B-30. Pharmacotherapy of autoimmune diseases. Flashcards
(39 cards)
1
Q
The role of Th1, Th2, Th17, and Tregs
A
2
Q
What inflammatory pathway does RA, IBD, and psoriasis most likely share?
A
Th-17 T-lymphocyte pathway
3
Q
How does the AI chronic inflammation most likely occur
A
Surface damage leads to appearance of antigens in the tissue present by APC. APC induce CD4+ T-cell by IL-6 and IL-23 and directly inducing neutrophils via IL-1
4
Q
Treatment goals of RA
A
- Slow down inflammation process (achieve remission)
- Relieve symptoms
- Prevent joint and organ damage
- Improve physical function and overal well being
- Reduce long-term complications
5
Q
Treatment options in RA
A
- Conventional synthetic disease modifying antirheumatic drugs (CsDMARDs) as soon as possible:
- Methotrexate (first option)
- Alternatives cytotoxic drugs
- short term, tapered glucocorticoid or local steroids
- If necessary: add biological and so-called targeted synthetic DMARDs
- In case of ineffeciency other biological and tsDMARDS can be used
6
Q
Alternative csDMARDs used in RA
A
- Leflunomide
- Sulfasalazine
- Chloroquine
- Cyclosporin-A
- Cyclophosphamide
- Azathioprine/6-mercaptopurine
7
Q
Non DMARDs used in RA
A
- NSAIDs
- Corticosteroids
8
Q
NSAIDs are used in RA to? Long term issues?
A
- They are also essential in the treatment but only symptomatic: they improve the symptoms, but do not slow the progression (even they could facilitate it)
- Long term issues are
- GI ulcerations
- Cardiovascular risk in RA increased- COX2 inhibition could worsen it
9
Q
Corticosteriod use in RA? Dosing?
A
- In acute exacerbation they are the most effective drugs
- They can also suppress the progression
- Dosing
- High dose (transient treatment)
- Low dose (maintained treatment)
- Intraarticular local treatment is also used
10
Q
RA treatment algorithm phase I
A
- Start methotrexate
- +Combine with short term glucocorticoids
- Start Leflunomide or sulfasalazine
- If the patient goes into remision then lower dose
- If patient doesn’t go into remission, go to phase II
11
Q
RA treatment algorithm phase II
A
- Prognostically unfavorable factors present (RF/CPA/high disease activity/early joint damage)
- Add a bDMARD or Jack inhibitor
- Prognostically unfavorable factors not present
- Change to or add a second conventional synthetic DMARD (Leflunomide, sulfasalazine, methotrexate)
12
Q
Phase III of RA
A
- Change the bDMARD
- Abatacept
- IL-inhibitor
- Rituximab
- (second)TNF-inhibitor
- Or add a Jak-inhibitor
13
Q
Biologics used in treatment of RA
A
- TNF alpha antagonist (infliximab, adalimumab, certolizumab pegol, etanercept, golimumab)
- CTLA4- containing fusion protein (abatacept)
- IL-1 receptor antagonist (anakinra)
- IL-6 receptor antagonisst (tocilizumab, sailumab)
- CD20 antagonist (rituximab)
14
Q
Targeted synthetic DMARDS
A
- Jak inhibitors
- Tofacinitib
- Baricitinib
15
Q
Mild therapeutic approach of IBDs
A
- Mild
- 5-aminosalicylic acid (both in CD and UC)
- Locally applied 5-ASA and glucocorticoids
- Budesonide (both in CD and UC)
16
Q
Moderate (or refractory to the mild form of IBD) treatment
A
- Moderate IBD treatment
- Oral glucocorticoids (both CD and UC)
- Azathrioprine/6-mercaptopurine (both in CD and UC)
- Methotrexate (CD)
17
Q
Severe IBD treatment and if this fails what is next?
A
- Severe IBD treatment
- IV glucocorticoids
- TNFalpha antagonist (Infliximab, Adalimumab, Golimumab)
- Cyclosporine (UC)
- IL12/IL23 antagonist (Ustekinumab) (CD)
- Integrin antagonist (Natalizumab, Vedolizumab) (CD)
- If these treatments fail or in conjuncture with them you migh have to do surgery
18
Q
Glucocorticoids in IBDs
A
- Usually short term treatment to avoid adverse effects
- If possible locally acting glucocorticoids (e.g. hydrocortisone enema) or drugs with high first pass metabolism (budesonide controlled release preparations) are preferred
- If necessary prednisolone (predenisonein theU.S.) per os o rmethylprednisolone (oral or injection) are given
19
Q
Treatment goals in psoriasis
A
- Successful treatment: decrease in the psoriasis Area and Severity Index (PASI) score of 75% or greater
- Unsuccessful treatment: improveent is lower than 50% in the PASI score→change in the treatment
20
Q
Drug classes treatments of psoriasis
A
- PUVA
- Topically applied drugs
- Systemically applied drugs
- Biologics
21
Q
What is PUVA?
A
UV beam after taking 8-methoxypsoralene orally or applying a cream or bath. The drug makes the plaques photosensitive
22
Q
Topically applied drugs in psoriasis
A
- Topically applied drugs
-
Glucocorticoid creams alone or with tar or Vit. D3 analogs
- calcipotriol with betamethasone (cream or gel)
- or tacalcitol emulsion
- Retinoids
- tazaroten
-
Glucocorticoid creams alone or with tar or Vit. D3 analogs
23
Q
Vit. D analogs do what in psoriasis
A
Vitamen D analogs inhibit keratocyte proliferation, used only in localized plaque psoriasis
24
Q
Systemically applied drugs in psoriasis
A
- Systemically applied drugs
- Acitretin
- Immunosuppresive drugs
- Cyclosporin
- Methotrexate
- Leflunomide
- Dimethyl-fumarate
- PDE-4 inhibitors
- Apremilast
- Biologicals
- More later
25
Acitretin in psoriasis
Inhibits synthesis of keratin precursors, decreases hyperkeratosis
26
Dimethyl-fumarate in psoriasis
Stimulates transcription factors
27
Apremilast (PDE-4 inhibitor) function in psoriasis
Inhibits expression of TNF-alpha, IL-23, IL-17, and other inflammatory cytokines
28
Mechanism of action and retinoid drugs used in psoriasis
* MOA: Inhibition of cell proliferation and differentiation (they bind to nuclear retinoid receptor RAR and/ or RXR)
* Drugs
* Tazaroten (locally applied)
* Acitretin (systemic)
29
Acitretin (systemic) use, adverse effects
* Can be used in more severe psoriasis
* Adverse effects may include...
* Dry mucosa (e.g. xerophtalmia=dry eyes)
* Iitching
* Several skin problems (e.g. hairloss, exfoliation, dermatitis, pyogen granuloma)
* Extremely teratogenic-!!! Getting pregnant must be avoided duringand 3 years after terminating the treatment!!!
30
Biologics used in the treatment of psoriasis
* L-23R antagonists
* **ustekinumab** (IL-12R/IL-23R), **guselkumab, risankizumab**
* IL-17 antagonists
* **ixekizumab, secukinumab**
* IL-17R antagonist
* **brodalumab**
* TNFalpha antagonists
* **adalimumab, etanercept, infliximab**
31
Therapy of mild atopic dermatitis
* Therapy depends on severity
* Mild form
* Local creams (**emollients, pimecrolimus, glucocorticoids**)
* Systemic steroids only in acute exacerbation for a short time
32
Therapy for more severe forms of atopic dermatits
* More severe forms: systemic drugs
* **Cyclosporin-A**
* Or IL4R/IL3R antagonist **dupilumab**
33
Treatment options in MS classes
1. Interferons
2. Glatiramers
3. Antimetabolites
4. Leukocyte depletion
5. T-cell inhibition
6. B-cell depletion
7. Other (dimethyl-fumarate)
8. Improving motoric functions
34
Which **interferons** are used in in MS
1. INF-B1a
2. INF-B1b
35
**Glatiramers** are
Mixture of short peptides corresponding myelin building blocks
36
Antimetabolites drugs? how are they taken?
* Taken orally
* Drugs
* **Teriflunomide** (dihyroorotate-dehydrogenase inhbitor)
* **Cladribine** (purine analog)
37
Leukocyte depletion drug
* **Alemtuzumab**- CD53 inhibitor, T and B cell depletion, IV induction treatment
38
Other treatments in MS
* Orally taken **Dimethyl-fumarate**
* Nuclear factor (erythroid derived 2)-like 2 (Nrf2) transcription pathway stimulator- increases the level of antioxidant enzymes
39
MS drugs improving motoric function
* **Fampridine** (4-aminopyridine)- K+-channel blocker
