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Term III: Pharmacology > Immunomodulators > Flashcards

Immunomodulators Flashcards

1
Q

What are the four general mediators of inflammation that can be found in mast cell granules? What would you use as a drug against each one?

A
  • Histamine (anti-histamines)
  • Prostaglandins (COX inhibitors)
  • Leukotrienes (LOX inhibitors or LT blockers)
  • Cytokines (steroids)
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2
Q

What is the effect on smooth muscle when acting at H1 and H2 receptors?

A

H1 - constricts smc

H2 - dilates smc

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3
Q

Dipenhydramine (Benadryl)

A

First generation anti-histamine
H1 blocker, inverse agonist

Enters CNS

Allergies

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4
Q

Fexofenadine (Allegra) and Loratadine (Claritin)

A

Second generation anti-histamines

H2 receptor blockers - do not enter CNS

Allergies

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5
Q

**tidines (Cimetidine, Ranitidine, Fomatidine)

A

H2 blockers, decrease acid secretion

Ulcers, GERD

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6
Q

Where do the cell bodies of histamine releasing neurons sit in the hypothalamus?

A

Tuberomamillary nucleus

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7
Q

What does histamine do in the CNS?

A

Controls alertness, keeps us awake

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8
Q

What 3 places in the CNS is histamine released?

A

cortex, brainstem, & spinal cord

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9
Q

Zileuton

A

LOX inhibitor

Allergies

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10
Q

Montelukast (Singulair)

A

LT receptor blocker

Allergies

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11
Q

Cromolyn sodium (Nasalcrom)

A

Mast cell stabilizer - inhibits mast cell degranulation

Prophylaxis for asthma and allergic rhinitis

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12
Q

Chloroquine

A

Lysosomal membrane stabilizer - stops lysosomes from degrading proteins and presenting them to immune system

Malaria, rheumatoid arthritis, lupus

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13
Q

Which one of these anti-asthma drugs works ONLY prophylactically?

A. Albuterol (beta 2 agonist)
B. Cromolyn sodium
C. Ipratropium (muscarinic blocker)
D. Montelukast (Leukotriene antagonist)
E. Theophylline
A

B

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14
Q

Which one of these drugs is a non-sedating anti-histamine?

A. Fexofenadine (Allegra)
B. Diphenhydramine (Benadryl)
C. Chlopromazime (Phenergan)
D. Metoclopramide (Reglan)
E. Scopolamine (Hyoscine)
F.  Loratadine (Claritin)
G. Montelukast (Singulair)
A

A and F

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15
Q

What molecule are steroids derived from?

A

Cholesterol

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16
Q

What do you treat Bell’s Palsy with?

A

Steroids

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17
Q

What is multiple sclerosis? What do you treat it with?

A

Autoimmune disease - IgG against central myelin made by oligodendrocytes

Steroids and IFN-gamma

18
Q

What is SCID? What do you treat it with?

A

Severe combined immune deficiency - lack of adenosine deaminase –> imbalance of dNTPs –> cannot make DNA

Recombinant enzyme: PEG-enzyme

19
Q

What is Guillain-Barre syndrome (GBS)? What do you treat it with?

A

Autoimmune - IgG against peripheral myelin made by Schwann cells

Treat with respiratory support, IVIG (pooled Ig)

20
Q

What infectious organisms can cause the following autoimmune diseases and what protein do they target?

  1. Rheumatic heart disease
  2. Guillain-Barre
  3. Myasthenia gravis
  4. Multiple sclerosis
  5. Rheumatoid arthritis
A
  1. Staphylococci - mitral valve protein
  2. Campylobacter jejuni - peripheral myelin
  3. Polio virus - ACh receptor
  4. Herpes, EBV - myelin basic protein
  5. Mycobacterium - cartilage protein
21
Q

Methotrexate

A

Inhibits dihydrofolate reductase (DHFR) and decreases purine synthesis

Low doses - immunosuppression, acute gout

High doses - cancer

22
Q

Azothioprine

A

Purine structural analog with sulfur, inhibits purine synthesis

Cancer, immunosuppression

23
Q

Anti-metabolites inhibit all rapidly dividing cells by blocking synthesis of and depleting nucleotides needed for DNA synthesis. What side FX do anti-metabolites have on the following?

  • GI epithelia
  • Hair follicles
  • Blood cells
A
  • Inflammation of stomach lining
  • loss of hair
  • myelosuppression (inhibit prolif of lymphocytes)
24
Q

Mycophenolate

A

Inhibits IMP dehydrogenase and thus lowers GTP and dGTP levels

Cancer, immunosuppression

25
Q

What is Methotrexate toxicity treated with?

A

Folinic acid - Leucovorin

26
Q

Lefluonomide

A

Inhibits dihydroorotate dehydrogenase and thus inhibits pyrimidine biosynthesis

Cancer, immunosuppression

27
Q

What are the two pathways with which cells get purines and pyrimidines?

A
  1. De novo synthesis from AA’s and folate

2. Salvaged/recycled from old/dead cells

28
Q

Cyclophosphamide

A

Alkylating agent–kills (rapidly dividing) immune cells by blocking DNA replication and inducing cell death via apoptosis

Autoimmune diseases with unwanted B cell responses (lymphomas, RA, MS,)

29
Q

What is a toxic metabolite of cyclophosphamide that damages the bladder mucosa?

A

Acrolein

30
Q

Mycophenolate mechanism of action is:

A. Inhibits dihydrofolate reductase, lowers purine levels
B. Gets incorporated into nucleic acids
C. Lowers pyrimidine nucleotide levels
D. Inhibits IMP dehydogenase, lowers dGTP levels

A

D.

31
Q

Cyclosporine (Restasis, Sandimmune)

A

Inhibit early helper T cell activation via calcineurin inhibition (binds cyclophilin), preventing IL-2 release

Prevent transplant rejection

32
Q

Tacrolimus (Prograf)

A

Inhibit early helper T cell activation via calcineurininhibition (binds FKBP), preventing IL-2 release

Prevent transplant rejection

33
Q

Sirolimus (Rapamycin)

A

Inhibit late helper T cell activation by inhibiting protein synthesis (via mTOR pathway), preventing autocrine effects of IL-2

Inhibits B cell activation by inhibiting IL-10

Prevent transplant rejection (esp. for coating stents), EBV B-cell lymphomas

34
Q

Infliximab (Remicade)

A

Fixes complement against TNF-alpha and may form neutralizing antibodies

Auto-immune like RA, ankylosing spondylitis

35
Q

Adalimumab (Humira)

A

Fully human MAB against TNF-alpha, fixes complement

#1 biologic drug

Auto-immune like RA, ankylosing spondylitis

36
Q

Etanercept (Enbrel)

A

Binds circulating and membrane-bound TNF-a and prevents activation/binding by other pro-inflammatory cytokines

Auto-immune like RA, ankylosing spondylitis

37
Q

Rituximab

A

Anti-CD20 mab (B-cell specific)

Auto-immune diseases like vasculitis
Cancer (B-cell lymphomas)

38
Q

Which one of the following drugs is most likely to be specific against B lymphocytes?

A. Sirolimus
B. Tacrolimus
C. Cyclosporine
D. Etanercept
E. Anti-CD19/20 MABs
F. Prednisone
A

E.

39
Q

Anti-inflammatory steroids, like prednisone, are commonly prescribed to suppress inflammation. Mechanism is:

A. Activation of Phospholipase A2 by binding lipocorin
B. Inhibition of lipoxygenase by binding lipocortin
C. Inhibition of phospholipase A2 by binding lipocortin
D. Increasing levels of arachidonic acid
E. Decreasing synthesis of IF-kB protein

A

C

40
Q

Promethazine (Phenergan)

A

First-generation histamine
H1 blocker, inverse agonist, enters CNS

Anti-emetic

Term III: Pharmacology (19 decks)

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