Pathways

Prednisone is a medication that is used to suppress the immune system. It works by interrupting cytokine pathways type 1 and type 2. It is administered orally, through tablet, or solution (concentrated or non-concentrated). Prednisone is a glucocorticoid, and as well as being used for immune system suppression, it is used for its anti inflammatory properties. It exerts these properties by binding to glucocorticoid receptors in the cell, which inhibits inflammatory cells. This prevents inflammatory mediators from being expressed.

Prednisone is a synthetic, anti-inflammatory glucocorticoid that derives from cortisone. It is biologically inert and converted to prednisolone in the liver. The glucocorticoid receptor is located intracellularly within the cytoplasm and, upon binding, trans-locates rapidly into the nucleus, where it affects gene transcription and causes inhibition of gene expression and translation for inflammatory leukocytes and structural cells such as epithelium.

Pregabalin is an anticonvulsant drug used to treat neuropathic pain conditions and fibromyalgia, and for the treatment of partial onset seizures in combination with other anticonvulsants. Pregabalin is structurally similar to gamma-aminobutyric acid (GABA) - an inhibitory neurotransmitter. Its properties include anxiolytic, anticonvulsant and analgesic effects. Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity. In glutamatergic neurons, glutamate is synthesized from the amino acid glutamine and transported into synaptic vesicles by excitatory amino acid transporter and stored until an action potential arrives at the nerve terminal. When an action potential does arrive at the nerve terminal, this triggers the opening of voltage gated L-type calcium channel, leading to the influx of calcium ions into the presynaptic nerve terminal. The influx of calcium triggers the release of the stored neurotransmitter into the synapse via exocytosis. Glutamate is an excitatory neurotransmitter, thus, once it gets in the synapse it activates NMDA and AMPA receptors. Activation of NMDA receptors results in calcium ions being transported into the post synaptic neuron. Activation of AMPA receptor results in sodium being transported into the post synaptic neuron. The influx of cations into the post synaptic neuron leads to depolarization/ excitation of the neuron. Pregabalin inhibits subunit alpha-2/delta-1 of the voltage gated L-type calcium channel. This prevents the influx of calcium ions when an action potential arrives at the nerve terminal. With low calcium concentration in the presynaptic neuron, excitatory neurotransmitters like glutamate cannot be released and thus the electrical signal is terminated. This is beneficial in conditions like seizures, to prevent the uncontrolled electrical activity that occurs in the brain during an epileptic episode. Pregabalin is an oral drug administered in the fasted state, pregabalin absorption is rapid, and extensive. Common side effects of taking pregabalin include drowsiness, dizziness, blurred vision, difficulty with concentration/attention, dry mouth, edema, and weight gain. Following rapid or abrupt discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache, anxiety, nervousness, irritability, hyperhidrosis, and diarrhea. Chronic use of pregabalin can result in physical dependence, and there is a risk of abuse associated with its use, especially in patients on opioid medicines or who have a history of substance abuse.

PreQ0 or 7-cyano-7-carbaguanine is biosynthesized by degrading GTP. GTP first interacts with water through a GTP cyclohydrolase resulting in the release of a formate, a hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound then interacts with water through a 6-carboxy-5,6,7,8-tetrahydropterin synthase resulting in a acetaldehyde, triphosphate, 2 hydrogen ion and 6-carboxy-5,6,7,8-tetrahydropterin. The latter compound then reacts spontaneously with a hydrogen ion resulting in the release of a ammonium molecule and a 7-carboxy-7-deazaguanine. This compound then interacts with ATP and ammonium through 7-cyano-7-deazaguanine synthase resulting in the release of water, phosphate, ADP, hydrogen ion and a 7-cyano-7-carbaguanine. The degradation of 7-cyano-7-deazaguanine can lead to produce a preQ1 or a queuine by reacting with 3 hydrogen ions and 2 NADPH through a 7-cyano-7-deazaguanine reductase. PreQ1 then interacts with a guanine 34 in tRNA through a tRNA-guanine transglycosylase resulting in a release of a guanine and a 7-aminomethyl-7-deazaguanosine 34 in tRNA. This nucleic acid then interacts with SAM through a S-adenosylmethionine tRNA ribosyltransferase-isomerase resulting in a release of a hydrogen ion, L-methionine, adenine and an epoxyqueuosine

PreQ0 or 7-cyano-7-carbaguanine is biosynthesized by degrading GTP. GTP first interacts with water through a GTP cyclohydrolase resulting in the release of a formate, a hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound then interacts with water through a 6-carboxy-5,6,7,8-tetrahydropterin synthase resulting in a acetaldehyde, triphosphate, 2 hydrogen ion and 6-carboxy-5,6,7,8-tetrahydropterin. The latter compound then reacts spontaneously with a hydrogen ion resulting in the release of a ammonium molecule and a 7-carboxy-7-deazaguanine. This compound then interacts with ATP and ammonium through 7-cyano-7-deazaguanine synthase resulting in the release of water, phosphate, ADP, hydrogen ion and a 7-cyano-7-carbaguanine. The degradation of 7-cyano-7-deazaguanine can lead to produce a preQ1 or a queuine by reacting with 3 hydrogen ions and 2 NADPH through a 7-cyano-7-deazaguanine reductase. PreQ1 then interacts with a guanine 34 in tRNA through a tRNA-guanine transglycosylase resulting in a release of a guanine and a 7-aminomethyl-7-deazaguanosine 34 in tRNA. This nucleic acid then interacts with SAM through a S-adenosylmethionine tRNA ribosyltransferase-isomerase resulting in a release of a hydrogen ion, L-methionine, adenine and an epoxyqueuosine

Metabolites of sildenafil are predicted with biotransformer.