Metabolic causes

The consequence of the relationships of Table 5.3 and Fig. 5.2 is that for a neutral thermal sensation, at steady state, the core temperature increases while the skin temperature decreases with increased metabolic activity (Fig. 5.3). The increase in metabolism causes sweating which decreases skin tem-perature. 

FIGURE S.45 (o) Mechanism of induchon of xenobiotic metabolism caused by TCOO and pofyt/C ... 

It appears that organisms at the top of aquatic food chains are not exposed to substantial levels of PAH in food because of the detoxifying capacity of organisms beneath them in the food chain. On the other hand, fish, birds, and aquatic mammals feeding on mollusks and other invertebrates are in a different position. Their food may contain substantial levels of PAH. Although they can achieve rapid metabolism of dietary PAH, it should be remembered that oxidative metabolism causes... 

Defects in Fructose Metabolism Cause Disease (Figure 20-5)... 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Serum electrolytes and chemistries may indicate metabolic causes of symptoms. 

Active hyperemia. The increase in blood flow caused by enhanced tissue activity is referred to as active hyperemia. Assuming a constant blood pressure, then according to Ohm s law (Q = AP/R), the increase in blood flow is the result of a decrease in local vascular resistance. Tissue metabolism causes several local chemical changes that can mediate this metabolic vasodilation. These include ... 

A second class of disorders of glycogen and fatty acid metabolism causes progressive weakness 699... 

Defects of energy metabolism cause profound disturbances in the function of muscle and brain. Such defects may present as a myopathy, encephalopathy or encephalo-myopathy. Clinical features are best appreciated by understanding the preferred oxidizable substrates for brain and muscle. 

Phenytoin, carbamazepine, phenobarbital, oxcarbazepine, and valproic acid may interfere with vitamin D metabolism, causing asymptomatic high-turnover bone disease with normal bone density or decreased bone mineral... 

Of 50 adult rats used in a reproductive/developmental study, 22% of those that received 6 mg/kg/day heptachlor in the diet developed lens cataracts 4.5-9.5 months following exposure. In addition, 6-8% of the pi offspring and 6% of the p2 offspring of these rats also developed cataracts 19-21 days after birth (Mestitzova 1967). The author of this study eliminated the possibility of a vitamin B deficiency or a recessive genetic trait as the cause of the cataracts. She could not rule out the possibility of altered vitamin B metabolism caused by heptachlor. 

Other seizures Hydantoins are not indicated in seizures caused by hypoglycemia or other metabolic causes. 

Mecfianism of Action A phenylalkylamine sympathomimetic with activity similar to amphetamines that stimulates the central nervous system (CNS) and elevates blood pressure (BP) most likely mediated via norepinephrine and dopamine metabolism. Causes stimulation of the hypothalamus. Therapeutic Effect Decreases appetite. Pharmacokinetics The pharmacokinetics of phendimetrazine tartrate has not been well established. Metabolized to active metabolite, phendimetrazine. Excreted in urine. Half-life 2-4 hr. 

Mechanism of Action A sympathomimetic amine structurally similar to dextroamphetamine and is most likely mediated via norepinephrine and dopamine metabolism. Causes stimulation of the hypothalamus. Therapeutic Effect Decreased appetite. 

Acetone and several other ketones are produced naturally in the liver as a result of fat metabolism. Ketone blood levels are typically around 0.001%. The lack of carbohydrates in a person s diet results in greater fat metabolism, causing ketone levels in the blood to increase. This condition is called ketosis. People on low-carbohydrate diets and diabetics may have problems with ketosis because of a greater amount of fat in the diet. An indicator of ketosis is the smell of acetone on a persons breath. 

Although of much less clinical relevance, it must be emphasized that certain disturbances of HDL metabolism cause familial aggregation of elevated HDL cholesterol... 

A recent example of a species difference in metabolism causing a difference in toxicity is afforded by the alicyclic hydroxylation of the oral antiallergy drug, proxicromil (Fig. 5.11). After chronic administration, this compound was found to be hepatotoxic in dogs but not in rats. It was found that dogs did not significantly metabolize the compound by alicyclic oxidation, whereas rats, hamsters, rabbits, and man excreted substantial proportions of metabolites in the urine. In the dog, biliary excretion was the route of elimination of the unchanged compound,... 

Allyl isovalerate has low irritancy potential. It is deduced that one of its metabolites, isovaleric acid, is toxic, based upon the effects of an inborn error of leucine metabolism caused by isovaleiy l-coenzynie A dehydrogenase deficiency. This is a sx ndrome of neonatal vomiting and lethargy progressing to coma, pancytopenia and ketoacidosis that can be alleviated by glycine treatment, which enhances the synthesis and excretion of iso-valerylglycine (Cohn et al., 1978 lARC, 1985). 

On the other hand, primary respiratory alkalosis occurs as a result of alveolar hyperventilation. This condition is associated with a number of pulmonary diseases, bui also may appear during pregnancy, liver disease, and salicylate intoxication, among others. The sequence of events proceeds along these lines (I) Ventilation removes CO faster than the gas is produced by metabolism, causing a decrease tn pCO in the blood and body fluids, including a reduction of venous pCO . This reduces the gradient... 

Myotoxicity linked to ezetimibe has been described in a 45-year-old overweight man with McArdle disease, which is the most common disorder of muscle carbohydrate metabolism, caused by mutations in the gene that encodes myophosphorylase (5). 

Once-daily administration of modified-release formulation of fluvastatin 80-320 mg/day was generally safe and well tolerated in 40 patients with primary hypercholesterolemia over 13 days (7). However, fluvastatin 640 mg in this formulation was not well tolerated six of seven patients had adverse events, including diarrhea, headache, and rises in serum transaminases. In addition, the pharmacokinetics of fluvastatin were non-linear at this dose, possibly because of saturation of first-pass metabolism, causing higher than expected serum drug concentrations. 

Melegh B, Pap M, Molnar D, Masszi G, Kopcsanyi G. Carnitine administration ameliorates the changes in energy metabolism caused by short-term pivampicillin medication. Eur J Pediatr 1997 156(10) 795-9. 

In addition to its usage in the treatment of respiratory ailments, coltsfoot is also used to treat diarrhea, purify the blood, stimulate metabolism, cause diuresis and swelling, and topically as a wound treatment. Today, products containing coltsfoot are promoted as antihistamines, decongestants, and expectorants. 

Benzodiazepines + cimetidine, disulfiram —> inhibition of benzodiazepine metabolism causing increased sedation. 

Disorders of Bile Pigment Metabolism Causing Jaundice. 280... 

---