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Flashcards in Pharmacology Deck (99)
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1

Effects of Glucocorticosteroids

Anti-inflammatory
Bind & block promoter sites of proinflammatorty genes IL-1 alpha & IL-2 beta
Decreased production of TNF alpha
Multiple cell specific effects

2

Proinflammatory Mediators Glucocorticosteroids Inhibits

Phospholipase A2
Cyclooxygenase 2
Nitric oxide synthetase
Prostaglandins
Leukotrienes
Thromboxanes

3

Effect of Glucocorticosteroids on Leukocytes

Can't exit circulation as readily
Entry to site of infection & tissues injury impaired

4

Glucocorticosteroids & Suppression of Inflammatory Response

Increased neutrophils
Decreased eosinophils
Decreased monocytes
Decrease lymphocytes

5

Glucocorticosteroids & Effects of Acquired Immunity

Decreased APCs
Decreased T cells
Decreased B cells

6

Increased Infection Risk with Glucocorticosteroids

Immediate reduction of phagocytic responses
Main infections on long term therapy: herpes zoster, staph, candida

7

Monitoring for Toxicity of Glucocorticosteroids

BP
Serum glucose
Lipid profile
Eye exam
Bone density

8

Pros of Steroids

No dose adjustment in renal impairment
Good symptom relief of pain secondary to inflammation

9

Short Term Symptom Management for RA

NSAIDs
Steroids

10

NSAIDs & RA

May alleviate the symptoms
Do not prevent irreversible joint damage

11

Glucocorticoids & RA

Quick symptoms relief
Avoid long term administration due to toxicities
Not a profound effect on decreasing joint destruction

12

DMARDs & RA

Variable response
Discontinuation rate high
Continued indefinitely unless significant toxicity
Biological & non-biological

13

Non-Biological DMARDs

Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
D-penicillamine
Gold salt
Azithroprine
Cyclosporine

14

Biological DMARDs

Etanercept (Enbrel)
Adilimumab (Humira)
Infliximab (Remicade)
Aakinra (Kineret)
Abatacept (Orencia)

15

2nd Line if Failure to Achieve RA Remission in 3 Months

Change DMARD
Go to combination therapy

16

How to decide on which drug for RA?

Disease severity
Prognostic factors
Patient preference

17

Methotrexate (Rheumatrex)

DMARD of choice for RA
Generally well tolerated

18

MOA of Methotrexate (Rheumatrex)

Stimulates adenosine release
Reduced neutrophil adhesion
Suppression of cell mediated immunity
Anti proliferative effect on synovial fibroblasts & endothelial
Inhibition of IL-1, IL-6, & IL-8
Inhibits synovial collegenase gene suppression

19

What do all patients on methotrexate need?

Folic acid supplemet

20

Contraindications of Methotrexate (Rheumatrex)

Women contemplating pregnancy
Pregnancy
Liver disease or excessive ETOH intake
GFR less than 30 mL/min

21

SE of Methotrexate (Rheumatrex)

Hepatotoxicity
Pulmonary toxicity
Myelosuppression
Nephrotoxicity
Fatigue
Decreased ability to concentrate
Alopecia
Nausea
Stomach upset
Loos stools
Soreness of the mouth
Rash on the extremities
Headache
Fever

22

Toxicities of Methotrexate (Rheumatrex)

Myelosuppression
Hepatotoxicity including cirrhosis
Pulmonary toxicity

23

Monitoring of Methotrexate (Rheumatrex)

CBC
LFTs
Albumin
Creatinine
Pre treatment CXR

24

2nd Line Drug for RA

Sulfasalazine (Azulfidine)

25

MOA of Sulfasalazine (Azulfidine)

Inhibition of PMN cell migration
Reduced lymphocyte responses
Inhibits angiogenesis
Decreases inflammatory cytokines & IgM RF production

26

Contraindications of Sulfasalazine (Azulfidine)

Sulfa allergy
Pregnancy category D
GI or GU tract obstruction
Porphyria
Platelet count less than 50K
LFTs > 2x ULN
Hepatitis
Men wanting to conceive

27

SE of Sulfasalazine (Azulfidine)

Nausea & diarrhea
Intestinal or urinary obstruction
Oral ulcers
Orange-yellow pigmentation of the skin
Headache
Depression
Neutropenia
Thrombocytopenia
Agranulocytosis

28

Toxicity of Sulfasalazine (Azulfidine)

Myelosuppression

29

Monitoring of Sulfasalazine (Azulfidine)

CBC monthly x3
CBC every 3 months

30

Effects Leflunomide (Avara)

Anti-inflammatory
Antiproliferative
Decreases progression of joint erosions & joint space narrowing