Block 1/2 Flashcards
(25 cards)
Dosage for calcium supplementation
500-600 mg/day
What are the two types of anabolic medications for OP?
- PTH analogs (teriparatide / abaloparatide)
- Sclerostin inhibitors (romosozumab)
Teriparatide
(class, MOA, effects)
Class: PTH analog
MOA: pulsatile increase in PTH signalling targets OBs –> increased OB # and activity
Effect: more bone formation
** Terry accumulates more
Abaloparatide
(class, MOA, effects)
Class: PTHrP analog
MOA: pulsatile increase in PTH signalling targets OBs –> increased OB # and activity
Effect: more bone formation
** Abs formed on bones
Romosozumab
(class, MOA, effects)
Class: sclerostin inhibitor
MOA: inhibits Wnt pathway that decreases OB activity –> decrease in RANKL via OPG & increased activity of OBs in non-affected sites
Effect: more/extra bone formation
3 types of anti-resorptive medications for OP
- RANKL inhibitors
- bisphosphonates
- SERMs
Raloxifene
(class, MOA, effects)
Class: SERM (selective estrogen receptor modulator)
MOA: estrogen needed for BMSCs and OBs –> higher estrogen signalling —> more OPG —> lower RANKL —> low OC formation
Effect: less bone resorption
** Ralox = relax, we’ll fix your menopause
Denosumab
(class, MOA, effects)
Class: RANKL inhibitor
MOA: lower RANKL signalling —> low OC formation
Effect: less bone resorption
** similar effects to SERMs like raloxifene
Etidronate
Alendronate
Risedronate
Zolendronate (zolendronic acid)
(class, MOA, effects)
Class: bisphosphonates
MOA: bind to exposed Ca2+ on surface of bone, inhibiting Ca2+ release; taken up by OC & inhibits FPPS in mevalonate pathway —> no ruffling (prenylation) of OC –> less contact w/ bone = early apoptosis
Effect: less bone resorption
** dron = harden bone
4 types of conventional synthetic drugs for RA (csDMARDs)
Methotrexate
Leflunomide
Salazopyrine
Hydroxychloroquine
Methotrexate: MOA, effect & dosage
MOA: purine antagonist; inhibits DHFR and TYMS in folic acid pathway
Effect: lowers excessive T cell expansion (and B cell)
Dosage: up to 20 mg weekly
Leflunomide: MOA, indications & side effects
MOA: pyrimidine antagonist; active form (teriflunomide) blocks dehydroorate dehydrogenase (DHODH)
Indications: alone or in comb.
Side effects: Leave Room In Case of Danger
- abnormal liver function tests
- diarrhoea
- rash
- infection
- cytopenias
Sulfasalazine: proposed MOA, indications & side effects
Proposed MOA: weak COX inhibitor; inhibits NFKB pathway & immune cell recruitment/proliferation
Indications: alone in sero(-) RA or in combination
SEs: nausea, headache, rash
Lots of pills (4-6/day)
Hydroxychloroquine: MOA, indications & side effects
MOA: inhibits antigen presentation on MHCII; increases pH in lysosomes —> failure to degrade & process self-antigens —> less self-reactive T/B cell clonal expansion
Indication: combination therapy
SE: TONS - incl. GI intolerance, rash, retinal complication (rare)
See notes for more dets
What do biologic DMARDs target?
IL-1
IL-6
TNF
ixns between T cells and APCs / B cells”
Infliximab
Adaluminab
Golimumab
Etanercept
Certolizumab
Class, MOA, effects
Class: bDMARDs
MOA: TNF inhibitors (Abs against TNF or TNFR)
Effects:
- reduction of cytokines/chemokines
- reduces VEGF / angiogenesis
- inhibit COX / PG synthesis
- reduced inflammation, immune cell activation/prolif./diff/chemotaxis
Tocilizumab: Class and MOA
Class: bDMARD (Ab)
MOA: IL-6 inhibitors (block JAK/STAT pathway)
Effect: similar to TNF inhibitors;
reduced cytokines/chemokines,
reduced inflammation & immune cell activation/proliferation/diff./chemotaxis
Which tsDMARDs target the JAK/STAT pathway like tocilizumab?
Tofacitinib
Baricitinib
Upadacitinib
- all inhibit JAK (1/2/3)
Tofacitinib: Class, MOA, effect, indications, side effects
Class: tsDMARD
MOA: Janus kinase (JAK) inhibitor; blocks signal transduction & cell activation
Effects: similar to TNF inhibitors;
reduced cytokines/chemokines,
reduced inflammation & immune cell activation/proliferation/diff./chemotaxis
Indication: used w/ or w/o methotrexate (when eligible to use bDMARD)
Side effects: Not Really Loving This
mild liver & renal dysfunction, neutropenia, thrombosis
Which two bDMARDs are targets of B cells? What specifically do they target?
- rituximab (CD20)
- abatacept (receptor for CTLA-4 on APC)
Rituximab: Class, MOA & effect
Class: bDMARD
MOA: Ab to CD20 on B cells; rituximab-coated B cells bind Fcγ receptors (FcγRIII) on NK cells, macrophages, and neutrophils –> release of granzymes and perforin, inducing apoptosis of B cells
Effect: depletes B cells
Abatacept: Class, MOA, effect
Class: bDMARD
MOA: agonistic monoclonal Ab; typically, after an immune response, T cells down-regulate APCs by expressing CTLA-4 instead of co-stimulatory CD28 - Abatacept is a CTLA-4 agonist (agnostic monoclonal Ab)
Effect: signals B cells to stop presenting antigen
Probenecid: Indication & MOA
Indication: Gout treatment
MOA: inhibits re-uptake of uric acid in kidney (blocks URAT1)
Allopurinol: Indication & MOA
Indication: Gout treatment
MOA: inhibitor of xanthane oxidase (XO); inhibits production of uric acid
