MSK L16 Pharmacology MSK Flashcards Preview

Cardio > MSK L16 Pharmacology MSK > Flashcards

Flashcards in MSK L16 Pharmacology MSK Deck (38):
1

Drugs used: in RA

NSAIDS
DMARDS

2

DMARDS role

• Aim to halt or slow the inflammatory joint destruction
• Slow onset of actions
• May have little long-term effect on disease

3

Molecular Mechanisms in RA: Highly complex multi-factor mediation of the pathological process

1. Auto-immune response – auto-antibodies and immune complex
2. T-cell mediated antigen-specific responses
3. T-cell independent cytokine networks

4

Molecular Mechanisms in RA: What is certain



1. T cells are a/the major driving force
2. Nuclear factor (NF) –kB is activated in the synovium and regulates genes involved in inflammation e.g. TNF, IL etc iNOS and COX-2
3. MAP kinases are activated in rheumatoid tissues – key regulator of cytokine and metalloproteinase production

5

NSAIDS

role

Symptomatic treatment – block eicosanoid synthese
→ Provides symptomatic relief of pain and stiffness, but do not alter disease progression.

6

DMARDS role

1. To prevent erosive damage
2. If patient intolerance to NSADS
3. Extra-articular manifestations of RA
4. Poor response to NSAIDS

7

DMARDS MOA

Sulphasalazine
Gold (aurothiomalalte and auranofin)
Methotrexate

8

DMARDS example

B and T cell action blocking bt unclear

9

Sulphasalazine: Epi

Cheap and commonly first choice in UK

10

Sulphasalazine: Combination of

Sulphapyridine combind with salicycate

11

Sulphasalazine: Hydrolysed by and to

By gut bacteria to sulphapyrieine and 5-aminosalicylic acid

12

Sulphasalazine: Suphapyridine action

Reduces absorption of antigens from colon that may promote joint inflammation

13

Sulphasalazine: 5-aminosalicyclic acid action

Reduces synthesis of inflammatory mediators e.g. eicosanoids and cytokines

14

Sulphasalazine: Side effects

• GI
• Reversible decrease in sperm count
• Sulphonamide idiosyncratic blood dyscrasias (reducetion in WBC and platelet)
• Analyphylaxis

15

Gold (aurothiomalate and Auranofin: Possible MOA

1. Inhibit lymphocyte proliferation
2. Inhibit release and activity of Lysosomal enzymes
3. Decrease production of toxic O2 metabolites from phagocytes
4. Inhibit chemotaxis of neutrophils
5. Inhibit induction of IL-1 and TNF-alpha

16

Gold (aurothiomalate and Auranofin: Acts where

Binds to tissue proteins and accumulates widely, incuding in synovium of inflamed joints

17

Gold (aurothiomalate and Auranofin: Toxicity

Can be serious:
1. blood disorders – agranulocytosis, aplastic anaemia
2. Skin rashes
3. Diarrhoea
4. Glomerulonephritis
Serious toxic effects in 10% of patiens

18

Methotrexate: Action speed

Rapid

19

Methotrexate: Use in

DMARD for RA and Chrohns

20

Methotrexate: MOA

Not via inhibition of dihydrofolatereductase (DHFR) – for DMARD unsure

21

Methotrexate: MOA thoughts

Thought to be via inhibition of enzymes involved in purine metabolism:
1. Accumulation of adenosine
2. Inhibition of T cell activation
3. Suppression of adhesion molecule expression by by T-cell

22

Methotrexate
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

1-2 months
Moderate
Myelosuppression
Hepatic fibrosis and cirrhosis
Pulmonary infiltrates

23

Hydroxychloquine
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

2-6 months
Low
Macular Damage

24

Leflunomide
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

4-12 wks
Low
Diarrhea
Alopecia
Rash
Headache
Risk of immunosuppression infection

25

Sulfasalazine
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

1-3 months
Low
Myelosuppresion

26

Cyclosporin
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

4-8 wks
High
Renal insufficiency
Anaemia
Hypertension

27

Gold, oral
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

4-6 months
Low
Myelosupression
Proteinuria

28

Gold, parentral
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

3-6 months
Moderate
Myelosupression
Proteinuria

29

Azathioprine
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

2-3 months
Moderate
Myelosupression
Hepatotoxicity
Lymphoproliferative disorders

30

Minocycline
Time to Benefit
Potential for Toxicity
Toxcities to Monitor

1-3 months
Low
Hyperpigmentation
Dizzines
Vaginal yeast infections

31

Corticosteroids and RA: Uses

1. Intra-articular injections of individual joints (e.g. knee)
2. In active disease short causes of oral prednisolone, can produce a rapid onset before other drugs

32

Corticosteroids and RA: Standard therapy

Combination of low-dose glucocorticoids and sulphasalazine/methotrexate

33

Corticosteroids and RA:Mechanisms

• Immunosuppressants (act on cell-mediated immune responses)
• Decrease transcription of IL-2, TNF-alpha, interferon-y

34

Gout →Acute arthritis

Due to deposition of urate crystals in the synovial tissue – very painful

35

Gout →Metabolic disorder

Plasma urate concentration increased due to overproduction of purines and/or impaired excretion of purines
→ Seen with poor renal degradation
→ High red meat diet
→ Mostly genetic

36

Gout →Pathology

1. Crystal deposition leads to kinin release/generation of LTB4
2. Phagocytic neutrophil accumulation
3. Free radical formation
4. Call damage and lysis

37

Gout → Treatment

Inhibit uric acid synthesis
Increase uric acid secretion (uricosuric drugs)
Inhibit inflammatory cell migration into joints
Give anti-inflammation/analgesic drugs (NSAIDs)

38

Gout →Drugs for Gout

Allopurinol → blocks formation of uric acid
Colchicine → inhibits leckocyte migration into joints
Acute → NSAIDS not Aspirin

Decks in Cardio Class (108):