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MSK > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

First-line agent for osteoporosis

A

Bisphophonates

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2
Q

MOA of bisphosphonates

A

Slow bone loss by increasing osteoclast cell death

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3
Q

Contraindications of bisphosphonates

A

IV:
- Hypocalcemia
- CrCl < 35

PO:
- Hypocalcemia
- CrCl < 35
- Oropharyngeal & GI complications
- Inability to sit upright for at least 30 mins, aspiration risk
- Pregnancy & lactation

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4
Q

Maximum duration for bisphosphonate therapy

A

5 years for PO therapy
3 years for IV therapy

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5
Q

MOA of denosumab

A

Human Mab against RANKL, preventing osteoclast development and bone desorption

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6
Q

Administration of denosumab

A
  • SC injection q6 months
  • Should be co-administered with 1000 mg Ca & at least 400 IU vit D daily
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7
Q

Contraindications & cautions of denosumab

A
  • Hypocalcemia
  • Pregnancy

Caution:
- Do not discontinue due to risk of spinal column fractures when discontinued
- Avoid in CrCl < 10
- Caution in eczema

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8
Q

MOA of raloxifene

A
  • Selective estrogen receptor modulator
  • Mixed oestrogen receptor agonist/antagonist
  • Mimics the effect of oestrogen on bone density
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9
Q

Contraindications & cautions for raloxifene

A
  • CrCL < 30
  • Current VTE
  • Hepatic impairment

Cautions:
- Increased risk of thromboembolism
- Hot flushes

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10
Q

MOA of calcitonin

A
  • A peptide hormone secreted by the parafollicular cells of the thyroid gland
  • Opposes effect of PTH
  • Reduces blood Ca levels
  • Inhibits osteoclast activity
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11
Q

Route of administration of calcitonin

A

IV, SC, IM, IN

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12
Q

Contraindications of calcitonin

A
  • Hypersensi
  • Hypocalcemia
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13
Q

MOA of romosozumab

A
  • Humanised mouse Mab against sclerostin
  • Removes inhibitory effect of sclerostin on the canonical Wnt signalling pathway which regulates bone growth
  • Increases bone formation & decreases bone resorption
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14
Q

Administration of romosozumab

A

SC injection every month for 12 months

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15
Q

Contraindications of romosozumab

A
  • Hypersensi
  • Uncorrected hypocalcemia
  • History of MI/stroke in the last 1 year

Caution:
- CrCl < 30

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16
Q

MOA of teriparatide

A
  • Synthetic parathyroid hormone
  • Stimulates new bone formation and increases bone strength
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17
Q

Administration of tertiparatide

A

Once daily SC injection for not more than 24 months

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18
Q

Max duration of therapy wth teriparatide

A

24 months

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19
Q

Contraindications of teriparatide

A
  • Hypersensi
  • Unexplained elevation of alkaline phosphatases
  • Pre-existing hypercalcemia
  • Metabolic bone diseases (Paget’s disease, hyperparathyroidism)
  • Skeletal malignancies
  • Hereditary disorders predisposing to osteosarcoma
  • Previous implant or radiation therapy to the bones
  • Severe renal impairment (CrCl < 30)
  • Pregnancy
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20
Q

Endogenous roles played by prostaglandins

A
  • BP & heart
  • Vascular constriction, platelet aggregation
  • Inflammation
  • Lungs
  • Gastric secretions
  • Intestinal motility
  • Fat breakdown
  • Kidneys
  • Uterine contraction during delivery
  • Release of eggs
  • Synovial joints
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21
Q

Contraindications of NSAIDs

A
  • Severe renal impairment
  • Severe HF
  • Active GI ulcer or bleeding
  • Bleeding disorders
  • Use of systemic corticosteroids or antithrombotics
  • Multiple risk factors for NSAID toxicity
  • Third trimester of pregnancy
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22
Q

MOA of intra-articular hyaluronic acid

A
  • Large glycosaminoglycan that is naturally occurring in synovial fluid
  • Provides shock absorption, traumatic energy dissipation, protective coating of cartilage and lubrication
  • Induces biosynthesis of HA and extracellular matrix in the synovial fluid
23
Q

MOA of colchicine

A
  • Binds to tubular and prevents tubular polymerisation into microtubules
  • Inhibits leukocyte migration and phagocytosis
  • Inhibits leukotriene B4 and prostaglandin production
24
Q

MOA of probenecid

A
  • Inhibits proximal tubular anion transport
  • Inhibits uric acid reabsorption
  • Increases uric acid excretion
25
Q

Caution of probenecid

A
  • Urolithiasis –> Drink plenty of fluids
  • Use alkaline salts (e.g. potassium citrate) to keep urine pH > 6
  • Precipitate flare –> Start only 2-3 weeks after acute attack
  • Not effective in CrCl < 50
26
Q

MOA of methotrexate

A
  1. Increases adenosine levels due to AICAR transformylase & ATIC inhibition
  2. Inhibits DHFR & thymidylate synthetase
  • Increases extracellular adenosine levels and activation of adenosine A2a receptors
  • Antiproliferative effects on T cells and inhibits macrophage fuctions
  • Decrease proinflammatory cytokines
27
Q

MOA of sulfasalazine

A
  • Metabolised into sulfapyridien & 5ASA
  • Modulates gut flora activity and:
  • Decreases IgA & IgM rheumatoid factors
  • Suppresses T & B cells and macrophages
  • Decrease inflammatory mediators
  • Inhibits leukotriene & TNF
28
Q

MOA of leflunomide

A
  • Converted to active teriflunomide metabolite
  • Inhibits dihydroorotate dehydrogenase
  • Decreases pyrimidine synthesis and arrests growth at G1 phase
  • Inhibits T cell proliferation & B cell autoantibody production
  • Inhibits NF-kB activation of pro inflammatory pathway
29
Q

MOA of chloroquine & hydroxychloroquine

A
  • Reduced MHCII expression & antigen presentation
  • Reduced TNF-a and IL1 and cartilage resorption
  • Exerts antioxidant activity

YKZ:
- Inhibits locomotion of neutrophils
- Inhibits chemotaxis of eosinophils
- Inhibits complement-dependent antibody action

30
Q

MOA of JAK inhibitors

A
  • Inhibits the janus kinase pathway
  • Prevents cytokine production by blocking JAK-STAT activation of gene transcription
31
Q

MOA of anakinra

A
  • Modified IL-1 receptor antagonist protein
32
Q

MOA of tocilizumab

A

Irreversible inhibitor of IL-6 receptor, prevents homodimerisation of IL-6Rb signalling

33
Q

Contraindications of TNF blockers

A
  • Live vaccination
  • Hepatitis b
  • Severe HF
34
Q

MOA of abatacept

A
  • Fusion protein with CTLA-4-FcIgG1
  • Binds to CD80 & CD86 and prevents CD28 activation
35
Q

MOA of rituximab

A
  • Chimeric mAb IgG1 directed at CD20 on naive & mature B cells, depleting CD20+ B cells
36
Q

DDI for methotrexate

A
  • NSAIDs/coxibs
  • PPI
  • Probenecid
  • Vaccines
  • Alcohol
37
Q

DDI for hydroxychloroquine

A
  • CYP2C9 inhibitors e.g. cimetidine
  • Drugs causing qtc prolongation e.g. FQs
38
Q

DDI for leflunomide

A
  • Cholestyramine
  • Activated charcoal
  • Rosuvastatin
  • Warfarin
  • Vaccines
  • Alcohol
39
Q

DDI for colchicine

A

3A4 substrate
- Macrolides
- Azoles
- Statins
- Verapamil, diltiazem

40
Q

DDI for allopurinol

A
  1. Increased bone marrow suppression with:
    - 6 mercaptopurine
    - Azathioprine
    - Cyclophosphamide
  2. Increased hypersensitivity with:
    - ACE inhibitors
    - Loop diuretics
    - Thiazide diuretics
    - Ampicillin / amoxicillin
  3. Increased concentrations of:
    - Carbamazepine
    - Warfarin
    - Theophylline
  4. Increased toxicity of pegloticase
41
Q

DDI for calcium

A

Space 2 hours apart
1. Iron
2. Levothyroxine
3. Fluoroquinolones
4. Tetracyclines
5. Bisphosphonates

Others:
- PPI
- Fibre

42
Q

DDI for vit D

A
  1. Rifampicin
  2. ASM
  3. Cholestyramine
  4. Orlistat
  5. Aluminium
43
Q

Contraindications for intraarticular glucocorticoids

A
  • Periarticular infection
  • Septic arthritis
  • Periarticular fractures
  • Joint instability
  • Juxtaarticular osteoporosis
44
Q

Drug-induced hyperuricemia

A
  • Thiazide, loop diuretics
  • Aspirin
  • Cyclosporin
45
Q

Contraindications of methotrexate

A
  • Pre-existing liver disease
  • Immunodeficiency
  • Blood dyscrasias
46
Q

Contraindications of sulfasalazine

A
  • G6PD deficiency
  • Sulfonamide allergy
47
Q

DDI of sulfasalazine

A
  • Antibiotics
  • Warfarin
  • Iron
48
Q

Dose adjustment for methotrexate

A
  • AST/ALT > 3x ULN: 75% of dose
  • CrCl < 50: 50% of dose
  • CrCl < 30: Avoid
49
Q

Dose adjustment for sulfasalazine

A
  • eGFR < 60: Use lower dose
  • Dialysis: 250 mg OD, up to 1 g OD
50
Q

Contraindication of hydroxychloroquine

A
  • Pre-existing retinopathy
  • G6PD deficiency (use with caution)
51
Q

Dose adjustment for leflunomide

A
  • ALT > 2xULN: Avoid
52
Q

Contraindications for leflunomide

A
  • Pre-existing liver disease
  • Immunodeficiency
53
Q

Metabolism of allopurinol

A

Renal metabolism

54
Q

Metabolism of febuxostat

A

Hepatic metabolism

MSK (5 decks)

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