Drugs - last two lectures Flashcards
1
Q
Corticosteroid Effects
A
- increased transcription and synthesis of Lipocortin
- lipocortin blocks phospholipase A2 from breaking down
membrane lipids to arachidonic acid -> inflammation
- lipocortin blocks phospholipase A2 from breaking down
- CS prevent expression of FcR - less phagocytosis
- CS inhibits increase of endothelial cell adhesion molecules
- less leukocytes travel to site of infection
- DECREASES vascular permeability
- Increases neutrophils in blood
- more produced in bone marrow, less leaves blood to go to
site of infection
- more produced in bone marrow, less leaves blood to go to
- T-cell lymphopenia, little to no effect on B-cells
** Overall - rapid decrease WBC at infection, block pro-inflam cytokines, activates both innate and adaptive immune
2
Q
Major Side effects of corticosteroids
A
- Infection risk
- osteopenia - loss of trabecular bone - decrease Ca absorption increased excretion
- HPA Axis suppression via negative feedback
- means you can’t activate it when get stressed - shock
- give more steroids when stressed
- weight gain
- myopathy
- atherosclerosis
3
Q
Normal function of Cox1
A
- Cox1 breaks arachodonic acid into leukotrines/thromboxane
- normal house keeping
- protects GI, homeostasis
- kidney function
- platelet aggregation
- vasoconstriction
4
Q
Cox2 function
A
- Cox2 breaks arachidonic acid into prostagladins
- inflammation
- fever
- pain
- vasodilation
5
Q
NSAIDS
A
- block both COX
- decrease inflammation
- can harm other things from COX1 like stomach
6
Q
- selective COX2 inhibitors
A
- rofecoxib
- only blocks formation of prostaglandins by COX2
- so should leave normal housekeeping
- problem increased thrombotic events (MI, stroke)
- stops inflammation but also does uncontrolled vasoconstriction and platelet aggregation from COX1
7
Q
Anti-malarials (hydroxychloroquine, plaquenil) main features
A
- least toxic
- immuno-modulators
- can be combined with any other immuno suppresent
- SLOW - like 6 weeks to work
- safe for pregnancy
8
Q
Anti-malarials mechanism + main side effect
A
- weak base - increases pH of lyosomes, prevents peptide preparation,
- messes with peptide/MHC-II unit
- decrease antigen presentation = decrease CD4 T-cell activation
- also good for LDL receptor, slows degradation of insulin, inhibits thrombosis
- watch for macular eye damage - eye exams and amsler
9
Q
Methotrexate indications
A
- All connective tissue disease
- RA - all ppl get methotrexate
- JIA
- SLE
- AS, ReA, PsA
- PM & DM
- Vasculitis
10
Q
2 mechanisms of methotrexate
A
- methotrexate blocks dihydrofolate reductase - prevents formation of reduced folates (Folate ->DHF ->THF)
- Reduced folates needed to make purines
- blocks AICAR
- also blocks synthesis of purines
- so blocks rapidly proliferating cells - aka lymphocytes in response to infection
11
Q
Methotrexate side effects and monitoring
A
- Liver fibrosis
- ILD, pneomonitis - rare but not dose dependent
- infection
- mucosa, skin
- increased risk of lymphomas
- bad pregnancy
- low blood cells
monitor
- chest x-ray, CBC, liver function - no alcohol - don't need to add more liver stress
12
Q
Leflunomide
A
- lets just copy MTX
- only approved for RA
- blocks pyrimidine formation instead of purine
- really long half life - 1-2 years
13
Q
Azathiprine
A
- transplant med
- blocks synthesis purine,
- Aza -> 6 MP->thiopurine
- thiopurine prevents purine synthesis - kills cells
- patients with low TPMT - danger myelosuppression
- bone marrow suppresion, infection, hypersensitivity, lymphoma
Good for:
- SLE, Sjogren - PM/DM - Vasculitis - RA - IBD - ILD
14
Q
Cyclosporin
A
- RA, eye, PM/DM, PsA, SLE, Uvetis
- inhibits calcineurin - blocks NFAT, blocks T-cell signal transduction
- blocks IL-2 transcription (IL-2 = t-cell growth factor)
- side effects: kidney, hypertension, high blood sugar, high lipid
15
Q
Mycophenolate mofetil
A
- another transplant
- used in sever lupus, vasculitis, systemic sclerosis
- blocks inosine monophosphate dehdrogenase - blocks purine syntheis
- cytopenia, Gi, infection, liver toxicity
