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Therapeutics > Exam 4 lecture 2 > Flashcards

Exam 4 lecture 2 Flashcards

1
Q

Symptoms of mild/moderate active UC

A

4-6 stools per day
no fever

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2
Q

How is mild/moderate active UC grouped depending on where it is occuring? WHat is used to treat them?

A

Left sided disease- within reach of enemas

Proctitis- within reach of suppository

Extensive disease pancolitis- requires systemic tx

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3
Q

Should we use oral and/or topical ASAs for mild-moderate active UC

A

extensive disease- oral- ASA
left sided- topical mesalamine enema
proctitis- mesalamine suppository
Combo of oral and topical may be more effective for left sided/extensive disease

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4
Q

If orally treating Mild/moderate UC, Which drug is better tolerated?

A

Mesalamine derivatives better tolerated than sulfasalazine

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5
Q

What to do if pa tient is unresponsive to 5-ASA for mild/moderate active UC

A

Consider changing formulation (if on mesalamine, try sulfasalazine)

Or bump up the dose of the drug

remember combo therapy is more effective

alternative drug

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6
Q

What are alternate drugs we use for mild/moderate active UC if unresponsive to oral/topical ASA

A

CR budesonide (limit to 8-16 weeks)
PO corticosteroids (prednisone) for pts refractory to ASA

topical corticosteroids (foams, enemas, suppositories) (are effective for distal disease)

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7
Q

symptoms of mod/severe active UC

A

4-6 stools per day
blood/mucous in stool
Weightloss, lab abo=normalities (increase in ESR)

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8
Q

Tx of mod/severe active UC

A

5-ASA therapy possible for moderate, but not severe disease

Systemic corticosteroids (PO prednisone)
(for moderate use oral budesonide)

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9
Q

What is pts are not responsive to Corticosteroids/ASA or steroid dependent for moderate/severe

A

TNF-a inhibitors/biologics (potentially newer small molecules)

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10
Q

What are TNF inhibitors used for moderate-severe active UC? Anti integrins? IL 12-23 inhibitors? JAK inhibitors? SP1 inhibitors?

A

TNF- infliximab, adalimumab, golimumab
ANti-integrin- Vedolizumab
IL 12-23- ustekinumab, mirikizumab, risankizumab
JAK- upadactinib, tofactinib (black box warning for RA pts for CV events), only used if failed TNF inhibitors)
SP-1 ozanimod, estranimod

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11
Q

for moderate/severe active UC, can we use methotrexate for induction or maintenance? Is biologic monotherapy an option? Can we use thiopurine monotherapy for induction? maintenance?

A

It is suggested that we do not use methotrexate for induction or maintenance

Biologic monotherapy is an option.

Thiopurine monotherapy should not be using for induction. Can be used for maintenance

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12
Q

What combinations to use for moderate-severe active UC rather than monotherapy? Who mau choose biologic monotherapy?

A

Reccomendations for combining TNF antagonists, vedolizumab or usketinumab with thiopurines or methotrexate rather than monotherapy.

Patients with less severe disease or those who place relative value on minimizing ADRs vs maximizing efficacy may choose biologic monotherapy.

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13
Q

should we use biologics early or gradually stepup?

A

early use of biologics is recommended rather than gradual step up. Those with less severe disease who place a higher value on the safety of 5-ASA may prefer gradual step up

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14
Q

Is certolizumab approved for UC? What about golimumab?

A

certolizumab is NOT approved. Golimumab is approved

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15
Q

sx of severe fulminant UC? How is it treated?

A

6-10 BMs/day, blood present, systemic sx

consider NPO

Parenteral corticosteroids (methylprednisolone or hydrocortisone)

consider TNF-a inhibitors (infliximab) if unresponsive to IV steroids

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16
Q

for UC, what do we use as maintenance of remission

A

for mild, if we used ASA and they responded to mesalamine in induction, we can use that.
If on severe disease and they responded to induction by TNF inhibitor, we continue that. SO it depends on what we used to induce the tx

no role for corticosteroid in maintenance

Choices are mesalamine derivatives for mild disease or biologic/small molecule inhibitor for severe

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17
Q

What are some rules for maintenance of remission for ASAs

A

newer mesalamine derivatives are better tolerated than sulfasalazine

Use mesalamine enemas (if left sided disease) or suppositories (if proctitis)

May use combination of topical/systemic (more effective than either alone)

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18
Q

For maintenance of remission in UC, in patients who are steroid dependent or unresponsive to ASAs, what do we do?

A

Use azathioprine or 6-MP (slow to work-> 3-6 months)

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19
Q

maintenance of remission for UC patients that responded to TNF-a antagonists for induction? What about for patients who failed azathioprine?

A

TNF antagonist used for maintenance

Can also be used for pts who fail azathioprine

We can combine TNF antagonists with azathioprine to decrease ADAs

20
Q

What are other biologics/ small molecule drugs that we can use to maintain remission and induction

A

Anti-integrin (vedolizumab)

IL 12-23 (ustekinumab, mirikizumab, risankizumab)

JAK inhibitor (upadactinib, tofactinib)

SP1 inhibitor (ozanimod, etrasimod)

21
Q

Can we use mesalamine derivatives for CD?

A

Mesalamine derivatevies have minimal efficacy and are no longer recommended

22
Q

symptoms of mild-moderate active CD? TX?

A

ambulatory, minimal systemic sx

CDAI<220

Sulfasalazine marginally effective for treating symptoms of milf/mod CD

controlled release budesonide to induce remission (8-16 wks)

23
Q

Symptoms of mod/severe active CD? Tx options?

A
  • failed treatment for mild/mod disease, systemic symptoms (fever, wt loss, abdominal pain/tenderness, anemia, vomiting, dirrhea)

CDAI- 220-450

systemic corticosteroid (PO prednisone)- treat until resolution of symptoms and resumption of wt gain, then do gradual steroid taper.

hospitalized pts may receive IV corticosteroids (methylprednisolone or hydrocortisone)

early biologic therapy (with or without immunomodulators) may be beneficial

24
Q

Biologic therapy used for moderate-severe active CD

A

TNF-a antagonists

25
Q

Are TNF-a antagonsists effective in moderate-severe active CD who have failed immunosuppressives (like thiopurines)? Steroid dependent pts?

A

Yes for both

26
Q

What should TNF antagonists be combined with for moderate-severe active CD

A

Infliximab + AZA are efficacious together

it is suggested to use infliximab or adalimumab plus thiopurine for induction and maintenance over monotherapy in those native to biologics and immune modulators

27
Q

What are otehr biologics used for moderate-severe active CD

A
  • vedolizumab
  • natalizumab (not recommended due to PML)
  • IL12-23 antagonists (uske, risan)

JAK inhinitor (upadactinib) used if failed TNF inhibitor

28
Q

is immunomodulator monotherapy recommended to induce remission for moderate-severe active CD? what about for maintenance

A

Immunomodulators like AZA and 6-MP monotherapy not recommended to induce remission (may help maintain remission after induced w steroids, may be steroid sparing)

May be used in maintenance

29
Q

Can methotrexate be used as a monotherapy for induction in moderate/severe active CD? What about maintenance? cyclosporine? ASA/sulfasalazine?

A

mtx can be used for induction (especially in steroid dependent CD) and for maintenance of remission?

Cyclosporine only used in UC, ASA or sulfasalazine should not be used

30
Q

symptoms of severe-fulminant CD

A

persistent s/s despite corticosteroids or biologic tx, cachexia (look like malnutritioned)
In patient tx
Consider NPO
CDAI>450

31
Q

tx of severe/fulminant CD

A

parenteral corticosteroids (if no abscess)
(methylprednisolone or hydrocortisone) for 3-7 days that transition to PO

May consider infliximab (or other biologic) if not attempted prior

infliximab may be preferred if fulminant

32
Q

maintenance of remission of CD

A

mild- not a lot works well. sulfasalazine/mesalamine may be used (def not in moderate/severe.

No role for systemic corticosteroids

Budesonide has minimal long term efficacy->not recommended for >4 months

AZA and 6-MP are effective (especially in steroid induced or infiliximab induced remission)

Methotrexate (alternative to AZA and 6-MP, esp in pts w initial resoinse to MTX), SQ only

TNF antagonists are often times first choice

33
Q

How to use TNF-a antagonist for maintenance remission of CD

A

Use of infiliximab or adalimumab in combination with AZA or 6-MP in pts who are naive to biologics and immunomodulators

in moderate to severe disease, it is suggested early introduction with biologic +/- immunomodulator to be used vs delaying their use while trying 5-ASAs and/or corticosteroids

34
Q

What are other biologics that can be used for maintenance of remission of CD

A

Anti integrin- vedolizumab

IL-12 and 23 antagonists- ustekinumab, risankizumab
(natalizumab not recommended)

35
Q

SDOH and IBD

A

lower socioeconomic status may be associated with worse outcomes in IBD

36
Q

What are symptoms of IBD that we should collect in PCP? What are social hx and drug hx that are pertinent? Labs?

A

Symptoms- abdominal pain, stool freq, hematochezia, extraintestinal sx

smoking
NSAIDS make them worse

Labs- CRP, ESR, WBC, fecal, c diff

37
Q

Follow up of IBD?

A

Resolution of active disease symptoms (24-48 hrs for hospital pts, 7-14 days for outpatient)
monitor ADRs
Monitor for symptoms and toxicity/efficacy

38
Q

What to use for mild ulcerative proctitis (left sided)? What drugs to dc

A

mesalamine derivaive (sulfasalazine, mesalamine)

use topical (suppository)

dc NSAIDs

39
Q

if patient returns with ulcerative proctitis (left sided) after giving mesalamine suppository what drug do we give?

A

oral + topical combination works better.
Short course of budesonide could work too if that does not work
mesalamine better tolerated than sulfasalazine

40
Q

treatment options for moderate/severe ulcerative proctitis (left sided)

A

systemic steroids
(maybe budesonide if not as severe, but prednisone if severe) until sx improve and taper off

Ensure ASA dose is optimized

Use enema

41
Q

Short term and long term ADRs of steroids

A

SHort term- Hyperglycemia, gastritis, mood changes, elevated BP, difficulty sleping

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

42
Q

What type of substrate is budesonide (CYP)

A

3A

43
Q

What to supplement patients on steroids?

A

Calcium (1000-1500mg/day) and vitamin D (800 U/day)

May consider bisphosphonates in pts w risks of osteoporosis and patients using > 3 months

Consider DEXA in pts >60

44
Q

5-ASA ADRs? Drug interations?

A

common (>10%)- N/V/H
Olasalazine- Diarrhea (up to 25%)

drug i/a- antiplatelet/anticoags/NSAIDs-> May increase bleeding risk

PPIs, H2RAs, Antacids-> affect gastric PH and influence release of drug

45
Q

how to treat severe UC

A

steroids- corticosteroids
Pain control and fluid control
Biologics should be used (TNF inhibitor probably, or small moleculed rugs approved for UC or using steroid for remission and using thiopurine for maintenance)

46
Q
A

Therapeutics (38 decks)

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