Y2 ENDOCRINE PHARMACOLOGY Flashcards
main use of corticosteroids?
- suppress inflammation, suppress immune system, replacement therapy.
activation of the renin angiotensin system leads to?
angiotensin II production causing vasoconstriction and indirect increase in BP (aldosterone).
renin angiotensin system is activated in response to?
aldosterone production
aldosterone production is regulated by?
renin angiotensin system and plasma potassium
sodium and water are controlled by?
- mineralocorticoid activity and ADH.
mineralocorticoid receptors are found?
- kidneys, salivary glands, gut and sweat glands.
aldosterone acts on mineralocorticoid receptors to?
- regulate BP
- balance Na+ and K+
- regulate ECF volume
management of adrenal insufficiency?
- hydrocortisone (cortisol) 15-30m/day in divided doses to try mimic diurnal variation.
- fludrocortisone (aldosterone) - carefully monitor BP and K.
adrenal cortex is a major source of?
human glucocorticoids - cortisol, mineralocorticoids - aldosterone and androgens.
cortisol/androgen secretion is regulated by?
pituitary ACTH secretion by a negative feedback mechanism.
aldosterone regulates?
BP and electrolyte excretion
how do you manage phaeochromocytoma medically?
full α and β blockade - α before β!!!
- α: phenoxybenzamine.
- β: propranolol/ atenolol/ metoprolol.
- fluid +/or blood replacement.
- careful anaesthetic assessment.
how do you manage phaeochromocytoma surgically?
laparoscopically:
- total excision when possible.
- tumour de-bulking where full removal not possible.
management of acute hypercalcaemia?
- fluids 4-6L of 0.9% saline over 24 hours.
- loop diuretics? once rehydrated (not thiazide)
- bisphosphonates
- steroids if sarcoidosis.
management of acute malignant hypercalcaemia?
- chemo e.g. in myeloma
- fluids 4-6L of 0.9% saline over 24 hours
- bisphosphonates
what are bisphosphonates?
anti-resorptive agents (bone).
They are pyrophosphate analogues that adsorb onto bone within the matrix.
examples of bisphosphonates?
- alendronate and risedronate
action of bisphosphonates?
prevent bone loss at all sites vulnerable to osteoporosis
why are bisphonates used?
to reduce the risk of hip and spine fracture
bisphosphonates are ingested by?
osteoclasts to cause cell death - inhibiting bone resorption
bisphosphonates allow filling of resorption sites by new bone to increased BMD by?
5-8%
Bisphosphonates e.g. alendronate and risedronate reduce the risk of fragility fracture by?
= 50% in those with post-menopausal osteoporosis.
what long term concerns are associated with bisphosphonate therapy?
- osteonecrosis of the jaw.
- oesophageal carcinoma
- atypical fractures
zoledronic acid is given as?
- a once/year IV infusion for 3 years.
- 5mg in 100ml NaCl ver 15 mins.
how many experience an acute phase reaction with 1st infusion of zoledronic acid?
1:3
how do you manage an acute phase reaction with 1st infusion of zoledronic acid?
paracetamol
zoledronic acid reduces fracture risk by?
- 70% for vertebral fracture
- 40% for hip fracture
what monoclonal antibody targets and binds to RANKL to prevent activation of RANK receptor and thus inhibiting development and activity of osteoclasts?
denosumab
decreases bone resorption and increases bone density
how is densoumab (monoclonal antibody) administered for osteoporosis?
subcut. injection every 6 months
side effects of denosumab?
- cellulitis
- eczema
- hypocalcaemia (can be fatal)
what is teriparatide?
a recombinant parathyroid hormone
action of teriparatide?
stimulates bone growth instead of reducing bone loss.
- anabolic agent
when is teriparatide prescribed?
- if <65 yrs with T-score of equal to or less than -4.
- if T score of 2 fractures.
- if 55-64y/o with T score less than or equal to -4 + >2 fractures + unsatisfactory response to oral agents
how do corticosteroids directly impact bone?
- reduce osteoblast activity and life span
- suppress replication of osteoblast precursors
- reduce calcium absorption
how do corticosteroids indirectly impact bone?
- inhibit gonadal and adrenal steroid production
management of Paget’s
- analgesia
- bisphosphonates if pain doesn’t respond to analgesia
management of addisonian crisis?
high dose oral hydrocortisone and fludrocortisone