pharmacology Flashcards
RANK
expressed on osteoclast precursor cells,
wen RANK activated, osteoclasts are activated
RANKL
expressed on osteoblasts.
these activate RANK on osteoclasts to activate osteoclasts =increase bone resroption
OPG
osteoprotegerin
soluble forms of RANK. mops up RANKL, stopping it from activating RANK i.e. bone protective
CALCITRIOL
- active form of Vit D
- Maintains Ca2+ in the plasma by increasing GIT uptake and decreasing renal exretion
- AE: hypercalcemia (manifesting as nausea, vomiting, constipation, anorexia, sweating and polyuria)
CALCIUM
• Sucks by itself, give with other anti-resorptive agents eg calcitriol
SERM
- Selective Estrogen Receptor Modulators
- Drug: raloxifene
- Modulates receptors on bone, increases estrogenic activity (oestrogen promotes bone mineralization), increases bone density.
- AE: Venous thromboembolism.
BISPHOPHONATES
- Drug: old/oral: alendronate (core drug), risedronate. New/intravenous: zoledronate, ibandronate
- Firstline for post-menopausal women!
• MOA:
o Biphosphonates are analogs of pyrophosphate
o They are taken into bone, concentrated in bone, layed down in mineralized matrix of bone for many years-reducing rate of bone turnover.
o Also: reduce resorption of bone by inhibiting formation n activity of osteoclasts
• AE of biphosphonate generally:
o Osteonecrosis of jaw
o Atypical fractures (eg they are ok, bone density ok, no trauma ,but they suddenly present with pain froma hip fracture etc
o Anterolateral thigh pain
• AE of alendronate (core drug), risedronate
o GIT disturbances
o Ulceration – oesophagitis
• Complicated administrations for oral bisphosphonates
taking biphophonates
o Take first dose early in the morning • Take on an empty stomach (30 min before food) o Separate administration of other medications from bisphosphonate dose • Swallow tablet whole – do not crush, chew or suck • Take with a full glass of water • Patient to remain upright for 30 minutes to 1 hour after dose
DENOSUMAB
- Monoclonal antibody against RANKL=decrease osteoclast activity
- Used in postmenopausal women where bisphosphonates are unsuitable
- Has negative immune systemic effects
CALCITONIN & SALCITONIN
- inhibits osteoclasts activity, low efficacy
* calcitonin has (longer 1/2 life) than calcitonin
OESTROGEN/HORMONAL REPLACEMENT THERAPY
- Increases OPG (decoy) thereby inhibiting osteoclasts.=inhibit bone loss
- Aes: Increase risk of cancer and cardiovascular effects (not usually recommended).
BONE ANABOLIC AGENTS
PTH/PTH FRAGMENTS
STRONTIUM RANELATE
PTH/PTH FRAGMENTS
- Drug: teriparatide
- PTH segemtns mightseem contradictory, but if u give intermitteitnly by a dialy subcuuatnous regime., it actually causes bone anabolis (bone build up) n stimulatie osteobalst activey
- Restricted use of 18mnth only in a pt’s lifetime. due to risk of osteosarcoma
- used when high risk of fracture & other treatments unsuitable-later resort
STRONTIUM RANELATE
- inhibits bone resorption, stimulates bone formation,
- Increases OPG (decoy).
- Decrease RANKL
- Still in trials, question bout long term safety –seizrues, blood clots etc
metformin
first line for type 2 dm
increase tissue sensitivity to insulin
don’t give in pt with renal problem
SE: weight loss, nausea, diarrhoea
pioglitazone/rosiglitazone
class: glitazone/TZD
increase tissue sensitivity to insulin -bind to PPAR gamma
inhibit hepatic gluconeogenesis
SE: weight gain,
rosiglitazone - has issues with long term safety- CVD issues
sulphonylureas
drug: glicazide
stimulate release of insulin by acting on pancreas cells
block ATP-sensitive K+ channels=cause depolarisation of beta cells=insulin released from cells.
SE: hypoglycaemia , weight gain (appetite stimulating), high protein binding
glicazide
block ATP-sensitive K+ channels
the ORIGINAL
glitinide
use if pt allergic to sulphon/glicazide
same MOA/job as glicazide/sulphonylureas
shorter duration of action to sulphon
alpha glucosidase inhibitors
delay breakdown of carbo
carbo broken down to glucose by glucosides
drug= acarbose
acarbose
delay breakdown of carbo by inhibiting glucosides
=helps with reducing the rising surge of blood glucose levels after a meal
SE= flatulance, diarrhoea
exenatide
incretin mimetic
mimics effects of GLP-1
GLP-1 stimulates pancreas to release insulin wen we eat
=get initial rapid release of endogenous insulin
sitagliptin
block DPP-4
DPP-4 is used to break down GLP-1 n GIP
=increase levels of GLP-1 n GIP
GIP/GLP-1
stimulate pancreas to release insulin
