Pathways

Bezafibrate is a lipid-lowering fibrate used in the management of primary and secondary hyperlipidaemia, when there is a lack of clinical improvement following lifestyle modifications or correction of the underlying disorder. Bezafibrate acts in the nucleus where is activates the peroxisome proliferator-activated receptor alpha (PPARα). PPARα binds to the retinoic acid receptor alpha (RXRα). This PPARα-RXRα complex regulate gene transcription/translation of proteins and enzymes involved lipolysis, fatty acid transport and biosynthesis, vLDL and HDL synthesis. Fatty acid biosynthesis is decreased due to the decrease expression of the enzyme acetyl-coA carboxylase. This enzyme is involved in one of the first steps in fatty acid synthesis by converting acetyl-coA to malonyl coA. Fatty acid uptake from the plasma into the liver is increased. This is because there is an upregulation of the fatty acid transporter. This decreases the amount of circulating fatty acids. Fatty acid metabolism is also increased due to upregulation of acyl coA synthase, an enzyme involved in fatty acid oxidation. These 3 alterations ultimately decrease fatty acids in the body, making less fatty acids available for triglyceride synthesis. Bezafibrate also increases HDL synthesis by upregulating apolipoprotein A1 (APOA1) and apolipoproteins A2 (APOA2), which forms part of HDL. HDL is considered good cholesterol. VLDL and LDL are considered bad cholesterol. These levels are decreased due to downregulation of APOB which forms part of triglyceride-rich vLDL and LDL. Finally, triglyceride levels are decreased by 30%-60% via upregulation of lipoprotein lipase (LPL). LPL hydrolyses triglyceride, thus breaking it down. Other proteins that affect LPL are also altered. For instance, APOA5 activates LPL and it’s expression is increased with bezafibrate. APOC3 inhibits lipolysis by inhibiting LPL, therefore, bezafibrate decreases the expression of APOC3. Overall, bezafibrate lowers LDL-C, total-C, triglycerides, and Apo B, while increasing HDL-C.

Bezitramide is a narcotic analgesic that has been withdrawn due to overdoses. It is taken orally with a long duration of action. Bezitramide binds to opioid receptors, stimulating the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as GABA is inhibited. Opioids close N-type voltage-operated calcium channels and open calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization and reduced neuronal excitability. Morphine acts at A delta and C pain fibres in the dorsal horn of the spinal cord. By decreasing neurotransmitter action there is less pain transmittance into the spinal cord. This leads to less pain perception.

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

Bictegravir is an integrase inhibitor used to treat HIV-1 and HIV-2 infections. Bictegravir is indicated in the management of HIV-1 infection in patients not previously treated with antiretroviral therapy. Additionally, Bictegravir is indicated in the management of HIV-1 infection in patients who are virologically suppressed (HIV-1 RNA <50 c/mL) on a regular antiretroviral regimen for a minimum of three months without a history of failure in treatment and no known factors associated with the resistance to the individual components of the medication. In vitro, bictegravir has shown powerful antiviral activity against HIV-2 and various subtypes of HIV-1. It is used in combination with tenofovir and emtricitabine. Bictegravir is transported into the infected cell then transported into the nucleus via importin nuclear transporter. The viral RNA is injected into the cell then transcribed into viral DNA via reverse transcriptase. It is then transported into the nucleus where it is integrated into the host DNA. Bictegravir inhibits HIV integrase which prevents the viral DNA from being integrated into the host DNA. This prevents viral replication and further progression of the virus. It is used in combination with reverse transcriptase inhibitors which further prevents viral replication and progression of the virus.

Bifonazole is an azole anti-fungal drug used to treat fungal skin infections, such as dermatomycosis and athlete's foot. It comes as a cream which is spread on the infected skin. Bifonazole 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.