Pharmacological Management Project
Pharmacological Management Project
Student Name
NSG6005
Faculty name
Pathophysiology of assigned disease
Assigned Disease: Primary Biliary Cholangitis
Pathophysiology: Primary biliary cholangitis (PBC, formerly known as primary biliary cirrhosis) is an uncommon cholestatic liver disease characterized by immune-mediated destruction of biliary epithelial cells. PBC is female preponderant and typically presents in the fifth or sixth decade of life. The clinical presentation may include generalized pruritus, dryness of eyes and mouth, fatigue, and upper abdominal discomfort; patients may be asymptomatic. Typical laboratory findings are elevations in serum alkaline phosphatase levels, increased serum immunoglobulin M levels, and the presence of antimitochondrial antibodies or specific subtypes of antinuclear antibodies. A diagnosis of PBC is usually made without histologic examination. When used, liver biopsy typically reveals nonsuppurative granulomatous cholangitis with loss of small bile ducts and lymphocytic portal inflammation. Patients who do not achieve an adequate biochemical response to first-line therapy have a greater risk of disease progression to cirrhosis and may ultimately require liver transplantation.
Definition of the two assigned drug Classifications
Classification 1: Bile Acid Analog
Bile acids aid in the digestion and solubilization of lipophilic nutrients and drugs in the small intestine, they signal endocrine molecules that regulate the glucose, lipid, and energy metabolism through complex and intertwined pathways that are largely mediated by activation of nuclear receptor farnesoid X receptor (FXR) and cell surface G protein-coupled receptor 1, TGR5 (also known as GPBAR1).
Classification 2: Immunomodulatory therapy
Immunomodulatory drugs modify the response of the immune system by increasing (immunostimulators) or decreasing (immunosuppressives) the production of serum antibodies. Immunostimulators are prescribed to enhance the immune response against infectious diseases, tumours, primary or secondary immunodeficiency, and alterations in antibody transfer, among others. Immunosuppressive drugs are used to reduce the immune response against transplanted organs and to treat autoimmune diseases.
Discussion of 4 medications – 2 from each drug classification (you are to choose the drugs – they must belong to the drug class)
Classification 1: Bile Acid analog
Drug 1: Actigall (ursodiol)
13 – 15 mg/kg/day orally given in 2 – 4 divided doses
Give with food
Drug 2: Obeticholic acid
5 – 10 mg PO qD
Start 5mg PO qd x 3 months, then may increase to 10mg PO qd if needed
Classification 1: immunomodulatory therapy
Drug 1: prednisone
20 – 30 mg PO qd initially for one month, titrate downward according to IgG concentration
Drug 2: Mycophenolate mofetil
500 – 1000 mg PO qd BID
Pharmacokinetics, Pharmacodynamics, safety/monitoring & pregnancy/lactation of the 4 Medications you discussed earlier
Drug 1: actigall (ursodiol)
Metabolism: Liver, GI Tract, CYP450; half-life unknown
Excretion: feces primarily; urine
Mechanism of Action: decreases cholesterol synthesis, secretion, and absorption; alters bile cholesterol composition
Monitoring Parameters: liver function tests q months x 3months, then q6 months
Pregnancy: may use during pregnancy; no known risk of fetal harm based on human data
Lactation: may use while breastfeeding; no known risk of infant harm based on limited human data
Drug 1: obeticholic
Metabolism: live; no CYP450; enterohepatically recirculated; active metabolites
Excretion: feces 87%; urine <3%; half-life 24 hours
Mechanism of Action: agonizes farnesoid X receptor, decreasing intracellular hepatocyte concentrations of bile acids
Monitoring Parameters: liver function tests at baseline, then frequently, especially if there is an increase in risk of hepatic decompensation or before dose adjustment; lipid panel
Pregnancy: caution advised during pregnancy; inadequate human data available to assess risk
Lactation: caution advised while breastfeeding; no human data available to assess risk of infant harm or effects on milk production
