Immune And Chemotherapy Flashcards
What should you use if your goal is to reduce secondary inflmmation?
Anti-inflammatory
What should you use if your goal is to significantly decrease the immune response
Immunosuppression
What should you do if your goal is to reduce cell replication and/or kill unwanted cells
Chemotherapy
What are your anti-inflammatory therapies?
NSIAD
Glucocorticoids
Cytokines inhibitors
Immunomodulators
What are your selective/preferential COX2 inhibitors?
Meloxicam
Deracoxib
Piroxicam
Firocoxib
Robenacoxib
Carprofen
What are the non selective cox inhibitors
Flunixin megulamine
Phenylbutazone
What would i used to somatic pain in my equine patients?
Phenylbutazone
What do I use to treat visceral pain in equines?
Visceral
T/F: flunixin meglumine is administered IM in horse
False
IM injection causes muscle necrosis
Don’t do that!
A dose of 0.5-1mg/kg/day of prednisone has _____________ effect, a dose of 2mg/kg/day has a _______________ effect
Anti-inflammatory; immunosuppressive
How does the potency of dexamethasone compare to prednisone?
Dexamethasone is 7-8x more potent than prednisone
Dosage should be adjusted accordingly
Glucocorticoids inhibit what part of the inflammatory pathway?
Inhibits phospholipase formation of acrachidonic acid
NSAIDS inhibit what part of the inflammatory pathway?
Cyclooxygenase
COX1 or COX2 or both
COX1 has what role in normal homeostasis ?
Mediates thromboxane A2 -> promoting platelet aggregation
Prostaglandin E1 -» GI mucosal maintenance and vasodilation of the kidney.
What is the role of COX2 in normal homeostasis
Indictable production of prostaglandins during inflammation ?
Which of the following NSAIDS would I choose if GI ulceration was a problem
A. Flunixin megutamine
B. Meloxicam
C. Phenylbutazone
D. Aspirin
B. Meloxiam
This is a selective COX2 inhibitor
All the others are have inhibitory activity on COX1 -> inhibit prostaglanin E => GI ulceration
How does a Janus Kinase inhibitor have immunomodulatory activity
Inhibits JAK1 and JAK3
-> no production of pro-inflammatory cytokines
How do anti-histamines have an immunomodulatory effect?
Antagonist at the histamine receptor -> block action of histamine
What is the first-line for general immunosuppression
High dose glucocoricoids
Prednisone or dexamethasone
What are common side effects seen with glucocorticoids therapy?
PU/PD/PP/Panting
How do glucocorticoids cause immunosuppression ?
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
What might you use in conjunction with glucocorticoids to have a dose-sparing effect?
Azathioprine
Start high-dose pred and azathioprine
Azathioprine should work after the first two weeks and prednisone can be tapered off
What is the MOA of antimetabolites? What are the drugs in this category?
Impair nucleic acid synthesis (DNA) in rapidly dividing immune cells and can block signaling on Tcells
Azathioprine
Mycophenolate mofetil
Leflunomide
T/F: azathioprine can be used int cats to have a dose-sparing effect for prednisone
False
Azathioprine is toxic to cats -> bone marrow and liver toxicity
When would I use mycophenolate?
Mycophenolate is often reserved for immune disease that is resistant to other therapies
$$$$
How are azathioprine, mycophenolate, and leflunomide administered?
Orally
Mycophenolate can also be given IV very slowly
What are the Tcell inhibitors?
Cyclosporine
Tacrolimus (topical)
What is the MOA of cyclosporine?
Polypeptide that blocks cyclophilin/calcineurin which reduces T-cell activation and response, inhibits production of various cytokines to alter function of other WBC’s
Cyclosporine is used topically in the eye to treat?
Keratocnjuctivitis sicca (KCS)
In dog
What is cyclosporine used to treat systemically?
Perianal fistulas or as an adjunct with glucocorticoids for other immune disease (IMHA)
Allergic/autoimmune dermatitis
What are major side effects of cyclosporine?
GI upset
Gingival proliferation
Nephrotoxicity
Hepatotoxicity
Tacrolimus is used topically to treat????
Dermatological disease
Perianal fistula
Aggressive cellular inhibiton of what therapy?
Chemotherapy
T/F: cancer chemotherapy have a relatively narrow therapeutic index and require special handling
T
What relatively low toxicity chemotherapeutics are used to manage immune-mediated diseases?
Cyclophosphamide (immune mediated hemolytic anemia)
Chorambucil (IBD)
Cytosine arabinoside (granulomatous meningioencephalitis)
How should chemotherapy drugs be administered?
Vesicant drugs- catheter placement first try
Long infusion
Body surface area dosing
Why do we used body surface dosing for chemotherapy drugs and levothyroxine?
Reflects the metabolic ‘size’ of the patient
What is levothyroxine and what do we use it to treat?
AKA thyro-tabs
T4
Treat hypothyroid in dog - direct replacement of hormone
What drugs are contraindicated with levothyroxine use?
Phenobarbital Zonisamide Sulfonamides Glucocorticoids Phenylbutazone Quindine
What precautions should the owner take when handling chemotherapy?
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
What are the two most common adverse effects of chemotherapy ?
GI signs
-> nausea (use anti-emetic) before/during treatment
Bone marrow suppression/immunosuppression
- > monitor CBC
- > neutropenia>thrombocytopenia>anemia
What do you call the lowest neutrophil count
Nadir
Generally predictable based on the drug used
- > drop below a certain expected point -> delay chemo
- > severe start prophylactic antibiotics
Are we concerned about alopecia in our chemotherapy patients?
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
What drugs would be useful to treat the nausea associated withe chemotherapy and what is their MOA?
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
Why is metoclopramide more useful in dogs than cats?
Dogs have a higher number of D2 receptors than cats
Can still be used in cats because of its action on 5-HT receptor
What species is more susceptible to nephrotoxicity caused by chemotherapeutic platinum agents?
Cats
What is acute tumor lysis syndrome?
Massive killing of cancer cells leading to severe systemic diseases (shock, DIC)
Convention chemotherapy dosing uses ___________ to achieve the greatest efficacy
Maximum tolerated dose
Why would one use a multi-drug chemotherapy protocol?
Reduce resistance development in the cancer cell population and minimize toxicity to the patient
What is metronomic chemotherapy ?
Lower doses are given over longer periods of time
Caution: risk of owner exposure
What phases of the cell cycle can chemotherapeutic drugs act?
M-phase: mitosis
S-phase: DNA synthesis
G2 phase: protein and RNS synthesis
