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C-peptide concentration is not (‘amyotrophy’) is common in uncontrolled diabetics order kamagra gold 100mg line. Microvascular complications include retino- Diabetes mellitus (fasting blood glucose concentration pathy generic kamagra gold 100 mg on line, which consists of background retinopathy (dot and of 7mmol/L) is caused by an absolute or relative lack of blot haemorrhages and hard exudates which do not of them- insulin discount 100mg kamagra gold with mastercard. Diabetic neuropathy causes a glove and stocking time their food intake accordingly cheap kamagra gold 100 mg amex. Simple sugars should be distribution of loss of sensation with associated painful restricted because they are rapidly absorbed buy 100mg kamagra gold overnight delivery, causing post- paraesthesiae. Approximately one-third of diabetic patients prandial hyperglycaemia, and should be replaced by foods develop diabetic nephropathy, which leads to renal failure. Saturated fat ciation (pointed out by Reaven in his 1988 Banting Lecture at and cholesterol intake should be minimized. Low fat sources the annual meeting of the American Diabetes Association) of protein are favoured. There is no place for commercially between diabetes and obesity, hypertension and dyslipidaemia promoted ‘special diabetic foods’, which are expensive and (especially hypertriglyceridaemia), and type 2 diabetes is also often high in fat and calories at the expense of complex strongly associated with endothelial dysfunction, an early carbohydrate. Animal insulins have been almost improved diabetic control reduces microvascular complications. These are of consistent quality and cause fewer ment associated with diabetes mellitus in order to reduce the allergic effects. So-called ‘designer’ insulins are syn- achieved by the patient performing blood glucose monitoring at thetic polypeptides closely related to insulin, but with small home and learning to adjust their insulin dose accordingly. The changes in amino acid composition which change their prop- treatment regimen must be individualized. For example, a lysine and a proline residue are is to combine injections of a short-acting insulin before each switched in insulin lispro, which consequently has a very meal with a once daily injection of a long-acting insulin to pro- rapid absorption and onset (and can therefore be injected vide a low steady background level during the night. Follow up immediately before a meal), whereas insulin glargine is very must include structured care with assessment of chronic gly- slow acting and is used to provide a low level of insulin activ- caemic control using HbA1c and regular screening for evidence ity during the 24-hour period. This is especially important in the case of proliferative retinopathy and maculopathy, because prophy- lactic laser therapy can prevent blindness. Use By contrast, striving for tight control of blood sugar in type 2 Insulin is indicated in all patients with type 1 diabetes melli- patients is only appropriate in selected cases. Tight control tus (although it is not strictly necessary during the early ‘honey- reduces macrovascular complications, but at the expense of moon’ period before islet cell destruction is complete) and increased hypoglycaemic attacks, and the number of patients in about one-third of patients with type 2 disease. Insulin is that needs to be treated in this way to prevent one cardiovascu- usually administered by subcutaneous injection, although lar event is large. In contrast, aggressive treatment of hyperten- recently an inhaled preparation has been licensed for use in sion is of substantial benefit, and the target blood pressure type 2 diabetics. In older type 2 tive dose of human insulin is usually rather less than that of patients, hypoglycaemic treatment aims to minimize symptoms animal insulins because of the lack of production of blocking of polyuria, polydipsia or recurrent Candida infection, and to pre- antibodies. Formulations of human insulins are available in It is important to achieve and maintain ideal body weight on a various ratios of short-acting and longer-lasting forms (e. The small dose of soluble insulin controls hyper- emergency operations, but more frequent measurements of glycaemia just after the injection. When starting a sometimes be managed without insulin, but the blood glucose diabetic on a two dose per day regime, it is therefore helpful to must be regularly checked during the post-operative period. Hyperglycaemia leads to osmotic diuresis and in whom diet and/or oral hypoglycaemic drugs fail. Conservation of K is even less efficient Unfortunately, insulin makes weight loss considerably more than that of Na in the face of acidosis and an osmotic diuresis, difficult because it stimulates appetite, but its anabolic effects are and large amounts of intravenous K are often needed to valuable in wasted patients with diabetic amyotrophy. Fat is mobilized from adipose tissue, releasing free sify home blood glucose monitoring when they have a cold or fatty acids that are metabolized by β-oxidation to acetyl coen- other infection (even if they are eating less than usual) and zyme A(CoA). In the absence of glucose breakdown, acetyl CoA increase the insulin dose if necessary. The dose will subsequently is converted to acetoacetate, acetone and β-hydroxybutyrate need to be reduced when the infection has cleared. These are buffered by plasma bicarbonate, leading to often causes patients incorrectly to stop injecting insulin (for a fall in bicarbonate concentration (metabolic acidosis – with an fear of hypoglycaemia) and this may result in ketoacidosis.

Vitamins were discovered during investigations of clinical syndromes that proved to be a consequence of deficiency Key points states (e kamagra gold 100 mg generic. They are nutrients that are essen- Major categories of vitamins tial for normal cellular function buy kamagra gold 100mg, but are required in much smaller quantities than the aliments (carbohydrates cheap kamagra gold 100mg online, fats and • Originally identified by characteristic deficiency states proteins) 100 mg kamagra gold free shipping. Vitamins are essential cofactors to or components of (now uncommon in most developed countries) generic 100mg kamagra gold free shipping. Vitamin deficiency usually results from either inad- equate dietary intake, increased demand (e. Retinol (vitamin A1) is a primary alcohol and is present in the The concept that various vitamin supplements might tissues of animals and marine fishes; 3-dehydroretinol (vita- decrease the incidence of a variety of diseases, including can- min A2) is present in freshwater fish; retinoic acid shares some cer and atheroma, has been under investigation. Carotene is provitamin A prospective placebo-controlled intervention trials have inves- and is readily converted into retinol in the body. Vitamin A has tigated these hypotheses, but to date evidence of clear clinical many physiological functions (Figure 35. Not all vitamins are harmless when taken in retards growth and development, and causes night blindness, excess (especially vitamins A and D). Dietary should only be prescribed for the prevention or treatment of sources of vitamin A include eggs, fish liver oil, liver, milk and vitamin deficiency. Thiamine defi- Cofactor in Cofactor in Normal ciency leads to the various manifestations of beriberi, including cholesterol mucopolysaccharide soft tissue peripheral neuropathy and cardiac failure. Increased carbohy- synthesis synthesis growth drate utilization requires increased intake because thiamine is Figure 35. It is therefore use- ful to express thiamine needs in relation to the calorie intake. If the diet provides more than this, the excess is supplementation of vitamin A may be necessary in patients excreted in the urine. The Adverse effects body possesses little ability to store thiamine and with absolutely Long-term ingestion of more than double the recommended deficient intake, beriberi develops within weeks. Chronic toxicity includes: This is especially important in alcoholics and thiamine replace- ment should precede intravenous dextrose in alcoholic patients 1. Thiamine is hypertension), irritability and headache; found in many plant and animal foods (e. Thiamine is used in the treatment of beriberi and other states of thiamine deficiency, or in their prevention. Such conditions Acute poisoning causes: include alcoholic neuritis, Wernicke’s encephalopathy and the 1. Once the deficiency state has been Pharmacokinetics corrected, the oral route is preferred, unless gastrointestinal dis- Gastro-intestinal absorption of retinol via a saturable active ease interferes with ingestion or absorption of the vitamin. Esterified retinol reaches peak plasma concentrations Anaphylactoid reactions following parenteral thiamine dos- four hours after ingestion. Retinol is partly conjugated to a glu- ing have been reported, so parenteral administration should curonide and undergoes enterohepatic circulation. Absorption of thiamine following intramuscular injection is Contraindications rapid and complete. Thiamine is also well absorbed through the mucosa of the upper part of the small intestine by both Excess vitamin Aduring pregnancy causes birth defects (closely active and passive mechanisms, and surplus intake is excreted related compounds are involved in controlling morphogenesis unchanged in the urine. Therefore pregnant women should not take vita- min A supplements, and should also avoid liver in their diet. Niacin can be generated in the body in treat certain uncommon inborn errors of metabolism, includ- small amounts from tryptophan. Large doses are sometimes used pellagra, that can manifest clinically as a syndrome complex to treat premenstrual syndrome, and there is a lobby of enthu- which includes dementia, dermatitis and diarrhoea. Adverse effects Uses There have been reports of ataxia and sensory neuropathy fol- 1. If oral lowing administration of large doses (2g/day) of pyridoxine treatment is not possible, intravenous injections are for more than two months. Physiology Adverse effects Ascorbic acid is present in large quantities in citrus fruits, tomatoes and green vegetables.

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The place of medical somatostatin cheap 100 mg kamagra gold with amex, which is also synthesized in D cells of the islets treatment is as an adjunct to this when surgery has not effected a of Langerhans in the pancreas order 100mg kamagra gold amex. The visual fields and size of the pitu- deficiency in children causes growth retardation and short stature 100mg kamagra gold otc. Octreotide and lanreotide are long-acting analogues of somatostatin which lower somatotropin levels cheap kamagra gold 100 mg without prescription. They are given Somatropin is the synthetic recombinant form of human by intermittent injection discount kamagra gold 100mg overnight delivery. It is used for acromegaly growth is mediated by somatomedin (a small peptide synthe- with an inadequate response to surgery, radiotherapy and sized in the liver, secretion of which depends on somatotropin). It has a range of gastro-intestinal, meta- Somatropin is used to treat children with dwarfism due to bolic, neurological and other adverse effects and should be isolated growth hormone deficiency or deficiency due to hypo- used only by physicians experienced in treating acromegaly. Somatropin treatment also increases height in children which inhibits peptide release from endocrine-secreting tumours with Turner’s syndrome. It reduces symptoms of flushing, diarrhoea or protein which in females controls development of the primary skin rash, but does not reduce the size of the tumour. It is more ovarian follicle, stimulates granulosa cell proliferation and effective than bromocriptine (now mainly used in Parkinson’s increases oestrogen production, while in males it increases disease, see Chapter 21) in lowering somatotropin levels in spermatogenesis. It induces ovula- patients with acromegaly, but it is not generally an acceptable tion, stimulates thecal oestrogen production and initiates and alternative to surgery, and must be administered parenterally maintains the corpus luteum in females. Gastro-intestinal side effects are minimized if with secondary ovarian failure in whom treatment with octreotide is given between meals. Treatment must be super- octreotide formulation in poly (alkyl cyanoacrylate) nanocap- vised by specialists experienced in the use of gonadotrophins sules is administered intramuscularly once a month. Gonadotrophins are also effective in the treatment of These include: oligospermia due to secondary testicular failure. They are, of • gastro-intestinal upset, including anorexia, nausea, course, ineffective in primary gonadal failure. Ultrasound evaluation of the gall bladder is be used in a single intravenous dose to assess anterior pituitary recommended before starting therapy and if biliary reserve. Buserelin is given Key points intranasally, and goserelin is usually given by subcutaneous injection/implant into the anterior abdominal. Induction of ovulation prior for acromegaly when conventional treatment has failed. The use of oxytocin for induction of labour is Menopausal symptoms are common in addition to decreased described in Chapter 41. Key points Pharmacokinetics Physiology of the pituitary Gonadorelin analogues are peptides and are given paren- Anterior pituitary terally. Tetracosactide is used as a diagnostic test in the Answer evaluation of patients in whom Addison’s disease (adrenal insuf- The most likely cause of his symptoms worsening in the first ficiency) is suspected. Thus this patient should be given adequate analge- and paraventricular hypothalamic nuclei and transported sia and an androgen receptor antagonist (e. Goserelin can then be restarted in for storage and subsequent release (neurosecretion). Corticotropin-releasing hormone and its receptors; an evaluation at the transcription level in vivo. Combined therapy with pharmacology of nonpeptide vasopressin receptor antagonists. The duration of therapy depends on the nature of the Bacteria are a common cause of disease, but have beneficial as infection and response to treatment. For example, the gastrointestinal bac- The British National Formulary provides a good guide to ini- terial flora of the healthy human assists in preventing colo- tial treatments for common bacterial infections. The widespread use of antibacterial regional variations in patterns of bacterial resistance, these drugs has led to the appearance of multiresistant bacteria may be modified according to local guidelines. Consequently, antibacterial therapy should not be information on local prevalence of organisms and sensitivities. It is the drugs that kill bacteria and bacteriostatic drugs that prevent minimal concentration of a particular agent below which bac- their reproduction, elimination depending on host defence terial growth is not prevented. This difference is relative, as bacteriostatic drugs useful information for comparing the susceptibility of organ- are often bactericidal at high concentrations and in the pres- isms to antibacterial drugs, it is an in vitro test in a homoge- ence of host defence mechanisms.

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In a fight response purchase kamagra gold 100 mg line, eyes dilate so you can see better and lungs inspire more oxygen while increasing your heart rate purchase 100mg kamagra gold amex. Salivary glands reduce the secretion of saliva giving the person the dry mouth feeling in an emergency cheap kamagra gold 100mg otc. Instead kamagra gold 100mg mastercard, the flight response is really the opposite of fight and allows the individual to relax and function normally discount kamagra gold 100 mg with amex. Beta2-adrenergic receptors are in the smooth muscle of the lungs, arterioles of skeletal muscles, and the uterine muscles. Adrenergics also stimulate the dopaminergic receptor located in the renal, mesenteric, coronary, and cerebral arteries to dilate and increase blood flow. They promote reuptake of the transmitter back into the neuron (nerve cell terminal). Transmitters are transformed or degraded by enzymes making them unable to attach to a receptor. Sympathomimetic drugs stimulate andrenergic receptors and are classified into three categories according to its effect on organ cells. Indirect-acting sympathomimetics—stimulate the release of norepineph- rine from terminal nerve endings. Mixed-acting sympathomimetics—have the effect of both direct-acting sympathomimetics and indirect-acting sympathomimetics. They simulate the adrenergic receptor sites and stimulate the release of norepinephrine from terminal nerve endings. Ephedrine is an example of a mixed-acting sympathomimetic and is used to treat idiopathic orthostatic hypotension and hypotension resulting from spinal anesthesia. Ephedrine also stimu- lates beta2-receptors to dilate bronchial tubes and is used treat mild forms of bronchial asthma. For example, epinephrine (Adrenalin) acts on alpha1-, beta1-, beta2-receptor sites. These receptor sites include an increase in blood pressure, pupil dilation, increase in heart rate (tachycardia), and bronchodilation. Alpha-adrenergic blockers inhibit the response at the alpha-adrenergic recep- tor sites. There are two types of alpha-adrenergic blockers: selective and nonse- lective blockers. Doxazosin (Cardura) is a selective alpha1-blocker and phentolamine (Regitine) is a nonselective alpha adrenergic blocker. However, alpha-adrenergic blockers can cause orthostatic hypotension (drop in blood pressure when an individual stands up), dizziness, and reflex tachycar- dia. Beta-adrenergic blockers (see chart)—also known beta blockers—decrease heart rate and decrease blood pressure resulting in bronchoconstriction. For example, metoprolol tartrate (Lopressor) is a selective beta- adrenergic blocker that blocks beta1 receptors to decrease pulse rate and decrease blood pressure. Selective Beta Adrenergics Metoprolol tartrate Management of hypertension, angina pectoris, postmyocardial (Lopressor)—beta1 infarction. Acetylcholine (Ach) is a neurotransmitter located in the ganglions and terminal nerve endings of parasympathetic nerves that connect to receptors in organs, tissues, and glands. Some cholinergic med- ications are selective and affect either muscarinic receptor or nicotinic receptors while other cholinergic medications are non-specific and affect both receptors. Indirect-acting cholinergic drugs inhibit the action of cholineresterase (acetyl- cholinesterase) by forming a chemical complex that permits acetylcholine to per- sist and attach to the receptor. Pilocarpine is a commonly used direct-acting cholinergic that is used to treat glaucoma. Pilocarpine reduces intraocular pressure by constricting pupils and opening the Canal of Schlemm enabling aqueous humor (fluid) to drain. A reversible inhibitor binds to the cholinesterase enzyme for a period of time and then unbinds enabling the cholinesterase enzyme to properly function. Other effects include a decreased heart rate and blood pressures while increas- ing secretion of the salivary glands. Anticholinergics Anticholinergics drugs (see chart) inhibit acetylcholine by occupying the acetyl- choline receptors. Anticholinergics are also called parasympatholytics, choliner- gic blocking agents, cholinergic or muscarinic antagonists, antiparasympathetic agents, antimuscarinic agents, or antispasmodics. Antiparkinsonism-Anticholinergic Drugs Antiparkinsonism-anticholinergic drugs are used to treat the early stages of Parkinson’s disease.

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