pharmacology for bone disorders and inflammation Flashcards
what two major types of drugs are used in bone disorders
antiresorptive agents (anti-osteoclast) bone anabolic agents (pro-osteoblasts and osteocyt
what are the drugs used that are anti-resorptive agents for bone disorders
bisphosphates
selective oestrogen receptor moedulators
RANK Ligand inhibitors
what are the drugs used that are bone anabolic agents for bone disorders
parathyroid hormone
oral calcium
oral vitamin D analogues
calcitonin
what is an example of a drug that is a bisphosphonate
alendronate
what are bisphosphonates
resistant analogues of pyrophosphate (analogue of the bone matrix)
action of bisphosphonates
- inhibit the recruitment of osteoclasts
- promote apoptosis of osteoclasts
explain the administration of bisphosphonates
administered weekly
what is the disadvantage of taking bisphosphonates
- oesophagitis risk
- oesophageal cancer risk
- atypical fracture risk
- osteonecrosis of the jaw risk
how is oestrogen administered for bone disorders
administered with a progestagen
side effects of taking oestrogen for bone disorders
increased risk of cardiovascular disease and breast cancer
what do we use now instead of giving oestrogen for treating bone disorders
selective oestrogen receptor modulators (SERM’s)
what is an example of a drug that is a SERM
Raloxifene
what is the action of Raloxifene
- agonist at oestrogen receptors in bone and cardiovascular tissue
- antagonist at oestrogen receptors in mammary tissue and uterus
what is Denosumab
a RANK ligand inhibitor
action of Denosumab
binds to RANKL and inhibits RANKL activity –> reducing osteoclastic activity
what is the advantage of Denosumab over other drugs for bone disorders
it has been shown to increase bone density in post menopausal women
explain the paradoxical behaviour of PTH
- Acutely: promotes osteoblast development and activity –> favours bone anabolism
- Continuous/high exposure: promotes osteoclast activity –> promotes bone catabolism
what are the side effects of taking oral calcium for bone disorders
GI disturbances
what are 2 drugs called that are oral calcium drugs
calcium gluconate
calcium lactate
when is Vitamin D drug treatment used
- deficiency states (rickets and osteomalacia)
- endocrine dysfunction (hypoparathyroidism)
- chronic renal disease (where calcitriol cannot be generated in kidney)
how do you give Vitamin D to a patient (other than sunlight)
- Vit D2 –> converted to D3 in liver
- calcitriol (biologically active)
what are the two types of calcitonin medications
natural calcitonin (porcine) synthetic calcitonin (salcatonin)
how do you administer calcitonin to a patient
given by SC or IM injection or nasal spray
anti inflammatory medications target what
eicosanoids
how are glucocorticoids anti-inflammatory
they inhibit AA release and metabolism –> suppressing the formation of pro-inflammatory prostaglandins and leukotrienes
how are NSAIDs anti-inflammatory
inhibit COX 1 and 2 –> suppresses the formation of pro-inflammatory prostaglandins
how are CysLT1 receptor antagonists anti inflammatory
they block LTC4 and LTD4 actions
what is the difference between COX1 and COX2
COX1 - constitutively expressed in most cells
COX2 - expressed in inducible inflammatory cells
what cells express COX2
macrophages
fibroblasts
SM
endothelium
what are the effects of cannabinoid 1 and 2 receptors
appetite stimulation anti-nauseant analgesia sedation psychoactivity ANTI-INFLAMMATORY
where is the distribution of CB1 and CB2 receptors
CB1 - CNS
CB2 - in the periphery
what are two drugs that are used that mimic the actions of prostaglandins
epoprostenol PGI2 analgoue
misoprostol PGE1 analogue
what is the action of epoprostenol PGI2 analogue
vasodilates the pulmonary vasculature - used in pulmonary hypertension
what is the use of misprostol PGE1 analogue
as an adjuvant to mifepristone as abortifacient
what are the effects and indications of NSAIDs
- anti-inflammatory - acute and chronic inflammatory conditions
- analgesic - headache, menstrual pain…
- anti-pyretic
- (anti-aggregatory)
why is aspirin contraindicated in gout
because aspirin and uric acid crystals use the same anion transporter in the kidney
what are the adverse effects of NSAIDs
- gastrointestinal ucers
- increased bleeding time
- renal effects
- pulmonary effects
why do NSAIDs cause gastrointestinal side effects
because it inhibits mucosal synthesis of PGI2 and PGE2 which are protective in the stomach
what are the roles of PGE2 in the stomach
- increases mucus secretion
- reduces gastric acid secretion
- promotes blood flow
- promotes angiogenesis
why do NSAIDs cause an increased bleeding time
because they decrease TXA2 synthesis –> impaired platelet aggregation
how can NSAIDs cause renal effects
- because they cause a decreased prostacyclin synthesis –> decreased dilatation of renal artery
- may decrease PGE2 –> decreased natriuresis –> increased blood pressure
NSAIDs may cause renal failure in which kind of patients
- hypovolaemic patients
- patients with underlying renal disease
- patients with heart failure
how can NSAIDs cause pulmonary effects
can push the arachadonic acid pathway down the leukotriene route –> aspirin sensitive asthma
what are the 2 effects of aspirin
- irreversible acetylation of COX –> PGI2/TXA2 ratio increased
- acetylated COX synthesis aspirin triggered lipoxins (ATLs)
what is the action of aspiring triggered lipoxins
pro resolution mediatory –> turns off the infiltration of the tissue by neurtrophils
why is paracetamol special
it is analgesic and antipyretic… but NOT anti-inflammatory
what is celecoxib
a selective COX2 inhibitor
why was celecoxib made
because COX2 selective means:
- less GI adverse effects
- less anti-platelet effect
3 principle mechanisms of glucocorticoids
direct transactivation
direct transrepression
tethered transrepression
