Drugs and the Immune System Flashcards

1
Q

Two pro-inflammatory mediators that corticosteroids inhibit

A

IL-1 and IFNg

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2
Q

What does azathioprine do?

A

It is a prodrug which inhibits purine and DNA synthesis

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3
Q

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

A

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

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4
Q

Toxic effects of mycophenolate mofetil (MMF)

A

Leukopenia, GI disturbances, CMV infections

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5
Q

Four drugs that produce generalized immunosuppression

A

Corticosteroids, azathioprine, cyclophosphamide, and MMF

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6
Q

Three drugs that produce selective inhibition of lymphocytes

A

Cyclosporine, Tacrolimus, Sirolimus

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7
Q

How does cyclosporine work?

A

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

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8
Q

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

A

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)

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9
Q

How does tacrolimus work?

A

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

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10
Q

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

A

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

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11
Q

How does Sirolimus work?

A

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

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12
Q

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

A

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

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13
Q

Two toxicities from antibody treatments

A

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

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14
Q

ATG and ALG and what they do?

A

Antithymocyte and Antilymphocyte globulin, bind to T cells

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15
Q

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

A

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

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16
Q

Muromonab CD3 (OKT-3)

A

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

17
Q

Daclizumab and Basiliximab

A

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

18
Q

Infliximab

A

Humanized mAb to TNF-a used in Crohns and RA

19
Q

Etanercept

A

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)

20
Q

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

A

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

21
Q

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

A

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

22
Q

How does Rho(D) immune globulin work

A

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)

23
Q

Difference between narrow spectrum and wide spectrum antibiotics?

A

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

24
Q

Definition of sensitivity?

A

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.

25
Q

Bactericidal vs bacteriostatic

A

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.

26
Q

Reasons for prophylactic therapy?

A

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)

27
Q

Superinfection

A

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

28
Q

Mechanisms of action of antibiotics

A

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

29
Q

Cell Wall Synthesis Inhibitor Antibiotics and their Actions

A

Penicillins, ampicillins, cephalosporins, Vancomycin: Inhibit cell wall synthesis or damage peptidoglycan

Bacitracin: Regeneration of specific membrane lipid carriers

All bactericidal

30
Q

Cell Membrane Inhibitor Antibiotics and Actions

A

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

Bactericidal

31
Q

Nucleic Acid Inhibitor Antibiotics and Actions

A

Quinolones: Modify DNA synthesis, bactericidal

Rifampin: Modify RNA synthesis, can be bactericidal or bacteriostatic

32
Q

What defines an immunocompromised host?

A

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.

33
Q

How is neutropenia defined?

A

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

34
Q

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

A

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.

35
Q

What are the most frequent causes of neutropenia?

A

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

36
Q

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.

A

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

37
Q

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.

A

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.