Kidney caffeine, effects

C7H9N402- M.p. 337 C, an alkaloid obtained from cacao seeds or prepared synthetically. Constitutionally it is similar to caffeine, and is also a weak base. It is usually administered as the sodium compound combined with either sodium ethanoate or sodium salicylate, and is employed almost entirely as a diuretic. Physiologically theobromine resembles caffeine, but its effect on the central nervous system is less, while its action on the kidneys, is more pronounced. 

Caffeine and the related dimethylxanthines have similar pharmacological or therapeutic effects and similar toxic effects. The primary actions include stimulation of the central nervous system, relaxation of bronchial muscles, mild cardiac muscle stimulation, and diuretic effects on the kidney. 

Caffeine is a weak diuretic because it nonspecifically and weakly blocks adenosine receptors that participate in the control of proximal tubule Na+ reabsorption in the kidney. A new class of drugs, the adenosine A1 receptor antagonists, have recently been found to have potent vasomotor effects in the renal microvasculature and to significantly blunt both proximal tubule and collecting duct NaCI reabsorption (see under Heart Failure). One of these drugs, rolofylline (KW-3902), should soon receive final Food and Drug Administration (FDA) approval. 

The methylxanthines have effects on the central nervous system, kidney, and cardiac and skeletal muscle as well as smooth muscle. Of the three agents, theophylline is most selective in its smooth muscle effects, whereas caffeine has the most marked central nervous system effects. 

Certain foreign compounds may cause the retention or excretion of water. Some compounds, such as the drug furosemide, are used therapeutically as diuretics. Other compounds causing diuresis are ethanol, caffeine, and certain mercury compounds such as mersalyl. Diuresis can be the result of a direct effect on the kidney, as with mercury compounds, which inhibit the reabsorption of chloride, whereas other diuretics such as ethanol influence the production of antidiuretic hormone by the pituitary. Changes in electrolyte balance may occur as a result of excessive excretion of an anion or cation. For example, salicylate-induced alkalosis leads to excretion of Na+, and ethylene glycol causes the depletion of calcium, excreted as calcium oxalate. 

A much milder and legal stimulant is caffeine, depicted in Figure 14.27. A number of mechanisms have been proposed for caffeines stimulatory effects. Perhaps the most straightforward mechanism is caffeine s facilitating of the release of norepinephrine into synaptic clefts. Caffeine also exerts many other effects on the body, such as dilation of arteries, relaxation of bronchial and gastrointestinal muscles, diuretic action on the kidneys, and stimulation of stomach-acid secretion. 

Caffeine, by blocking the action of the body s adenosine, affects a wide variety of organs, as well as the brain, the gut, and basic metabolism. Theophylline works more actively on respiration and the heart. Caffeine is more active in the gut and in the central nervous system. Theobromine has very weak, if any, effect on the brain, but it retains the methylxanthine effect on the kidneys, increasing urination. 

Metabolic processes speed up appreciably under the influence of caffeine. Fatty acids are released into the blood, and a general increase in metabolism is evident as there is increased muscle activity, raised temperature, or both. More calcium is made available through caffeine s action in the muscles for contraction, but this effect is evident only at caffeine doses higher than people commonly use. Gut motility and secretion increase with a release of stomach acid and digestive enzymes. Urination is also stimulated caffeine directly affects the kidneys, cutting into their ability to reabsorb electrolytes and water. For every cup of coffee or two to three cans of caffeinated soft drink consumed, about 5 mg of calcium is lost in the urine. 

Caffeine s primary action is stimulation of CNS activity but, as we saw, caffeine is distributed freely throughout the body. Such distribution is evidenced by caffeine s actions outside the CNS contraction of striated muscle, including the heart relaxation of smooth muscle, especially the coronary arteries, uterus, and bronchi diuretic effects on the kidneys at higher doses, a stimulating effect on respiration elevation of basal metabolism and various endocrine and enzymatic effects (Levenson Bick, 1977 Rail, 1990a). Caffeine s effects on the body s systems provide good evidence for the blockade of adenosine receptors as its mechanism of action because caffeine s effects essentially arc opposite to those of adenosine (Leonard et al., 1987). 

Very few fatalities have ever been reported (or studied), but it appears that the therapeutic index for ephedrine is very great. A 1997 case report described a 28-year-old woman with two prior suicide attempts, who died after ingesting amitriptyline and ephedrine. The blood ephedrine concentration was 11,000 ng/mL, and the liver concentration was twice that value (kidney, 14 mg/kg brain, 8.9 mg/kg). The amitriptyline concentration was 0.33 mg/kg in blood and 7.8 mg/kg in liver (131). Values in a second case report (where methylephedrine concentrations were nearly 6000 ng/mL) may or may not be relevant to the problem of ephedrine toxicity, as the individual in question took massive quantities of a calcium channel blocker, and it is not known whether methylephedrine exerts all the same effects as ephedrine (132). Baselt and Cravey mention the case of a young woman who died several hours after ingesting 2.1 g of ephedrine combined with 7.0 g of caffeine, but tissue findings were not described. Her blood ephedrine level was 5 mg/L, whereas the concentration in the liver was 15 mg/kg (133). 

Caffeine causes several centrally mediated side effects including nervousness, irritability, and sleeplessness. Caffeine also acts on kidneys to increase diuresis. Convulsions and increased heart rate can occur with particularly high doses of the drug. 

Methylxanthines, including caffeine, stimulate the central nervous system and the heart, elicit a diuretic effect in the kidneys, and relax smooth muscles. 

Caffeine is one of the most studied substances in science. It stimulates the central nervous system it counteracts adenosine in the brain, thereby inhibiting its effect causing a feeling sleepiness. Caffeine also increases the level of adrenaline (a hormone) and dopamine (a neurotransmitter). Caffeine, contrary to some beliefs, does not wake people up, it only inhibits the effects of adenosine, increases the rate of heartbeat, dilates certain blood vessels and narrows some others, and makes it easier for muscles to contract. Caffeine also boosts pattern separation memory in humans. In addition to this general stimulating action, side effects may include irritability, nervousness, headache or insomnia, especially if unreasonably high amounts are consumed. Caffeine has been linked to a number of negative effects as well (heart, liver and kidney disease, cancer, osteoporosis, ulcers. 

---