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Therapeutics > Exam 4 lecture 1 > Flashcards

Exam 4 lecture 1 Flashcards

1
Q

What is IBD? What are the two types?

A

IBD: Is an inflammatory condition with chronic or recurring immune response and inflammation of the GI tract.

Two types
1) Ulcerative colitis (UC): Mucosal inflammation (superficial) confined to rectum and colon. Smoking is protective.

2) Crohn’s disease (CD): Transmural (deeper and thicker) inflammation of GI tract that can affect any part from mouth to anus. You see fistulas. Smoking is a risk factor.

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2
Q

What signs and symptoms are consistent with IBD

A

Frequent bowel movements.
Include blood and mucous.
FInd out if they smoke? Gluten allergy?
Nsaids cause IBD aswell.

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3
Q

What is an imprtant goal of therapy for IBD

A

Inducing and maintaining remission , Mucosal healing associated with better long term outcomes.

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4
Q

Nutrition support for IBD

A

No specific diet shown to be beneficial
Nutritional support to address nutritional deficiencies, impaire absorption (supplement vitamin/mineral deficiencies like calcium/vit D, folate), EN/PN

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5
Q

Pharmacologic therapy for IBD

A

None of them are curative. They get patients into remission.

  1. ASAs (aminosalicylates)
    - SUlfasazine, Mesalamine (5-ASA)
  2. Corticosteroids
  3. Immunomodulators (immunosuppressives)
    - Azathropine, mercaptopurine, cyclosporine, methotrexate
  4. Biologics
    - anti TNF agents (infliximab, adalimumab, certolizumab, golimumab)
    - Other- Natalizumab, vedolizumab, ustekinumab, risankizumab
  5. Tofactinib, upadactinib, ozanimod, estrasimod
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6
Q

Name ASA agents

A

Sulfasazine, Meslamine

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7
Q

What is sulfasazine made of? WHat happens to it in the body? What is associated with ADRs? WHat is the inactive component? active component?

A

Made up of sulfapyridine + 5- ASA (mesalamine)

cleaved by colonic bacteria to release sulfapyridine (absorbed and renally excreted) and 5- ASA (mainly remains in lumen, excreted in stool)

Sulfapyridine is inactive, but is associated with ADRs

5-ASA is active component

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8
Q

Can we administer mesalamine alone ( to prevent ADRs?) Explain

A

Yes we can. It is rapidly and completely absorbed in small intestine, but not colon. It is important to deliver to affected area.

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8
Q

How can we get Mesalamine to colon (past small instestine)

A

Suppository (for patients with Proctitis
Enema (for patients with left sided disease)

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9
Q

Is topical or oral mesalamine more effective? Can we use both together?

A

Topical is more effective

We can give both

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10
Q

ASA agents ADRs? how to avoid?

A

Sulfasalazine-> Sulfapyridine is associated with ADRs

  • > 10% nausea, vomiting, headache, anorexia, rash

-Initiate with low dose and titrate up slowly
-<10% anemia, hepatotoxicity, thrombocytopenia

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11
Q

What in sulfasalazine causes ADRs? What to monitor? Drug interactions of sulfasalazines

A

May be associated with hypersensitivity rxns in sulfonamide allergy

MOnitor CBC and LFTs at baseline, every other week for first 3 months, monthly for second three months and perioically there after

Monitor BUN/Scr periodically

Drug i/a with antiplatelets/anticoags/NSAIDs-> increase bleeding risks

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12
Q

If sulfasalazine is not tolerated, what drug is used? Side effects?

A

Mesalamine (much better tolerated)

N/V, headaches
olsalazine has diarrhea (up to 25%)

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13
Q

Drug i/a of mesalamine

A

Antiplatelets/anticoags/NSAIDs may increase bleeding risk

Agents affecting gastric PH (PPIs, H2RAs, antacids) could influence release of drug in PH dependent dosage forms

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14
Q

MOA of coticosteroids? ROA? use?

A

Antiinflammatory (systemic or local)

Can be used parenterally (severe exacerbation, orally or rectally)

systemic corticosteroids may be used for induction of remission, but not for maintenance

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15
Q

tOPICAL FORMULATIONS FOR IBD

A

RECTAL HYDROCORTISONE (Suppositories, foam, enema)

Budesonide (can be inhaled), systemic absorption is lower than other steroids, can be used for 16 weeks

Prednisone/prednisolone

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16
Q

What are the two types of budesonide

A

Entocort- Pill
Uceris- foam

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17
Q

Budesonide drug i/a

A

CYP3A4 inhibitors (ketoconazole, grapefruit juice), may increase systemic exposure

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18
Q

What are IV steroids used in IBD

A

Methylprednisolone\Hydrocortisone

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19
Q

ADRs for corticosteroids

A

Short term- hyperglycemia, gastritis, mood changes, elevated BP

Long term- aseptic necrosis, cataracts, obesity, growth failure, HPA suppression, Osteoporosis

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20
Q

What supplemets should be given for patients on systemic corticosteroids

A

Give calcium and vitamin D while on steroids

May give bisphosphonates for patients with high risk for osteoporosis, patients using for more than 3 months or recurrent users

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21
Q

Monitoring for corticosteroids

A

BP, blood glucose baseline and every 3-6 months
Consider occasional bone mineral density scan (DEXA) in pts > 60 years old, at risk for osteoporosis, patients using for more than 3 months or recurrent users

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22
Q

What are immunosuppresants used in IBD

A

Thiopurines
1) Azathropine (AZA)
2) Mercaptopurine (MP, 6-MP)

AZA is a prodrug rapidly converted to 6-MP

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23
Q

What are the uses AZA and MP? WHo can use them? MOA? Can they be used in other drugs?

A

can be used n long term tx of UC and CD

Reserved for pts who fail tx with ASA or refractory to steroids.

Can maintain remission, but are not used in induction

They can be use din conjunction with ASA, steroids, TNF

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24
Q

ADRs of AZA and 6-MP? Monitoring?

A

Hematologic effects :(life threatening anemia) due to bone marrow suppression

GI: N/V/D, anorexia

Hepatic: Hepatotoxicity

Monitoring
Baseline- TOMT, CBC, LFTs

CBC- weekly for 1st months and every 1-2 weeks after dose change.

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25
Q

Use of cyclosporine in IBD? Can be used long term? WHo is itreserved for?

A

Can be effective in inducing remission in patients with refractory UC (not recommended for CD)

NOt used long term

Generally reserved for pts who are refractory to steroids

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26
Q

ADRs of cyclosporine? Monitoring?

A

nephrotoxicity (dose related)
Neurotoxicity
Metabolic (HTN, HLD, hyperglycemia)
other: GI upset, hirsutism, gingival hyperplasia

Monitoring
Baseline BP, BUN/SCr, LFTs, Cya tr. concentration

BP- q visit
BUN/SCr- q 2 weeks until stable, then periodically
LFTs- q 2 weeks until stable, then periodically

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27
Q

cyclosporine drug i/a? drugs/food that iincreases cyclosporine concentrations? Drugs that decrease cyclosporine concentrations

A

substrate CYP3A and p- glycoprotein

Increase cyclosporone concentration
- azole antifungal, macrolide antibiotics, calcium channel blockers, grapefruit

decrease cyclosporine
phenytoin, rifampin

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28
Q

Methotrexate use?

A

Can be used in tx and maintenance of CD (not UC)
May have steroid sparring effects, assist in inducing remission, allow steroid tapering

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29
Q

Methotrexate ADRs

A

Hematologic (bone marrow suppression) (thats why we add folic acid 1 mg/day)
GI: N/V/D, mucositis
Hepatic: Cirrhosis, hepatitis, fibrosis
Pulmonary: Pneumonitis
derm: rash, urticaria, alopecia
teratogenic drug (contraception)

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30
Q

CI of methotrexate? Monitoring

A

CI
Pregnancy
pleural effusions
chronic liver/EtH abuse
Immunodeficiency
preexisting blood dyscrasias
CrCl<40
leukopenia/thrombocytopenia

Monitoring
Baseline: Chest x ray, CBC, SCr, LFTs, pregnancy,

check CBC, Scr and LFTs q 4-8 weeks

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31
Q

What are some biologic TNF-a antagonist drugs

A

infliximab
adalimumab
golimumab
certolizumab

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32
Q

Which TNF-a antagonists treat CD? UC? both? are they anti TNF-a? human monoclonal or human pegylated (only know UC OR CD FOR EXAM)

A

infliximab (remicade) - Anti- TNF-a antibody for CD AND UC

adalimumab (humira)- anti TNF-a antibody for CD AND UC

golimumab- human monoclonal anti- TNF only used for UC

Certolizumab pegol- human pegylated anti TNF-a Fab fragemnt. Only used in CD

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33
Q

What are anti integrin bilogics used in CD and UC? Which drug is used inwhich?

A

Natalizimab- CD
Vedolizumab (UC and CD

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34
Q

What are some IL biologics that target CD and UC? Which ones can we use them for?

A

Ustekinumab- CD and UC
Risankizumab (skyrizi)- CD and UC
mirikizumab-mrkz- UC

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35
Q

WHat are some small molecule biologics used in IBD? Which one do they treat?

A

Tofactinib- UC

upadacitinib- UC, UD

Ozanimod- UC

estrasimod- UC

36
Q

TNF-a inhibitors ADRs

A
  1. increased risk of infection (bacterial, viral, fungal)
    - avoid if active infection
    - tuberculin test (PPD), CXR, hepatitis prior to therapy
    - ensure vaccinations up to date
    -live vaccines contraindicated during tx and for 3 months after
  2. Injection site rxn and infusion related rxns
  3. Risk of malignancy (lymphoma)
    - hepatosplenic T cell lymphoma
  4. Risk of demyelinating disease
    Contraindocated in pts with history of cancer, demyelinating CNS disease, optic neuritis
  5. May exacerbate CHF
  6. hepatotoxicity
37
Q

Monitoring TNF inhibitors

A

Baseline
chest x ray, PPD, s/s infection

Maintenance (every 8-12 wks)
s/s of infection, UA, CBC, Scr, LFTs (for LFTs q 1-2 wks for first 1-2 months)

38
Q

what is infliximab approved for? ROA? Induction/maintenance use?

A

mod-severe CD and UD.
used as induction and maintenance therapy
IV infusion

39
Q

What is a common thing to worry about with all biologics

A

development of antibodies (they are foreign proteins that may cause immune response)

It this immune response occur the drug becomes less efficacious

These are called ADA (anti drug antibodies) or ATIs (anti treatment antibodies)

40
Q

What does development of ADAs (antidrug antibodies) lead to? How common is it in infliximab? How to counteract?

A

ADAs lead to decreased response and potentially increased chance of infection.

Up to 10% of pts/year need to discontinue infliximab

Combining with immunosuppressives (AZA or MTX) may be of value, but will increase risk of ADRs

Can escalate dose or decrease dosing interval

41
Q

What happens if Infliximab is co administered with azathioprine?

A

Hepatosplenic t cell lymphoma (HSTCL) risk

Infliximab could also cause infusion related rxns

42
Q

monitoring of infliximab

A

Maintenance
s/s of infection
vitals (each dose)
Infusion rxn (each dose)
TDM (consider if tx failure)

43
Q

What is adalimumab used for? Induction/maintenance? biggest difference with infliximab?

A

Mod- severe active CD and UC, steroid dependent

can use for pts with poor response to infliximab

induction and maintenance therapy

Biggest d/c is that it is an SQ injection not an infusion (self injection technique is needed)

44
Q

What is more likely to give you ADAs infliximab or adalimumab

A

adalimumab is less likely than infliximab

45
Q

What is golimumab approved for? Induction/maintenance?
ROA?
Are ADAs likley compared to infliximab

A

Mod-severe UC
induction and mainetnance
SQ inj (self injection)
ADAs possible, but less likely than infliximab

46
Q

What is certolizumab pegol used for? ROA? Induction/maintenance?, ADAs?

A

Used for CD
SQ injection (self administration)
Induction and maintenance
develops ADAs

47
Q

What type of drug is natalizumab? What IBD is it used in? Induction/maintenance? Which patients use it? Which patients can not use it? When to discontinue?

A

Natalizumab is an anti integrin (prevents leukocyte adhesion/migration)

Used in CD

induction and maintenance

Can use in pts who fail/do not tolerate TNF inhibitors

Not to be used in combination with immunisuppressants or TNF inhibitors

discontinue in patients with no benefits by 12 weeks and/or steroid dependent within 6 months

48
Q

Why is natalizumab not commonly used

A

Associated with progressive multifocal leukoencephalopathy (PML) (rare CNS disorder related to JC virus)

Test for JC antibody. Even if JC virus negative, it is not impossible to get PML

49
Q

What is vedolizumab used for? ADRs?

A

UC and CD

No PML risk (but still monitor for it)
Can see infection, HS rxn, ADAs

50
Q

What are IL antagonist drugs

A

Ustekinumab

51
Q

What is ustekinumab used for? What kind of IL antagonist is it? Induction/maintenance?

A

CD and UC

IL 12 and 23 antagonist

induction and maintenance

52
Q

ADRs of ustekinumab

A

ADAs
HS rxn
Possible neurotoxicity (RPLS, PRES)
reports of rapidly developing cutaneous cell carcinomas

53
Q

Monitoring Ustekinumab baseline

A

Baseline
Check pt for TB/ hepatitis
CXR (chest x ray), PPD, Hep B and C

Lipids, LFTs, renal function, infection, skin

54
Q

Monitoring Usketinumab maintenance

A

Lipids and LFTs- 1-2 months after start and then periodically

renal function- periodically
infection- monitor for s/s
skin- annually

55
Q

What kind of drug is Skyrizi? What is it used for? Induction/maintenance?

A

Selective IL 23 antagonist

CD and UC

USed for induction and maintenance

56
Q

Adverse effects of skirizi

A

common- Headache, nasopharyngitis, arthralgia, abdominal pain, anemia, nausea

infection/latent infection (TB)
HS rxn possible
ADAs possible

Potential hepatotoxicity (increases LFTs)
increase in lipids

57
Q

Monitoring skyrizi

A

Monitor LFTs and bilirubin at baseline and by week 12

58
Q

What kind of drug is mirikizumab? What does it treat? Induction/maintenance?

A

IL 23 p 19 antagonist

Only used in UC

induction and maintenance (infusion and then maintenance SQ)

59
Q

ADRs of mirikizumab

A

COmmon- headache, arthralgia, rash, inj site rxn

Infection/latent infections (TB)
Upper repsiratory tract infection
HS rxn
ADAs

Potential hepatotoxicity (increase LFTs) (monitor)

60
Q

Monitoring Mirikizumab

A

Similar to other IL inhibitors

Baseline
CXR, PPD
HEP B, C

Lipids and LFTs (1-2 months after start)
renal func
infection (monitor for s/s)

61
Q

WHat is TDM? Use?

A

Therapeutic drug monitoring

Potential for determining concentrations of drugs and ADAs

62
Q

Why consider TDMs?

A

Consider if loss of treatment response (check ADA concurrently) always do both together

63
Q

For TDM of biologics, what are 3 things we do at IBD treatment fauilure

A

Confirm inflammation (biomarkers)
Exclude infection and non compliance to treatment
Send for serum drug TLs and ADA levels

64
Q

What TDM to do if detectable ADAs at subtherapeutic drug levels

A

This could be caused by “immune mediated PK failure “(insufficient bioavailability of drug as a result of induced immunogenicity resulting n increased drug clearence

Change to alternate drug within the same class

65
Q

What TDM to do for subtherapeutic drug levels with undetectable ADAs

A

Could be caused by non-immune mediated PK failure (insufficient availability of drug)

Escalate dose

66
Q

What to do for therapeutic drug levels with detectable ADAs? What could it be caused by?

A

False positive OR mechanistic failure

repeat TDM levels

If repeat results consistent, switch to out of class biologic agent

67
Q

What to do for therapeutic drug levels with undetectable ADAs? What could it be caused by?

A

Could be caused by mechanistic failure (not effective drug), switch to out of class biol0gic

68
Q

What type of drug is tofactinib? What is it approved for? Who can use it? ROA? WHen to discontinue

A

It is an oral janus kinase (JAK) inhibitor

Approved for UC only

Used for patients who have had an inadequate response or who are intolerant to TNF blocker

Orl drug

Dx after 16 weeks if repsponse is not adeqyate

69
Q

Tofactinib should not be used in conjunction with

A

Immunosuppressants (AZA, CYA) or biologics

70
Q

ADRs of tofactinib

A

COmmon- Diarrhea, elevated cholesterol, headache, herpes (shingles), rash, nasopharyngitis, URI,

rare- malignancy (lymphoma), serious infection (TB and Hep B and C) (activation of latent TB), neutropenia, HS rxn

Live vaccines CI during tx and 3 months after

71
Q

blackbox warning of tofactinib

A

Increase mortality in RA patients 50 years and older with atleast one cV risk factor

increase in thrombosis in same population

72
Q

Monitoring tofactinib

A

baseline- CXR, PPD, HEP B, C

maintenance
ANC (q 3 months) , CBC (q 1-2 months then q 3 months), lipids (1-2 months after start, then periodically), LFTs (1-2 months after start) , renal fun, infection, skin exam

73
Q

What type of drug is upadacitinib? WHat is it approved for?

A

oral selective JAK inhibitor (like tofactinib)
UC and CD (different dosing)

74
Q

What should upadactinib not be used in combo with? Who is it an option for?

A

Immunosuppressants or biologics

option for pts who fail biologics

75
Q

upadactinib Blackbox? WHne to avoid? COntraindications?

A

Blackbox similar to tofactinib (Increase mortality in RA patients 50 years and older with atleast one cV risk factor

increase in thrombosis in same population)

ADRs increase of risk of serious infection (bacterial, viral, fungal)

Avoid if active infection present, pregnant or breast feeding

Live vaccines contraindicated immediately prior to and during therapy (ensue=re vaccines are up to date)

76
Q

common ADRs of upadactinib

A

Common

upper respiratory tract infection, acne, increased creatine phosphokinase, elevated cholesterol, headache, herpes, shingles

rare- malignancy (lymphoma), serioud infection, increase in LFTs, anemia, neutropenia

77
Q

Monitoring for ipadactinib

A

Same as tofacitinib

78
Q

What type of drug is ozanimod? MOA? UC or CD? How is it dosed? WHne not to use it? WHat to do if patient misses dose in first 2 weeks

A

S1P receptor modulators

Prevents lymphocyte mobilization to inflammatory sites

Only for UC

7 day dose titration, if missed dose within 2 weeks, we reinitiate the whole thing

should not be used with non corticosteroid immunosuppressants or immunomodulators

79
Q

CI of ozanimod

A

CVevents within last 6 months (TIA, MI< unstabe angina)

sleep apnea
MAO inhibitor

80
Q

ADRs of ozanimod

A

increased risk of infection (PML), vaccinate with varicella prior to txm live vaccines CI
bradycardia/AV conduction delays
liver injuries (LFTs)

81
Q

Drug interaction of ozanimod (exam)

A

Inhibition of MAO (exam)

BB and CCB
adrenergic and serotonergic drugs

82
Q

Monitoring with ozanimod

A

CXR, PPD
HEP B, C
CBC
LFTs
Infection
BP
Spirometry
ECG
optho

83
Q

What kind of drug is estrasimod? UC or CD? When not to be used?

A

Oral S1P receptor modulator
Approved for UC only
not used with non corticosteroid immunosuppressives or immune modulating drugs

84
Q

CI of estrasimod

A

CV event in last 6 months

85
Q

ADRs of estrasimod

A

Potential risk of infection (potential for PML), recommended to vaccinate against varicella prior to tx, live vaccines CI

Bradycardia/AV conduction delays

86
Q

ADRs of estrasimod

A

Liver injuries
Moderate increase in BP
edema
RPLS/PRES
respiratory effects

87
Q

monitoring of estrasimod

A

Same as ozanimod

Therapeutics (38 decks)

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