age groups to consume calcium, but because calcium deposition onto bone is at its greatest through adolescence, it is important to consume quantities of calcium equal to the daily adequate intake (AI) of, depending on age, 500 to 1,300 mg day. Younger people can obtain their calcium from diet, primarily dairy. Older individuals may need to take calcium supplements. Paralleling adequate calcium intake is vitamin D consumption. The current adult AI is 5 to 10 g...

Effect of HPA Axis on the Reproductive Axis

Other studies in humans have linked hypothalamic-pituitary-gonadal (HPG) axis abnormalities to HPA axis activation. These include exercise-induced amenorrhea, anorexia nervosa, and hypothalamic amenorrhea. In all three syndromes, hypercortisolemia has been observed, indicating overactivity of the HPA axis (Berga et al. 1989 Casanueva et al. 1987 Hohtari et al. 1988 Loucks et al. 1989 Suh et al. 1988 Villanueva et al. 1986). In all three syndromes, CRH has been used as a challenge to evaluate pituitary and adrenal function. The response to exogenous CRH challenge demonstrates diminished ACTH or cortisol responses, suggesting that high baseline cortisol exerts negativefeedback effects on the hormonal responses to CRH (Berger et al. 1983 Biller et al. 1990 Gold et al. 1986 Hohtari et al. 1991). In anorexia nervosa, the hormonal abnormalities in both HPA and HPG axes are secondary to weight loss. Weight restriction and low body weight are also observed in exercise-induced amenorrhea, and...

Colloidal Silver Dictionary

Gastroenteritis An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species consumption of irritating food or drink or psychological factors such as anger, stress, and fear. Called also enterogastritis. EU

Drug Treatment Of Psychoses

Neuroleptic agents are effective antipsychotics and are superior to sedatives (e.g., barbiturates and benzodiazepines), or alternatives (e.g., ECT, other medical or psychological therapies). The target symptoms for which antipsychotic agents are especially effective include agitation, com-bativeness, hostility, hallucinations, acute delusions, insomnia, anorexia, poor self-care, negativism, and sometimes withdrawal and seclusiveness. More variable or delayed are improvements in motivation and cognition, including insight, judgment, memory, orientation, and functional recovery. The most favorable prognosis is for patients with acute illnesses of brief duration who had functioned relatively well prior to the illness.

Fludarabine Phosphate

Toxic manifestations include myelosuppression, nausea and vomiting, chills and fever, malaise, anorexia, and weakness. Lymphopenia and thrombocytopenia are dose limiting and possibly cumulative. CD4+ T cells are depleted with therapy. Opportunistic infections and tumor lysis syndrome have been reported. Peripheral neuropathy may occur at standard doses. Altered mental status, seizures, optic neuritis, and coma have been observed at higher doses and in older patients. Rarely, CLL patients may develop an acute hemolytic anemia or pure red cell aplasia during fludarabine treatment. Severe pneumonitis responsive to glucocorticoids has been encountered. Because a significant fraction of drug ( 25 ) is eliminated in the urine, patients with compromised renal function should be treated with caution, and initial doses should be reduced proportionate to serum creatinine levels.

Diseases Affecting The Vasopressin System

SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE (SIADH) SIADH is a disease of impaired water excretion with accompanying hyponatremia and hypo-osmolality caused by the inappropriate secretion of vasopressin. The clinical manifestations of plasma hypotonicity resulting from SIADH may include lethargy, anorexia, nausea and vomiting, muscle cramps, coma, convulsions, and death. A multitude of disorders can induce SIADH, including malignancies, pulmonary diseases, CNS injuries diseases (e.g., head trauma, infections, and tumors), and general surgery. The three drug classes most commonly implicated in drug-induced SIADH include psychotropic medications (e.g., fluoxetine, haloperidol, and tricyclic antidepressants), sulfonylureas (e.g., chloropropamide), and vinca alkaloids (e.g., vincristine and vinblastine). Other drugs strongly associated with SIADH include thiazide diuretics, clonidine, enalapril, ifosphamide, and methyldopa. In a normal individual, an elevation in plasma...

Sympathomimetics Stimulants

Although the literature is limited by number of subjects, duration, and trial design, there is some evidence to support the use of methylphenidate (5-15 mg two to four times daily), donepezil (5-10 mg daily), and modafinil (200-400 mg daily) for the pharmacologic management of opioid-induced sedation and fatigue (Larijani et al. 2004, Reissig and Rybarczyk 2005). Potential adverse effects can include overstimulation (e.g., anxiety, insomnia, and even paranoia), appetite suppression, exacerbation of motor abnormalities (e.g., tics, dyskinetic movements), and confusion. Contraindications for stimulant use include glaucoma, poorly controlled hypertension, arrhythmias, and cardiovascular disorders, anorexia, seizure disorders, and hyperthyroidism. Methylphenidate is a schedule II medication under federal regulatory control caution is advised in patients with current or preexisting substance use disorders, especially prior stimulant abuse (e.g., cocaine).

Pharmacotherapy Of Anxiety

Anxiety is a symptom of many psychiatric disorders and an almost inevitable component of many medical and surgical conditions. Symptoms of anxiety commonly are associated with depression and especially with dysthymic disorder (chronic depression of moderate severity), panic disorder, agoraphobia and other specific phobias, obsessive-compulsive disorder, eating disorders, and many personality disorders. Sometimes, no treatable primary illness is found, or if one is found and treated, it may be desirable to deal directly with the anxiety at the same time. In such situations, antianxiety medications are frequently and appropriately used. SSRIs are agents of choice in obsessive-compulsive disorder and in the syndromes of impulse dyscontrol or obsessive preoccupations (e.g., compulsive gambling, trichotillomania, bulimia, but usually not anorexia nervosa and body dysmorphic disorder). Despite their limited benefits, SSRIs offer an important advance in the medical treatment of these often...

The Alcohol Addictive Patient

Driving under the influence or a history of two or more non-sport-related traumatic events (after age 18 years) are considered at high risk for substance abuse 42 . Therefore, the prescribing physician should be alert to the eating disorder, addiction, and sexual abuse triad - if two are present, look for the third 49 . It is because of this triad that researchers have recommended that all women entering substance abuse treatment should be screened for eating disorders 50 . During the initial assessment ask for the following 3. Be alert to the eating disorders, addiction, and sexual abuse triad. If two are present, look for the third.

Acute Intoxication

After local exposure to vapors or aerosols or after their inhalation, ocular and respiratory effects generally appear first. Ocular manifestations include marked miosis, ocular pain, con-junctival congestion, diminished vision, ciliary spasm, and brow ache. With acute systemic absorption, miosis may not be evident due to sympathetic discharge in response to hypotension. In addition to rhinorrhea and hyperemia of the upper respiratory tract, respiratory effects include tightness in the chest and wheezing due to bronchoconstriction and increased bronchial secretion. GI symptoms occur earliest after ingestion and include anorexia, nausea and vomiting, abdominal cramps, and diarrhea. With percutaneous absorption of liquid, localized sweating and muscle fasciculations in the immediate vicinity are generally the earliest symptoms. Severe intoxication is manifested by extreme salivation, involuntary defecation and urination, sweating, lacrimation, penile erection, bradycardia, and...


The SNRI atomoxetine is playing a growing role in the treatment of ADHD. Translational studies indicate that this agent modulates prefrontal noradrenaline (and dopamine), and is capable of improving response inhibition, a cognitive function dependent on the right inferior frontal gyrus and under likely noradrenergic control. Further clinical trials are required to explore the efficacy and safety of atomoxetine into the longer term in the treatment of ADHD, in children and in adults, and to evaluate the efficacy of this agent in the treatment of other disorders. For example, registered ongoing trials are exploring the utility of atomoxetine in the treatment of alcohol substance abuse, Parkinson's disease, and Binge Eating disorder (www.clinicaltrials.gov). In addition to further clinical trials, it will also be important to explore the role of different components of the brain noradrenaline system in cognition (i.e., sub-receptors) in translational research and to evaluate the effects...


Two phase I cohort dose escalation clinical trials using DAB389EGF have been conducted in patients with EGF receptor expressing malignancies. As reported by Theodoulou et al. (1995), 52 patients with various malignant diseases were enrolled in the two studies. One study employed the same five consecutive day dosing regimen used in the initial clinical studies using DAB389IL-2. The other study used an episodic dosing regimen on days 1, 8, 9, 15, 16 every 28 days. The doses ranged from 0.3 to 15 g kg day. Adverse effects were similar to those seen with DAB389IL-2, and included fever, malaise, nausea vomiting, hypoalbuminemia, hypertension, and anorexia. During the first course of treatment, 52 of patients exhibited reversible elevations of serum levels of hepatic transaminases. Renal toxicity included the elevation of serum levels of creatinine in 25 of patients. One patient experienced proximal renal tubular acidosis which resolved with electrolyte supplementation. Dose-limiting...


Overlap between different diagnostic phenotypes reflect an overlap between involved genes Family and twin studies show a large overlap between them (Torgersen 1990 Kendler 1992). A more careful twin study about comorbidity analysing different disorders, found evidences of two clusters of genetic factors one is related to MD and Generalized Anxiety Disorder, the other is involved in Panic Disorder, Bulimia and Phobic Disorder (Kendler 1995). Even if comorbidity could represent a bias, molecular and genetic researches would provide some evidence for disentangling the overlap of these two pathologies.


Manyinflorescenced Sweetveich Root is the dried root of Hedysarum polybotrys Hand. -Mazz, (Fam. Legminosae). Action To reinforce qi and strengthen the superficial resistance, to cause diuresis, and to promote the drainage of pus and the growth of new tissue. Indications Deficiency of qi with lack of strength, anorexia atld loose stools sinking of the spleen qi marked by protracted diarrhea and prolapse of the rectumi hema-tochezia and abnormal uterine bleeding spontaneous sweating due to weakened superficial resistance i edema due to deficiency of qi j abscess or boil difficult to burst* anemia diabetes mellitusi albuminuria in chronic nephritis. Dosage 9 30g. Indications Dificiency of qi with lack of strength, anorexia and loose stools. Dosage 9 -30g.


Fatigue, poor memory, hallucinations, anorexia, impotence and muscular pain in the lower extremities. This is followed by speech disorders, clumsiness in movements and loss of facial expressions. Finally, muscular rigidity, staggering gait and tremor of the upper limbs occur.26 The affinity of manganese to the basal ganglia in the brain suggests that this mineral might have a role in the pathogenesis of hepatic encephalopathy.27 Another effect of prolonged exposure might be impotence, as sperm motility and sperm counts were reduced in mice given high manganese doses.28

Valproic Acid

TOXICITY The most common side effects are transient GI symptoms, including anorexia, nausea, and vomiting in -16 of patients. CNS effects include sedation, ataxia, and tremor these symptoms occur infrequently and usually respond to a decrease in dosage. Rash, alopecia, and stimulation of appetite have been observed occasionally, and weight gain has been seen with chronic valproic acid treatment. Elevation of hepatic transaminases is observed in up to 40 of patients and often occurs asymptomatically during the first several months of therapy.

Clinical Summary

Constipation is exceedingly common with opioids, and stool softeners and laxatives should be initiated early. Amphetamines have demonstrable mood-elevating and analgesic effects and enhance opioid-induced analgesia. However, not all terminal patients require the euphoriant effects of amphetamine, and some experience side effects, such as anorexia. Although tolerance does develop to oral opioids, many patients obtain relief from the same dosage for weeks or months. In cases where one opioid loses effectiveness, switching to another may improve pain relief. Cross-tolerance among opioids exists, but cross-tolerance among related -receptor agonists is not complete.

Other Clinical Uses

The most common symptoms associated with these drugs are GI, including anorexia, nausea, dyspepsia, abdominal pain, and diarrhea. These symptoms may be related to the induction of gastric or intestinal ulcers, which is estimated to occur in 15-30 of regular users. Ulceration may range from small superficial erosions to full-thickness perforation of the muscularis mucosa. There may be single or multiple ulcers, and ulceration can be accompanied by gradual blood loss leading to


Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). One of the earliest of these drugs to be developed, it is widely perceived in the popular culture to be paradigmatic of the class. It is commonly used in the treatment of depression and the more severe anxiety disorders (e.g., obsessive-compulsive disorder, panic disorder). Fluoxetine is also approved for the treatment of bulimia nervosa, anorexia nervosa, and premenstrual dysphoric disorder. A distinguishing pharmacokinetic feature of the drug is its long elimination half-life (up to 4-6 days during long-term use and up to 2 weeks for the major active metabolite norfluoxetine). As with other SSRIs, the most common troublesome side effect of fluoxetine is sexual dysfunction (dysorgasmia and erectile dysfunction) mild side effects include drowsiness, headache, and nausea. Some patients develop a syndrome of psychomotor activation upon starting the drug, which has been characterized as similar to akathisia.


Stimulants may have analgesic effects when combined with opioids (Forrest et al. 1977 Laska et al. 1984). Dextroamphetamine (5-15 mg two or three times daily) or methylphenidate (5-15 mg two to four times daily) has been used to augment opiate analgesia. These drugs have also been used to reduce the sedation, dysphoria, and cognitive inefficiency that may accompany opiate use. Both pemoline (up to 75 mg day) and caffeine (65 mg two or three times daily) have likewise been used for such purposes. However, use of stimulants may be limited by intervening adverse effects, including overstimulation (e.g., anxiety, insomnia, paranoia), appetite suppression (problematic in patients who are undernourished and cachectic), and confusion. Additionally, in persons who are predisposed to motor abnormalities, tics and other dyskinetic movements may be exacerbated. When these drugs are taken in overdose, an extreme form of these adverse effects may occur, resulting potentially in hypertension,...


Of a hyperactive HPA axis in depressed patients 295 . Compared with controls, women with anorexia nervosa 296 , bulimia nervosa 297 , binge eating disorder 298 , and the night eating syndrome 299 had higher basal cortisol. Exaggerated cortisol responses to stress have been observed in women with anorexia nervosa 300 , bulimia nervosa 301 , and obesity 302 . Eating is thought to be suppressed during stress because of anorectic effects of CRH, and increased during recovery from stress because of appetite-stimulating effects of residual cortisol 33, 303 . Cortisol secretion is a major component of the stress response 301 , and it has been implicated as a potential mediator for increased energy intake in healthy males 260 and females 33 . Typically, responses to stress result in anorexia and, if the stress is sufficiently persistent, weight loss. The longstanding view is that stress produces sympathetic arousal that results in reductions rather than increases in eating. For example, in...

Abdominal pain

Tumors of the small and large bowel causing abdominal pain include Kaposi's sarcoma and non-Hodgkin's lymphoma (NHL). NHL can occur even when patients have relatively well-preserved immunity and in HIV can present in unusual sites such as the mouth or anus.57 Abdominal colic can accompany infections such as HIV or CMV colitis, cryptosporidium, or Mycobacterium avium complex. Patients are likely to be relatively immunocompromised, experiencing severe diarrhea and anorexia. An acute presentation of colic may be caused by intussusception as a result of enlarged mesenteric lymph nodes.

Sickness Behaviors

In concert with immunological changes, pathogens promote several adaptive behavioral styles. Yet, the biological or behavioral strategies deployed may have both immediate and protracted adverse consequences, including increased vulnerability to psychological disturbances. Activation of the immune system (e.g., by bacterial endotoxins) or direct administration of products of an activated immune system (e.g., IL-ip, IL-6, and TNFa) induce an array of behavioral symptoms referred to as sickness behavior (Kent, Bluthe, Kelley, & Dantzer, 1992). As discussed in other chapters of this volume, in addition to fever and curled body posture, systemic IL-lp and TNFa provoke anorexia, increased sleep, and reduced locomotor activity, each of which minimizes energy expenditure and sustains body temperature (Bluthe, Dantzer, & Kelley, 1989 Dantzer et al., 1996 Elmquist, Scammell, & Saper, 1997 Hellerstein, Meydani, Meydani, Wu, & Dinarello, 1989 Holden & Pakula, 1996 Kent, Rodriguez, Kelley, &...

Clinical assessment

A positive response with respect to neurological symptoms may indicate spinal tumor or cerebrovascular disorder. Cardiovascular risk factors prompt consideration of aneurysms. Respiratory features, genitourinary features, or a history of thyroid cancer warrant consideration of spinal metastases. Weight loss and anorexia suggest neoplasia. Diarrhea and skin lesions suggest spondylarthropathy, as do peripheral features of inflammatory arthropathy. Neck pain in the elderly warrants consideration of myeloma or other tumors. Hyper-parathyroidism is a possible cause of spinal pain that is easily overlooked because of its rarity.

Untoward Effects

The most common side effects of amantadine and rimantadine are GI and CNS complaints, including nervousness, light-headedness, difficulty concentrating, insomnia, and anorexia or nausea. CNS side effects occur in 5-33 of patients treated with amantadine at doses of200 mg day but are significantly less frequent with rimantadine. Especially in the elderly, the neurotoxic effects of amantadine may be increased by concomitant use of antihistamines and psychotropic or anticholinergic drugs. Amantadine dose reductions are required in older adults (100 mg day) because of decreased renal function, but 20-40 of infirm elderly experience side effects even at the lower dose. At 100 mg day, rimantadine is significantly better tolerated in nursing home residents than is amantadine.


The nadir of the leukopenia that follows the administration of vinblastine usually occurs within 7-10 days, after which recovery ensues within 7 days. Other toxic effects of include neurological manifestations as described above. GI disturbances including nausea, vomiting, anorexia, and diarrhea may be encountered. The syndrome of inappropriate secretion of antidi-uretic hormone has been reported. Loss of hair, stomatitis, and dermatitis occur infrequently. Extravasation during injection may lead to cellulitis and phlebitis. Local injection of hyaluronidase and application of moderate heat to the area may be of help by dispersing the drug.


Mitotane (lysodren) is administered in initial daily oral doses of 2-6 g, usually given in 3 or 4 divided portions, but the maximal tolerated dose may vary from 2 to 16 g day. Treatment should be continued for at least 3 months if beneficial effects are observed, therapy should be maintained indefinitely. Spironolactone should not be administered concomitantly, since it interferes with the adrenal suppression produced by mitotane. Treatment with mitotane is indicated for the palliation of inoperable adrenocortical carcinoma, producing symptomatic benefit in 30-50 of such patients. Although the administration of mitotane produces anorexia and nausea in 80 of patients, somnolence and lethargy in 34 , and dermatitis in 15-20 , these effects do not contraindicate the use of the drug at lower doses. since this drug damages the adrenal cortex, administration of corticosteroids is indicated, particularly in patients with evidence of adrenal insufficiency, shock, or severe trauma.


Marijuana is the most commonly used illicit substance in the United States. Also known as pot, grass, weed, hash, or tetrahydrocannabinol (THC), it is a hallucinogenic agent prepared from the dried leaves of Cannabis sativa. Its primary psychoactive constituent is THC. The medical use of cannabis in the treatment of pain and other symptomatology has long been practiced. The first recorded use of medical cannabis dates back to 2700 BC in the United States, medical marijuana was routinely used until 1942. However, because of growing concerns over its addictive potential, the medical and psychosocial side effects of its chronic use, US physicians had been prohibited by the federal government to prescribe these drugs. Other countries such as the Netherlands and Canada still routinely use medical marijuana in the treatment of pain and other disorders such as anorexia (Cohen 2008).


High doses of folic acid are rather nontoxic however, at least one study has shown that 15 mg day for 1 month can result in gastrointestinal disturbances (including anorexia, nausea, and pain) and CNS effects (including sleep disturbances, vivid dreams, malaise, irritability, and increased ex-citability).213 The primary danger of excessive folate intake is the masking of vitamin B12 deficiency. Folic acid can correct the anemia caused by vitamin B12 deficiency, but it has no effect on the neurological damage. The potential for high doses of folic acid to mask B12 deficiency explains why large daily doses of folic acid are best avoided in the general population.

Sodium Nitroprusside

TOXICITY AND PRECAUTIONS The short-term adverse effects of nitroprusside are due to excessive vasodilation. Close monitoring of blood pressure and the use of a continuous variablerate infusion pump will usually prevent an excessive hemodynamic response to the drug. Less commonly, toxicity may result from conversion of nitroprusside to cyanide and thiocyanate. Toxic accumulation of cyanide leading to severe lactic acidosis usually occurs when sodium nitroprusside is infused at a rate 5 ,ug kg min, but also can occur in some patients receiving doses of 2 ,ug kg min for a prolonged period. The limiting factor in the metabolism of cyanide appears to be the availability of sulfur-containing substrates in the body (mainly thiosulfate). The concomitant administration of sodium thiosulfate can prevent cyanide accumulation in patients who are receiving higher-than-usual doses of sodium nitroprusside the efficacy of the nitroprusside is unchanged. The risk of thiocyanate toxicity increases when...


Interferon gamma-1b (actimmune) is a recombinant polypeptide that activates phagocytes and induces their generation of oxygen metabolites that are toxic to a number of microorganisms. It is indicated to reduce the frequency and severity of serious infections associated with chronic granu-lomatous disease. Adverse reactions include fever, headache, rash, fatigue, GI distress, anorexia, weight loss, myalgia, and depression.


Methyldopa also produces adverse effects that are unrelated to its pharmacological action. Hepa-totoxicity, sometimes associated with fever, is an uncommon but potentially serious toxic effect. Prompt diagnosis of hepatotoxicity requires a low threshold for considering the drug as a cause for hepatitis-like symptoms (e.g., nausea, anorexia) and screening for hepatotoxicity (e.g., with determination of hepatic transaminases) after 3 weeks and again 3 months after initiation of treatment. The incidence of methyldopa-induced hepatitis is unknown, but 5 of patients will have transient increases in hepatic transaminases in plasma. Hepatic dysfunction usually is reversible with prompt drug discontinuation but will recur if methyldopa is given again a few cases of fatal hepatic necrosis have been reported. It is advisable to avoid the use of methyldopa in patients with hepatic disease.


297 Pirke KM, Platte P, Laessle R, Seidl M, Fichter MM. The effect of a mental challenge test of plasma norepinephrine and cortisol in bulimia nervosa and in controls. Biol Psychiatry 1992 32 202-206. 298 Gluck ME, Geliebter A, Hung J, Yahav E. Cortisol, hunger, and desire to binge eat following a cold stress test in obese women with binge eating disorder (BED). Psychosom Med 2004 66 876-881. 300 Abell TL, Malagelada JR, Lucas AR, Brown ML, Camilleri M, Go VL, et al. Gastric electromechanical and neurohormonal function in anorexia nervosa. Gastroenterology 1987 93 958-965. 301 Koo-Loeb JH, Costello N, Light KC, Girdler SS. Women with eating disorder tendencies display altered cardiovascular, neuroendocrine, and psychosocial profiles. Psychosom Med 2000 62(4) 539-548. 305 Shimizu N, Oomura Y, Kai Y. Stress-induced anorexia in rats mediated by serotonergic mechanisms in the hypothalamus. Physiol Behav 1989 46(5) 835-841.

SSRIs History

As clinical experience with SSRIs has grown, it has become apparent that they have their own share of adverse effects. Also, the equivalence of SSRIs' efficacy to TCAs' has been challenged, and still remains a matter of some controversy. Even with these concerns, SSRIs are widely used and are effective in a wide range of psychiatric disorders other than depression, such as anxiety disorders, obsessive-compulsive disorder (OCD), panic disorder, bulimia nervosa, social phobia, posttraumatic stress disorder (PTSD), premenstrual dysphoric syndrome (PMDS), dysthymia, and seasonal affective disorder. SSRIs are the most widely prescribed antidepressants in America and worldwide (32).

Mutant Mice2C

The functional status of this above-described pathway appears to be necessary for expression of SSRI-evoked anorexia. For example, fluvoxamine does not mediate its usual anorectic effect in mice with intact melanocortin signaling but constitutively lacking functional 5-HT2CRs (Nonogaki et al. 2009). However, fluvoxamine again has anorectic action (potentially through 5-HT1B receptor signaling) in mice with a combined homozygous deletion of 5-HT2CRs and a hemizygous mutation of b-endorphin. Thus, SSRI-evoked anorexia appears to require intact signaling at both the 5-HT2CR POMC neuron and MC4R arcuate neuron. Mice with constitutive 5-HT2CR knockout also show a similar resistance to the anorectic effects of d-fenfluramine, a potent stimulator of serotonin release and inhibitor of serotonin reuptake (Vickers et al. 1999). This finding was seen in analyses of behavioral satiety sequences, where it was noted that intermediate doses of d-fenfluramine had a much-blunted effect of suppressing...

Pancreatic pain

An alternative is the use of the adrenoreceptor antagonist phen-tolamine. This agent is available only in a parenteral formulation. It has shown to be of some value in treating a variety of pain conditions including the visceral pain associated with porphyria, chronic pancreatitis, and complex regional pain syndrome type 1. What unifies these conditions is that at least part of the pain is sympathetically mediated. Given that celiac plexus block destroys sympathetic nerves and reduces pancreatic cancer pain then one would expect phentolamine to temporarily replicate this effect, which it can do. Intravenous infusion given over a 1-day period can reduce pancreatic cancer pain for several weeks at a time. Complications associated with use include palpitations and postural hypotension, which can be minimized if the patient receives a fluid preload prior to commencement of infusion. Unfortunately since nausea and vomiting along with anorexia often complicate pancreatic cancer, the chances...


Dronabinol is a synthetic form of D9-tetrahydrocannabi-nol, the main psychoactive substance in marijuana cannabis. It is a cannabinoid agonist acting on cannabi-noid CB1 and CB2 receptors. The cannabinoid CB1 are mostly located in the brain and involved in addictive properties of marijuana the CB2 receptors are located in the periphery notably in the immune system, but may be also located in the brain. Dronabinol has been used in AIDS-related anorexia associated with weight loss and in nausea and vomiting associated with cancer chemotherapy. It has the potential to be abused and is a controlled substance.


The most common adverse drug reactions are diarrhea, rash, acne, pruritus, dry skin, nausea, vomiting, and anorexia. A higher rate of most of these adverse events is observed in patients treated with 500 mg day of gefitinib as compared to treatment with 250 mg day. Most adverse events are of mild-to-moderate grade. Less than 2 of patients have permanently discontinued therapy. Adverse drug reactions usually occur within the first month of therapy and generally are reversible. Asymptomatic increases in liver transaminases have been observed and periodic liver function testing should be performed. Interstitial lung disease, which may be acute in onset, has been observed uncommonly in patients receiving gefitinib, and some cases have been fatal. The overall frequency of interstitial lung disease is 0.3 outside of Japan and 2 in Japan.


Cachexia is a wasting syndrome involving reduced appetite, loss of body weight, and muscle atrophy. In contrast to other causes of weight loss such as anorexia nervosa or dieting, weight loss due to cachexia is involuntary. Individuals with cachexia are not actively attempt to lose weight. These symptoms are commonly observed in cancer patients undergoing chemotherapy treatment. Eating Disorder Anorexia Nervosa


While the first generation slow-release MPH formulation left much room for improvement, formulations using an osmotic controlled release system (OROS MPH) and formulations combining rapid delivery and extended delivery elements in various proportions have been embraced by clinicians and patients. Efficacy is reported to be comparable with that of IR-MPH, with robustly significant improvements over placebo (Findling 2008). Mild adverse effects are comparable, e.g., headache (2-14 vs. 3-10 for placebo), abdominal pain (6-7 vs. 1 for placebo), emotional lability, anorexia (3-10 vs. 0-3 ), and insomnia (3-7 vs. 0-5 ). A new formulation consists of a MPH transdermal delivery system (MTS), which has been reported in a study sponsored by the manufacturer to show good efficacy and tolerability, with minimal adverse effects (headache was reported by 4 in both treatment and placebo groups), but a subsequent study found somewhat higher rates of adverse effects with MTS treatment than with...


Impulsivity is a characteristic of normal everyday behavior, but excessive impulsiv-ity may take on a pathological nature that is exhibited in a diversity of psychiatric disorders including aggression, attention deficit hyperactivity disorder (ADHD), drug abuse, and eating disorders (Hollander and Rosen 2000 Moeller et al. 2001). Impulsivity is not a unitary construct and encompasses a variety of different types of behavior, which may well be independent of each other (Evenden 1999). Two forms of impulsivity have been especially well studied in animal models. Impulsive action, which refers to the tendency to make premature responses in anticipation of an expected event, reflects a loss of inhibitory control over behavior. Impulsive choice is a description of the situation in which individuals prefer a small reward that is available immediately to a larger reward that is available after a delay. Operationally, this is studied in animals tests by allowing subjects to choose between one...


The most common side effects are anorexia, nausea and vomiting, and diarrhea. Hypersensi-tivity reactions occur occasionally, including fever, leukopenia, granulocytopenia, hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency, cholestatic jaundice, and hepatitis. Acute pneumonitis may occur acutely the symptoms usually resolve quickly after drug discontinuation. Subacute reactions also may occur, including interstitial pulmonary fibrosis. Elderly patients are especially susceptible to the pulmonary toxicity. Severe polyneuropathies affecting both sensory and motor nerves also have been reported, most often in patients with impaired renal function and in persons on long-term treatment.

Opioid Receptors

Opioid Receptor

Opioid receptors are glycoproteins found in cell membranes at multiple sites in the central nervous system and in the periphery. Opioid receptors have multiple subtypes the most important are i, k, and 8, and the opioid receptor-like receptor (ORL) (Table 7.1). Morphine and morphine-like opioids bind primarily to the receptors. These receptors are located in the periaqueductal gray matter (brain) and the substantia gelatinosa (spinal cord) (Carr and Lipkowski 1993). i receptors can be further subdivided into 1 and 2 receptors. 1 activation produces analgesia, and 2 activation produces euphoria, respiratory depression, nausea, vomiting, decreased gastrointestinal motility, urinary retention, tolerance, dependence, histamine release, miosis, and or anorexia (Ferrante 1993). The structural andpharmacochemical differences between opioid agonists can affect the binding and affinity with the mu receptor leading to varied analgesic responses.

Heroin and Methadone

Opioid overdose is manifested by coma, circulatory collapse, pinpoint pupils, bradycardia, hypothermia, and severe respiratory depression. On the other hand, when symptoms of insomnia, dysphoria, restlessness, tachycardia, tachypnea, hypertension, and mydriasis occur, acute opioid withdrawal should be suspected and may initiate 4-6 h after the last opioid use and peaks about 48-72 h. Rhinorrhea, lacrimation, tremors, piloerection, and yawning are often signs of craving for the drug. Flu-like signs and symptoms such as anorexia, muscle aches, nausea, vomiting, hot and cold flashes, abdominal pain, and increased temperature are common. Heroin overdose can result to the development of pulmonary edema, myocardial involvement, or death.


Anorexia and malnutrition are common elements of the aging process. Nutritional interventions are therefore advocated to slow or reverse the progression of sarcopenia (Parise and Yarasheski, 2000 Hebuterne et al, 2001). The primary goal has been to increase amino acid availability and thereby facilitate resynthesis of muscle protein. In addition, aged muscle may be especially susceptible to the loss of nutritional antioxidants (Ji, et al., 1998). Therefore, an increased intake of antioxidant nutrients might partially counteract the ROS and NO contribution to age-related losses (Weindruch, 1995). This concept has not been confirmed. In principle, however, age-related oxidative damage could be blunted in muscle cells by increasing the availability of antioxidant nutrients such as reduced thiols, vitamins E and C, (3-carotene, carotenoids and a-Iipoic acid. Nutritional antioxidants may also enhance NO signaling (Carr and Frei, 2000), potentially restoring age-related losses. Antioxidant...


(121, 122), panic disorder (123), social phobia (124-126), eating disorders (127), premenstrual dysphoric disorder (128), and GAD (129). To summarize, the SSRI antidepressants remain the first-line treatment for major depression, dysthymia, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social phobia, PTSD, and bulimia. They have a favorable side effect profile as compared to older antidepressants, better patient tolerability, ease