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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
Q

Which JAK is important for Th1 immune response

A

TYK2

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26
Q

Effect of inhibition of JAK1

A

*Impaired T cell proliferation, differentiation
*Impaired signaling, esp Th2 cytokines

(infections, hypercholesterolemia, possible NK cell impairment)

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27
Q

Effect of inhibition of JAK2

A

*Impaired erythropoiesis and myelopoiesis

(infections, anemia, neutropenia)

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28
Q

Effect of inhibition of JAK3

A

Impaired T cell proliferation

(infections)

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29
Q

Effect of inhibition of TYK2

A

Impaired Th1 and Th17 response

(infections)

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30
Q

What is the active metabolite of azathioprine (pro-drug)

A

6-mercaptopurine

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31
Q

MOA of azathioprine

A

6-MP blocks purine metabolism, interferes with DNA synthesis

“antimetabolite”

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32
Q

Why are lymphocytes susceptible to azathioprine

A

They have de novo purine synthesis

Reduces B and T cell proliferation

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33
Q

Elevation in which enzyme makes some animals more susceptible to hepatotoxicity 2’ azathioprine

A

Thiopurine methyltransferase (TPMT)

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34
Q

Do cats and horses have a HIGH or LOW activity of their TPMT (azathioprine enzyme)

A

LOW activity

Makes cats at higher risk for myelosuppression

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35
Q

Why do horses have a LOWER risk of myelosuppression with azathioprine at standard doses

A

Low bioavailability of azathioprine in horses

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36
Q

Which metabolite of azathioprine is immunosuppressive

A

6 thioguanine nucleotides

“false purine” stops cell cycle –> apoptosis

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37
Q

Which medication should NOT be combined with azathioprine

A

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
Q

Which medication should NOT be combined with azathioprine, as it inhibits TPMT

A

Sulfasalazine

Myelosuppression

39
Q

Category of medication of chlorambucil

A

Nitrogen mustard alkylating agent

40
Q

MOA chlorambucil

A

Cross-links DNA during all phases of the cell cycle. INTERstrand is most cytotoxic

Cell cycle arrest –> Apoptosis

Effects B and T cells

41
Q

AE of chlorambucil

A

Myelosuppression

GI upset
Reversible myoclonic neurotoxicity
Fanconi syndrome (cats)

42
Q

Main metabolite of mycophenolate mofetil

A

Mycophenolic acid

43
Q

Function of Mycophenolic acid

A

Inhibits inosine-5’-monophosphate dehydrogenase

Depletes guanosine nucleotides in activated B and T cells –> inhibits proliferation and antibody formation

44
Q

Higher doses of Mycophenolate mofetil increase the risk of _____ side effect

A

GI issues (diarrhea, hematochezia, vomiting)

45
Q

T or F: it is crucial to monitor for myelosuppression with mycophenolate mofetil

A

False. GI side effects primarily

46
Q

Why are IVIg beneficial for autoimmune diseases

A

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
Q

What are the risks of IVIg

A

Hypercoagulation
Renal failure
Hypotension
Hypersensitivity
Anaphylaxis (xenoproteins!)

48
Q

Which cytokines does doxycycline inhibit

A

IL-1
IL-6
IL-8
TNFa

49
Q

4 anti-inflammatory mechanisms of doxycycline

A

1) Decrease cytokines (IL-1, IL-6, IL-8, TNFa)
2) Inhibit MMPs
3) Reduce leukocyte chemotaxis
4) Reduces NO synthase function

50
Q

MOA of niacinamide

A

Endogenous inhibitor of PARP-1

1) Inhibits proinflammatory cytokines
2) Reduces ICAM-1 expression (decreased neutrophil chemotaxis)
3) Reduces B cell differentiation

51
Q

Mechanisms of colchicine

A

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
Q

Which immunomodulatory medication works primarily on neutrophils

A

Colchicine

(niacinamide works on neuts via ICAM, but also B cells)

53
Q

Most common AE from colchicine

A

GI upset (nausea, vomiting, diarrhea, abdominal pain)

54
Q

Which medication should be avoided with colchicine

A

Cyclosporine

Both are p-glycoprotein substrates!

55
Q

Immunomodulatory effects of hydroxychloroquine

A

*Inhibits TLR7, TLR9 signaling on pDC
*Disrupts IFNs, TNFa, IL-6 production
*Inhibits prostaglandin production
*Changes antigen presentation

(For CLE in people)

56
Q

Diseases in vet med that hydroxychloroquine has been used in

A

ECLE
GDLE

57
Q

Drugs that ACCELERATE glucocorticoid metabolism by the liver

A

*Rifampin
*Phenobarbital
*Trimethoprim
*Azathioprine
*Clindamycin

INDUCE cytochrome p450 enzymes, so faster metabolic clearance

58
Q

How do glucocorticoids cause neutrophilia

A

Decrease ICAM, ECAM expression on endothelial cells –> less neutrophil migration to tissues.

Less margination

More released from bone marrow

Less neutrophil apoptosis

59
Q

Impact of glucocorticoids on lipcortin 1

A

Increased

Results in decreased PLA2 on cell membrane, so less arachidonic acid

Decreased PAF

60
Q

Order of most to least impact on leukocytes by GC

A

Decrease in CD4 T cells&raquo_space; CD8 T cells&raquo_space;» least impact on B cells

61
Q

GC impact on IL-1, TNFa, histamine

A

IL-1, TNFa by monocytes

Decreased histamine synthesis by mast cells

62
Q

GC impact on antibody synthesis

A

ONLY decreases Ig synthesis at HIGH DOSES, long term

63
Q

How do glucocorticoids cause PUPD in dogs

A

Interference with ADH –> polyuria

64
Q

How do glucocorticoids cause PUPD in cats

A

Glucosuria and osmotic diuresis

65
Q

Which steroid is the most diabetogenic in cats

A

Dexamethasone

66
Q

How do aminoglycosides cause nephrotoxicity

A

Accumulate in proximal renal tubules

Apoptosis of renal tubular epithelium and glomerular damage

67
Q

Which antibiotic should be avoided in patients with myesthenia gravis? Why?

A

Aminoglycosides

Can cause neuromuscular blockade

68
Q

Mechanism of why fatty acids can decrease pruritus

A

Fatty acids compete with COX/LOX enzymes, so decreased arachidonic acid metabolism

Also induce less inflammatory byproducts during fatty acid metabolism

69
Q

Immunomodulatory and rheologic effects of pentoxifylline (6)

A

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
Q

Which enzymes does melatonin inhibit

A

*21-hydroxylase (decreased cortisol levels)
*aromatase (decreased estradiol levels)

71
Q

Which enyzme does phytoestrogens inhibit

A

3-B hydroxysteroid dehydrogenase

(sama as trilostane)

72
Q

Which bacteria is inherently resistant to TMS

A

Enterococcus

73
Q

Which bacteria are resistant to aminoglycosides

A

Anaerobes

Aminoglycosides require oxygen to be transported to cytoplasm

(Aminoglycosides are best for gram negative bacteria, with more LPS)

74
Q

Which breeds are more likely to have hypersensitivity reactions to TMS

A

Doberman pinschers&raquo_space;

Samoyeds, mini schnauzers

75
Q

How does erythromycin cause GI upset

A

Stimulates motilin hormone –> smooth muscle contractions

76
Q

Why should you be cautious when combining macrolides with other medications

A

Affect cytochrome p450. Can increase concentration of other drugs

77
Q

What is an adverse effect of linezolid

A

Inhibits MAO –> interferes with SSRIs.

Bone marrow suppression

78
Q

Which antibiotics affect cell wall synthesis

A

*Beta lactams (PBP, peptidoglycan linking)
*Glycoprotein (vancomycin, Ala-ala crosslinking)

79
Q

Which antibiotics affect bacterial protein synthesis

A

*Lincosamides (50s)
*Macrolides (50s)
*Chpc (50s)
*Linezolid (50s)
*Aminoglycosides (30s)
*Tetracyclines (30s)

80
Q

Which antibiotics affect nucleic acid synthesis

A

*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
Q

Which tetracycline is ok to give with food, but should be avoided in CKD

A

Doxycycline

82
Q

Why is doxycycline immunomodulatory

A

*Decreased nitric oxide synthase activity
*Decreased TNFa

83
Q

TetM offers resistance to ____

A

ALL tetracyclines (including mino)

84
Q

Amitraz MOA

A

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
Q

High dose, off-label Apoquel can affect which cytokines (4)

A

IL-2
IL-15
IL-18
IFNg

86
Q

Which animals have LOW levels of TPMT, resulting in more bone marrow suppression with azathioprine use

A

Cats
Giant Schnauzers

87
Q

Which species have HIGH levels of TPMT, resulting in LESS azathioprine toxicity (but also less efficacious)

A

Malamutes

88
Q

Dapson affects which cell type

A

Dapson decreases neutrophil production

89
Q

Which cytokines does cyclosporine inhibit (4)

A

IL-2

IL-4
IFNg
TNFa

90
Q

Which cytokines does Imiquimod stimulate

A

IFNa
TNFa
IL-12

Via TLR7

91
Q

Which immunomodulatory medication kills cats

A

5-FU

Pyrimadine analog

92
Q

How is mycophenolate excreted

A

Kidney (+ bile)

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