Thyroid and Osteoporosis Drugs Flashcards
Thyroid is regulated by
- TSH
-
iodide
- low iodide in diet would stimulate thyroid gland; high iodide in diet can inhibit thyroid hormone production but body can overcome this by homeostasis
function of thyroid hormones
- increases basal level of metabolism
- important for growth and maturation (including CNS)
hypothyroidism in children can lead to
cretinism
Which thyroid hormone is most prevalent
Thyroid glands makes more T4
Thyroid hormones act through which receptors
- act through nuclear receptors
- therapy takes time
How is T3 made
- secreted by thyroid
- metabolite of T4 by peripheral cells
Which thyroid hormone is more effective (biologically active)
T3 is 3-5x more effective than T4
clinical presentation
- slow metabolic rate, weight gain, hypothermia
- sensitivity to cold
- fatigue
Hypothyroidism (low thyroid hormone)
DOC for hypothyroidism
- Levothyroxine sodium (T4)
Dose of Levothyroxine sodium
- drug levels must be carefully titrated to the individual
- TSH levels
- patient signs and symptoms
what is the major sign of primary hypothyroidism
- primary: failure of thyroid gland
- High TSH -> goiter
- thyroid is growing too big
MOA of Liothyronine sodium
- T3
- used for initial therapy of severe hypothyroidism (rapid levels) but not maintenance
- then switch over to levothyroxine sodium
clinical presentation
- fast metabolsim
- tachycarida
- fatigue
- hot
- tremor
- insomnia
- diarrhea
hyperthyroidism
what is graves disease
- antibodies to TSH receptor
- stimulate gland to produce too much T3/T4
what is toxic nodular goiter
- adenoma of the thyroid that produces too much thyroid hormone
List the treatment options of Hyperthyroidism
- remove gland: surgery
- destroy gland: 131 I
- decrease T4 and T3: Thioamides, iodide
- block the symptoms: B-blockers
List the Thioamides
- Propylthiouracil
- Methimazole : more potent
MOA of Thioamides
- decrease synthesis and release of T4
- Propylthiouracil: blocks conversion of T4 to T3
- effects are gradual (use B-blockers)
- circulating T3/T4 lasts a week or so
DOC graves disease
Methimazole
adverse effects of Propylthiouracil specifically
- black box warning
- severe liver injury, acute liver failure
When is Propylthiouracil used over Methimazole
- allergy to Methimazole
- early pregnancy
adverse effects of Thioamides
- itching and skin rash
- granulocytopenia
- agranulocytosis
- goiter: may need to add T4 to reduce TSH levels
MOA of Iodide
- rapidly decreases synthesis and release of T4/T3
- short term effect (2-8 weeks)
when is iodide indicated
- decreases vascularity and thyroid content of gland
- used for 7-10 days before surgery
- can decrease likelihood of thyroid storm
- can use in radioactive emergencies
MOA of radioactive iodine (131I)
- small amounts uCi = diagnostic
- large amounts mCi: destroys gland
when is radioactive iodine (131I) used instead of thyroidectomy
- used in elderly patients and those with heart disease
adverse effects of radioactive iodine (131I)
- thyroid storm risk
- decrease risk by use of thioamide prior to tx
MOA of Propranolol
- beta blockers: decreases many of the signs and symtpoms of hyperthyroidism
- specifically inhibits the peripheral conversion of T4 to T3
when is Propranolol used in hyperthyroid patients
- used to prepare for surgery and while waiting for thioamides or 131 I to take effect
when is Propranolol contraindicated
asthma
function of osteoclasts
break down and resorb bone
function of osteoblasts
form and deposit bone
human bone remodeling is dominant to what
- resorption dominant:
- 3 weeks required to dig a resorption pit
- osteoblasts take 3-4 months to fill in new bone formation
- ***decreasing bone resportion is key to osteoporosis tx
function of parathyroid hormone
- stimulated when blood calcium is low
-
increase circulating Ca2+ by
- increase osteoclasts activity and number-> RANK ligand
- increase renal ability to reabsorb calcium
- decrease Ca2+ excretion
- Increase PO4 excretion
- stimulates production of calcitriol
function of Vitamin D
-
increase circulating Ca2+ by
- stimulating osteoclast activity through RANK ligand
- stimulate collagen synthesis in osteoblasts
- increases intestinal absorption
- decrease renal excretion
- works in conjunction with PTH
function of calcitonin
- secreted by circulating Ca2+ is too high
- decreases circulating Ca2+ by
- inhibiting osteoclasts to decrease bone resorption
- will maintain bone in pregnancy and lactation
- stimulated by estrogen
what is going on in osteoporosis
- amount of bone is decreased
- structural integrity of trabecular bone is impaired
- cortical bone becomes more porous and thinner
- makes the bone weaker and more likely to fracture
list the risk factors for osteoporosis
- postmenopausal women
- long-term glucocorticoid use
- thyrotoxicosis
- alcoholism
- malabsorption syndrome
DOC for post-menopausal osteoporosis
Bisphosphonates
treatment options for osteoporosis
- calcium + vitamin D
- HRT
- calcium-regulating hormones (PTH, calcitonin)
- bisphosphonates: DOC
use of calcium + vitamin D to tx osteoporosis, how is it given
- not all calcium preparations are absorbed equally
- chewable safest bet
- vitamin D must be adequate for optimal absorption of calcium
- *calcium and vit D can’t prevent or treat osteoporosis alone
MOA of calcitonin (Miacalcin)
- decreased bone resorption of Ca2+
- antagonizes PTH hormone
how is calcitonin (Miacalcin) given
- nasal spray
- injection
adverse effects of calcitonin (Miacalcin)
- nasal spray: rhinitis/sinusitis
- injection: N/V
what is Teriparatide
- recombinant parathyroid hormone
- intermittent administration produces bone growth
what is the only anabolic drug for osteoporosis
Teriparatide
how is Teriparatide given
subcutaneous injection: intermittent- once or twice daily
when is Teriparatide contraindicated
- osteosarcoma
MOA of Denosumab
- antibody against RANK ligand, the factor made by osteoblasts that is necessary for formation of mature osteoclasts
- inhibits bone resorption
- DEN - density
- OS: osteo
- U: human
- MAB: monoclonal antibody
when is Denosumab indicated
- osteoporosis in men and postmenopausal women at high risk for fx
Denosumab increases bone mass and strength in both
cortical and trabecular bone
adverse effects of denosumab
- osteonecrosis of the jaw
- hypocalcemia
When is Denosumab contraindicated
- hypocalcemia: fix first
- pregnanc Category X
how is Denosumab given
- S.C. injection, once6 months
List the Bisphosphonates
- Alendronate
- Risedronate
- Ibandronate
- Zoledronic Acid
- off label use
- Etidronate
- Pamidronate
MOA of Bisphosphonates
- Phosphate-calcium-phosphate analogs of pyrophosphate
-
substitutes for PO4 in Ca2+ binding
- incorporates into bone
-
inhibits osteoclast acitivity and bone resorption
- drug will be in bone rest of life
what special precautions must you know for the oral Bisphosphonates
- absorption is very poor
- must be taken on an empty stomach
- 1/2 glass of water
- stay upright for 30 minutes after taking it to decrease esophageal irritation
adverse effects of oral Bisphosphonates
- abd pain
- upper GI irritation
- esophageal ulceration
- constipation
- diarrhea
- flatulence
adverse effects of IV Bisphosphonates
renal toxicity if given too fast
adverse effects of ALL adverse effects of oral Bisphosphonates
- N/V
- increased incidence of osteonecrosis of the jaw after major dental work
Which of the Bisphosphonates are taken orally
- Alendronate
- Risedronate
- Ibandronate
- Etidronate:
Which of the Bisphosphonates are taken through IV
- Zoledronic Acid
- Pamidronate
- Etidronate
- Ibandronate
