Browsing Pathways

Tizanidine is an alpha-2 adrenergic agonist used for the management of muscle spasm, which may result from the effects of multiple sclerosis, stroke, an acquired brain injury, or a spinal cord injury. Spasticity is an increase in muscle accompanied by uncontrolled, repetitive contractions of skeletal muscles which are involuntary. Activation of alpha-2 adrenergic receptors on the presynaptic spinal motor neurons lead to the activation of Gi signaling cascade. This inhibits adenylyl cyclase and inactivates protein kinase A, thus decreasing calcium ion entry into the cell. Calcium in the cell is responsible for triggering the release of excitatory neurotransmitters such as glutamate (and aspartate) into the synapse. Glutamate acts on AMPA and NMDA receptors on the post synaptic motor neurons. Activation of AMPA receptors causes the influx of sodium in the post synaptic neuron. Activation of NMDA receptors causes an influx of calcium into the post synaptic neuron. The influx of positive ions in the cytosol causing depolarization of the motor neurons which then transmits a signal to muscle, causing muscle contraction/excitation. With reduced calcium entry in the presynaptic neuron, glutamate release is inhibited and less NMDA and AMPA receptors are activated, preventing depolarization of motor neurons and decreasing muscle contractions and spasms. Common adverse effects of taking tizanidine include drowsiness, blurred vision, dry mouth, weakness, constipation, nervousness, dizziness, hallucinations, dyskinesia, rhinitis.

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

Tixagevimab is an extended half-life recombinant monoclonal IgG1κ antibody directed against the SARS-CoV-2 S protein for COVID-19 prophylaxis in individuals unable to undergo COVID-19 immunization.Tixagevimab, in combination with cilgavimab, was issued an FDA emergency use authorization on December 9, 2021. The combination of drugs was packaged as EVUSHELD and was granted marketing authorization by the EMA on March 28, 2022, then it was approved in Canada later on April 14, 2022. Certain SAR-CoV-2 Omicron subvariants may be associated with resistence to EVUSHELD. SARS-CoV-2 enters host cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Cilgavimab inhibits S glycoprotein by blocking the interaction between it and the host ACE2 protein. This inhibits the binding and entry of the virion into the host cell. This prevents viral replication and propagation.

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

Tivozanib, marketed as FOTIVDA, is a kinase inhibitor primarily used to treat renal cell carcinoma (RCC) in adult patients who have not responded to previous systemic therapies or have experienced relapsed disease. RCC is a relatively common cancer that predominantly affects adults between the ages of 65 to 74. Tivozanib offers hope as a therapeutic option for individuals with advanced RCC who have not had success with other treatments. It is approved in the United States for those who have undergone two or more systemic therapies for RCC. In the UK and some other countries, it is indicated as the first-line therapy for adults with advanced RCC who have not previously received VEGFR and mTOR pathway inhibitors after their disease has progressed following one prior treatment with cytokine therapy. Tivozanib works by inhibiting growth factor receptors, specifically targeting renal cell carcinoma. In preclinical studies using mice and rats, tivozanib demonstrated its ability to inhibit tumor angiogenesis, slow tumor growth, and reduce vascular permeability. However, it's important to note that tivozanib can often lead to hypertension, which must be managed before initiating therapy. Additionally, while a cardiac QT segment prolongation was reported in a tivozanib cardiac safety study, these reactions were not deemed clinically serious. Furthermore, clinical studies have shown a decrease in serum soluble VEGFR2 (sVEGFR2) levels over time with tivozanib exposure, and sVEGFR2 can serve as a pharmacodynamic marker of VEGFR inhibition.