Degenerative joint pharmacology Flashcards
the aims of RA treatment in early stage and late stage respectively
early stage emphasizes on the suppresion of inflammation
late stage emphasises on pain relief, improving joint function and reconstruction
General measures for RA also include
* Rest
* Splint/support
* Physiotherapy
pharmacological treatment for RA if disease is mild or palindromic
what about if it is not
Hydroxychloroquine
If no:
cDMARDS monotherapy, i.e. Methotrexate
OR leflunomide or sulfasalazine as soon as possible and ideally within 3 months of onset of persistent symptoms and escalate dose as tolerated
Consider Glucocorticoids as short term bridging treatment (usual dose 60mg daily)
aim of treatment in RA
Treat active RA in adults with the aim of achieving a target of remission or low disease activity if
remission cannot be achieved.
name some monitoring requirements for RA until target is achieved
using the DAS-28 score to determine the severity of rheumatoid arthritis using clinical and laboratory data
CRP or ESR
RF
VG-PAS (a patient self-assessment using visual scales)
these are the main ones
how conventional DMARDs work in RA
they modify the course of the disease, slowing down join erosion
they also provide some symptomatic relief
time it takes to see cDMARD effect
4-16 weeks
the main cDMARDs
Methotrexate
* Leflunomide
* Sulphasalazine
* Hydroxychloroquin
methotrexate class of drug
antimetabolite
folate antagonist
methotrexate MoA
inhibits dihydrofolate reductase, which is an enzyme essential for folate synthesis. this causes it to interfere with purine and pyrimidine synthesis. folate is important for cell division
first choice DMARD for RA
methotrexate
can methotrexate be taken chronically, i.e, > 5yrs ?
yes
main side effects of methotrexate
Side effects are liver cirrhosis and blood dyscrasias
(myelosuppression, Immunosuppression, anaemia),
interstitial pneumonitis, sore throat, bruising, mouth
ulcers
what supplement do we take to reduce the side effects of methotrexate
folic acid supplements
some other effects that we see with methotrexate at low doses, which are more relevant to RA
Inhibiting neutrophils
2) Inhibiting T cells
3) Increasing intracellular adenosine
MoA Hydroxychloroquine
note that it has multiple MoAs
Accumulation in lysosomes and autophagosomes of phagocytic cells
Reduce MHC Class II expression and antigen presentation;
**Inhibit production of pro-inflammatory cytokines **[e.g. interleukin-1 (IL-1) tumour necrosis factor-α (TNFα)];
Reduced toll-like receptor-9 activation; and Reduce leucocyte generation of reactive oxygen species (ROS); i.e. antioxidant activity.
May indirectly affect T and B cells
May also protect against cytokine-mediated cartilage resorption.
Hydroxychloroquine can cause ocular toxicity, true or false
true, although this is quite rare
MoA of leflunomide
Inhibit dihydroorotate dehydrogenase, an enzyme involved in synthesising purine and pyrimidine
Inhibits metabolism of activated lymphocytes
note that it is fully absorbed and converted into it’s active metabolite, A77 1726
sulfasalazine MoA
unknown
it is thought to scavange toxic oxygen metabolites from neutrophil, but this is not definitive
Side effects include GIT disturbances, malaise and headache
some of the main common side effects of corticosteroids
osteoporosis,
hypertension, dermal atrophy, increased infection
susceptability
in the long run, benefits outweight the side effects of corticosteroids, true or false
note corticosteroid withdrawal is very difficult.
also the beneficial effects of corticosteroids are not sustained past 9 months
false
side effects usually outweigh benefits
