Immune And Chemotherapy

Question 1

What should you use if your goal is to reduce secondary inflmmation?

Answer 1

Anti-inflammatory

Question 2

What should you use if your goal is to significantly decrease the immune response

Answer 2

Immunosuppression

Question 3

What should you do if your goal is to reduce cell replication and/or kill unwanted cells

Answer 3

Chemotherapy

Question 4

What are your anti-inflammatory therapies?

Answer 4

NSIAD
Glucocorticoids
Cytokines inhibitors
Immunomodulators

Question 5

What are your selective/preferential COX2 inhibitors?

Answer 5

Meloxicam
Deracoxib
Piroxicam

Firocoxib
Robenacoxib

Carprofen

Question 6

What are the non selective cox inhibitors

Answer 6

Flunixin megulamine

Phenylbutazone

Question 7

What would i used to somatic pain in my equine patients?

Answer 7

Phenylbutazone

Question 8

What do I use to treat visceral pain in equines?

Answer 8

Visceral

Question 9

T/F: flunixin meglumine is administered IM in horse

Answer 9

False

IM injection causes muscle necrosis
Don’t do that!

Question 10

A dose of 0.5-1mg/kg/day of prednisone has _____________ effect, a dose of 2mg/kg/day has a _______________ effect

Answer 10

Anti-inflammatory; immunosuppressive

Question 11

How does the potency of dexamethasone compare to prednisone?

Answer 11

Dexamethasone is 7-8x more potent than prednisone

Dosage should be adjusted accordingly

Question 12

Glucocorticoids inhibit what part of the inflammatory pathway?

Answer 12

Inhibits phospholipase formation of acrachidonic acid

Question 13

NSAIDS inhibit what part of the inflammatory pathway?

Answer 13

Cyclooxygenase

COX1 or COX2 or both

Question 14

COX1 has what role in normal homeostasis ?

Answer 14

Mediates thromboxane A2 -> promoting platelet aggregation

Prostaglandin E1 -» GI mucosal maintenance and vasodilation of the kidney.

Question 15

What is the role of COX2 in normal homeostasis

Answer 15

Indictable production of prostaglandins during inflammation ?

Question 16

Which of the following NSAIDS would I choose if GI ulceration was a problem

A. Flunixin megutamine
B. Meloxicam
C. Phenylbutazone
D. Aspirin

Answer 16

B. Meloxiam
This is a selective COX2 inhibitor

All the others are have inhibitory activity on COX1 -> inhibit prostaglanin E => GI ulceration

Question 17

How does a Janus Kinase inhibitor have immunomodulatory activity

Answer 17

Inhibits JAK1 and JAK3

-> no production of pro-inflammatory cytokines

Question 18

How do anti-histamines have an immunomodulatory effect?

Answer 18

Antagonist at the histamine receptor -> block action of histamine

Question 19

What is the first-line for general immunosuppression

Answer 19

High dose glucocoricoids

Prednisone or dexamethasone

Question 20

What are common side effects seen with glucocorticoids therapy?

Answer 20

PU/PD/PP/Panting

Question 21

How do glucocorticoids cause immunosuppression ?

Answer 21

Inhibit the production of local chemotactic factors

Inhibit secretion of destructive proteolytic enzymes

Redistribute monocytes and lymphocyte from peripheral to bone marrow

Reduced Tcell activation and cytotoxicity

Suppress cytokine activity and alter macrophage function

Question 22

What might you use in conjunction with glucocorticoids to have a dose-sparing effect?

Answer 22

Azathioprine

Start high-dose pred and azathioprine
Azathioprine should work after the first two weeks and prednisone can be tapered off

Question 23

What is the MOA of antimetabolites? What are the drugs in this category?

Answer 23

Impair nucleic acid synthesis (DNA) in rapidly dividing immune cells and can block signaling on Tcells

Azathioprine
Mycophenolate mofetil
Leflunomide

Question 24

T/F: azathioprine can be used int cats to have a dose-sparing effect for prednisone

Answer 24

False

Azathioprine is toxic to cats -> bone marrow and liver toxicity

Question 25

When would I use mycophenolate?

Answer 25

Mycophenolate is often reserved for immune disease that is resistant to other therapies $$$$

Question 26

How are azathioprine, mycophenolate, and leflunomide administered?

Answer 26

Orally | Mycophenolate can also be given IV very slowly

Question 27

What are the Tcell inhibitors?

Answer 27

Cyclosporine Tacrolimus (topical)

Question 28

What is the MOA of cyclosporine?

Answer 28

Polypeptide that blocks cyclophilin/calcineurin which reduces T-cell activation and response, inhibits production of various cytokines to alter function of other WBC's

Question 29

Cyclosporine is used topically in the eye to treat?

Answer 29

Keratocnjuctivitis sicca (KCS) In dog

Question 30

What is cyclosporine used to treat systemically?

Answer 30

Perianal fistulas or as an adjunct with glucocorticoids for other immune disease (IMHA) Allergic/autoimmune dermatitis

Question 31

What are major side effects of cyclosporine?

Answer 31

GI upset Gingival proliferation Nephrotoxicity Hepatotoxicity

Question 32

Tacrolimus is used topically to treat????

Answer 32

Dermatological disease | Perianal fistula

Question 33

Aggressive cellular inhibiton of what therapy?

Answer 33

Chemotherapy

Question 34

T/F: cancer chemotherapy have a relatively narrow therapeutic index and require special handling

Answer 34

T

Question 35

What relatively low toxicity chemotherapeutics are used to manage immune-mediated diseases?

Answer 35

Cyclophosphamide (immune mediated hemolytic anemia) Chorambucil (IBD) Cytosine arabinoside (granulomatous meningioencephalitis)

Question 36

How should chemotherapy drugs be administered?

Answer 36

Vesicant drugs- catheter placement first try Long infusion Body surface area dosing

Question 37

Why do we used body surface dosing for chemotherapy drugs and levothyroxine?

Answer 37

Reflects the metabolic 'size' of the patient

Question 38

What is levothyroxine and what do we use it to treat?

Answer 38

AKA thyro-tabs T4 Treat hypothyroid in dog - direct replacement of hormone

Question 39

What drugs are contraindicated with levothyroxine use?

Answer 39

``` Phenobarbital Zonisamide Sulfonamides Glucocorticoids Phenylbutazone Quindine ```

Question 40

What precautions should the owner take when handling chemotherapy?

Answer 40

Wear gloves No crushing or splitting pills Make sure pet consumed the pill Elimination -> wear gloves to collect excretion, seal in plastic bag for disposal in trash several days after drug administration

Question 41

What are the two most common adverse effects of chemotherapy ?

Answer 41

GI signs -> nausea (use anti-emetic) before/during treatment Bone marrow suppression/immunosuppression - > monitor CBC - > neutropenia>thrombocytopenia>anemia

Question 42

What do you call the lowest neutrophil count

Answer 42

Nadir Generally predictable based on the drug used - > drop below a certain expected point -> delay chemo - >severe start prophylactic antibiotics

Question 43

Are we concerned about alopecia in our chemotherapy patients?

Answer 43

No. Most animals will not lose excessive hair or go bald Some breeds with continuously growth hair coats may show more hair loss Cats whiskers may fall out Shaved areas can be slow to regrow

Question 44

What drugs would be useful to treat the nausea associated withe chemotherapy and what is their MOA?

Answer 44

Maropitant (dog and cat)->NK1 antagonist ->block subP at CRTZ Metoclopramide (more useful in dog, cat)->D2 receptor and 5-HT antagonist @vomiting center Ondasetron (dog and cat)-> 5-HT receptor antagonist @vomiting center

Question 45

Why is metoclopramide more useful in dogs than cats?

Answer 45

Dogs have a higher number of D2 receptors than cats Can still be used in cats because of its action on 5-HT receptor

Question 46

What species is more susceptible to nephrotoxicity caused by chemotherapeutic platinum agents?

Answer 46

Cats

Question 47

What is acute tumor lysis syndrome?

Answer 47

Massive killing of cancer cells leading to severe systemic diseases (shock, DIC)

Question 48

Convention chemotherapy dosing uses ___________ to achieve the greatest efficacy

Answer 48

Maximum tolerated dose

Question 49

Why would one use a multi-drug chemotherapy protocol?

Answer 49

Reduce resistance development in the cancer cell population and minimize toxicity to the patient

Question 50

What is metronomic chemotherapy ?

Answer 50

Lower doses are given over longer periods of time | Caution: risk of owner exposure

Question 51

What phases of the cell cycle can chemotherapeutic drugs act?

Answer 51

M-phase: mitosis S-phase: DNA synthesis G2 phase: protein and RNS synthesis