Drugs and the Immune System

Question 1

Two pro-inflammatory mediators that corticosteroids inhibit

Answer 1

IL-1 and IFNg

Question 2

What does azathioprine do?

Answer 2

It is a prodrug which inhibits purine and DNA synthesis

Question 3

What is cyclophosphamide used to treat, what are toxic side effects, and how does it work?

Answer 3

Treats SLE, Wegners Granulomatosis, and Autoimmune Hemolytic anemia. Toxicity is pancytopenia, hemorrhagic cystitis. Alkylates and cross-links DNA, interfering with DNA synthesis.

Question 4

Toxic effects of mycophenolate mofetil (MMF)

Answer 4

Leukopenia, GI disturbances, CMV infections

Question 5

Four drugs that produce generalized immunosuppression

Answer 5

Corticosteroids, azathioprine, cyclophosphamide, and MMF

Question 6

Three drugs that produce selective inhibition of lymphocytes

Answer 6

Cyclosporine, Tacrolimus, Sirolimus

Question 7

How does cyclosporine work?

Answer 7

Binds cyclophilin and thus inhibits activation of calcineurin, which activates NFAT, leading to T-cell activation (and IL-2 production). Thus, cyclosporine inhibits T-cell activation

Question 8

What is cyclosporin used to treat and what are the toxic effects?

Answer 8

Used in transplant pts to prevent rejection, also autoimmune diseases. Can cause nephrotoxicity, neurotoxicity, hyperlipidemia, and hypertension (also metabolized by CYP 3A4, so has drug-drugs)

Question 9

How does tacrolimus work?

Answer 9

Binds FK binding protein (FKBP), preventing calcineurin activation, which activates NFAT, leading to T-cell activation (and IL-2 production) . Thus, tacrolimus inhibits T-cell activation

Question 10

What is tacrolimus used to treat and what are its toxic effects?

Answer 10

Used to avoid transplant rejection, also autoimmune diseases. Nephrotoxicity, neurotoxicity, hypertension, hyperglycemia, diabetes (esp with steroids). Also metabolized by CYP 3A4, so has drug-drug interactions

Question 11

How does Sirolimus work?

Answer 11

Binds FK binding protein (FKBP), like tacrolimus, but this complex inhibits mTOR (which regulates cell cycle in T cells)

Question 12

What is sirolimus used to treat and what are its toxic effects?

Answer 12

Used with tacrolimus or cyclosporine to prevent graft rejection. Associated with increases in cholesterol and triglycerides. Also metabolized by CYP 3A4, so may have drug-drug ints

Question 13

Two toxicities from antibody treatments

Answer 13

HAMA reaction and serum sickness (depends on source and type of Abs)

Question 14

ATG and ALG and what they do?

Answer 14

Antithymocyte and Antilymphocyte globulin, bind to T cells

Question 15

What are ATG and ALG used for and what are their toxic effects?

Answer 15

Organ transplantation, graft rejection. Toxicities are serum sickness and glomerulonephritis (Type III hypersensitivity rxns)

Question 16

Muromonab CD3 (OKT-3)

Answer 16

Purified IgG2 directed at CD3. Blocks T-cell function, used in graft rejection. Toxic effect is excessive cytokine release (due to Fc crosslinking)

Question 17

Daclizumab and Basiliximab

Answer 17

Humanized mAbs against IL-2 receptor, inhibit T-cell activation (requires IL-2). Used for acute graft rejection

Question 18

Infliximab

Answer 18

Humanized mAb to TNF-a used in Crohns and RA

Question 19

Etanercept

Answer 19

Chimeric molecule of human TNF-a receptor couples to Fc region of human IgG, used in Crohns and RA, employed in a similar fashion to Infliximab (mAb to TNF-a)

Question 20

What cancers is IL-2 used in the treatment of and what are its AEs?

Answer 20

Metastatic renal cell carcinoma and melanoma. AEs include chills, fever, fluid retention, capillary leak syndrome, and disseminated infection (impaired neutrophil function)

Question 21

What diseases are interferons used in the treatment of and what are their AEs?

Answer 21

Leukemias, lymphomas, Hep B and Hep C, and MS (IFNb). AEs include fever, myalgia and fatigue

Question 22

How does Rho(D) immune globulin work

Answer 22

It is IgG anti-D (anti-RhD) which destroys fetal Rh D positive RBCs in the maternal circulation (preventing maternal immune response which might damage baby)

Question 23

Difference between narrow spectrum and wide spectrum antibiotics?

Answer 23

Narrow spectrum only affects a small number of microorganisms, while wide spectrum affects a large number.

Question 24

Definition of sensitivity?

Answer 24

Concentration of a drug at site of infection must inhibit microorganism and remain below level toxic to human cells and be a level that can be clinically achieved at site of action.

Or the mother of Mark. She is a sensitive woman.

Question 25

Bactericidal vs bacteriostatic

Answer 25

Bactericidal antibiotics kill organisms and must be used for life-threatening infections, whereas bacteriostatic antibiotics prevent microorganisms from growing/replicating, but require a functional immune system to remove the infecting microorganism.

Question 26

Reasons for prophylactic therapy?

Answer 26

1) To protect healthy patients (rifampin for meningococcal meningitis exposure) 2) To protect immune suppressed or at-risk patients (in chemotherapy) 3) To prevent post-operative wound infections (Clean surgeries)

Question 27

Superinfection

Answer 27

Evidence of a new infection occurring during drug treatment of an existing infection

Question 28

Mechanisms of action of antibiotics

Answer 28

1) Cell Wall Synthesis Inhibitors 2) Cell Membrane Inhibitors 3) Nucleic Acid Inhibitors 4) Microbial Protein Synthesis Inhibitors 5) Microbial Metabolism Inhibitors or Modifiers

Question 29

Cell Wall Synthesis Inhibitor Antibiotics and their Actions

Answer 29

Penicillins, ampicillins, cephalosporins, Vancomycin: Inhibit cell wall synthesis or damage peptidoglycan Bacitracin: Regeneration of specific membrane lipid carriers All bactericidal

Question 30

Cell Membrane Inhibitor Antibiotics and Actions

Answer 30

Polymyxins: inhibit synthesis of or damage microbial cytoplasmic membrane, affecting permeability and resulting in intracellular content leakage Bactericidal

Question 31

Nucleic Acid Inhibitor Antibiotics and Actions

Answer 31

Quinolones: Modify DNA synthesis, bactericidal Rifampin: Modify RNA synthesis, can be bactericidal or bacteriostatic

Question 32

What defines an immunocompromised host?

Answer 32

Alteration in phagocytic, cellular, or humoral immunity that increases risk of infection or other opportunistic process. Patients may also be immunocompromised if they have an alteration/breach of their skin/mucosal defense barriers.

Question 33

How is neutropenia defined?

Answer 33

A neutrophil count of less than 500/mm3. Patients with a count below 100 are at even greater risk.

Question 34

In addition to the number of circulating neutrophils, what other factors are important determinants of infection in a patient with neutropenia?

Answer 34

The rate of neutrophil decline and the duration of neutropenia. A rapid decline and prolonged duration (greater than 10 days) are major risk factors for infection.

Question 35

What are the most frequent causes of neutropenia?

Answer 35

Hematologic malignancies (leukemia/lymphoma), stem cell transplantation, and cytotoxic chemotherapeutic regimens.

Question 36

True or False: Colony stimulating factors (CSFs) have led to a reduction in neutropenia induced by chemotherapy, a reduction in infectious complications, and an improvement in mortality.

Answer 36

False. While CSFs have led to reductions in chemotherapy-induced neutropenia and infectious complications, there have been no overall improvements in mortality.

Question 37

True or False: Because neutrophils are responsible for many of the clinical manifestations of infection, signs and symptoms may be subtle or atypical in a neutropenic patient.

Answer 37

True. Fever develops in most patients with prolonged neutropenia, and erythemia and pain may also be present, but many clinical manifestations (including purulence or induration) require neutrophils.