Pharmacology Flashcards
1
Q
First-line agent for osteoporosis
A
Bisphophonates
2
Q
MOA of bisphosphonates
A
Slow bone loss by increasing osteoclast cell death
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
4
Q
Maximum duration for bisphosphonate therapy
A
5 years for PO therapy
3 years for IV therapy
5
Q
MOA of denosumab
A
Human Mab against RANKL, preventing osteoclast development and bone desorption
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
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
8
Q
MOA of raloxifene
A
- Selective estrogen receptor modulator
- Mixed oestrogen receptor agonist/antagonist
- Mimics the effect of oestrogen on bone density
9
Q
Contraindications & cautions for raloxifene
A
- CrCL < 30
- Current VTE
- Hepatic impairment
Cautions:
- Increased risk of thromboembolism
- Hot flushes
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
11
Q
Route of administration of calcitonin
A
IV, SC, IM, IN
12
Q
Contraindications of calcitonin
A
- Hypersensi
- Hypocalcemia
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
14
Q
Administration of romosozumab
A
SC injection every month for 12 months
15
Q
Contraindications of romosozumab
A
- Hypersensi
- Uncorrected hypocalcemia
- History of MI/stroke in the last 1 year
Caution:
- CrCl < 30
16
Q
MOA of teriparatide
A
- Synthetic parathyroid hormone
- Stimulates new bone formation and increases bone strength
17
Q
Administration of tertiparatide
A
Once daily SC injection for not more than 24 months
18
Q
Max duration of therapy wth teriparatide
A
24 months
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
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
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
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
Caution of probenecid
- 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
MOA of methotrexate
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
MOA of sulfasalazine
- 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
MOA of leflunomide
- 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
MOA of chloroquine & hydroxychloroquine
- 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
MOA of JAK inhibitors
- Inhibits the janus kinase pathway
- Prevents cytokine production by blocking JAK-STAT activation of gene transcription
31
MOA of anakinra
- Modified IL-1 receptor antagonist protein
32
MOA of tocilizumab
Irreversible inhibitor of IL-6 receptor, prevents homodimerisation of IL-6Rb signalling
33
Contraindications of TNF blockers
- Live vaccination
- Hepatitis b
- Severe HF
34
MOA of abatacept
- Fusion protein with CTLA-4-FcIgG1
- Binds to CD80 & CD86 and prevents CD28 activation
35
MOA of rituximab
- Chimeric mAb IgG1 directed at CD20 on naive & mature B cells, depleting CD20+ B cells
36
DDI for methotrexate
- NSAIDs/coxibs
- PPI
- Probenecid
- Vaccines
- Alcohol
37
DDI for hydroxychloroquine
- CYP2C9 inhibitors e.g. cimetidine
- Drugs causing qtc prolongation e.g. FQs
38
DDI for leflunomide
- Cholestyramine
- Activated charcoal
- Rosuvastatin
- Warfarin
- Vaccines
- Alcohol
39
DDI for colchicine
3A4 substrate
- Macrolides
- Azoles
- Statins
- Verapamil, diltiazem
40
DDI for allopurinol
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
DDI for calcium
Space 2 hours apart
1. Iron
2. Levothyroxine
3. Fluoroquinolones
4. Tetracyclines
5. Bisphosphonates
Others:
- PPI
- Fibre
42
DDI for vit D
1. Rifampicin
2. ASM
3. Cholestyramine
4. Orlistat
5. Aluminium
43
Contraindications for intraarticular glucocorticoids
- Periarticular infection
- Septic arthritis
- Periarticular fractures
- Joint instability
- Juxtaarticular osteoporosis
44
Drug-induced hyperuricemia
- Thiazide, loop diuretics
- Aspirin
- Cyclosporin
45
Contraindications of methotrexate
- Pre-existing liver disease
- Immunodeficiency
- Blood dyscrasias
46
Contraindications of sulfasalazine
- G6PD deficiency
- Sulfonamide allergy
47
DDI of sulfasalazine
- Antibiotics
- Warfarin
- Iron
48
Dose adjustment for methotrexate
- AST/ALT > 3x ULN: 75% of dose
- CrCl < 50: 50% of dose
- CrCl < 30: Avoid
49
Dose adjustment for sulfasalazine
- eGFR < 60: Use lower dose
- Dialysis: 250 mg OD, up to 1 g OD
50
Contraindication of hydroxychloroquine
- Pre-existing retinopathy
- G6PD deficiency (use with caution)
51
Dose adjustment for leflunomide
- ALT > 2xULN: Avoid
52
Contraindications for leflunomide
- Pre-existing liver disease
- Immunodeficiency
53
Metabolism of allopurinol
Renal metabolism
54
Metabolism of febuxostat
Hepatic metabolism
