Smooth muscle, caffeine, effects

Caffeine has been shown to have a bronchial and smooth muscle relaxant effect and to improve skeletal muscle contractility. Significant increases in hand tremor and forearm extensor electromyogram were observed in human subjects after the ingestion of 6mgkg of caffeine. This effect is more likely due to a CNS stimulatory effect than to direct action on the muscle fibers. Skeletal muscle fatigue can be reversed by high concentrations of caffeine obtained only in vitro but not in vivo. 

Dreja K, Nordstrom I, Hellstrand P 2001 Rat arterial smooth muscle devoid of ryanodine receptor function effects on cellular Ca2+ handling. Br J Pharmacol 132 1957-1966 Martin C, Hyvelin JM, Chapman KE, Marthan R, Ashley RH, Savineau JP 1999 Pregnant rat myometrial cells show heterogeneous ryanodine- and caffeine-sensitive calcium stores. Am J Physiol 277 C243-C252... 

These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see Box 14.3) and subsequent release of adrenaline. This leads to the major effects a stimulation of the central nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

Methylxanthines have a number of other effects, including effects on smooth muscles and the cardiovascular system. The most notable effect on smooth muscles is relaxing the bronchi of the lungs. Theophylline is prescribed to treat mild forms of asthma. While both caffeine and theophylline will relax the bronchial smooth muscles, theophylline is used therapeutically because of its longer half-life. This allows the drug to stay in the therapeutic range longer. 

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. 

CNS, smooth muscle T diuresis X- pit aggregation Available forms Daily t doses w/ max 3 g PO daily Contra Avoid in PRG lactation, CAD, hyperthyroidism, anxiety disorders d/t high, caffeine content Notes/SE Insomnia, tach, anxiety, N/V, HA, HTN, Sz Interactions T Effects OF anticoagulants, anti-pits, BBs, bron-choclilators T risk of hypertensive crisis W/ MAOIs T effects W/ cimetidine, ciprofloxacin, ephedrine, hormonal contraceptives, dieophylline, cola, coffee X-effects OF adenosine, antihypertensives, benzodiazepines, Fe, X- effects W/ smoking EMS Tinctures contain EtOH may exacerbate GI disorders HTN T effects of anticoagulants and BBs... 

Caffeine is used medicinally as a CNS stimulant, usually combined with another therapeutic agent, as in compound analgesic preparations. Theobromine is of value as a diuretic and smooth muscle relaxant, but is not now routinely used. Theophylline is an important smooth muscle relaxant for relief of bronchospasm, and is frequently dispensed in slow-release formulations to reduce side-effects. It is also available as aminophylline (a more soluble preparation containing theophylline with ethylenediamine) and choline theophyllinate (theophylline and choline). The alkaloids may be isolated from natural sources, or obtained by total or partial synthesis. 

Breathing rate increases in response to caffeine. The effect on respiration occurs at the level of the brain stem s respiration control center. Theophylline has the most potent action of all the methylxanthines, affecting the smooth muscle of the bronchial tree in the lungs. This is why theophylline is a treatment for asthma. Doctors may recommend weak tea for their asthmatic patients with colds this bronchodilating action of the theophylline in the tea will aid in clearing mucus. 

The major bases found in nucleic acids are adenine and guanine (purines) and uracil, cytosine, and thymine (pyrimidines). Thymine is found primarily in DNA, uracil in RNA, and the others in both DNA and RNA. Their structures, along with their chemical parent compounds, purine and pyrimidine, are shown in Figure 10.1, which also indicates other biologically important purines that are not components of nucleic acids. Hypoxanthine, orotic acid, and xanthine are biosynthetic and/or degradation intermediates of purine and pyrimidine bases, whereas xanthine derivatives—caffeine, theophylline, and theobromine—are alkaloids from plant sources. Caffeine is a component of coffee beans and tea, and its effects on metabolism are mentioned in Chapter 16. Theophylline is found in tea and is used therapeutically in asthma, because it is a smooth muscle relaxant. Theobromine is found in chocolate. It is a diuretic, heart stimulant, and vasodilator. 

The general properties of the methylxanthines (theophylline, caffeine) are discussed elsewhere (see p. 194). Their mild diuretic action probably depends in part on smooth muscle relaxation in the afferent arteriolar bed increasing renal blood flow, and in part on a direct inhibitory effect on salt reabsorption in the proximal tubule. Their uses in medicine depend on other properties. 

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). 

The acute effects of caffeine include diuresis, stimulation of the heart and CNS, relaxation of smooth muscles, and stimulation of gastric acid. 

Theophylline occurs in such a low concentration in all xanthine drugs that extraction is not profitable. Theophylline can be produced by demethylation of caffeine or by total synthesis. Theophylline has a spasmolytic effect on smooth muscles, which is apparent in a pronounced bronchodilating action, hence it is used in asthma either on its own or combined with ethylenediamine to produce aminophylline. Furthermore, theophylline has a diuretic action. 

However, cADPR may not be a universal regulator of RyRs in smooth muscle cells. In permeabilized strips of guinea pig vas deferens smooth muscle, cADPR at concentrations as high as 100 iM, in contrast to the effects of IP3 and caffeine, failed to contract these preparations (Nixon et al., 1994). 

Caffeine enters the bloodstream about ten minutes after its ingestion and stays in the body for up to twelve hours. Like other alkaloids, caffeine has powerful physiological effects on humans and animals. It stimulates heart muscle and relaxes certain structures that contain smooth muscle, including the coronary arteries and the bronchi. It is a diuretic. Theophylline and theobromine, two other plant alkaloid derivatives of xanthine, have physiological effects similar to those of caffeine. 

The drug produces CNS stimulation and skeletal muscles but to a much lesser extent as compared to caffeine however, it exhibits a greater effect on the coronary dilatation, smooth muscle relaxation, diuresis and cardiac stimulation than caffeine. 

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