A very concise set of notes covering the important aspects of musculoskeletal drugs & diseases required to pass the GPhC exam. Topics include:
- Rheumatoid Arthritis
- Gout
- Nocturnal Leg Cramps
- Spasticity
QUICK PATHOPHYSIOLOGY RECAP:
- RA = Chronic autoimmune polyarthritis which is SYMMETRICAL
- Like many other autoimmune disorders (e.g. asthma, IBDs), RA causes FLARE UPS
SYMPTOMS (Joint Pain & Stiffness)
- Morning stiffness of affected joints > 1 hour RA typically affects small,
- Swelling of affected joints during the day interphalangeal joints of hands & feet
- Joint pain at NIGHT awakening – but can affect larger joints too
Like tremor in Parkinson’s, pain is worse at rest but improves with activity
COMPLICATIONS OF RA: (if left untreated)
- Joint deformities: chronic inflammation bone & cartilage erosion joint
misalignment deformities
- Extra-articular inflammation: inflammation can occur at other organs e.g. mucosa,
heart, lungs (this can be FATAL)
- Carpal tunnel syndrome: inflamed carpal tunnel compression of median nerve
DIAGNOSTIC MARKERS OF RA (from blood tests):
- C-reactive protein (CRP) – INCREASED in RA CRP & ESR are non-
o CRP is involved in activating the complement system specific biomarkers of
- Erythrocyte Sedimentation Rate (ESR) – INCREASED in RA INFLAMMATION
RA TREATMENT
OVERVIEW:
- Like IBDs, RA-treatment aims to INDUCE & MAINTAIN REMISSION (prevent relapse)
- As soon as Dx is confirmed – START DMARD treatment (even if symptoms are mild)
TREATMENT REGIMEN:
1- Start with conventional DMARD (MTX, SSZ, Leflunomide) w/ or w/out a STEROID
o DMARDs take 2-3 MONTHS before they start working – steroids work
instantly – so creates a bridge until DMARDs kick in
o DMARDs can be used chronically, but steroids CANNOT complications:
Osteoporosis
Adrenal insufficiency
Psychiatric reactions
2- If still no remission – combine TWO conventional DMARDs
3- If still no remission – combine ONE conventional DMARD w/ ONE biological DMARD
NSAIDs can be used for short courses to relieve pain – but be cautious of INTERACTIONS:
- NSAIDs & Steroids = both inhibit COX increase GI bleeding risk
- NSAIDs & MTX = NSAIDs renal impairment MTX toxicity (so monitor MTX-level)
NSAIDs do NOT have notable interactions with other DMARDs (only MTX)
, Although it’s a DMARD,
HCQ can worsen PSORIASIS
– cautionary use
HYDROXYCHLOROQUINE (HCQ)
MOA:
- Similar to calcineurin inhibitors inhibits synthesis/activity of IL-2 less T & B-cell
activation immunosuppression (NOT as strong as other DMARDs)
INDICATIONS: Normally used where other conventional DMARDs have failed in RA
SIDE EFFECTS:
1- RETINOPATHY: can present as blurred vision, change in iris colour – damage can be
IRREVERSIBLE (so regular eye checks are important)
- HCQ-induced retinopathy is uncommon – but incidence increased by RISK FACTORS:
o Using HCQ > 5 years (greater cumulative exposure)
o Having renal and/or hepatic impairment (less clearance of drug)
2- Other ADRs of immunosuppressants: infection risk, anaemia, GI effects
GOUT
PATHOPHYSIOLOGY RECAP:
- GOUT = chronic monoarthritic disorder characterised by HYPERURICAEMIA
- Uric acid (UA) levels are naturally very high in many of us due to purine metabolism
- Many people w/ hyperuricaemia are ASYMPTOMATIC (not considered to have gout)
- When UA precipitates out of ECF sharp UA crystals accumulate in joints & SC
tissue arthritis (inflamed joints)
CAUSES:
- Increased consumption of purines (metabolised to UA)
o Shellfish, Red Meat, Organ Meats (e.g. Liver) & Alcohol (source of purines)
- Reduced clearance of UA
o Renal impairment reduces excretion of UA
- Side effects of drugs:
o Diuretics: have hypovolemic effect increases risk of UA precipitation
o Cytotoxics: risk of TLS release of purines into ECF metabolised to UA
SYMPTOMS
- Inflammation in the 1st metatarsal phalangeal (MTP) joint – AKA the big toe joint
- Gouty tophi: UA build-up in SC tissue painful nodules – often affects ears/fingers
- Kidney stones: late COMPLICATION of gout (if left untreated)
Like RA, gout causes flare ups – these are EXTREMELY PAINFUL – so reducing
hyperuricaemia is essential in maintaining remission
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