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Rheumatology > Rheum Pharmaco > Flashcards

Rheum Pharmaco Flashcards

1
Q

What are the MOA of hydroxychloroquine in SLE?

A
  • By↑ cellular pH, inhibits Toll-like receptor mediated activation of the innate immune system -> inhibition of IFN-a expression and thereby prevents activation of multiple IFN-α-mediated pathways and resultant widespread inflammatory damage
  • Anti-thrombotic
  • Anti-lipidemic
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2
Q

What is the MOA and indications of cyclophosphamide?

A

Uses

  • Remission induction in SLE/CTD with major organ involvement
  • Myeloablative: cancer treatment (requires different dosage)

Mechanism of action: - Alkylating agent; inhibits DNA synthesis, hence Cytotoxic!

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3
Q

What are the common adverse reactions of cyclophosphamide?

A

Common adverse reactions

  • GI: nausea, vomiting
  • Haematological: myelosuppresive (leukopenia, pancytopaenia)
  • Bladder toxicity: haemorrhagic cystitis/bladder cancer (due to renally excreted toxic metabolites \r)
  • Ovarian failure, subfertility/ sterility. Sperm storage, oocyte preservation in adults of child-bearing age
  • Teratogenicity

Opportunistic infections & Reactivation of Latent infections

  • Reactivation: Herpes Zoster, HSV, EBV, CMV, Tb, Hep B
  • Pneumocystis Jirovecii (give prophylactic co-trimoxazole)

Dose adjustment in renal impairment

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4
Q

What is the MOA and indication of Mycophenolate mofetil (MMF)?

A

Remission induction or maintenance in SLE/CTD with major organ involvement e.g. diffuse proliferative lupus nephritis in women of child-bearing age (subfertility risk with cyclophosphamide)

Mechanism of action

  • An ester prodrug of the active agent mycophenolic acid (MPA)
  • MPA non competitively and reversibly inhibits inosine monophosphate dehydrogenase (IMP‐DH), which catalyses a rate limiting step in the de novo synthesis pathway of purine nucleotides
  • Lymphocytes are dependent on the de novo pathway
  • MMF inhibits the proliferation of both B and T lymphocytes and decreases antibody production
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5
Q

What are the common adverse reactions of Mycophenolate mofetil (MMF)?

A
  • GI: nausea, diarrhea, abdominal discomfort
  • Haematological: leukopenia, anaemia, thrombocytopaenia
  • Common and opportunistic infections e.g. Herpes Zoster, HSV, EBV, CMV, Tb, Hep B
  • Teratogenicity
  • Cancer risk (lymphoma, skin cancers) in post-transplant patients receiving MMF
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6
Q

What is the MOA and indications of Azathrioprine?

A

Uses: MAINTAIN Remission of SLE/CTD; and RA

Prodrug that is Converted to 6-mercaptopurine, inhibits de novo purine synthesis in lymphocytes

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7
Q

What are the common adverse effects of Azathrioprine?

A

Common adverse effects

  • GI: nausea/vomiting
  • Haematological: leukopaenia, pancytopenia
  • Liver: hepatitis(AZT is hepatotoxic)
  • Hair loss (which can also be an effect of SLE)
  • Not teratogenic

ADR w ALLOPURINOL (dangerous myelotoxicity)

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8
Q

What is the MOA of ciclosporin?

A

Uses:

  • Usually given to post-transplant patients
  • AI Conditions – RA, psoriasis etc

Inhibits Ca-dependent T-cell signalling pathways by preventing Calcineurin Activation

  • CsA first binds to Cyclophilin (cytoplasmic receptor) -> inhibits Calcineurin activation -> Prevents IL2 production
  • IL2 is impt for T Cell proliferation -> hence inhibits T Cell activity
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9
Q

What are the common adverse reactions of ciclosporins?

A
  • Hypertension
  • ↑ K, Cr, uric acid
  • Headache, nausea, vomiting, abdominal pain
  • Tremors, hirsuitism, gum hypertrophy
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10
Q

What are the indications for IVIg?

A
  • Refractory haemolytic anaemia, thrombocytopaenia
  • Severe, active disease with major organ involvement
  • Kawasaki
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11
Q

What is the MOA + indications of Rituximab?

A
  • Anti-CD20 monoclonal Ab
  • Mechanism of action: B cell depletion
  • Indications: Induction of remission in refractory disease
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12
Q

What are the adverse reactions or Rituximab?

A
  • Risk of infection with repeated course

- Hypogammaglobulinaemia

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13
Q

What are the side effects of NSAIDS and COX 2 inhibitors?

A

Non-Selective: Decreased risk for CV ents GI Side Effects (Dyspepsia, PUD, bleeds, perforation)

COX2 Selective (-coxibs): Increased risk of CV Side Effects (AMI, Strokes), decreased GI side effects

ALL NSAIDs: Nephrotoxic due to afferent VasoC! Hence C/I in renal impairment

NSAID Hypersensitivity 2 Main types: (TBL)
1) Pseudoallergy (pathophysio not well understood)
• Result of COX1 Inhibition, hence can be caused by MANY drugs
• Degree of COX1 inhibition = severity of Pseudoallergy
• Presents with Urticaria & Angioedema / Asthma / Both

2) Allergy (IgE Mediated)
• Elicited by a SINGLE NSAID
• A prior sensitization event w less severe symptoms
• Present similar to Pseudoallergy OR even anaphylaxis!

Always check for PUD, Reflux, Renal Insufficiency, Allergy before prescribing!

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14
Q

What are the side effects of glucocorticoids?

A
  • Dermatologic: skin atrophy, acne, Cushingnoid appearance
  • Ophthalmic: cataracts (posterior subcapsular)
  • Renal: hypokalemia, hypertension (cross-reactivity w mineralocorticoid receptor)
  • Endocrine/metabolic : hyperglycemia/DM
  • Cardiac: ischaemic heart disease
  • MSK: osteoporosis, hence can give calcium and vitamin D supplements, Avascular Necrosis of Hip,
  • GI: gastrointestinal bleeding (esp. w concurrent NSAID use), give PPI cover
  • ID: infections (due to immunosuppression)
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15
Q

What are the common side effects of DMARDs?

A
  • BM Suppression (Myelotoxicity) -> Infection
  • Hepatotoxicity
  • GI S/E (can be very severe!)
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16
Q

What are the baseline tests before starting DMARDs AND during DMARDs provision!

A

FBC (cytopenias), LFT (hepatotoxicity), Renal Panel (for drug excretion)

Assess for LATENT infections to avoid reactivation PRIOR to provision

  • HBsAg, anti-HCV (hepatitis B/C reactivation), Tb, HSV
  • CXR (TB, pneumonitis) -> assess latent Tb using IGRA + CXR

Assess G6PD Def (for SSZ and HCQ) – PRIOR to provision

Ophthalmology Assessment (for HCQ) – both PRIOR and DURING

17
Q

What is the MOA of Methotrexate? What are the indications?

A

Mech: anti-metab and anti-folate drug (competitive inhibition of dihydrofolate reductase) hence give folic acid supplements too

Competitive inhibition of dihydrofolate reductase –> prevent regen of dihydrofolate of tetrahydrofolate –> no folate cofactors –> no purine and pyramidine pdtn

ANCHOR DRUG in RA treatment” most effective single drug for RA

  • Always give MTX to all RA patients, unless C/I by ILD!
  • Can be given as monotherapy / combi therapy for RA

Give Folic Acid 5mg once a week (given the day after MTX)

18
Q

What are the C/Is of MTX?

A
  • C/I in renal impairment, liver cirrhosis, HBV/HCV carrier
  • C/I in pregnancy
  • C/I in ILD
  • Avoid Bactrim given for UTI treatment (too high dose, cause excessive myelosuppression); However, dosage for PCP prophylaxis is alright
19
Q

What are the S/Es of MTX?

A
  • Marrow toxicity -> pancytopenia
  • Hepatitis: Toxicity to liver, causing transaminitis
  • Pneumonitis and ILD (Due to hypersensitivity reaction) -> is a C/I
  • GI: N&V (can be reduced via weekly IM / SC)
  • Teratogenic; avoid pregnancy 6 months after stopping MTX for both sexes
20
Q

What is the indications of Leflunomide (LEF)?

A

In the setting of RA, LEF is used when MTX is not tolerated / is C/I

21
Q

What are the S/Es of Leflunomaide (LEF?)

A
  • GI: diarrhoea and nausea
  • Haem (cytopenias): leukopenia, thrombocytopenia
  • Dermatologic: alopecia and skin rash (drug eruption)
  • Cardioresp: respiratory tract infection, hypertension
  • CNS: headache
  • Liver: hepatitis & derangement
  • Teratogenic; cholestyramine/activated charcoal washout after stopping LEF if pregnancy intended (6 months before conception), or during toxicity
22
Q

What is the MOA of sulfasazine?

A

Azo-linkage of SSZ is reduced by colonic azoreductases, releasing 5-ASA & sulfapyridine

5-ASA: Anti-inflammatory action of 5-ASA eg NF-(kappa) B activation, inhibition of production of inflammatory mediators and antioxidant action

Recall: 5ASA include Olsalazine & Mesalazine, used to treat IBD

23
Q

What are the side effects of sulfasazine?

A

S/E (safe in renal impairment and pregnancy)

  • GI: N&V, dyspepsia
  • Haem: haemolysis (G6PD deficiency), thrombocytopenia, leukopenia
  • Liver: hepatitis (less than MTX and LEF, hence can be used w alcohol unlike MTX and LEF)
  • Drug reaction: maculopapular/others
  • CNS: headache

NOT Teratogenic!

The SAFEST in renally impaired patient

24
Q

What are the side effects of hydroxychloroquine?

A

Common: GI (N&V, abdominal cramps, diarrhoea), headache, light-headedness

Bull’s Eye maculopathy (serious!)

  • Ophthalmology consultation BEFORE commencing (baseline fx)
  • Yearly reviews from 5th year onwards
  • Retinal exam, Humphrey visual field testing (HVF), spectral domain coherence tomography, Amsler’s Chart for Macular Function

Hyperpigmentation with prolonged use

Anaemia in G6PD Deficiency

Not teratogenic! Can be continued in pregnancy

25
Q

What are the the general adverse reactions of biologics?

A

Infections

  • Reactivation: TB (pulmonary/extrapulmonary -> esp TNF), chronic hepatitis B
  • Hence important to screen with TST / IGRA + HbsAg + CXR & treat accordingly
  • Other bacterial, mycobacterial, viral, fungal infections
  • Give Vaccination prior to biologics!

Demyelination (anti-TNFi)

Heart failure (anti-TNFi)

Malignancy

Hypersensitivity/allergic reactions

26
Q

What are important drug/ food interaction with ciclosporins

A

Drug/food interactions (important ones)

  • Calcium channel blockers (CCB)
  • Statins
  • Grapefruit juice: increase CsA levels by decreasing breakdown

Rheumatology (26 decks)

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