Browsing Pathways

Tipranavir is a sulfonamide-containing dyhydropyrone and a nonpeptidic protease inhibitor used to treat HIV-1 resistant to more than 1 protease inhibitor. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. The HIV virus binds and penetrates the host cell. Viral RNA is transcribed into viral DNA via reverse transcriptase. Viral DNA enters the host nucleus and is integrated into the host DNA via integrase. The DNA is then transcribed, creating viral mRNA. Viral mRNA is translater into the gag-pol polyprotein. HIV protease is synthesized as part of the Gag-pol polyprotein, where Gag encodes for the capsid and matrix protein to form the outer protein shell, and Pol encodes for the reverse transcriptase and integrase protein to synthesize and incorporate its genome into host cells. HIV-1 protease cleaves the Gag-pol polyprotein into 66 molecular species, including HIV-1 protease, integrase, and reverse transcriptase. Tipranavir competitively binds to the active site of HIV-1 protease. This inhibition prevents the HIV virion from fully maturing and becoming infective. Using the lipid bilayer of the host cell, a virus is formed and released. The inhibition of HIV-1 protease prevents the necessary molecular species from forming, therefore preventing maturation and activation of viral particles. This forms immature, non-infectious viral particles, therefore, Tipranavir prevents the virus from reproducing.

Tioguanine is an antineoplastic agent from the purine analog class. This drug also has antimetabolite action. Tioguanine is indicated for remission induction and remission consolidation in the treatment of acute nonlymphocytic leukemias. When this drug enters the cells, it competes with hypoxanthine and guanine for the hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP is a cytotoxic agent, it will interfere with the synthesis of guanine nucleotides by inhibiting the glutamine-5-phosphoribosylpyrophosphate aminotransferase (de novo pathway of purine ribonucleotide synthesis) enzyme by pseudofeedback. Furthermore, TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA. The final result is the sequential blockade of the usage and synthesis of purines, leading to apoptosis in the S phase of the cell cycle. This drug is administered as an oral tablet. An overdose of tioguanine may result in symptoms like nausea, vomiting, malaise, hypotension, and diaphoresis.

Tioconazole is an imidazole antifungal drug used primarily for vulvovaginal candidiasis (vaginal yeast infection), but it can be used for skin infections such as ringworm, jock itch, athlete's foot, and tinea versicolor or "sun fungus". Tioconazole is applied topically to the infected area then absorbed into the infected cell to target the fungal cells. It can also be taken orally. Terconazole inhibits lanosterol 14-alpha demethylase in the endoplasmic reticulum of fungal cells. Lanosterol 14-alpha demethylase is the enzyme that catalyzes the synthesis of 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol from lanosterol. With this enzyme inhibited ergosterol synthesis cannot occur which causes a significant low concentration of ergosterol in the fungal cell. Ergosterol is essential in maintaining membrane integrity in fungi. Without ergosterol, the fungus cell cannot synthesize membranes thereby increasing fluidity and preventing growth of new cells. This leads to cell lysis which causes it to collapse and die. Through unknown mechanisms, tioconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.

Tinzaparin is a low molecular weight heparin (LMWH), it is an anticoagulant that halts the formation of thrombi. It binds to antithrombin III forming a complex that speeds up the inhibition of factor Xa. This stops the generation of thrombin and the coagulation cascade, it is administered via subcutaneous injection. Through the liver, it is metabolized through sulfation and polymerization and is eliminated through the kidneys. There is some risk of osteoporosis with increasing duration of use, bleeding, alopecia, and heparin-induced thrombocytopenia (HIT). It can interact with herbs and supplements, so avoid those with anticoagulants and antiplatelet activity such as garlic, ginger, bilberry, danshen, piracetam and ginkgo bilba.