Peripheral oedema

Beri-beri or clinically manifest thiamin deficiency exists in several subforms infantile beri-beri and adult beri-beri. Infantile beri-beri occurs in exclusively breastfed infants of thiamin-deficient mothers. Adults can develop different forms of the disease, depending on their constitution, environmental conditions, the relative contribution of other nutrients to the diet as well as the duration and severity of deficiency. First of all, there is a so called dry or atrophic (paralytic or nervous) form, including peripheral degenerative polyneuropathy, muscle weakness and paralysis. Second, a wet or exudative (cardiac) form exists. In this form, typical symptoms are lung and peripheral oedema as well as ascites. Finally, there is a cerebral form, that can occur as Wernicke encephalopathy or Korsakoff psychosis. Tli is latter form mostly affects chronic alcoholics with severe thiamin deficiency. 

The indications for these agents are in principle identical to those of the non-selective NSAIDs although the substances have not yet received approval for the whole spectrum of indications of the conventional NSAIDs. Because they lack COX-1-inhibiting properties, COX-2-selective inhibitors show fewer side effects than conventional NSAIDs. However, they are not free of side effects because COX-2 has physiological functions that are blocked by the COX-2 inhibitors. The most frequently observed side effects are infections of the upper respiratory tract, diarrhoea, dyspepsia, abdominal discomfort and headache. Peripheral oedema is as frequent as with conventional NSAIDs. The frequency of gastrointestinal complications is approximately half that observed with conventional NSAIDs. 

Other adverse effects noted are restlessness, insomnia, peripheral oedema, and sexual difficulties. Drug interactions... 

Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity. However the incidence of this is markedly reduced by the administration of corticosteroid therapy starting the day before treatment and continued for 3 days. 

Raloxifene is a selective oestrogen receptor modulator (SERM). Its role in osteoporosis is to slow down bone loss. It has been shown to increase bone density by 0.5-1%. It is licensed for the prevention and treatment of postmenopausal osteoporosis. Its side-effects include a small increase in the frequency of hot flushes, leg cramps, peripheral oedema and thrombosis risk (Tanna 2005). 

The aim is to remove the fluid gradually with a maximum weight loss of 0.5 kg/day in the absence of peripheral oedema, or 1.0 kg/day if peripheral oedema is present. Too rapid a diuresis will result in intravascular fluid loss rather than the peripheral oedema. The diuretic should be stopped if the serum sodium falls below 120 mmol/L or if there is a rising serum creatinine. Urinary electrolytes should be monitored to ensure that the spironolactone therapy is effective. The aim is to reverse the sodium/potassium ratio in the urine so that more sodium than potassium is excreted. Most frequent side-effects of spironolactone are those related to its anti-androgenic activity, such as decreased libido, impotence and gynaecomastia in men and menstrual irregularities in women. Other side-effects include hyperkalaemia, uraemia, hyponatraemia and nausea. 

Calcium channel blockers are well known to cause peripheral oedema, in particular ankle oedema. This occurs as the vasodilatation induced by the drug tends to make the blood vessel walls leaky, and so fluid escapes to, and accumulates in the surrounding tissues. Unfortunately, this condition is unresponsive to diuretic therapy, and so the only way to reverse it is to discontinue the drug. 

Q6 Thiazide diuretics are moderately powerful diuretic agents acting on the distal tubule of the nephron. They reduce reabsorption of sodium chloride and water by blocking the electroneutral sodium chloride (NaCl) transporter system at the luminal border of the distal tubular cells. In addition there are direct relaxant effects on vascular smooth muscle which reduces BP. Diuretics help patients in heart failure by reducing peripheral oedema and decreasing blood volume, which in turn reduces BP. In this way both preload and afterload are decreased and the work of the heart is diminished. 

Ng B, Postlethwaite A, Rollnik J. Peripheral oedema in patients taking olanzapine. Int Clin Psychopharmacol 2003 18 57-9. 

Pale stool and dark urine Peripheral oedema... 

Peripheral oedema is caused by fluid retention in the legs and ankles due to activation of the renin-angiotensin-aldosterone system. There are many causes of peripheral oedema other than liver dysfimction. 

ITRACONAZOLE KETOCONAZOLE t itraconazole levels, with risk of toxic effects Ketoconazole is a potent inhibitor of the metabolism of itraconazole by the CYP3A4 and a potent inhibitor of P-gp, which is considered to T bioavailability of itraconazole Warn patients about toxic effects such as swelling around the ankles (peripheral oedema), shortness of breath, loss of appetite (anorexia) and yellow discoloration of the urine and eyes (jaundice), i dose if due to interaction... 

Leuprolclin [LHRH anafoguc) Transient increase in bone pain and ureter,nl obstruction in patients with metastatic prostatic cancer hot flushes Impotence testicular atrophy gynaccomastia peripheral oedema... 

Interferon alfia Fever chills myalgias facigue headache arthralgias hypotension Bone marrow depression anorexia neutropenia anaemia confusion depression renal toxicity hepatic toxicity, facial and peripheral oedema cardiac arrhythmias... 

Occasionally, scrotal oedema and anasarca are detectable. Ascites does not correlate with the incidence and extent of peripheral oedema, (s. figs. 16.2, 16.13)... 

The peritoneum has a surface area of about 2 m. It has the effect of a semipermeable membrane and can transport a total of 720-840 ml/day between the plasma and the peritoneal cavity. Spontaneous diuresis allows 300 mllday to be excreted, whereas with the use of diuretics some 500 mllday are possible. The presence of peripheral oedema, however, permits a loss of fluid of about 900 mllday (L. Shear et al., 1970). 

The therapeutic target is a weight reduction of about 1.5 kg in 3 days (maximum 500 ml/day) without oedema and of 3.0 kg in 3 days (maximum 0.7-1.0 1/ day) with concomitant peripheral oedema. (130)... 

Rodger JC. Peripheral oedema in patients treated with isosorbide dinitrate. BMJ (Clin Res Ed) 1981 283(6303) 1365-6. 

Haviv YS, Kuper A. Severe peripheral oedema associated with valproic acid. Clin Drug Invest 2000 19 385-7. 

Peripheral oedema—beware ascites leural effusion. 

Investigations in a phase I trial determined the MTD with 2.5 mg/m and neutropenia, peripheral oedema as well as liver function test abnormalities as dose-limiting toxicities [89]. Phase II trails in patients with malignant melanoma noted only a small percentage of responders, but significant duration of response in patients with liver metastases [90]. Only a few data are published on ILX-651 developed by Ilex Oncology. Data from a phase I study have been reported showing reasonable tolerability but short plasma half-life [91]. ILX 651 is currently in multicentric phase II studies in advanced melanoma or NSCLC patients with additional trials scheduled. 

Pioglitazone and rosiglitazone may cause fluid retention and peripheral oedema, which can worsen or cause heart failure. There is evidence that the incidence of these effects is higher when combined with insulin. The incidence of hypoglycaemia may also be increased. 

Although the anaphylactoid reaction in normal rats is characterized by gross peripheral oedema a shock-like condition, often resulting in death from haemorrhage in the small intestines, occurs when rats pretreated with thyroxine are injected with egg-white or ovomucoid in contrast, the severity and incidence of the egg-white anaphylactoid reaction is reduced in thyroidectomized animals [401, 404, 670]. The potentiating action of the thyroid hormone may be related to actions in reducing intestinal histaminase and increasing the level of tissue histamine and 5-hydroxytryptamine [220, 481], or to an increased sensitivity of tissues and blood vessels to the release of these 2 amines [491]. 

Beriberi is a nervous system disorder caused by a thiamine deficiency. Wet beriberi primarily affects the cardiovascular system, while dry beriberi affects the nervous system. Wet beriberi can also be characterized by vasodilation, peripheral oedema, shortness of breath and swelling of the lower legs. Dry beriberi causes partial paralysis resulting from damaged peripheral nerves and can be characterized by difficulty walking, loss of muscle function, mental confusion and involuntary eye movements. 

Heart failure without increased cardiac output, and no peripheral oedema, may also occur acutely, associated with severe lactic acidosis. This was a common presentation of deficiency in Japan, where it was called shoshin (= acute) beriberi in the 1920s some 26,000 deaths a year were recorded. 

Urinary tract A 27-year-old male developed peripheral oedema and interstitial nephritis after 4 years of treatment with quetiapine he was switched to olanzapine and the condition recurred, both incidents followed dose increases [229A]. 

Immunologic A case of peripheral oedema associated with risperidone oral solution has been described [269 ]. A case of angioedema periorbital oedema, swelling over the face, dyspnoea, dysphagia) in a 45-year-old woman 3 days after receiving her first injection of risperidone microspheres is reported [270 ]. 

HP(J N, Kalkan HS. Acute generalized exanthematous pustulosis associated with the use of quetiapine. BCP 2012 22(2) 194-7. McSkimming AJ, Dham P, Alexander J, Dinesh A. Peripheral oedema in quetiapine therapy. Aust N Z J Psychiatry 2012 46(8) 790-1. Gutman S, Layland J. Intolerable fever a previously unreported side-effect of quetiapine. Aust N Z J Psychiatry 2012 46(l) 72-3. 

Sitaxsentan was withdrawn from the worldwide market in December 2010 (SEDA-35) on accoxmt of hepatic damage that did not resolve on withdrawal of the drug but eventually proved fatal. A double-blind randomised controlled trial PO -] was conducted prior to the withdrawal to assess the efficacy and safety of lower dose range of sitaxsentan (50 or 100 mg) compared to placebo. Most adverse events documented by the authors including headaches, peripheral oedema, dizziness, nausea, extremity pain were said to be mild/moderate. Increased liver transaminases greater than three times of the upper limit was reported for one patient in each treatment arm, but reversed back to normal on discontinuation of the drug. 

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