Lipodystrophy

Before an antiviral agent becomes a drug, advanced toxicity testing, pharmacological combination, and drug-interaction studies are needed. The use of new cell-based assays that can predict mitochondrial toxicity, lactic acidosis, peripheral neuropathy, anemia, hypersensitivity, lipodystrophy, and other potential side effects can alleviate these issues (Stuyver et al. 2002). 

Zerit 40-mg caps 40 mg bid (ml/minute) greater than 60 kg less than 60 kg lipodystrophy ... 

Protease inhibitors Hepatotoxicity hyperlipidemia, nephrolithiasis, lipodystrophy... 

Ad hoc groups for excipient, lipodystrophy, and antiretroviral medicinal products have been formed. A multidisciplinary group has been set up to evaluate medicinal products containing thiomersal with a view to limiting exposure to mercury and or-ganomercurial compounds. 

Fig. 32. The 30-year-old male patient with acquired generalized lipodystrophy (AGE) shows lacking lipids in the subcutaneous layer and in the musculature in a Ti-weighted spin-echo image (a) and in a fat selective image (b). Only marrow fat in the tibia and fibula of the patient seems to be not affected by the disease. Comparison between a spectrum from a insulin resistant subject without AGE (c) and the spectrum from the AGE patient (d) reveals that the AGE patient has nearly lacking EMCE and markedly reduced IMCE content.

Unwanted effects. Hypoglycemia results from absolute or relative overdosage (see p. 260). Allergic reactions are rare—locally redness at injection site, atrophy of adipose tissue (lipodystrophy) systemically urticaria, skin rash, anaphylaxis. Insulin resistance can result from binding to inactivating antibodies. A possible local lipohypertrophy can be avoided by alternating injection sites. 

Highly purified (single component) and human Insulins Local insulin allergy, immunologic insulin resistance, injection-site lipodystrophy temporary insulin use (ie, surgery, acute stress type 2 diabetes, gestational diabetes) newly diagnosed diabetic patients. 

The number and size of daily doses, time of administration, and diet and exercise require continuous medical supervision. Dosage adjustment may be necessary when changing types of insulin. Rotate administration sites to prevent lipodystrophy. Do not administer within 1 inch of the same site for 1 month. It may be best to rotate sites within an area rather than rotating areas. 

Dermatologic- Injection-site reaction, lipodystrophy, pruritus, rash. 

Lipodystrophy Rarely, administration of insulin subcutaneously can result in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue). 

Adverse reactions occurring in at least 3% of patients include diarrhea, abdominal discomfort nausea vomiting rash vomiting pruritus lipodystrophy fever pneumonia. 

Fluid retention is a frequently occurring adverse reaction. Hypersensitivity reactions and lipodystrophy at injection sites can occur. 

In 1995 the FDA approved saquinavir, the first protease inhibitor, for use in combination with other nucleoside analogue medications. In 1999 a soft gel capsule formulation of saquinavir with considerably improved absorption characteristics was developed. Ritonavir and indinavir have been approved for use alone or in combination with nucleoside analogue medications in people with advanced HIV disease. Nelfinavir is the first protease inhibitor labeled for use in children. Amprenavir is the newest of the protease inhibitors. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. The most disturbing adverse reactions to protease inhibitors consist of the lipodystrophy syndrome with severe hyperlipidemia and unpredictable fat redistributions over the body... 

Somogyi effect, including rebound hyperglycemia with chronically excessive insulin dosages systemicallergic reaction, marked by rash, angioedema, and anaphylaxis lipodystrophy or depression at injection site due to breakdown of adipose tissue lipo-hypertrophy or accumulation of subcutaneous tissue at injection site due to inadequate site rotation Rare... 

I Unlabeled Uses Treatment of HIV lipodystrophy syndrome, metabolic complications of AIDS, polycysfic ovary syndrome, prediabefes, weighf reducfion... 

Stavudine NRTI1 Immediate release 30-40 mg bid, depending on weight3 Peripheral neuropathy, lipodystrophy, hyperlipidemia, rapidly progressive ascending neuromuscular weakness (rare), pancreatitis Avoid concurrent zidovudine and neuropathic drugs (eg, ddl, zalcitabine, isoniazid)... 

In combination with other antiretroviral agents, stavudine has caused fatal lactic acidosis in some patients. It is also associated with motor weakness in which case it should be discontinued. Peripheral neuropathy is the most common toxicity associated with stavudine, which is more prevalent at high doses (4mg/kg per day). Neuropathy in these patients generally is associated with numbness, tingling or pain in feet or hands. Patients treated with the combination of stavudine and didanosine may also exhibit liver function abnormalities (hepatic steatosis) and pancreatitis. It may also be associated with the etiology of HIV lipodystrophy syndrome. 

The adverse effects of saquinavir are mild but predominantly they are related to GI discomfort including abdominal discomfort, nausea, diarrhea and vomiting. Lipodystrophy may result from its long-term use. Rarely, saquinavir causes confusion, weakness, ataxia, seizures, headache and liver abnormalities. 

The adverse effects of ritonavir comprise GI discomfort including abdominal pain, nausea, diarrhea, vomiting, asthenia and neurological disturbances. Taste perversion, peripheral paresthesias and lipodystrophy including elevated levels of triglycerides and cholesterol have also been reported with its administration. 

Some patients receiving indinavir exhibit nephrolithiasis/urolithiasis including flank pain that may be accompanied by hematuria. The frequency of nephrolithiasis is dependent on the period of treatment with indinavir. Other side effects associated with indinavir include insulin resistance, hyperglycemia, asymptomatic hyperbilirubinemia, HIV lipodystrophy syndrome and skin abnormalities. Indinavir should not be coadministered with drugs that affect the cytochrome P-450 system (CYP3A4). Antacids are not recommended within 2 h of its administration, specifically didano-sine containing an antacid buffer. 

Six patients with pre-existing HIV-lipodystrophy developed symptomatic Cushing s syndrome when treated with... 

The effects of insulin are modified by various factors. The speed and extent of absorption of insulin depends, for example, on the site of injection (1), the depth of the subcutaneous injection, skin temperature (2), the presence of lipodystrophy, and variation in the extent of inactivation of injected insulin. The disposal of insulin depends on many factors. Exercise and hard work lower the blood glucose and thereby increase the effect of insulin. Infections and obesity reduce its effect. The timing of food intake and the composition of meals are also related to the action of insulin. A thin layer of fat, as sometimes occurs in the upper arm or in the thighs of thin men, can result in intramuscular injection, leading to faster absorption of long-acting insulins. This can reduce the absorption time by half (3). The major factors that affect the fate of injected insulin (and thereby also its risks) are listed in Table 1 (4). 

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