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IHOP > Immunosuppressants and Antirheumatic Pharmacology Dr. Covert EXAM 3 > Flashcards

Immunosuppressants and Antirheumatic Pharmacology Dr. Covert EXAM 3 Flashcards

1
Q

What is the pathophysiology of Multiple Sclerosis?

A

immune cells from the periphery cross the BBB into the CNS damaging myelin sheaths and axons (auto-immune)
-> leading to movement, cognitive, and speech issues

T-lymphocytes
B-lymphocytes
macrophages
antibodies, complements

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2
Q

Which type of MS is the most common and treated with the most autoimmune drugs?

A

Relapsing-remittent

symptoms flare up and go back to baseline

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3
Q

Which class of drugs are the First-Gen injectables for MS treatment? How do they work?

A

Interferon-β: Avonex, Rebif, Betaseron, Extavia, Plegridy
-SQ or IM

-suppress T-cell activity
-decrease IFN-γ secretion
-decrease macrophage activation
-decrease antigen presentation
-decrease BBB permeability

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4
Q

What are the side effects associated with Interferon-β drugs?

A

-injection site reaction
-flu-like symptoms
-weakness
-depression
-neutralizing antibodies (5-30%, may decrease the efficacy of the drug)

-increased LFT
-thyroid dysfunction
-lymphocytopenia

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5
Q

Which labs are important to monitor when using Interferon-β?

A

CBC
LFT

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6
Q

What is the MOA of Glatiramer acetate (Copaxone)?

A

-Induction of T-lymphocyte suppressor cells specific for myelin
-decreases the antigen-presenting function of T-cells

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7
Q

What are the side effects associated with Glatiramer acetate? What should be monitored?

A

-chest pain
-rash
-hypersensitivity reaction
-infection (since immunosuppressor)

monitor:
-latent infection screening in high-risk patients

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8
Q

What is the difference between First-Gen and Second Gens?

A

First-Gens are
-less potent immunosuppressants
-less infection as a side effect
-more frequent injections
-well-known

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9
Q

What is the MOA of Ocrelizumab (Ocrevus)?

2nd gen

A

-inhibition of CD-20-expressing B-cells
-IV

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10
Q

What are the side effects of Ocrelizumab (Ocrevus)?
!!!

A

-infections
-neutropenia
-infusion reactions (30-40%)
-depression

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11
Q

What should be monitored when using Ocrelizumab (Ocrevus)?

!!!

A

-HBV screening !!!
-latent infection screening (tuberculosis)

-immunoglobin levels
-infusion reaction 1h after infusion

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12
Q

Which anticancer drug binds to CD-20?
REMINDER

A

Rituximab

-infusion reaction
-Hep B reactivation

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13
Q

What is the MOA for Natalizumab (Tysabri)?
(also used for Crohn’s disease)

A

-Integrin receptor antagonist
-inhibits adhesion of and migration of leukocytes

-IV

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14
Q

What are the side effects of Natalizumab?
!!

A

-Infections
-depression
-muscle pain
-infusion-related reactions
-PML !!! progressive multifocal leukoencephalopathy, irreversible brain damage

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15
Q

What should be monitored when using Natalizumab?

!!!

A

-JC virus (negative required, bc of the risk for PML) !!!
-LFT
-infusion reactions, wait for 1h after infusion

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16
Q

What is the MOA for Alemtuzumab (Lemtrada)?

A

-Binds to CD52 on B and T cells causing cell
lysis
-IV

-strong immunosuppressant
-can also be used for solid transplant patients

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17
Q

What are the side effects of Alemtuzumab?

A

-Bone marrow suppression
-infections
-infusion reactions
-malignancy
-stroke

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18
Q

What should be monitored when using Alemtuzumab?

A

-REMS program
-CBC
-platelet count
-CD4 count
-CMV antigen (cytomegalovirus), may need CMV prophylaxis if positive
-latent infections

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19
Q

What is the MOA of Sphingosine 1 phosphate receptor modulators?

Fingolimod (Gilenya)
Ponesimod (Ponvory)
Ozanimod (Zeposia)

A

they stop lymphocytes from moving from the lymph nodes to the bloodstream and into the CNS

-PO

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20
Q

What are the side effects of Sphingosine 1 phosphate receptor modulators?

A

-Increased LFTs
-infection
-cardiovascular side effects (hypertension, edema, hypotension !!! -> avoid if they have heart failure

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21
Q

What should be monitored when using Sphingosine 1 phosphate receptor modulators?

A

-Complete blood count
-liver function tests
-EKG !!!

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22
Q

What is the MOA of Teriflunomide (Aubagio)?

A

-Inhibition of pyrimidine synthesis
-antiproliferative
-anti-inflammatory effects

-PO

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23
Q

What are the side effects of Teriflunomide?

A

-Teratogenic !! (others are teratogenic as well, this one is labeled though)
-hepatotoxicity -> avoid with cirrhosis
-alopecia

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24
Q

What should be monitored when using Teriflunomide?

A

-CBC
-LFT

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25
What is the MOA of Dimethyl Fumarate (Tecfidera)?
-Active metabolite activates a pathway that responds to cellular oxidative stress -exact MOA unknown
26
What are the side effects of Dimethyl Fumarate?
-flushing -abdominal pain
27
What should be monitored when using Dimethyl Fumarate?
-CBC -LFT
28
What is the pathophysiology of Rheumatic Arthritis?
1. Trigger 2. Immune system activation (attacks the fluid-filled part of the joints, Synovial fluid) 3. Inflammation, swollen, pannus formation
29
Which drugs are commonly used first for rheumatoid arthritis?
-Hydroxychloroquine (Plaquenil) -Methotrexate
30
What is the MOA of Hydroxychloroquine?
-inhibits movement of neutrophils and eosinophils
31
What are the side effects of Hydroxychloroquine?
Retinopathy
32
What should be monitored when using Hydroxychloroquine? !!!
-CBC -Ophthalmic exams !!!
33
What is the MOA of Methotrexate?
-Folic acid antimetabolite that inhibits DNA synthesis -Exact MOA for RA is unknown -can be reversed with Leucovorin
34
What are the side effects of Methotrexate?
-Teratogenic -cirrhosis -diarrhea -anemia -leukopenia -neutropenia
35
What should be monitored when using Methotrexate?
CBC, LFT, SCr
36
What is the MOA of Leflunomide? dont need to know?
-Inhibition of pyrimidine synthesis -antiproliferative -anti-inflammatory -less preferred
37
What are the side effects of Leflunomide? dont need to know?
-teratogenic -hepatoxicity -diarrhea
38
What should be monitored when using Leflunomide? dont need to know?
-CBC -LFT -SCr
39
What is the MOA of Sulfasalazine?
-5-ASA derivatives -modulates leukotrienes and scavenges free radicals
40
What are the side effects of Sulfasalazine?
-skin rash -GI upset -hepatotoxicity (rare)
41
What should be monitored when using Sulfasalazine?
-CBC -LFT
42
Which agents are preferred for severe and progressing disease states?
Biologic agents
43
What is the MOA of TNF-α Inhibitors? Infliximab, Etanercept, Adalimumab, Certolizumab, Golimumab
-Binds to TNF-alpha -reduced immune cell migration -SQ or IV
44
What are the side effects of TNF-α Inhibitors?
-Infections -malignancies -increased LFTs -leukopenia -thrombocytopenia
45
What should be monitored when using TNF-α Inhibitors?
-CBC -LFT -latent infection screening -> Hep B and TB reactivation -> screen for TB and hep B
46
What is the MOA of Interleukin-6 (IL-6) Antagonists? Tocilizumab, Sarilumab
-IL-6 inhibition -reduction in cytokine and acute phase reactants
47
What are the side effects of Interleukin-6 (IL-6) Antagonists?
-Serious infections (TB, fungal) -> make sure patients are not on an antibiotic or antifungal, risk for worsening of an active infection is high !!! -neutropenia
48
What should be monitored when using IL-6 Antagonists?
-Neutrophils -platelets -latent TB
49
What is the MOA of IL-1 Antagonists? Anakinra
IL-1 antagonism just know this about the drug
50
What are the side effects of an IL-1 antagonist? Anakinra
Increased LFTs monitor: -CBC -latent TB screening -SCr -LFTs
51
What is the MOA of Abatacept? T-Cell Co-Stimulation Blocker
-Inhibits T-cell activation by binding to CD80 and CD86 on APC -blocking T-cell activation
52
What are the side effects and monitoring points for Abatacept?
Nausea, anemia monitor: -Hypersensitivity reaction -latent infection screening
53
What is the MOA of Rituximab?
-Binding CD20 on B-cell -inhibition of cell cycle
54
What are the side effects of Rituximab?
-HTN -night sweats -diarrhea -anemia -neutropenia infections -angioedema -antibody development
55
What should be monitored when using Rituximab?
-CBC -platelets -HBV reactivation !!! -infusion reaction !!!
56
Which drug class is the only oral biologic? How do they work?
Janus Kinase (JAK) inhibitors -Inhibition of Janus kinase enzymes -resulting in reduction in immune cell function Tofacitinib, Baricitinib, Upadacitinib
57
What are the side effects of JAK inhibitors?
-Infections -malignancies -major cardiovascular events !!! -thrombosis !!!
58
What should be monitored when using JAK inhibitors?
-CBC -lipid panel -heart rate, blood pressure
59
What are the signals that cause an immune response, also seen when receiving an organ transplant?
Signal 1: Antigen to TCR/CD3 Signal 2: CD80/60 (APC) to CD28 of the T-cell -> Signals 1 and 2 activate the Calcineurin pathway (drug target) Signal 3: IL-2 activation of the mTOR pathway
60
What is the purpose of Induction and Maintenance immunosuppressive therapy in organ transplantation?
Induction: -deplete the immune system when receiving the transplant Maintenance: -suppress the immune system enough to prevent organ rejection but not so much that the risk for infections becomes too high
61
Which drug class are the most potent inducting agents? How do they work?
-Thymoglobulin, Alemtuzumab (Campath) Cell-depleting -Thymoglobulin: Depletion of CD4 lymphocytes -Alemtuzumab: CD52 binding causing cell lysis -they are very potent immunosuppressants, so use it for patients with high-risk for organ rejection, -patients who failed transplants before -multiple pregnancies (exposure to different antigens -> produce different antibodies)
62
What are the side effects of Thymoglobulin and Alemtuzumab?
-infections -malignancies monitor: -CBC (thrombocytopenia, neutropenia)
63
Which inducting agent is the only Non-Cell Depleting agent?
Basalixumab (Simulect) -Blocks the alpha-chain of IL-2 -resulting in reduced activity of T-cells -no side effects but less potent appropriate for patients who are not of risk for rejection: -not on dialysis -low immunologic risk -related donor
64
What are the maintaining agents after organ transplantation?
-Calcineurin inhibitors -> BACKBONE Tacrolimus, Cyclosporine -Antiproliferatives (myco causes diarrhea, Aza has an interaction with allpopurinol) Mycophenolate, Azathioprine -mTOR inhibitors -> if they fail calcineurin (side effects) Sirolimus, Everolimus -T-Cell Co-Stimulation Blocker (IV drug) Belatacept
65
What is the MOA of Calcineurin inhibitors?
-Binds to FKBP-12 to inhibit one step in T-cell activation Tacrolimus, Cyclosporine
66
What are the side effects of Calcineurin inhibitors?
-Infections -renal impairment (afferent arterial vasoconstriction, like NSAIDs) -electrolyte abnormalities -diabetes, HTN, hyperlipidemia
67
What should be monitored when using Calcineurin inhibitors?
-SCr -BG -BP -K, Ma
68
What is the MOA of the Antiproliferatives, Mycophenolate and Azathioprine?
-Mycophenolate: Inhibition of inosine monophosphate dehydrogenase, which blocks DNA synthesis, reducing T-cell response to antigens -Azathioprine: imidazolyl derivative that halts DNA replication
69
What are the side effects of the Antiproliferatives, Mycophenolate and Azathioprine?
Mycophenolate: Diarrhea, teratogenic Azathioprine: Bone marrow suppression, malignancy (skin cancer) -> monitor CBC -> avoid with allopurinol? like 6-MP
70
What is the MOA of mTOR inhibitors? Sirolimus, Everolimus
Binds to FKBP-12 to inhibit one step in T-cell activation Sirolimus, Everolimus -> don't confuse with Tacrolimus
71
What are the side effects of mTOR inhibitors? Sirolimus, Everolimus
-Impaired wound healing -hypertriglyceridemia monitor: TG wound healing
72
What is the MOA of Belatacept? !!!
Binding to CD80 and CD86 on APC to block interaction between APCs and T-cells -IV only don't confuse it with Basalixumab (which is an induction agent)
73
What is the side effect of Belatacept?
Post-transplant lymphoproliferative disorder (PTLD)
74
What should be monitored when using Belatacept?
EBV serostatus

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