ImmunoPharm #2

Question 1

Immunosuppressants
▪ Immunosuppressatory drugs act by a _____ of mechanisms
▪ These drugs interfere with combinations of critical pathways in the ___________ cascade
▪ “Cytotoxic” drugs: cause cell _______, _________, or impaired ________.
▪ “Lymphocyte” drugs: ______ immune system by inhibiting function or proliferation of _______, production of ______ etc
▪ Glucocorticoids: have many effects upon _____ and ______ immunity

Answer 1

variety, inflammatory, necrosis, apoptosis, proliferation, suppress, lymphocytes, cytokines, innate, adaptive

Question 2

Immunosuppressants: Classification

Answer 2

1. Antimetabolites
2. Inhibitors of Matrix Metalloproteinase (MMPs)
3. Other immunomodulators
4. Inhibitors of Cytokines

Question 3

Antimetabolites
➢ _______ synthesis inhibitors
✓ Azathioprine (ImuranR), ✓Mycophenolic acid
OR
➢ _______ synthesis inhibitor
B: ✓ Leflunomide

Answer 3

Purine, Pyrimidine

Question 4

An Inhibitors of Matrix Metalloproteinase (MMPs) is the drug?

Answer 4

Tetracycline

Question 5

Other Immunomodulators
➢ _____ Therapy (chrysotherapy)
✓ Auranofin
✓ Gold sodium thiomalate
OR
➢__________

Answer 5

Gold, Niacinamide

Question 6

❑ Inhibitors of Cytokines
➢ IL-__ inhibitors
✓ Cyclosporine
✓ Tacrolimus
OR
➢ _______ ________ ________ ____ (____) inhibitor
✓ Pentoxyfylline

Answer 6

2, Tumor-necrosis factor-α (TNFα)

Question 7

Azathioprine (________): a ________ Synthesis Inhibitor

Answer 7

ImuranR, Purine

Question 8

Antimetabolic drugs inhibit cellular synthesis of _______ _____ that are required for RNA and DNA synthesis resulting in cellular ______ and ______ arrest

Answer 8

nucleic acids, proliferation, function

Question 9

Azathioprine MOA: ______ DNA synthesis of __- and __-lymphocytes

Blocks ____ signaling on ___-cells resulting in impaired _____ synthesis

Answer 9

inhibits, B, T, CD28, T, RNA

Question 10

Azathioprine Uses
In conjunction with _______ to treat ______-mediated diseases such as?

Answer 10

steroids, immune

▪ Immune-mediated hemolytic anemia = dogs
▪ Immune-mediated thrombocytopenia
▪ Colitis and skin disease
▪ Myasthenia gravis
▪ Inflammatory bowel disease
▪ Immune-mediated inflammatory conditions and perianal fistulas in dogs
▪ Autoimmune skin disease in horses

Question 11

Azathioprine PK
▪ Azathioprine is a _______, well absorbed by the gut
▪ Several metabolic steps to become ___
▪ Detoxification is important, cats and ____% dogs are ____ in enzymes
▪ Do not give to _____

Answer 11

prodrug, active, 10, low, cats

Question 12

Azathioprine Adverse Effects
▪ _________ _______ suppression
▪ Fatal ______ and ________
▪ Increase risk for _____
▪ ____________ and ___ pancreatitis
▪ _________ (changes in genetic material), __________ (reversible structural malfunctions in fetus) and __________ (cancerous tumors) effects

Answer 12

Bone marrow, leukopenia, thrombocytopenia, infection, Hepatotoxicity, acute, Mutagenic, teratogenic, carcinogenic

Question 13

Leflunomide: a ________ Synthesis Inhibitor
MOA?

Inhibits _________ enzyme necessary for ____ ________ ______ synthesis
Affects particularly ___- and ____-lymphocytes DNA synthesis

Answer 13

Pyrimidine, mitochondrial, de novo pyrimidine, B-, T-

Question 14

Leflunomide Uses

Answer 14

▪ Immune-mediated hemolytic anemia
▪ Immune-mediated thrombocytopenia
▪ Immune-mediated polymyositis
▪ Multifocal nonsuppurative encephalitis/meningomyelitis
▪ Evan’s syndrome

Question 15

Leflunomide PK

▪ OP: good _________ of ____ metabolite
▪ High ______ bound
▪ _____ metabolism
▪ Conversion of Leflunomide to a toxic metabolite is ______ in cats then dogs

Answer 15

bioavailability, active, protein, Liver, slower

Question 16

Leflunomide Adverse Effects
▪ Uncommon in ____
▪ May include ___ disturbances
▪ ______

Answer 16

dogs, GI, Anemia

Question 17

Polymyositis is a relatively common ________ disease in ____ that causes muscle ________ and ______.
There are 3 main causes of polymyositis in dogs:
▪ Infectious agents (?)
▪ Immune-mediated ( ______diseases)
▪ ______________ causes (tumors affecting muscles, ex. Lymphoma)

Answer 17

inflammatory, dogs, weakness, fatigue

bacteria, viruses, protozoa or parasites, autoimmune, Paraneoplastic

Question 18

What are the signs and symptoms of polymyositis in dogs?
▪ __________ weakness that worsens with ______
▪ Muscle _____ and ___
▪ _______ (lack of _____)
▪ Exercise _________
▪ Muscle ___________

Answer 18

Generalized, exercise, swelling, pain, Anorexia, appetite, intolerance, wasting

Question 19

Treatment for polymyositis:

Answer 19

Azathioprine
Leflunomide
Cyclosporine
Prednisone
Polymyositis In Dogs: Causes, Symptoms And Treatment

Question 20

Cyclosporine: an IL-__ Inhibitor MOA

Cyclophillin is a mitochondrial protein expressed in ___ cells, important for protein ______. It bins to receptor in mitchondria of t cells.

Calcineurin is a protein phosphatase that activates _________ by then phosphorylating and translocating to the nucleus. It is important for dephosphorylation of NFAT__ –> NFAT__ which enters nucleus and activates IL-__.

___________ competes with ______ to bind to receptors and interfere with IL-2 proliferation.

Answer 20

2, T, folding, nuclear factor NF-ATc, c, n, 2, Cyclosporine, cyclophillin

Question 21

Cyclosporine: an IL-2 Inhibitor (cont)
Pharmacological effects?
▪ T-lymphocytes:
Decrease production of IL-?
Decrease production of _____
Decrease TNF__
Decrease proliferation of both CD__+ and CD__+ lymphocytes
Increase TGF__ (inhibits IL-__)
▪ Mast cells: Decrease _______ release in canine mast cells

Answer 21

2, IL-3, and IL-4, G-CSF, α, 4, 8, β, 2, histamine

Question 22

Cyclosporine Uses?
Uses:
▪ ________________ ________: topical application , increased ____ production
▪ _____________ ______: elimination/reduction in ____, OP, __-__ months of treatment
▪ ______: in conjunction with glucocorticoids

Answer 22

Keratoconjunctivitis sicca, tear, Perianal fistulas, size, 2-3, IMHA

Question 23

Cyclosporine PK?
PK:
▪ ____, not well ______
▪ Distribution: ?
▪ ____ metabolism
▪ ____/____ excretion

Answer 23

OP, absorbed,
liver, fat, red blood cell and lymphocytes
Liver,
bile/urine

Question 24

Cyclosporine Adverse Effects?
Adverse effects:
▪ ____ disturbances
▪ Gingival ________
▪ ___________ in dogs
▪ Viral infections in ____

Answer 24

GI, hyperplasia, Papillomatosis, cats

Question 25

Tacrolimus (FK-506): an IL-2 Inhibitor
MOA?

Answer 25

Tacrolimus, also called FK506, prevents the dephosphorylation of NF-AT by binding to FKBP12 –> Prevents IL proliferation

Question 26

Tacrolimus
Therapeutic uses?

Answer 26

▪ Keratoconjunctivitis sicca
▪ Localized topical treatment of immune-mediated dermatological disease

Question 27

Tacrolimus PK

Answer 27

Since it applied topically, very little is absorbed systemically

Question 28

Tacrolimus Adverse effects

Answer 28

Local irritation

Question 29

Pentoxyfylline (PTX): TNFα inhibitor
MOA: ? __________ the release and production of the _______ _____,
suppresses the production of __________-_______ factor, and
inhibits its action on _______.

Answer 29

downregulates, profibrotic TNF, platelet-activating, neutrophils

Question 30

Pentoxyfylline (PTX): TNFα inhibitor
Uses: ?

Answer 30

Canine skin diseases:
▪ Vasculitis
▪ Dermatomyositis
▪ Contact allergy
▪ Atopic dermatitis
▪ Vaccine-induced ischemic dermatitis
Equine:
▪ Systemic inflammatory response syndrome
▪ Caudal heal syndrome

Question 31

Pentoxyfylline PK ?
PK: rapid absorption in ____

Adverse effects?
Adverse effects: ___
▪ __ disturbance
▪ CNS ?

Answer 31

dogs, Rare, GI, excitement/nervousness

Question 32

Tetracyclines are a broad spectrum antibiotics

Question 33

Tetracyclines and tetracycline derivatives are able to inhibit ______ activity, _____________ of their anti-microbial action.

MMPs: play a major role in cell ?

Answer 33

MMP, independent
proliferation, diffferentiaon, migration, apoptosis, angiogenesis, and host defense.

Question 34

Describe the duration of action of the following drugs?

Answer 34

See below

Question 35

Tetracyclines uses?

Answer 35

▪ Systemic
▪ Topical ophthalmic

Question 36

Tetracycline adverse effects?

Answer 36

▪ Vomiting, diarrhea
▪ Kidney damage
▪ Liver damage
▪ Loss of appetite

Question 37

➢ Gold Therapy (chrysotherapy)
✓ __________
✓ _________ ____________ _________
1. MOA:
2. Uses: ?
3. Adverse effects: ?

Answer 37

Auranofin, Gold sodium thiomalate

1. Not completely understood [ inhibition of phagocytes (macrophages) and T-cells]
2. Idiopathic polyarthritis
   Rheumatoid arthritis
   Pemphigus foliaceus (PF)
   Chronic gingivitis/stomatitis
3. ▪ Stomatitis
   ▪ Skin lesions
   ▪ Hepatic necrosis
   ▪ Renal toxicity
   ▪ GI disturbances

Question 38

➢ Niacinamide is a vitamin _____ (nutritional supplement or with other medications)
MOA: ?
Uses: particularly in dogs?
PK:
▪ OP, well ______
▪ ______ distributed in the body
▪ ____ metabolism
▪ _____ excretion
Adverse effects:
▪ ___ disturbances
▪ _____
▪ Elevation of _____ enzymes

Answer 38

1. B3
2. poor understood (blocks mast cell degranulation and inhibits protease release from leukocytes)
3. ▪ Discoid lupus erythematosus
   ▪ Pemphigus erythematosus
   ▪ Pemphigus foliaceus (PF)
   ▪ Autoimmune diseases

absorbed, Widely, Liver, Urine, GI, Lethargy, hepatic

Question 39

Do not need to know

Answer 39

Do not need to know

Question 40

Autoimmune disorders
▪ Immune system attacks the ______ cells in the body by mistake
▪ The body has lost its ability to differentiate between antigens on its ______ cells and antigens on ______ cells
▪ Antibodies attack _____-antigens
▪ ______ is a major mechanism of tissue damage
Cause: ?

Answer 40

healthy, own, foreign, self, Inflammation, Genetic
Environmental

Question 41

Hemolytic Anemia in Dogs
▪ Autoimmune hemolytic anemia (AIHA) is an immune system disease, in which the body attacks and destroys its own _____ (_______).
▪ Immune-Mediated Hemolytic Anemia (IMHA) causes severe _____ in dogs and is
associated with considerable _____ and _____
▪ IMHA is the most common autoimmune disease in _____

Answer 41

RBCs, hemolysis, anemia, morbidity, mortality, dogs

Question 42

Management of IMHA:
Controlling the immune response:

Answer 42

Skipped?