Pathways

Tigecycline is a glycylcycline, a class of antibiotics derived from tetracycline. Tigecycline has broad spectrum antibacterial abilities and is not susceptible to traditional tetracycline resistance mechanisms such as ribosomal protection and efflux by tetracycline-specific pumps. Tigecycline inhibits bacterial protein synthesis by binding to the A site of the 16s rRNA on the 30S ribosomal subunit. By binding to the A site, tigecycline prevents tRNA from docking onto the 16S rRNA with it’s codon ultimately halting the addition of amino acids to elongate peptide chains used in protein structures.

Tigecycline is an intravenous antibiotic drug used to treat infections caused by a variety of gram-positive and gram-negative microorganisms including Mycoplasma pneumoniae, Pasteurella pestis, Escherichia coli, Haemophilus influenzae (respiratory infections), and Diplococcus pneumoniae. Tigecycline first clinically-available drug in the class of glycylcyclines antibiotics. Glycylcyclines are derived from tetracycline which are analogues are specifically designed to overcome tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection. In bacterial protein synthesis, transcription and translation occur in the cytoplasm. Tigecycline targets protein translation. Translation occurs using the bacterial 70S ribosome composed of a 50S and a 30S subunit. The ribosome has 3 binding sites, A (acceptor site), P (peptidyl site) and E (exit site). The charged tRNA with an amino acid attached (amino-acyl tRNA) binds to the A site. The P site binds to the tRNA holding the growing polypeptide chain and the E site binds to the uncharged tRNA.

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

Tiludronic acid is a first-generation bisphosphonate used to treat Paget's disease, similar to etidronic acid and clodronic acid. Tiludronic acid binds to hydroxylapatite in the bone, during bone resorption it is released and taken up by osteoclasts through endocytosis. Once inside the osteoclast, it is released into the cytosol and goes to interrupt osteoclast activity and function. Tiludronic acid has a structure similar to pyrophosphate and due to this can be incorporated into ATP analogues that cannot be hydrolyzed. Due to this the osteoclast cannot utilize ATP and begins to go through apoptosis. If a patient has an overdose they may present with hypocalcemia, which can be treated with supportive care. Tiludronic acid should be taken 2 hours before or after consuming a meal and/or calcium supplements. Avoiding taking it with antacids as it will greatly reduce the bioavailability.

Timolol is a beta blocker medication, making it part of the antihypertensive drug class. It relieves symptoms such as tachycardia, vascular headaches, hypertension, angina and tremors. Timolol, much like propranolol or oxprenolol, begins its journey by inhibiting the beta-1 adrenergic receptors in the heart. Entering the myocyte, this activates a G-protein signalling cascade, which activates cAMP -dependent protein kinase type 1-alpha regulatory subunit. From there, cAMP-dependent protein kinase catalytic subunit alpha activates outage-dependent L-type calcium channel subunit alpha 1C and 2 other transports which bring calcium into the myocyte from outside of the cell. cAMP-dependent protein kinase catalytic subunit alpha is activated through ryanodine receptor 2, which is also transporting calcium into the myocyte from the the sarcoplasmic reticulum. The calcium and calmodulin then activate myosin light chain kinase, which is located in the smooth vascular muscle. This, paired with the calcium activating a series of troponin enzymes that activate tropomyosin enzymes in the striated muscle, results in a muscle contraction. Then in the cell membrane we have PIP2(16:0/20:3(8Z,11Z,14Z)) catalyzing into DG(14:0/14:1(9Z)/0:0) and inositol 1,4,5-triphosphate with the help of the enzyme 1-phosphatidylinositol 4,5-biphosphate phosphodiesterase beta-1. This enzyme is activated through the G-protein signalling cascade, which stems from the type-1 angiotensin II receptor. Around the cell there are many transports happening through many different transporters, leading in and out of the cell Some of the transports into the cell include sodium and calcium, while transports are also working hard to constantly export potassium from the cell. Returning to the sarcoplasmic reticulum, cardiac phospholamban inhibits the transporter sarcoplasmic/endoplasmic reticulum calcium ATPase 2, which sees water and ATP catalyzed through it to become phosphorus and ADP, while transporting calcium into the sarcoplasmic reticulum.