книга / 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Immunopharmacology 1

Learning Objectives

Answer mechanism and side effect questions about cyclosporine, tacrolimus, mycophenolate, azathioprine, and anti-D immunoglobulin

List the most commonly used monoclonal antibodies

Explain information related to cytokines (recombinant forms)

CYCLOSPORINE AND TACROLIMUS

λMechanism of action:

–Bind to cyclophilin (cyclosporine) or FK-binding protein (tacrolimus) → ↓ calcineurin (cytoplasmic phosphatase) → ↓ activation of T-cell transcription factors → ↓ IL-2, IL-3, and interferon-γ

λUses:

–Cyclosporine is DOC for organ or tissue transplantation (+/– mycophenolate, +/– steroids, +/– cytotoxic drugs)

–Tacrolimus used alternatively to cyclosporine in renal and liver transplants

λSide effects: nephrotoxicity (both), gingival overgrowth (cyclosporine)

MYCOPHENOLATE

An inhibitor of de novo synthesis of purines, has adjunctive immunosuppressant actions, permitting dose reductions of cyclosporine to limit toxicity.

AZATHIOPRINE

Immunosuppressant converted to 6-mercaptopurine—same properties as 6-MP.

ANTI-D IMMUNOGLOBULIN

λHuman IgG antibodies to red cell D antigen (rhesus antigen)

λUses: Administer to Rh-negative mother within 72 hours of Rh-positive delivery to prevent hemolytic disease of newborn in subsequent pregnancy

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Section X λ Immunopharmacology

MONOCLONAL ANTIBODIES

Table X-1-1. Clinical Uses of Monoclonal Antibodies

CYTOKINES (RECOMBINANT FORMS)

Table X-1-2. Clinical Uses of Interferons

Chapter Summary

λThe mechanism of action, uses, and toxicities associated with cyclosporine are presented. Azathioprine converts to 6-mercaptopurine, making it a useful immunosuppressant.

λAnti-D immunoglobin is given to Rh-negative mothers shortly after parturition to prevent hemolytic disease in future births.

λTable X-1-1 summarizes the clinical uses of monoclonal antibodies. Table X-1-2 summarizes the clinical uses of recombinant cytokines.

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Immunopharmacology 2

Practice Questions

1.A patient is treated with an immunosuppressant drug following a liver transplant. The drug is known to bind to cyclophilin and inhibit the actions of calcineurin. For what drug toxicity should this patient be monitored?

A.Pulmonary fibrosis

B.Hypotension

C.Hypoglycemia

D.Nephrotoxicity

E.CHF

2.Which one of the following agents has utility in the management of acute coronary syndromes such as unstable angina?

A.Abciximab

B.Interferon-α

C.Aldesleukin

D.Filgrastim

E.Trastuzumab

Answers

1.Answer: D. This patient is being treated with cyclosporin, a drug that binds

to cyclophilin and inhibits calcineurin. As a result, the transcription of various T-cells factors such as IL-2, IL-3, and Interferon-γ are inhibited. Cyclosporin is associated with nephrotoxicity, gingival hyperplasia, hyperglycemia, hypertension, and hirsutism.

2.Answer: A. Abciximab is an antibody-based drug that targets glycoprotein IIb/IIIa receptors. Binding of the drug to these receptors results in decreased platelet aggregation by preventing the cross-linking reaction. It is useful in acute coronary syndromes such as unstable angina and post-angioplasty.

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SECTION XI

Toxicology

Chapter 1 λ Toxicology

ANTIDOTES

Table XI-1-3. Summary of Antidotes

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Section XI λ Toxicology

NATURAL MEDICINALS

“Natural” medicinals are available without prescription and are considered to be nutritional supplements rather than drugs. Herbal (botanic) products are marketed without FDA review of safety and efficacy, and there are no requirements governing the purity or the chemical identities of constituents. Evidence supporting the clinical effectiveness of herbal products is commonly incomplete.

Table XI-1-4. Characteristics of Selected Herbals

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