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EV ACVD Study > Pharmacology- random bits > Flashcards

Pharmacology- random bits Flashcards

1
Q

Immunomodulatory properties of doxycycline/niacinamide

A

Tetracycline:
1) suppresses antibody production
2) inhibits complement activation
3) inhibits prostaglandin synthesis
4) inhibits lipase and collagenase function

Niacinamide:
1) Blocks IgE-induced histamien release
2) Prevent mast cell degranulation
3) Decreased protease release
4) inhibit phosphodiesterases

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2
Q

Which comorbidity should you be cautious of when prescribing doxycycline to dogs

A

Hx seizures

(neurologic AEs reported in humans)

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3
Q

MOA of pentoxifylline

A

*Synthetic xanthine derivative

*Inhibits phosphodiesterase

ALLERGY: inhibits T and B cell activation, increase IL-10, PGE2, decrease leukocyte adhesion, decrease neutrophil superoxide, degranulation, IFNg, NK cell activity

*Rheological effects
*Improves wound healing (Increased fibroblast collagenases, decrease TNFa)

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4
Q

Borates + vacuuming can kill ____ in carpets and sofas for up to 6 months

A

House dust mites

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5
Q

Which inflammatory transcription factor do omega 3 fatty acids inhibit, thereby preventing TNFa production

A

NFkB

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6
Q

T or F: diphenhydramine is readily available in the horse

A

False. Poor bioavailability. Need injectables.

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7
Q

How do omega 3 fatty acids prevent prostaglandin synthesis

A

Inhibit prostaglandin H synthase

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8
Q

Which immunosuppressants target the T cells

A

*Glucocorticoids
*Azathioprine
*Cyclosporine
*Chlorambucil
*Mycophenolate
*Oclacitinib

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9
Q

Which immunosuppressants target antibodies (IgG)

A

IVIg
Plasmapharesis

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10
Q

Which immunosuppressants target tissue inflammation

A

*Glucocorticoids
*Doxycycline/Niacinamide
*Hydroxychloroquine

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11
Q

Primary cellular of glucocorticoid therapy

A

T cells

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12
Q

What do glucocorticoids bind? Where in the cell?

A

Glucocorticoid receptor

Bind in the cytoplasm

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13
Q

When GC is unbound to glucocorticoid receptor, what inhibits glucocorticoid receptor action

A

Chaperon molecule

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14
Q

What are the 4 possible actions of GCs once they bind GRs

A

1) Translocate to nucleus –> bind to GRE (glucocorticoid response element) on DNA
2) Translocate to nucleus –> bind to NEGATIVE GRE (nGRE)
3) GRs bind to a DIFFERENT transcription factor to repress inflammation (NKfB, STAT, AP-1)

4) NON-genomic effects. Direct action on cell membranes, adhesion molecules, membrane ion channels.
ie: increase expression of demosomal cadherins, for better keratinocyte adhesion

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15
Q

Why might dogs on high dose cyclosporine be more prone to fungal infections

A

Altered neutrophil function = increased susceptibility to opportunistic infections

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16
Q

T or F: NFAT is only present on T cells

A

False. NFAT present in almost every cell in body.

HIGH DOSE Cyclosporine can cause altered function in myeloid cells (macrophages, DCs, neut, MC, eos). Low dose cyclosporine is T cell only

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17
Q

Which transcription factor is blocked by cyclosporine

A

NFAT

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18
Q

Major cytokine made by NFAT

A

IL-2

(Cyclosporine blocks IL-2, blocks T cell proliferation)

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19
Q

Why does it take a few weeks for cyclosporine to work for lupus and AISBDs?

A

Limits antibody production via T-B cell interactions

It takes a few weeks after inhibiting T cells to then have an effect on antibody production

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20
Q

Binding to GRE induces transcription of these genes (3):

A

Antiinflammatory

1) Annexin-1
2) GC-induced leucine zipper, which inhibits NFkB, MAPK
3) Mitogen activated protein kinase phosphatase 1 (MAPKP1)

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21
Q

Binding to nGRE inhibits transcription of these genes (3):

A

1) CRH
2) b-endorphins
3) MSH

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22
Q

Name the 4 janus kinase family members

A

JAK1
JAK2
JAK3
TYK2

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23
Q

Apoquel: most-to-least potent effect on JAKS

A

JAK1>JAK3> JAK2, TYK2

Allegedly JAK1 specific

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24
Q

Which JAK is important for hematopoiesis

A

JAK2

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25
Which JAK is important for Th1 immune response
TYK2
26
Effect of inhibition of JAK1
*Impaired T cell proliferation, differentiation *Impaired signaling, esp Th2 cytokines (infections, hypercholesterolemia, possible NK cell impairment)
27
Effect of inhibition of JAK2
*Impaired erythropoiesis and myelopoiesis (infections, anemia, neutropenia)
28
Effect of inhibition of JAK3
Impaired T cell proliferation (infections)
29
Effect of inhibition of TYK2
Impaired Th1 and Th17 response (infections)
30
What is the active metabolite of azathioprine (pro-drug)
6-mercaptopurine
31
MOA of azathioprine
6-MP blocks purine metabolism, interferes with DNA synthesis "antimetabolite"
32
Why are lymphocytes susceptible to azathioprine
They have de novo purine synthesis Reduces B and T cell proliferation
33
Elevation in which enzyme makes some animals more susceptible to hepatotoxicity 2' azathioprine
Thiopurine methyltransferase (TPMT)
34
Do cats and horses have a HIGH or LOW activity of their TPMT (azathioprine enzyme)
LOW activity Makes cats at higher risk for myelosuppression
35
Why do horses have a LOWER risk of myelosuppression with azathioprine at standard doses
Low bioavailability of azathioprine in horses
36
Which metabolite of azathioprine is immunosuppressive
6 thioguanine nucleotides "false purine" stops cell cycle --> apoptosis
37
Which medication should NOT be combined with azathioprine
Allopurinol Allopurinol is a xanthine oxidase inhibitor, so more of the azathioprine is pushed to active metabolite form (XO would make inactive metabolite = safer)
38
Which medication should NOT be combined with azathioprine, as it inhibits TPMT
Sulfasalazine Myelosuppression
39
Category of medication of chlorambucil
Nitrogen mustard alkylating agent
40
MOA chlorambucil
Cross-links DNA during all phases of the cell cycle. INTERstrand is most cytotoxic Cell cycle arrest --> Apoptosis Effects B and T cells
41
AE of chlorambucil
Myelosuppression GI upset Reversible myoclonic neurotoxicity Fanconi syndrome (cats)
42
Main metabolite of mycophenolate mofetil
Mycophenolic acid
43
Function of Mycophenolic acid
Inhibits inosine-5'-monophosphate dehydrogenase Depletes guanosine nucleotides in activated B and T cells --> inhibits proliferation and antibody formation
44
Higher doses of Mycophenolate mofetil increase the risk of _____ side effect
GI issues (diarrhea, hematochezia, vomiting)
45
T or F: it is crucial to monitor for myelosuppression with mycophenolate mofetil
False. GI side effects primarily
46
Why are IVIg beneficial for autoimmune diseases
IVIg increases catabolism of pathogenic IgG IVIg preferentially binds to neonatal Fc receptors (**FcRn**). If bound to FcRn, Ig is protected from degredation. Because IVIg is taking all the FcRn spots, pathogenic IgG cannot bind--> so it is degraded.
47
What are the risks of IVIg
Hypercoagulation Renal failure Hypotension Hypersensitivity Anaphylaxis (xenoproteins!)
48
Which cytokines does doxycycline inhibit
IL-1 IL-6 IL-8 TNFa
49
4 anti-inflammatory mechanisms of doxycycline
1) Decrease cytokines (IL-1, IL-6, IL-8, TNFa) 2) Inhibit MMPs 3) Reduce leukocyte chemotaxis 4) Reduces NO synthase function
50
MOA of niacinamide
Endogenous inhibitor of PARP-1 1) Inhibits proinflammatory cytokines 2) Reduces ICAM-1 expression (decreased neutrophil chemotaxis) 3) Reduces B cell differentiation
51
Mechanisms of colchicine
1) Inhibits neutrophil chemotaxis, adhesion, and mobilization 2) Inhibits superoxide production 3) Inhibits NALP3 inflammasomes (IL-1b processing) Prevents tubulin polymerization, so poor neutrophil motility!! Cannot migrate through tissues!!
52
Which immunomodulatory medication works primarily on neutrophils
Colchicine (niacinamide works on neuts via ICAM, but also B cells)
53
Most common AE from colchicine
GI upset (nausea, vomiting, diarrhea, abdominal pain)
54
Which medication should be avoided with colchicine
Cyclosporine Both are p-glycoprotein substrates!
55
Immunomodulatory effects of hydroxychloroquine
*Inhibits TLR7, TLR9 signaling on pDC *Disrupts IFNs, TNFa, IL-6 production *Inhibits prostaglandin production *Changes antigen presentation (For CLE in people)
56
Diseases in vet med that hydroxychloroquine has been used in
ECLE GDLE
57
Drugs that ACCELERATE glucocorticoid metabolism by the liver
*Rifampin *Phenobarbital *Trimethoprim *Azathioprine *Clindamycin INDUCE cytochrome p450 enzymes, so faster metabolic clearance
58
How do glucocorticoids cause neutrophilia
Decrease ICAM, ECAM expression on endothelial cells --> less neutrophil migration to tissues. Less margination More released from bone marrow Less neutrophil apoptosis
59
Impact of glucocorticoids on lipcortin 1
Increased Results in decreased PLA2 on cell membrane, so less arachidonic acid Decreased PAF
60
Order of most to least impact on leukocytes by GC
Decrease in CD4 T cells >> CD8 T cells >>>> least impact on B cells
61
GC impact on IL-1, TNFa, histamine
IL-1, TNFa by monocytes Decreased histamine synthesis by mast cells
62
GC impact on antibody synthesis
ONLY decreases Ig synthesis at HIGH DOSES, long term
63
How do glucocorticoids cause PUPD in dogs
Interference with ADH --> polyuria
64
How do glucocorticoids cause PUPD in cats
Glucosuria and osmotic diuresis
65
Which steroid is the most diabetogenic in cats
Dexamethasone
66
How do aminoglycosides cause nephrotoxicity
Accumulate in proximal renal tubules Apoptosis of renal tubular epithelium and glomerular damage
67
Which antibiotic should be avoided in patients with myesthenia gravis? Why?
Aminoglycosides Can cause neuromuscular blockade
68
Mechanism of why fatty acids can decrease pruritus
Fatty acids compete with COX/LOX enzymes, so decreased arachidonic acid metabolism Also induce less inflammatory byproducts during fatty acid metabolism
69
Immunomodulatory and rheologic effects of pentoxifylline (6)
1) Fluid cell membrane 2) T cells flow better through vessels 3) Decreased response to IL-1, IL-4, IL-12, TNFa 4) Decreased platelet aggregation 5) Inhibit B and T cell activation 6) Decreased NK cell activity
70
Which enzymes does melatonin inhibit
*21-hydroxylase (decreased cortisol levels) *aromatase (decreased estradiol levels)
71
Which enyzme does phytoestrogens inhibit
3-B hydroxysteroid dehydrogenase (sama as trilostane)
72
Which bacteria is inherently resistant to TMS
Enterococcus
73
Which bacteria are resistant to aminoglycosides
Anaerobes Aminoglycosides require oxygen to be transported to cytoplasm (Aminoglycosides are best for gram negative bacteria, with more LPS)
74
Which breeds are more likely to have hypersensitivity reactions to TMS
Doberman pinschers >> Samoyeds, mini schnauzers
75
How does erythromycin cause GI upset
Stimulates motilin hormone --> smooth muscle contractions
76
Why should you be cautious when combining macrolides with other medications
Affect cytochrome p450. Can increase concentration of other drugs
77
What is an adverse effect of linezolid
Inhibits MAO --> interferes with SSRIs. Bone marrow suppression
78
Which antibiotics affect cell wall synthesis
*Beta lactams (PBP, peptidoglycan linking) *Glycoprotein (vancomycin, Ala-ala crosslinking)
79
Which antibiotics affect bacterial protein synthesis
*Lincosamides (50s) *Macrolides (50s) *Chpc (50s) *Linezolid (50s) *Aminoglycosides (30s) *Tetracyclines (30s)
80
Which antibiotics affect nucleic acid synthesis
*Fluoroquinolones (DNA gyrase, topoisomerase IV) *TMS (PABA analog, decreased dihydrophenoic acid, decreased folic acid) *Rifampin: (b-subunit of RNA synthase) *Metronidazole (electron acceptor ->nitroso -> ROS -> DNA damage)
81
Which tetracycline is ok to give with food, but should be avoided in CKD
Doxycycline
82
Why is doxycycline immunomodulatory
*Decreased nitric oxide synthase activity *Decreased TNFa
83
TetM offers resistance to ____
ALL tetracyclines (including mino)
84
Amitraz MOA
1) Monoamine oxidase inhibitor (avoid SSRIs, TCAs) 2) Alpha-2 adrenergic agonist (like dexdomitor. Avoid sedatives. Tx for toxicity = atipamezole, yohimbine) 3) Inhibits prostaglandin synthesis
85
High dose, off-label Apoquel can affect which cytokines (4)
IL-2 IL-15 IL-18 IFNg
86
Which animals have LOW levels of TPMT, resulting in more bone marrow suppression with azathioprine use
Cats Giant Schnauzers
87
Which species have HIGH levels of TPMT, resulting in LESS azathioprine toxicity (but also less efficacious)
Malamutes
88
Dapson affects which cell type
Dapson decreases neutrophil production
89
Which cytokines does cyclosporine inhibit (4)
IL-2 IL-4 IFNg TNFa
90
Which cytokines does Imiquimod stimulate
IFNa TNFa IL-12 Via TLR7
91
Which immunomodulatory medication kills cats
5-FU Pyrimadine analog
92
How is mycophenolate excreted
Kidney (+ bile)

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