Browsing Pathways

Ropivacaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Ropivacaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore ropivacaine preferentially inhibits neurons that are actively firing.

Escitalopram is a selective serotonin reuptake inhibitor that exerts antidepressive effects by selectively inhibiting serotonin reuptake in the brain. It does so by competing for the same binding site as serotonin on the the sodium-dependent serotonin transporter (SLC6A4). This increases the concentrations of serotonin in the synaptic cleft and reverses the state of low concentration seen in depression. Higher concentration of serotonin has also been shown to have long-term neuromodulatory effects. Binding of serotonin to certain serotonin receptors activate adenylate cyclase, which produces cAMP. cAMP activates protein kinase A which activates cAMP-responsive binding protein 1 (CREB-1). CREB-1 enters the nucleus and affects transcription of brain-derived neurotrophic factor (BDNF). BDNF subsequently stimulates neurogenesis, which may contribute to the long-term reversal of depression.

Oxycodone (also known as OxyContin or Dihydrohydroxycodeinone) is analgesic that can bind to mu-type opioid receptor to activate associated G-protein in the sensory neurons of central nervous system (CNS), which will reduce the level of intracellular cAMP by inhibiting adenylate cyclase. The binding of oxycodone will eventually lead to reduced pain because of decreased nerve conduction and release of neurotransmitter. Hyperpolarization of neuron is caused by inactivation of calcium channels and activation of potassium channels via facilitated by G-protein.

Remifentanil is a pharmacologically-active, synthetic, small molecule derived from fentanyl and belongs to a class of drugs called opioids. Opioids are therapeutically employed to achieve analgesia. Remifentanial’s rapid mechanism of action primarily involves its agonistic effects on mu-type opioid receptors which are inhibitory G-coupled protein receptors and lead to the inhibition of adenylate cyclase and decrease in cAMP production. Analgesia, anesthesia, and respiratory depression are a function of remifentanial’s action on these mu-type opioid receptors.

Emtricitabine (also known as FTC) is a nucleoside reverse transcriptase inhibitor (NRTI) for treating HIV infection by inhibiting the transcriptase reversibly. Emtricitabine is phosphorylated to form emtricitabine 5'-triphosphate so that emtricitabine 5'-triphosphate can compete with deoxycytidine 5'-triphosphate to inhibit HIV-1 reverse transcriptase, which lead to early chain termination. Emtricitabine 5'-triphosphate can also incorporate into viral DNA to inhibit the activity of HIV-1 reverse transcriptase (RT).

Nevirapine (also named as Viramune or BIRG587) is a medication that are used for the treatment of HIV/AIDS (especially HIV-1). Nevirapine binds and inhibits reverse transcriptase to create interruption on catalytic site of enzyme so that it can prevent the activities of RNA-dependent and DNA-dependent DNA polymerase, which lead to no complementary DNA (cDNA) produced.

Chloramphenicol, trade names Pentamycetin and Chloromycetin, is a broad spectrum antibiotic originally derived from Streptomyces venezuelae. It inhibits protein synthesis by binding the 50S ribosomal subunit to prevent bacterial growth. Bacterial resistance has occurred through decreased uptake or permeability, ribosomal mutation and inactivation by acetylation. Adverse side effects such as aplastic anemia, bone-marrow suppression or Gray syndrome in neonates and infants have resulted in limited use. However, due to ampicillin-resistance bacterial meningitis there has been a renewed interest in the drug.

Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is extensively metabolized in the liver by the cytochrome p450 enzymes CYP2C8 and CYP2C9 to para-hydroxy rosiglitazon, ortho-hydroxy rosiglitazone and N-desmethyl rosiglitazone. N-desmethyl rosiglitazone is the major metabolite and is further metabolized to N-desmethyl-p-hydroxyrosiglitazone, N-desmethyl glucuronide rosiglitazone and N-desmethyl-O-hydroxy rosiglitazone. Both para-hydroxy rosiglitazon and ortho-hydroxy rosiglitazone are excreted as sulfated or glucuronidated metabolites.

Alvimopan is prescribed to treat patient opioid-induced constipation, a common side effect of opioid therapy. This side effect results in delayed discharge for hospitalized patients following surgery. Alvimopan helps to increase gastrointestinal recovery following surgery for a shorter hospital stay. Opioids bind opioid receptors in the gut causing inhibition of gut motility which results in constipation. Alvimopan is a peripherally acting mu-opioid antagonist. The drug acts in the gastrointestinal tract by competing to bind the mu-opioid receptor. Alvimopan differs from other peripherally acting mu-receptor antagonists such as, methylnaltrexone, by the presence of a quaternary amine.

Levorphanol (also known as Levo-Dromoran) is an opioid medication that can bind to mu-type opioid receptor to activate associated G-protein in the sensory neurons of central nervous system (CNS), which will reduce the level of intracellular cAMP by inhibiting adenylate cyclase. The binding of levorphanol will eventually lead to reduced pain because of decreased nerve conduction and release of neurotransmitter. Therefore, levorphanol can reduce nerve conduction and decrease neurotransmitter release; so that perception of pain signals can be blocked.