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(D) Pharmacology > T3- Immune System Drugs > Flashcards

T3- Immune System Drugs Flashcards

1
Q

What is STEPS?

A

Safety
Tolerability
Efficacy
Price
Simplicity

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2
Q

What are the glucocorticoids?

A

Cortisone
Hydrocortisone
Prednisone
Prednisolone
Triamcinolone
Dexamethasone
Betamethasone

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3
Q

What are the 4 categories of immunomodulators?

A

Antimetabolites
Calcineurin inhibitors
mTOR kinase inhibitors
Other

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4
Q

What are the antimetabolites?

A

Methotrexate
Leflunomide
Azathioprine

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5
Q

What are the calcineurin inhibitors?

A

Cyclosporine
Tacrolimus

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6
Q

What are the mTOR kinase inhibitors?

A

Everolimus
Sirolimus

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7
Q

What are the other meds for immunomodulators?

A

Mycophenolate
Sulfasalazine
Hydroxychloroquine
Glatiramer
Fingolimod

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8
Q

What are the biologics?

A

Cytokine inhibitors
Other

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9
Q

What are the other meds for immunomodulators?

A

Mycophenolate
Sulfasalazine
Hydroxychloroquine
Glatiramer
Fingolimod

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10
Q

What are the Cytokine inhibitors?

A

Etanercept (Enbrel)
Adalimumab

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11
Q

What are the other biologics?

A

Rituximab
Belatacept
Abatacept

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12
Q

Which glucocorticoid is known for being small and hydrophobic?

A

Hydrocortisone

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13
Q

What drug categories prevent cell division?

A

Antimetabolites
Calcineurin inhibitors
mTOR kinase inhibitors

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14
Q

What are DMARDs?

A

Disease-modifying anti-rheumatic drugs.

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15
Q

What does the ending -mab mean?

A

monoclonal antibodies

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16
Q

What does the ending -cept mean?

A

It means it is a solublilized receptor, aka it floats around.

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17
Q

What are the 3 S’s?

A

Sugar (glucocorticoids)
Salt (mineralcorticoids)
Sex (androgens)

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18
Q

What is the primary hormone for glucocorticoids?

A

Cortisol

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19
Q

What medications are glucocorticoids?

A

Hydrocortisone
Cortisone
Prednisolone

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20
Q

What is the primary hormone for mineralcorticoids?

A

Aldosterone

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21
Q

What medications are mineralcorticoids?

A

Fludrocortisone

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22
Q

What is the primary hormone for androgens?

A

Testosterone

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23
Q

What medication is an androgen?

A

DHEA

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24
Q

What are the NS effects of a glucocorticoid?

A

In excess, we see:
Insomnia/euphoria, followed by depression (Steroid psychosis)

In deficiency, we see:
Depression

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25
Q

What are the widespread effects of glucocorticoids?

A

Carbohydrate, protein, and lipid metabolism

Electrolyte and water balance (increased sodium and fluid retention, decreased GFR)

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26
Q

What are the anti-inflammatory/immune effects of glucocorticoids?

A

Inhibits arachidonic acid, the precursor to prostaglandins, leukotrienes, and PAF.

Suppresses inflammatory cytokines, chemokines, and other mediators.
Inhibits macrophages and other APCs.

Reduces antibody formation in large doses, like >20mg of prednisone/day

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27
Q

Which glucocorticoid is often prescribed as a cream due to its equal antiinflammatory and relative mineralcorticoid activity?

A

Hydrocortisone

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28
Q

What are the contraindications for prescribing a glucocorticoid?

A

Systemic fungal infection

Live vaccines if you’re on high dose prednisone for >2 weeks.

Note:
Rashes can go away, but the fungal infection will eat the hydrocortisone to return even bigger. Hydrocortisone cream is capped at 1%.

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29
Q

What are glucocorticoids indicated for?

A

Many things… but big ones are respiratory diseases, rheumatic disorders, allergic states, and dermatologic conditions.

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30
Q

What does short-term glucocorticoid use cause?

A

Mood changes/steroid psychosis
Hyperglycemia
Hypernatremia, hypokalemia (think of the sodium/fluid retention)
Fluid overload
Acute pancreatitis
Peptic ulcers (similar to NSAIDs)
Increased appetite/weight gain

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31
Q

What does long-term glucocorticoid use cause?

A

Immunosuppression
Myopathy/muscle wasting
Impaired wound healing
Cataracts
Growth suppression in children

Etc…

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32
Q

What can prolonged use of hydrocortisone cream cause?

A

Thin skin

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33
Q

When do I usually administer a glucocorticoid?

A

Ideally, the largest dose is in the AM.

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34
Q

What is the general rule of thumb for stopping a glucorticoid?

A

Taper it down 10-20% daily.

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35
Q

What is the MOA of methotrexate?

A

As a folic acid analog, it binds and inhibits DHFR (dihydrofolate reductase).

This leads to inhibition of THF (tetrahydrofolate) synthesis

Inhibits synthesis of purine nucleotides and amino acids

Interferes with formation of DNA, RNA, cellular proteins.

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36
Q

What do all the antimetabolites essentially do?

A

Stop the formation of DNA, which in turn inhibits RNA and protein production.

Leflunomide is a pyrimidine analog, so it takes the place of the pyrimidines.

Azathioprine is a purine analog. (prine and purine)

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37
Q

What are the contraindications of methotrexate? (MTX)

A

Pregnancy
Alcoholism/chronic liver disease
Immunodeficiency syndromes
Blood dyscrasias
Live vaccines

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38
Q

What is the main black box warning for MTX?

A

Pregnancy!!!!!!!

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39
Q

What are the minor side effects of MTX generally due to?

A

Folate depletion

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40
Q

What should men and women of reproductive age use if they are on MTX?

A

Birth control!!

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41
Q

What are the indications of MTX?

A

RA, psoriasis, some cancers

42
Q

What are the off-label uses of MTX?

A

Crohn’s disease, MS, SLE, multiple conditions

43
Q

What do I need to supplement MTX use with?

A

Folic acid on the days you don’t use it.

44
Q

What is Leflunomide used for?

A

RA, via a PO admin only.

45
Q

What are the main black box warnings for Leflunomide?

A

Pregnancy, severe hepatic impairment, concomitant teriflunomide use.

46
Q

What is the half-life of Leflunomide?

A

18 days, because like the flu, Leflu seems to last forever.

47
Q

What is Azathioprine used for?

A

RA, MS, psoriasis, Crohn’s disease, and transplant maintenance.

48
Q

What are the contraindications for azathioprine?

A

Pregnancy
Alkylating agents

49
Q

What are the black box warnings for azathioprine?

A

Increased risk of malignancies

50
Q

In what situation do I need to adjust azathioprine dosing?

A

For renal function and low thiopurine methytransferase (TPMT)

51
Q

What is the primary function of calcineurin inhibitors?

A

Inhibition of T-lymphocyte activation

52
Q

What kind of transplant should I NEVER prescribe tacrolimus?

A

Liver

53
Q

When do I use calcineurin inhibitors?

A

Helping prevent graft/transplant rejection.

54
Q

What are the main side effects of Cyclosporine?

A

Gingival hyperplasia
Hirsutism

55
Q

What are the other indications for calcineurin inhibitors?

A

RA and psoriasis

Main is preventing graft/transplant rejection

56
Q

What is the MOA of mTOR kinase inhibitors?

A

Inhibition of T-lymphocyte activation and proliferation; synergy with calcineurin inhibitors.

57
Q

What transplants does everolimus do poorly in?

A

Renal grafts and heart transplants

(HR takes forever)

58
Q

What transplants does sirolimus do poorly in?

A

Liver and lung transplants.

serious losers lose

59
Q

What are the indications for mTOR kinase inhibitors?

A

Cancer
Organ transplantation
Complicatons of TB

60
Q

What is the route of administration for mTOR kinase inhibitors?

A

PO

61
Q

What drug can mycophenolate not be substituted with?

A

Mycophenolic acid

62
Q

What is the MOA of mycophenolate?

A

Inhibition of T and B cell proliferation via inhibition of the major enzyme used in nucleotide synthesis.

63
Q

What are the indications for mycophenolate?

A

Transplant maintenance, lupus nephritis, autoimmune hepatitis, myasthenia gravis.

64
Q

What does mycophenolate decrease the efficacy of?

A

Oral contraceptives

65
Q

What is the MOA of sulfasalazine?

A

5-aminosalicyclic acid derivative; immune modulator, specific mech unknown.

66
Q

What allergy contraindicates sulfasalazine use?

A

Sulfa or salicylate allergy.

67
Q

What are the indications for sulfasalazine?

A

RA and ulcerative colitis.

68
Q

What is suggested to supplement sulfasalazine use?

A

Folate supplements.

69
Q

What is the MOA of hydroxychloroquine?

A

Antimalarial drug with immune modulating functions (Inhibition of neutrophil and eosinophil motility and impairing complement antibody reactions)

70
Q

What are the contraindications of hydroxychloroquine?

A

None.

71
Q

What are the indications for hydroxychloroquine?

A

RA, SLE, malaria

Note:
Pregnant women with lupus can use this drug.

72
Q

What kind of dosing is hydroxychloroquine?

A

Weight-based

73
Q

What is the MOA of fingolimod?

A

Binds sphingosine receptors and blocks lymphocytes from leaving lymph nodes.

74
Q

What is fingolimod used for?

A

MS

75
Q

What do I need to watch for the first time I give fingolimod?

A

Bradycardia

76
Q

What is the MOA of Glatiramer acetate?

A

Not well-defined.
It is a mixture of polymers that mimic basic myelin protein.
It is thought to activate T-cell supressor cells.

77
Q

What is Glatiramer acetate indicated for?

A

MS, preferred agent in pregnancy.

78
Q

What are the 3 important cytokines?

A

TNF (tumor necrosis factor)
IL (interleukin)
IFN (interferon)

79
Q

Which cytokine do cytokine inhibitors inhibit?

A

TNF

80
Q

What are the two ways cytokines are inhibited?

A

MABs
Soluble receptors

81
Q

How does a MAB inhibit a cytokine?

A

It is a free-floating antibody that the inflammatory cytokine will bind to. It has no effect when bound.

82
Q

How does a soluble receptor inhibit a cytokine?

A

It is a free-floating receptor (not membrane bound) that the inflammatory cytokine will bind to. It has no effect when bound.

83
Q

What makes humira/adalimumab such an important MAB?

A

It is humanized, so the MABs can stay in the body for far longer and exert their effects. Our body does not recognize humira as foreign.

84
Q

Why do soluble receptors add a portion to the bottom of the receptor?

A

Extends the half-life.

85
Q

What must I screen for prior to starting an anti-TNF drug?

A

TB!!!!!

86
Q

What can I not give anti-TNFs with?

A

Biologic DMARDs or live vaccines.

87
Q

What are the indications for the anti-TNFs?

A

Many… (RA, Crohn’s, psoriasis)

88
Q

How do Belatacept and Abatacept differ from Entanercept?

A

These two are anti-CD80/86.
Essentially, APCs have a CD80/CD86 receptor that needs to bind to a T-cell to activate it. These drugs prevent that, putting T-cells into anergy.

(A+B = C)

89
Q

Why are the anti-CD80/86 drugs safe for T-cells?

A

Because they only place them in anergy, it is like they are sleeping. They can be reactivated once the drug is gone, unless they go to sleep for too long.

90
Q

What are the contraindications for anti-CD80/86 drugs?

A

Biologic DMARDs
Live vaccines
EBV positive transplant pts
TB screening needed

91
Q

What are the indications for anti-CD80/86 drugs?

A

Transplant (belatacept)
RA and psoriasis (Abatacept)

92
Q

What is rituximab?

A

An anti-CD20 monoclonal antibody drug.

93
Q

What is rituximab indicated for?

A

RA, chronic lymphocytic leukemia, and non-hodgkins lymphomas.

94
Q

How is rituximab given?

A

Parenterally.

95
Q

What should I always double check before giving an immune system drug?

A

Pregnancy
Live vaccine candidacy
Drug and disease interactions
Dose adjustments

96
Q

What should I do with glucocorticoids to prevent adrenal insufficiency?

A

Taper down high/long doses.

97
Q

What kind of cancers is MTX indicated for?

A

Lung, liver, kidney, bone marrow (LLKB) (look lets kickbox in the matrix)

98
Q

What two drugs need folic acid supplements?

A

MTX and sulfasalazine

99
Q

How should I administer all biologics?

A

Parenterally only.

100
Q

What are some safety concerns with biologics?

A

Screen for TB prior to use.
Avoid live vaccines concomitantly.
Refrigerate.
DO NOT COMBINE

(D) Pharmacology (18 decks)

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