Elder toxicity

The limited toxicity data available for endosulfan suggest that several subgroups of the population may be more susceptible to endosulfan exposure than the general population. These subgroups include the unborn and neonates the elderly and people with liver, kidney, or neurological diseases, - effects that have been better characterized in animal studies. 

Several studies conducted in experimental animals have demonstrated that diets deficient in protein exacerbate the oral toxicity of endosulfan (Boyd 1972 Boyd et al. 1970 Das and Garg 1981). These results suggest that people who consume low-protein diets, such as chronic alcoholics, dieters, food faddists, various cults, some ethnic groups, the elderly, and some people living in depressed areas or underdeveloped countries, may be more susceptible to the toxic effects of endosulfan. 

In the gut, many pathogens adhere to the gut wall and produce their toxic effect via toxins which pervade the surrounding gut wall or enter the systemic circulation. Vibrio cholerae and some enteropathic E. coli strains localize on the gut wall and produce toxins which increase vascular permeability. The end result is a hypersecretion of isotonic fluids into the gut lumen, acute diarrhoea and consequent dehydration which may be fatal in juveniles and the elderly. In all these instances, binding to epithelial cells is not essential but increases permeation ofthe toxin and prolongs the presence of the pathogen. 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

The common causes of thyrotoxicosis are shown in Table 41-6.29,30 Thyrotoxicosis can be related to the presence or absence of excess hormone production (hyperthyroidism). Graves disease is the most common cause of hyperthyroidism. Thyrotoxicosis in the elderly is more likely due to toxic thyroid nodules or multinodular goiter than to Graves disease. Excessive intake of thyroid hormone may be due to overtreatment with prescribed therapy. Surreptitious use of thyroid hormones also may occur, especially in health professionals or as a self-remedy for obesity. Thyroid hormones can be obtained easily without a prescription from health food stores or Internet sources. 

Hydroxyurea is an older agent still used occasionally today for patients with psoriasis however, there have been recent precautions about its use in the elderly and cutaneous vasculitic toxicities in patients with myeloproliferative disorders.29 Toxicity associated with tacrolimus has limited its use in psoriasis. Azathioprine has a slow onset and significant toxicity.29 Oral corticosteroids are reserved for severe or life-threatening conditions such as severe psoriatic arthritis or exfoliative psoriasis prolonged oral steroid use should be avoided.10... 

Blood urea nitrogen (BUN) and serum creatinine are needed to dose antibiotics appropriately and to minimize or prevent drug toxicity (especially in the elderly patient). 

The most commonly used dose for fludarabine is 20 mg/m2 intravenously daily for 5 consecutive days, whereas chlorambucil can be taken daily as an oral tablet with the dose ranging from 4 to 10 mg/day.21 Fludarabine is associated with more toxicities than chlorambucil, including myelosuppression and prolonged immunosuppression.19 Resulting infectious complications may occur during the periods of prolonged immunosuppression. The ease of administration and limited side effects make chlorambucil a practical option for symptomatic elderly patients who require palliative therapy... 

Elder leaves contain the alkaloid sambucine, a precursor of hydrocyanic acid, which is somewhat toxic. Thus, the leaves are used only topically in ointments for sprains or bruises. Bruised leaves can be rubbed on the body or worn under a hat to prevent being pestered by insects. Cooled strained leaf tea can be applied to plants to discourage aphids. 

Only the blue elderberries are edibleSambucus canadensis and S. carulea (found in North America) as well as the European variety S. nigra. The red elder Sambucus pubens has toxic red berries and flowers that are conical rather than flat-topped clusters. "Blue is true and red is dead," is a popular expression among herbal harvesters. 

Elderberries provide food for birds, bears, chipmunks, elk, moose, deer, foxes, rabbits, squirrels and woodchucks. Linnaeus said the berries were not good food for chickens and turkeys and might even be toxic to them. The fact that many wild animals relish the elderberries helps to proliferate this wonderful shrub, as the elder seeds are fertilized by animal droppings. 

Sambucus ebulus. Grows to 4 feet in Eurasia and northern Africa also grows in eastern and central U.S. Also known as dwarf elder, Dane s elder. Its black berries are toxic. Good dye source. The root has a history of being used to treat snakebite. 

The leaves, root and bark are considered safest for external use only. However, European elder has less toxicity than the western varieties. The bark, if used internally, should be only the European variety aged for at least one year to avoid cyanide toxicity. 

Certain subgroups of the population may be more susceptible to the toxic effects of lead exposure. These include crawling and house-bound children (<6 years old), pregnant women (and the fetus), the elderly, smokers, alcoholics, and people with genetic diseases affecting heme synthesis, nutritional deficiencies, and neurological or kidney dysfunction. This is not an exhaustive list and reflects only current data available, further research may identify additional susceptible subgroups. 

The answer is d. (Hardman, p 7502) The most consistent of the toxicides of ACT inhibitors is impairment of renal function, as evidenced by proteinuria. Elevations of blood urea nitrogen (BUN) and creatinine occur frequently, especially when stenosis of the renal artery or severe heart failure exists Hyperkalemia also may occur These drugs are to be used very cautiously where prior renal failure is present and in the elderly Other toxicides include persistent dry cough, neutropenia, and angioedema. Hepatic toxicity has not been reported... 

Elder JF, Collins JJ (1991) Fresh-water mollusks as indicators of bioavailability and toxicity of metals in surface-water systems. Rev Environ Contam Toxicol 122 37-79... 

Carbon monoxide (CO) is generated in incomplete combustion processes. In households the main sources are all kinds of fuel burners (fuel oil, wood, natural gas, coal etc.) and automotive exhaust gas. Carbon monoxide is an odorless and invisible gas, and, due to its affinity to hemoglobin, which is higher than that of oxygen, it reduces the blood s capacity to carry oxygen. Hence it is toxic, especially for unborn and small children as well as for the elderly or people with heart problems or anemia. Even small amounts of CO can be harmful. Tab. 5.6 gives an overview of the relation between CO concentration and the corresponding symptoms of intoxication. 

Lithium toxicity can occur with serum levels greater than 1.5 mEq/L, but the elderly may have toxic symptoms at therapeutic levels. Severe toxic symptoms may occur with serum concentrations above 2 mEq/L, including vomiting, diarrhea, incontinence, incoordination, impaired cognition, arrhythmias, and seizures. Permanent neurologic impairment and kidney damage may occur as a result of toxicity. 

Some indications for plasma level monitoring include inadequate response, relapse, serious or persistent adverse effects, use of higher than standard doses, suspected toxicity, elderly patients, children and adolescents, pregnant patients, patients of African or Asian descent (because of slower metabolism), cardiac disease, suspected noncompliance, suspected pharmacokinetic drug interactions, and changing brands. 

Dose adjustments should generally be made based on trough serum concentration results. A conservative therapeutic range of 8 to 15 mcg/mL is often targeted, especially in elderly patients, to minimize the likelihood of toxicity. Once a dose is established, concentrations should be monitored once or twice a year unless the disease worsens, medications that interfere with theophylline metabolism are added, or toxicity is suspected. 

Some dmgs are bound to plasma proteins in blood. Plasma protein levels in blood may be decreased in the elderly, but this is most often not clinically relevant since a drug s elimination increases when the free, unbound drug concentration is enhanced (Turnheim 1998). The plasma albumin level may however be markedly decreased in elderly suffering from malnutrition or severe disease. For those patients the concentration of the free unbound drug can reach toxic levels (Waiter-Sack and Klotz 1996). 

Elderly people s capacity to concentrate the urine decreases, which results in that they need larger amounts of urine to secrete the same amount of toxic waste products compared with younger adults. 

Treatment of epilepsy is often more complex in the elderly (Tallis et al. 2002). Plasma concentration of antiepileptic drugs that are adequate for younger patients may be toxic for older adults. Clinical response, and not only plasma concentration of the drug, is more important in the elderly for evaluation of antiepileptic treatment. 

---