Pathways

Calcium acetate is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Calcium acetate passes through the liver and is then excreted from the body mainly through the kidney.

Caffeine is a stimulant present in tea, coffee, cola beverages, analgesic drugs, and agents used to increase alertness. The cardiovascular effects are extensive and can help with headaches, migraines, or other types of pain in certain circumstances. Caffeine is mainly studied using coffee which has other chemicals present in it. This means that much of the research is not well understood, and there is much conflicting data on caffeine. Regular caffeine intake can alter adenosine receptor population, especially the population of adenosine A2A receptors. It can potentially alter the potency. Caffeine antagonizes adenosine A1 receptors in sympathetic nerves that innervate the heart muscles. Adenosine A1 receptors inhibit the release of catecholamines like norepinephrine from neurons that innervate the heart muscles. The antagonism of adenosine A1 receptors allows more norepinephrine to be released into the synapse where it causes contractions of the heart muscles through the norepinephrine subpathway. This leads to increased heartrate. In the endothelial cells of blood vessels, caffeine, through an unknown mechanism, activates the release of calcium from the endoplasmic reticulum through the ryanodine receptor. This calcium binds to calmodulin which activates Nitric oxide synthase. This catalyzes the reaction of L-Arginine into nitric oxide. Nitric oxide then transports from the endothelial cells into the myocytes of the blood vessel located in the media. In the myocyte nitric oxide then activates Guanylate cyclase which catalyzes GTP into cGMP. cGMP activates cGMP-dependent protein kinase. Activated protein kinase has many interactions within the myocyte. Protein kinase activates potassium channels which causes potassium to leave the myocyte. This causes hyperpolarization in the cell. This prevents the voltage-gated calcium channels from opening and allowing calcium into the cell. This is also prevented by protein kinase inhibiting the voltage-gated calcium channels. This along with the activation of calcium pumps out of the cell and into the sarcoplasmic reticulum causes the cytosolic concentration of calcium to be very low. Low concentrations of calcium cannot bind to calmodulin which means calmodulin cannot activate myosin light chain kinase. With myosin light chain kinase unable to activate, myosin light chain cannot be phosphorylated which means that it is dephosphorylated by myosin light chain phosphatase. The accumulation of myosin light chain causes myosin to unbind from actin and the muscle to relax. The relaxation of smooth muscles around blood vessels causes vasodilation. This effect is observed in the majority of the body except the head and neck. The opposite effects of caffeine is called the coffee-effect and based on the population of receptors in that area of the body, as well as their affinity for caffeine. This causes vasodilation in the majority of the human body, but vasoconstriction in the head and neck.

Caffeine is a central nervous system stimulant present in tea, coffee, cola beverages, analgesic drugs, and agents used to increase alertness. Consistent intake of caffeine increases the population of adenosine receptors, which can potentially lead to a change in potency. Caffeine stimulates wakefullness and arousal in the central nervous system. Caffeine does this by inhibiting adenosine A2A receptors on the nucleus accumbens. The activation of A2A receptors in the nucleus accumbens releases GABA into the locus coeruleus, the tuberomammillary nucleus, and the lateral hypothalamus in order to regulate these systems through GABA receptors. The inhibition of GABA release leads to the disinhibition of these areas of the brain. The low concentration of GABA cannot activate the GABAA receptors which would cause hyperpolarization of the neurons. The inhibition of GABA removes the restraints on the neurons of the tuberomammillary nucleus, the lateral hypothalmus, and the locus coeruleus. In the locus coeruleus caffeine activates the release of norepinephrine through an unknown mechanism. Norepinephrine accumulates in the synapse and activates Alpha-1 adrenergic receptors and beta-1 adrenrgic receptors. The inhibition of GABA also leads to the disinhibition of adrenergic neurons in the locus coeruleus, furthers increasing the activation of adrenergic receptors. This activates arousal systems which leads to wakefulness and alertness through different mechanisms throughout the brain. In the tuberomammillary nucleus, which is in the anterior hypothalamus, histamine activates the H1 histamine receptors. This increases arousal, which leads to increased wakefulness and alertness.The wakefulness center of the brain is suspected to be in the anterior hypothalamus as well. From here it sends projections throughout the brain to promote wakefulness. In the lateral hypothalamus caffeine inhibits adenosine A1A receptors which leads to the disinhibition of orexin. The inihition of GABA release also causes a disinhibition of orexin. Orexin is released through innervation by glutamate via the dorsomedial hypothalamus. Orexin release activates arousal which leads to the activation of wakefulness and alertness mechanisms throughout the brain. The lateral hypothalamus, the tuberomammillary nucleus, and the locus coeruleus inhibit the ventrolateral preoptic nucleus via GABA in a flip-flop arangment depending on the area of the brain that is stimulated more.Therefore arousal and wakefulness inhibits sleep, and sleep inhibits arousal and wakefullness. Caffeine also inhibits adenosine A2A receptors present in the ventrolateral preoptic nucleus which further prevents sleep.

Caffeine is obtained from diet including coffee and other beverages and is absorbed in the stomach and small intestine. In the liver, the cytochrome P450 oxidase enzyme system and specifically CYP1A2 metabolizes caffeine into paraxanthine to increase lipolysis and increase free fatty acids and glycerol levels in the blood, theobromine to dilate blood vessels and increase urine volume and theophylline which relaxes bronchi smooth muscles. In the lysosome, these metabolites undergo further metabolism into methyluric acids before being excreted in the urine. There is genetic variability in the metabolism of caffeine due to the polymorphism of CYP1A2. This variability can affect the pharmacokinetic and pharmacodynamic properties of caffeine and may affect an individual's consumption.