Pharmacological Management Project

Pharmacological Management Project

Student Name


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