Rheumatoid Flashcards
1
Q
Leflunomide
A
MOA:
-inhibits the de novo synthesis of rUMP (uridine monophosphate), which is critical for RNA and DNA synthesis in lymphocytes, causing cell cycle arrest in G1
SE:
- alopecia
- rash
- diarrhoea
- hepatoxicity
2
Q
Sulfasalazine
A
MOA:
- pro-drug, metabolised to 5 aminosalycilic acid and sulfapyridine by colonic bacteria
- 5 aminosalycilic acid may inhibit Cox
- sulfapyridine inhibits B cell functions
SE:
- Allergic reactions
- Fever
- Haemolysis in G6PD deficiency
3
Q
Methotrexate
A
MOA
- inhibits dihyrofolate reductase
- > prevents conversion of dihyrofolate to tetrahydrofolate
- > inhibits folate metabolism and DNA synthesis in inflammatory cells
SE
- GI distress
- stomatitis
- rash
- headache, mailaise, poor concentration
- alopecia
- drug fever
- macrocytosis
severe
- hepato/nephro/pulmonary toxicity
- myelosuppression (anaemia, leukopenia etc)
- lymphoproliferative disorders
4
Q
Aspirin
A
MOA
- Low dose (100mg once daily)
- > irreversibly acetylate cox-1
- > inhibits generation of thromboxane A2
- > anti-thrombotic
- Intermediate dose (300-900mg 4-6hrs)
- > inhibit cox1 and 2
- > blocks PG production
- > analgesic and antipyretic effect
- High dose (up to 15mg/kg every 6 hrs)
- > block cox-2 dependent PGE2 production
- > anti-inflammatory effect
SE
- GI
- > dyspepsia
- > asymptomatic blood loss/iron deficiency anaemia
- > upper GI haemorrhage/ulcer
- hypersensitivity
- > SJS
- > TEN
- intracranial haemorrhage
- worsen renal/heart failure
- worsen heart failure
- bronchospasm/angiooedema/rhinitis/urticaria
- toxicity (salicysm)
- > tinnitus
- > confusion/drowsiness
- > abdo pain
Precaution
- contraindicated in active bleeding
- caution intrathecal injections
- use with caution in severe renal disease
- surgery
- > consider stopping 7 days before
- > weigh risk of cardiac event
- elderly
- > increased risk upper GI bleed
- pregnancy
- > safe in low doses
- breast feeding
- > avoid due to Reye syndrome
5
Q
non-selective NSAIDs
A
ibuprofen, naproxen, indomethacin, ketorolac, sulindac
MOA
- reversible inhibition of cox 1 and 2
- analgesic, antipyretic and anti-inflammatory effect
SE
- hypersensitivity (anaphylaxis, SJS)
- gastrotoxicity
- hyperkalaemia, hyponatraemia (inhibit effect of renin)
- worsen HTN (PGs kidney)
- worsen CCF, associated with CVA and MI (mainly interfering with action of aspirin)
- hepatotoxicity
- bronchospasm
- bleeding (rare = leukopenia, aplastic anaemia)
- cardiovascular risk
- > increase BP
- > fluid retention
- > MI/CVA/CVD mortality
6
Q
Cox-2 selective
A
Celecoxib
- 200-300 fold selectivity for cox-2 at therapeutic dose
- analgesia and anti-inflammatory
SE
- reduced gastrotoxicity but inhibits gastric healing of ulcers
- no antiplatelet effect
- less bronchoconstriction
- other effects are same as non-selective
7
Q
paracetamol
A
MOA
- unknown
- no peripheral effect on PGs
- likely inhibits PGs in CNS
- anti-pyretic (hypothalamus) and analgesic effect (inhibitory serotinergic pathways)
SE
- overdose = hepatotoxic
- > minor metabolism pathway forms toxic metabolite which is inactivated by glutathione
- > overwhelmed in toxicity
- > centrilobular necrosis
- rash, GI distress, renal failure in chronic overuse
8
Q
Glucocorticoids
A
MOA
Binds to glucocorticoid receptor in cytoplasm. Translocated to nucleus where it binds to glucocorticoid response element, thus effecting gene transcription:
Stabilise lysosomal membranes –> decrease inflammatory signalling, impair phagocytosis
Decrease expression of integrins –> impair inflammatory influx
Decrease expression of interleukins
Inhibits phospholipase A2 (via lipocortin) –> decrease ecosanoids
Inhibits Cox 2
Also has mineralocoritoid action
SE
- derm/ appearance
- > thin skin
- > bruising
- > cushingoid
- > weight gain
- eyes
- > cataracts
- > glaucoma
- cardio
- > fluid retension and HTN
- > atherosclerosis -> MI/CVA
- > arrhythmias
- GI
- > ulcers
- musculoskeletal
- > osteoporosis
- > osteonecrosis
- > myopathy
- psych
- > depression
- > psychosis
- endocrine
- > hyperglycaemia
- > HPA axis suppression with adrenal crisis in withdrawal
Precautions
- Latent TB
- > may reactivate
- Peptic ulcer
- > increased risk
- Diabetes
- > may worsen Glycaemic control
- HTN/HF
- > may worsen due to Na/water retention
- Psychiatric disorders
- > may exacerbate
- Glaucoma
- > may increase pressures
- Infection
- > may increase risk and severity/mask symptoms
9
Q
COX
A
Cox
- catalyses conversion of arachadonic acid to PGH2
- > production of biologically active PGs
- cox-1 is a constitutive isozyme found in most tissues
- > gastric cytoprotection
- > vascular homeostasis
- > platelet aggregation
- > kidney function
- cox-2 expressed in inflamed tissue or in response to growth factor/cytokines
