Lecture 13: Immune System Drugs (RED ONLY)

Question 1

What are the 3 main drug classes with immune effects?

Answer 1

Glucorticoids
Immunomodulators
Biologics

Question 2

What are the 3 S?

Answer 2

Sugar (glucocorticoids)

Salt (mineralcorticoids)

Sex (Androgens)

Question 3

What are the main 3 glucocorticoids?

Answer 3

Hydrocortisone (main?)
Cortisone
Prednisolone

Question 4

What is the main hormone in the mineralcorticoids?

Answer 4

Aldosterone

Question 5

What is the main hormone in the androgens?

Answer 5

Testosterone

Question 6

What are the effects of GCs?

Answer 6

Widespread effects on carb, protein, and lipid metabolism, and electrolyte/water balance.

Excess = insomnia/euphoria followed by depression, aka steroid psychosis.

Deficiency = Depression

Question 7

What is the MOA of a GC’s antinflammatory/immune effects?

Answer 7

Inhibits production of precursors to prostaglandins, leukotrienes, and PAF.

Suppresses inflammatory cytokines, chemokines, and other inflammatory mediators.

Inhibits macrophages and other APCs

Reduces synthesis of arachidonic acid, which leads to reduction of COX 2, reducing prostaglandins.

Reduces antibody production in large doses.

Note:
NSAIDs are also COX inhibitors.

Question 8

Which GC is often prescribed as a cream and has similar anti-inflammatory effects and mineralcorticoid activity?

Answer 8

Hydrocortisone

Question 9

What is the MOA of methotrexate?

Answer 9

Binds and inhibits dihydrofolate reductase (DHFR)

Inhibiting tetrahydrofolate synthesis (THF)

Inhibiting synthesis of purine nucleotides and amino acids

Interfering with the formation of DNA, RNA, and cellular proteins

Question 10

What nucleic acids is leflunomide an analog for?

Answer 10

Pyrimidine

Question 11

What nucleic acids is azathioprine an analog for?

Answer 11

Purine

Note:
Prine purine

Question 12

What are the indications for MTX?

Answer 12

RA, psoriasis, several types of cancer.

Off-label use in Crohn’s disease, MS, SLE, and multiple conditions.

Question 13

What are the indications for leflunomide?

Answer 13

RA. PO administration only

Question 14

What are the indications for azathioprine?

Answer 14

RA, MS, psoriasis, Crohn’s disease, and transplant maintenance.

Question 15

What is the MOA of tacrolimus and cyclosporine?

Answer 15

Inhibiting T-lymphocyte activation.

Question 16

What is the tolerability of cyclosporine?

Answer 16

Gingival hyperplasia
Hirsutism

Question 17

What are the indications for the calcineurin inhibitors?

Answer 17

Transplant maintenance
RA
Psoriasis

Question 18

What is the MOA of the mTOR kinase inhibitors?

Answer 18

Inhibiting T-lymphocyte activation & proliferation.
Synergy with calcineurin inhibitors.

Question 19

What is the indication for the mTOR kinase inhibitors?

Answer 19

Cancer, Organ transplantation, complications of TB.

Question 20

What is the MOA for mycophenolate?

Answer 20

Inhibits T and B cell proliferation by inhibiting major enzyme involved in nucleotide synthesis.

Question 21

What are the indications for mycophenolate?

Answer 21

Transplant maintenance, lupus nephritis, autoimmune hepatitis, and myasthenia gravis.

Question 22

What is the MOA for sulfasalazine?

Answer 22

5-aminosalicyclic acid derivative. Immune modulator with an unknown mechanism.

Question 23

What are the indications for sulfasalazine?

Answer 23

RA, and ulcerative colitis

Question 24

What is the MOA for hydroxychloroquine?

Answer 24

Antimalarial drug with immune modulating factors (inhibits neutrophil and eosinophil motility and impairs complement antibody reactions)

Question 25

What are the indications for hydroxychloroquine?

Answer 25

RA
SLE
Malaria

Question 26

What is the MOA of fingolimod?

Answer 26

Binds sphingosine receptors and blocks lymphocytes from leaving lymph nodes

Question 27

What are the indications for fingolimod?

Answer 27

MS

Question 28

What is the MOA for glatiramer?

Answer 28

Not well defined.

Mixture of polymers that roughly mimics basic myelin protein; it is thought to activate T suppressor cells.

Question 29

What are the indications for Glatiramer?

Answer 29

MS (Preferred in pregnancy)

Question 30

What are the two Anti-TNFs?

Answer 30

Etanercept (Enbrel)
Adalimumab (Humira)

Question 31

What are the indications for etanercept and adalimumab?

Answer 31

RA, psoriasis, Crohn’s disease, and more.

Question 32

What are the two anti-CD80/86 drugs?

Answer 32

Belatacept
Abatacept

Question 33

What are the indications for Belatacept and Abatacept?

Answer 33

Transplant (belatacept)

RA, psoriasis (Abatacept)

Question 34

What is Rituximab and its use?

Answer 34

Anti-CD20 indicated for RA, chronic lymphocytic leukemia, and non-hodgkin lymphomas.

Question 35

What should you always double check when prescribing an immune system drug?

Answer 35

Pregnancy
Live vaccine candidacy
Drug and disease interactions
Dose adjustments

Question 36

What should you always do with GCs?

Answer 36

Taper down high or long doses to avoid adrenal insufficiency.

Question 37

What cancers is MTX for?

Answer 37

Lungs, liver, kidneys, bone marrow

Question 38

What should you always give with MTX and sulfasalazine?

Answer 38

Folic acid

Question 39

What should you always do when prescribing a biologic?

Answer 39

Parenteral only.
Screen for TB before use.
Avoid live vaccines.
Refrigerate
Don’t combine them!