Immunology Drugs

Question 1

Prednisone,Prednisolone

Answer 1

• Glucocorticoids
• lyse and cause redistribution of lymphocytes, monocytes, eosinophils, and basophils
• inhibit macrophages and APCs, phospholipase A2->arachidonic acid
• reduces formation of prostaglandin and leukotrienes
• increase infection rate, malignancy,growth retardation,slow would healing, hypertension, hyperglycemia, diabetogenic, osteopenia

Question 2

Antithymocyte globulin (ATG) 
Antilymphocyte globulin (ALG)

Answer 2

• Immunomodulatory polyclonal antibodies
• bind surface of immune cell and deplete lymphocytes and thymocytes by direct cytotoxicity
• use for transplants for induction, initial rejection, reduces GVH
• causes fever,chills,hypotension,serum sickness,glomerulonephritis,cytokine release syndrome

Question 3

Muromonab

Answer 3

• Immunmodulatory monoclonal antibody
• Ab against CD3, TCR complex
• blocks antigen recognition and cell function
• causes internalization of TCR, apoptosis/T cell death by complement path
• pretreat with steroids
• causes: CRS, systemic shock due to TNF-alpha,cytokine,IFNgamma release

Question 4

Daclizumab, Basiliximab

Answer 4

• Immunomodulatory monoclonal antibody
• Anti CD25 (IL-2R)
• MABs to alpha subunit of IL-2R on T cells when they are activated
• block IL2 stimulation and increase apoptosis of T cells
• lower toxicity and less cytokine release than muromonab, anaphylaxis is possible

Question 5

Rituximab

Answer 5

• Immunomodulatory monoclonal antibody
• Anti CD20 on B cells
• used for antibody mediated transplant rejection, B cell cancer, antibody dependent autoimmune disease

Question 6

Alemtuzumab

Answer 6

• Immunomodulatory monoclonal antibody
• Anti CD52 on T,B,NK, monocytes,macrophages
• Causes extensive lympholysis due to apoptosis, prolonged T/B cell depletion

Question 7

Abatacept

Answer 7

• Recombinant CTLA4 receptor protein - FcIgG
• inhibit T cell activation-costimulatory blockade, blocks CD80/CD86 attachment to CD28 to prevent activation and cause anergy
• fusion protein contains extra cellular domain of CTLA4 and Fc region that inhibits B7-CD28 binding

Question 8

Belatacept

Answer 8

• Recombinant CTLA4 receptor protein - FcIgG
• inhibit T cell activation-costimulatory blockade, blocks CD80/CD86 attachment to CD28 to prevent activation and cause anergy
• 2nd generation CTLA4-Fc fragment

Question 9

Cyclosporine (CsA)

Answer 9

• Calcineurin inhibitor
• binds cyclophilin in cell, makes CsA-CyP complex, binds PP2B and inhibits dephosphorylation of NF-ATc
• no NF-ATc in nucleus=no T cell transcription/activation
• inhibits signal transduction cascade, blocks IL2
• metabolized by liver, CYP450
• used for transplants, RA, psoriasis, autoimmune disorders
• nephrotoxicity,neurotoxicity,hypertension,hyperlipidemia,inhibit PGI2

Question 10

Tacrolimus (FK506)

Answer 10

• calcineurin inhibitor
• enters cell, binds FK506 binding protein 12 (FKBP12), complex binds PP2B, inhibits NF-ATc=no transcription/activation, blocks IL2
• metabolized by liver
• causes nephrotoxicity,neurotoxicity,hypertension,hyperkalemia,hyperglycemia
• diabetogenesis=glucocorticoids and tacrolimus

Question 11

Sirolimus (Rapamycin)

Answer 11

• Antiproliferative agents (mTOR inhibitors)
• binds to FKBP12 but complex then binds to and inhibits mTOR, fails to phosphorylate and activate CdK2 arrests G1 to S phase
• metabolized by CYP3A4 and transported by P-glycoprotein in bile
• use for coronary stents, pneumonia,cytomegalovirus,tuberous sclerosis
• cause myelosuppression,thrombocytopenia,anemia,delay wound healing
• combo of mTOR and calcineurin inhibitors help with renal transplants

Question 12

Mycophenolate mofetil

Answer 12

• antimetabolite
• prodrug hydrolyzed to mycophenolic acid
• reversible inhibitor of GMP pathway
• B&T cells are dependent on purine synthesis, selectively inhibited
• inhibits T,B,NK cell proliferation,cellular adhesion,migration
• causes leukopenia,diarrhea, vomiting

Question 13

Azathioprine

Answer 13

• Antimetabolite
• prodrug cleaved to 6MP, inhibits purine synthesis
• 6MP phosphorylated by salvage pathway and put in DNA-disrupts replication, transcription, and function
• metabolized by oxidation and methylation in liver
• causes bone marrow suppression, leukopenia,thrombocytopenia,anemia, hepatotoxicity, alopecia,pancreatitis, GI toxicity

Question 14

Nabumetone

Answer 14

• NSAID
• some selectivity for COX2
• prodrug

Question 15

Indomethacin

Answer 15

• NSAID

- use is associated with risk of CV events (MI)

Question 16

Aspirin

Answer 16

• Classic NSAID
• analgesic, antipyretic, antiplatelet, anti-inflammatory
• absorbed rapidly from stomach and intestine in unionized form
• irreversibly inhibits prostaglandin biosynthesis by acetylating COX

Question 17

Chlorpheniramine, diphenhydramine, promethazine

Answer 17

• 1st gen. H1 receptor competitive antagonists
• short lasting
• anticholinergic, anti alpha-adrenergic, antiserotonergic, sedative, antiemetic, anti motion sickness

Question 18

Loratadine, fexofenadine, cetirizine

Answer 18

“Allegra”,”Zyrtec”,”Claritin”

• 2nd/3rd gen. H1 receptor competitive antagonists/inverse agonists
• longer lasting
• more specific use

Question 19

Acetaminophen

Answer 19

• analgesic,antipyretic, NOT anti inflammatory

- severe hepatotoxicity with overdosage caused by reactive quinone species

Question 20

Celecoxib

Answer 20

• only approved COX2 inhibitor
• still bad for upper GI, reduced amt of small bowel inflammation and mucosal breaks
• negative impact on bone remodeling and ulcer repair
• reduces water and salt excretion by the kidneys

Question 21

Zileutron

Answer 21

• Leukotriene pathway inhibitors
• inhibits 5-lipoxygenase, inhibits CYP3A4
• for mild/moderate asthma
• blocks formation of leukotrienes

Question 22

Zafirlukast, Montelukast

Answer 22

• LTD4 receptor antagonists
• inhibit CYP3A4 and CYP2C9
• for mild/moderate asthma
• blocks actions of leukotrienes

Question 23

Infliximab

Answer 23

• chimeric antiTNF alpha monoclonal antibody
• given by IV in doses and then as maintenance dose
• cytokine blocker

Question 24

Etanercept

Answer 24

• Cytokine blocker

- human TNF receptor linked to Fc portion of human IgG1

Question 25

Adalimumab

Answer 25

- Cytokine blocker - Human monoclonal antibody specific for TNF alpha - methotrexate reduces clearance

Question 26

Anakinra

Answer 26

- Inhibitor of IL1 function - recombinant, nonglycosylated synthetic form of the human IL1 receptor antagonist - endogenous regulator of IL1 - used for RA

Question 27

Rituximab

Answer 27

- Inhibitor of B cell function - for pts that don't respond to anti TNF alpha therapy - chimeric monoclonal Ab against CD20 antigen - use glucocorticoid before each injection

Question 28

Tofacitinib

Answer 28

- JAK inhibitor - blocks JAK3 and JAK1, less JAK2 - for moderate-severe active RA

Question 29

Apremilast

Answer 29

- PDE4 inhibitor - indicated for moderate-severe plaque psoriasis - increases intracellular cAMP and decreases TNFa production