Immunomodulators Flashcards
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?
- Histamine (anti-histamines)
- Prostaglandins (COX inhibitors)
- Leukotrienes (LOX inhibitors or LT blockers)
- Cytokines (steroids)
What is the effect on smooth muscle when acting at H1 and H2 receptors?
H1 - constricts smc
H2 - dilates smc
Dipenhydramine (Benadryl)
First generation anti-histamine
H1 blocker, inverse agonist
Enters CNS
Allergies
Fexofenadine (Allegra) and Loratadine (Claritin)
Second generation anti-histamines
H2 receptor blockers - do not enter CNS
Allergies
**tidines (Cimetidine, Ranitidine, Fomatidine)
H2 blockers, decrease acid secretion
Ulcers, GERD
Where do the cell bodies of histamine releasing neurons sit in the hypothalamus?
Tuberomamillary nucleus
What does histamine do in the CNS?
Controls alertness, keeps us awake
What 3 places in the CNS is histamine released?
cortex, brainstem, & spinal cord
Zileuton
LOX inhibitor
Allergies
Montelukast (Singulair)
LT receptor blocker
Allergies
Cromolyn sodium (Nasalcrom)
Mast cell stabilizer - inhibits mast cell degranulation
Prophylaxis for asthma and allergic rhinitis
Chloroquine
Lysosomal membrane stabilizer - stops lysosomes from degrading proteins and presenting them to immune system
Malaria, rheumatoid arthritis, lupus
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
B
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 and F
What molecule are steroids derived from?
Cholesterol
What do you treat Bell’s Palsy with?
Steroids
What is multiple sclerosis? What do you treat it with?
Autoimmune disease - IgG against central myelin made by oligodendrocytes
Steroids and IFN-gamma
What is SCID? What do you treat it with?
Severe combined immune deficiency - lack of adenosine deaminase –> imbalance of dNTPs –> cannot make DNA
Recombinant enzyme: PEG-enzyme
What is Guillain-Barre syndrome (GBS)? What do you treat it with?
Autoimmune - IgG against peripheral myelin made by Schwann cells
Treat with respiratory support, IVIG (pooled Ig)
What infectious organisms can cause the following autoimmune diseases and what protein do they target?
- Rheumatic heart disease
- Guillain-Barre
- Myasthenia gravis
- Multiple sclerosis
- Rheumatoid arthritis
- Staphylococci - mitral valve protein
- Campylobacter jejuni - peripheral myelin
- Polio virus - ACh receptor
- Herpes, EBV - myelin basic protein
- Mycobacterium - cartilage protein
Methotrexate
Inhibits dihydrofolate reductase (DHFR) and decreases purine synthesis
Low doses - immunosuppression, acute gout
High doses - cancer
Azothioprine
Purine structural analog with sulfur, inhibits purine synthesis
Cancer, immunosuppression
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
- Inflammation of stomach lining
- loss of hair
- myelosuppression (inhibit prolif of lymphocytes)
Mycophenolate
Inhibits IMP dehydrogenase and thus lowers GTP and dGTP levels
Cancer, immunosuppression
What is Methotrexate toxicity treated with?
Folinic acid - Leucovorin
Lefluonomide
Inhibits dihydroorotate dehydrogenase and thus inhibits pyrimidine biosynthesis
Cancer, immunosuppression
What are the two pathways with which cells get purines and pyrimidines?
- De novo synthesis from AA’s and folate
2. Salvaged/recycled from old/dead cells
Cyclophosphamide
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,)
What is a toxic metabolite of cyclophosphamide that damages the bladder mucosa?
Acrolein
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
D.
Cyclosporine (Restasis, Sandimmune)
Inhibit early helper T cell activation via calcineurin inhibition (binds cyclophilin), preventing IL-2 release
Prevent transplant rejection
Tacrolimus (Prograf)
Inhibit early helper T cell activation via calcineurininhibition (binds FKBP), preventing IL-2 release
Prevent transplant rejection
Sirolimus (Rapamycin)
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
Infliximab (Remicade)
Fixes complement against TNF-alpha and may form neutralizing antibodies
Auto-immune like RA, ankylosing spondylitis
Adalimumab (Humira)
Fully human MAB against TNF-alpha, fixes complement
#1 biologic drug
Auto-immune like RA, ankylosing spondylitis
Etanercept (Enbrel)
Binds circulating and membrane-bound TNF-a and prevents activation/binding by other pro-inflammatory cytokines
Auto-immune like RA, ankylosing spondylitis
Rituximab
Anti-CD20 mab (B-cell specific)
Auto-immune diseases like vasculitis
Cancer (B-cell lymphomas)
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
E.
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
C
Promethazine (Phenergan)
First-generation histamine
H1 blocker, inverse agonist, enters CNS
Anti-emetic
