Pathways

Telbivudine is a synthetic thymidine nucleoside analog with specific activity against the hepatitis B virus. It is administered orally. Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate. Telbivudine 5'–triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'–triphosphate. This leads to the chain termination of DNA synthesis, thereby inhibiting viral replication. Incorporation of telbivudine 5'–triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. Telbivudine inhibits anticompliment or second-strand DNA. This causes DNA chain termination, preventing the growth of viral DNA. Less Viral DNA is transported into the nucleus, therefore, less viral DNA is integrated into the host DNA. Less viral proteins produced, fewer viruses can form.

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

Telithromycin is a semi-synthetic erythromycin derivative. It belongs to the chemical family called ketolides, a group belonging to the macrolide-lincosamide-streptogramin (MLS) class. Telithromycin prevents bacterial growth by inhibiting bacterial protein synthesis. Similar to macrolides, telithromycin directly blocks translation of the bacterial 23S ribosomal RNA; however, unlike macrolides, telithromycin also blocks bacterial ribosomal assembly (mechanism not shown). Telithromycin binds to two sites on the 50S ribosomal subunit, domains II and V of the 23S rRNA, whereas macrolides bind only to domain V. The C11-12 carbamate side chain is thought to contribute to a higher binding affinity of telithromycin compared to erythromycin A. In erythromycin A-susceptible bacteria, telithromycin exhibits 10 times greater affinity than erythromycin. Its relative binding affinity is further increased to 25 times greater in macrolide-resistant bacteria strains. This is likely due to the additional binding site on domain II since macrolide resistance occurs as a result of alterations in the domain V binding site.

Telithromycin is an oral antibiotic drug that is a semi-synthetic erythromycin derivative. Telithromycin is metabolized in the liver by cytochrome P450 and 3A4 enzymes. Telithromycin penetrates the bacterial cell wall and acts on the ribosomal subunits to interfere with protein synthesis. These compounds act by binding to the 50S subunit of the 70S ribosomal subunit this in turn blocks protein elongation of the bacterial ribosome. Telithromycin binds to domains II and V of the 23S RNA of the 50S subunit of the ribosome. As a result, protein synthesis is inhibited, preventing bacterial growth and this may even kill the bacteria. Common side effects from taking Telithromycin include dizziness, headache, and taste disturbances, with the chance of experiencing more adverse effects such as diarrhea, nausea, vomiting, loose stools, abdominal pain, flatulence and dyspepsia.

Metabolites of Telithromycin are predicted with biotransformer.

Telmisartan (also named Micardis) is an antagonist of angiotensin II receptor blockers (ARBs). Telmisartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of telmisartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Telmisartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.

Telmisartan is angiotensin receptor blocker (ARB) which block the action of angiotensin II by binding to the type 1 angiotensin II receptor. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Telmisartan used to treat hypertension, diabetic nephropathy, and congestive heart failure. Angiotensin has many vasoconstrictive effects by binding to angiotensin II type 1 receptors (AT1) in blood vessels, kidneys, hypothalamus, and posterior pituitary. In blood vessels AT1 receptors cause vasoconstriction in the tunica media layer of smooth muscle surrounding blood vessels increasing blood pressure. Blocking this AT1 receptor lowers the constriction of these blood vessels. AT1 receptors in the kidney are responsible for the production of aldosterone which increases salt and water retention which increases blood volume. Blocking AT1 receptors reduces aldosterone production allowing water retention to not increase. AT1 receptors in the hypothalamus are on astrocytes which inhibit the excitatory amino acid transporter 3 from up-taking glutamate back into astrocytes. Glutamate is responsible for the activation of NMDA receptors on paraventricular nucleus neurons (PVN neurons) that lead to thirst sensation. Since AT1 receptors are blocked, the inhibition of the uptake transporter is not limited decreasing the amount of glutamate activating NMDA on PVN neurons that makes the individual crave drinking less. This lowers the blood volume as well. Lastly, the AT1 receptors on posterior pituitary gland are responsible for the release of vasopressin. Vasopressin is an anti-diuretic hormone that cases water reabsorption in the kidney as well as causing smooth muscle contraction in blood vessels increasing blood pressure. Lowering angiotensin II action on activating vasopressin release inhibits blood pressure from increasing. All these effects of telmisartan contribute to an overall lowered blood pressure.