Pathways

Lamivudine (also known as 3TC) is an antiretroviral drug that can be used to treat HIV/AIDS. Lamivudine is phosphorylated to lamivudine triphosphate (L-TP), which is its active metabolite. Lamivudine triphosphate (L-TP) can bind and inhibit the HIV reverse transcriptase as well as HBV polymerase, which lead to DNA chain termination.

Lamivudine is a reverse transcriptase inhibitor used to treat HIV and hepatitis B infections. It is a nucleoside reverse transcriptase inhibitor (NRTI) that targets HIV infected cells in the body. When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell. Lamivudine enters the cell via solute carrier family 22 member 2 and is converted into lamivudine monophosphate by deoxycytidine kinase. UMP-CMP kinase protein then converts lamivudine monophosphate into lamivudine diphosphate. The lamivudine diphosphate is metabolized to lamivudine triphosphate via nucleoside diphosphate kinase A or phosphoglycerate kinase 1. Limuvudine triphosphate is an analog of deoxycytidine-5'-triphosphate (dCTP). Lamivudine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dCTP and by incorporation into viral DNA. Lamivudine triphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once lamivudine triphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed. Common side effects from taking lamivudine include headache, nausea, vomiting, diarrhea, weight loss, abdominal pain, fever, cough and nasal signs & symtpoms.

Lamivudine (2'-deoxy-3'-thiacytidine, 3TC) is a pyrimidine analog reverse transcriptase enzyme inhibitor used to treat human immunodeficiency virus type I (HIV-1), HIV-2, and Hepatitis B. When metabolized to its active triphosphate form, it competes with deoxycytidine triphosphate for binding to reverse transcriptase, resulting in chain termination when incorporated into the viral DNA. Lamivudine may enter the cells by passive diffusion or by active transported via SLC22A1, SLC22A2, and SLC22A3. Intracellularly, it is phosphorylated to its active triphosphate from via deoxycytidine kinase (3TC to 3TC-monophosphate), followed by cytidine monophosphate/deoxycytidine monophosphate kinase (3TC-monophosphate to 3TC-diphosphate), then 3'-phosphoglycerate kinase or nucleoside diphosphate kinase (3TC-diphosphate to 3TC-triphosphate). Dephosphorylation can occur via phosphatases or salvage pathways. Lamivudine is actively transported out of cell by efflux transporters ABCB1, ABCC1, ABCC2, ABCC3, ABCC4 and ABCG2 and primarily excreted unchanged in the urine.

Lamotrigine is a phenyltriazine antiepileptic used to treat some types of epilepsy and bipolar I disorder. It can be found under the brand name Lamictal. It is used in the treatment of both epilepsy and as a mood stabilizer in bipolar disorder. Lamotrigine is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. It is approved for use in more than 30 countries. The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters. Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states. Some side effects of using lamotrigine may include headaches, drowsiness, aggression, and tremors.

Lansoprazole is used to reduce gastric acid secretion, short term treatment of active gastric ulcers, active duodenal ulcers, erosive reflux oesophagitis, symptomatic gastroesophageal reflux disease, and non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers. It is also useful in the management of hypersecretory conditions including Zollinger-Ellison syndrome. Lansoprazole is effective at eradicating H. pylori when used in conjunction with amoxicillin and clarithromycin (triple therapy) or with amoxicillin alone (dual therapy).. Lansoprazole is a prodrug administered orally but since it degrades rapidly at low pH, the capsule contains enteric-coated granules. After undergoing absorption in the small intestine, it passes from the blood stream into the parietal cells in the stomach, then enters the stomach lumen. It is a weak base and thus, accumulates on the outside of cell in the acidic environment. Its main target is the H+/K+ ATPase in the parietal cells in the stomach. In parietal cells, carbonic anhydrase converts water and carbon dioxide to hydrogen bicarbonate ions and H+. The bicarbonate ions go into the blood via the chloride anion exchanger on the basolateral membrane which exchanges the hydrogen bicarbonate for Cl- ions. There is also the Na+/K+ ATPase which pumps Na+ out of the cell and K+ into the cell. The H+/K+ ATPase is located on the apical membrane and pumps the H+ from the cell into the stomach lumen and K+ from the lumen into the cell. Another transporter, the K+/Cl- symporter transports K+ and Cl- in the stomach lumen. The H+ and Cl- in the stomach lumen forms the HCl acid which, in excess, can cause disorders like ulcers. The acidic environment in the stomach converts the prodrug lansoprazole into its active form, sulfenamide. Sulfenamide then covalently binds to the cysteine residues on the alpha subunit of the H+/K+ ATPase via disulfide bridges. This binding of sulfenamide irreversibly inhibits the H+/K+ ATPase, preventing too much acid secretion in the stomach. Less acid in the stomach is favorable for symptomatic relief of disorders caused by the acid. Side effects of taking lansoprazole may include headache, diarrhea, vomiting, stomach pain, constipation, skin rashes, dizziness, fatigue, dry mouth.