Thyroid and Parathyroid Pharm- Burkin Flashcards
1
Q
What is this:
A protein synthesized in the thyroid gland; its tyrosine residues are used to produce thyroid hormone
A
thyroglobulin
2
Q
What is this:
Excess thyroid hormone
A
thyrotoxicosis
hyperthyroidism
graves disease
3
Q
What is this:
lack of sufficient thyroid hormone
A
hypothyroidism/hashimoto thyroiditis
4
Q
Thyroid follicular cells synthesize lare amounts of (blank)
A
thyroglobulin.
5
Q
Thyroglobulin is a glycoprotein hormone that is stores in the colloid in the (blank)
A
follicular lumen
6
Q
Thyroglobulin contains (blank) tyrosin residues
A
134
7
Q
TSH (thyrotropin) is secreted from cells in the anterior pituitary called (blank). What does TSH do?
A
thyrotrophs
Binds to receptors on epithelial cells in the thyroid gland and stimulates that gland to release thyroid hormones
8
Q
What does the thyroid hormone inhibit (i.e has negative feedback)?
A
TRH (from the hypothalamus)
TSH (from the pituitary gland)
9
Q
Explain the synthesis of thryglobulin?
A
- TSH stimulates Iodine to get pumped into follicular cells,
- Iodide is oxidized to hypoiodoate and combined with tyrosine residues on thyroglobuin.
- Thyroid peroxidase results in formation of DITs and MITs (thyronine residues) onto the thyroglobulin. Iodinated thyroglobulin is taken into follicular cell via endocytosis
- Iodinated thyroglobulin is taken into the follicular cell by endocytosis and thyroglobulin is degraded.
- three to five thyroxine molecules are released per Tg molecule in a ratio of T3:T4 1:4
10
Q
T4 is converted to T3 peripherally by an enzyme called (blank)
A
5-iodinase
11
Q
Where is Type I iodinase present?
What does it do?
How can you block this?
A
kidney and liver
formation of T3 for rest of body
Propylthiouracil
12
Q
Where is type II iodinase present?
What does it do?
A
Pituitary and adipose tissue
sensor for TSH
13
Q
How do you block iodine transport and thus inhibit formation of thyroid hormones?
A
- thiocyanate
- perchlorate
14
Q
Thyroid hormone circulates bound to (blank) and (blank)
A
thyroid binding globulin
albumin
15
Q
Only (blank) is active thyroid hormone and only 0.5% of this is free at any one time
A
T3
16
Q
What is the T 1/2 for T4?
For T3?
A
7 days
2 days
17
Q
T3 acts in responsive tissues in a manner similiar to the steroid homrones.
How so?
A
It binds unique receptors that bind to the genome and alter gene transcription
18
Q
Mammalial thyroid hormone receptors are encoded by (blank) genes which are alternatively spliced to generate (blank) different thyroid hormone receptors which are,,,,?
A
2
4
alpha 1, alpha 2, beta 1, beta 2
19
Q
Thyroid hormone receptors possess 3 functional domains what are they?
A
- a transactivation domain
- a DNA binding domain
- ligand-binding and dimerization domain
20
Q
What is this:
a domain at the amino terminus that interacts with other transcription factors to repress or activate transcription
A
Transactivation domain
21
Q
What is this:
a domain that binds to sequences of promoter DNA known as hormone response elements
A
DNA binding domain
22
Q
What is this:
domian located at the carboxy terminus
A
Ligand-binding and dimeriztion domain
23
Q
How do thyroid hormones affect growth and development?
So what happens if you have iodine deficiency during development?
A
- particularly important in the brain and nervous system (axonal and dendritic development)
- results in mental retardation in children
24
Q
How does thyroid hormone increase metabolic rate?
A
- increased O2 utilization in muscle and other metabolically active tissues
- maintains body temp
- T3 is inotropic and increases CO
25
How does T3 increase inotropy and CO?
-alters myosin isozymes (V1/V3) resulting in increased Ca2+ ATPase activity and increased contraction force
26
Thyroid disease affects (blank)% of the general population.
5-15%
27
Females (blank) more likely than males to develop thyroid disease
3-4X
28
Typical thyroid disease includes ....?
hypothyroidsm, hyperthyroidism, nodular disease and thyroid cancer
29
(blank) is an autoimmune disorder and most comon cause of primary hypothyroidism.
Hashimoto's thyroiditis
30
What are other causes (besides hashimotos thyroiditis) causes primary hypothyroidism?
- iatrogenic destruction of gland after radioiodie therapy or surgery
- drug induced hypothyroidism can occur in susceptible patients (tx with iodide, lithium, interferon-alph)
31
What is the most common form of hyperthyroidism?
| What are the other causes of hyperthyroidism?
Grave's disease
Toxic autonomous nodular goiter
32
What is the most common cause disorder of thyroid function?
| What do you call this when it is severe?
hypothyroidism
| myxedema
33
Hypothyroid caused by (blank) causing a goiter, remains a common worldwide problem
iodine deficiency
34
Primary hypothyroidism is characterized by high leves of circulating antibodies to (blank), (blank) or (blank)
thyroid peroxidase, thyroglobulin or TSH receptor
35
What causes primary hypothyroidism?
Secondary?
Tertiary?
Broken thyroid gland
Broken pituitary gland
Broken hypothalamus
36
What are the symptoms of hypothyroidism?
Fatigue, Lethargy, Cold intolerance, Mental slowness, Depression, Dry skin, Mild weight gain, Fluid retention, Muscle aches and stiffness, irregular menses, infertility, anemia
37
What are the common signs of primary hypothyroidism?
Goiter, bradycardia, delayed relaxation phase of the deep tendon reflexes, cool and dry skin, hypertension, nonpitting edema, and facial puffiness
38
What are the common signs of neonatal hypothyroidism?
feeding problems, failure to thrive, constipation, sleepiness, mental retardation, impaired linear bone growth and bone maturation
39
When can neonatal hypothyroidism cause permanent retardation of mental function?
if not treated so start treatment soon!
40
How do you diagnose thyroid hypofunction?
- elevated serum TSH
| - decrease T4 in central hypothyroidism
41
What are the drugs used to treat hypothyroidism?
- thyroid USP
- thyroglobulin (proloid)
- levothyroxine Na (synthroid)
- thyrotropin
- protirelin or thyrogen
42
What is this:
| acetone powder of pig thyroid gland
thyroid USP
43
What is this
| purified pig thyroid
thyroglobulin (proloid)
44
What is this:
| Na salt of T3 and available in 25-300 micrograms tablets
Levothyroxine Na (synthroid)
45
What is this:
| TSH from bovine pituitary (diagnostic)
Thyrotropin
46
What is this:
| synthetic or human recombinant TSH (stimulate thyroid gland)
Protirelin or thyrogen
47
(blank) is a condition caused by elevated levels o free thyroid hormones
Thyrotoxicosis
48
What is the most common way to get increased thyroid hormone?
- TSH receptor stimulation
| - increase iodine uptake by the thyroid gland
49
(blank) is an autoimmune disorder characterized by increased thyroid hormone production, diffuse goiter and IgG antibodies that bind to and activate the TSH receptor.
Graves disease
50
At what age do you commonly get graves disease? and in what gender?
females
| 20 and 50 but may occur at any age
51
What are these symptoms of:
Excessive heat production, increased motor activity, and increased production of catecholamines, warm, moist and flush skin, muscles are weak and tremulous, heart rate is rapid, heartbeat is forceful, atrial pulses are prominent and bounding. Increased appetite, weight loss, insomnia, intolerance to heat, increased bowel movements, angina, arrhythmias, Heart failure in older patients, muscle wasting.
thyroxicosis
52
How do you diagnosis thyrotoxicosis (thyroid hyperfunction)?
- TSH
| - T4
53
(blank) (thyrotropin alfa) is available to test the ability of thyroid tissue to take up radioactive iodine and release thyroglobulin.
Recombinant human TSH
54
What are the kinds of thiourylene anti thyroid drugs?
- methimazole
- propylthiouracil
- thiourea
- carbimazole
55
What do thiourylenes do?
| How long does it take to start working?
- bind and inactivate peroxidase enzymes
| - takes several weeks to see effects due to resevoir of hormone in the gland
56
Why is propylthiouracil different than all the other thiourylenes?
-it blocks peripheral conversion of T4 to T3
57
What are the ionic inhibitor anti-thyroid drugs?
-thiocyanate and perchlorate which intefere with uptake of iodide by the thyroid gland
58
Why do you give iodide in hyperthyroidism?
it has a paradoxical effect (KI solution) so it will dessicate (dry up) that gland prior to surgery
59
What is radioiodine [131 I] and what is it used for?
- T 1/2= 8 days
- emits x-rays, radio-ablation of the gland, emits x rays and b particles. selectively irradiates the parenchymal cells of the gland
60
(blank) directly interferes with the first step in thyroid hormone biosynthesis in the thyroid gland
Methimazole
61
How does methimazole work?
binds to thyroid peroxidase and inhibits the incorporation of iodide into the thyroglobulin. Thyroid hormone depleted
AND
inhibits iodotyrosyl residue coupling thus inhibition of thyroglobulin synthesis. THyroglobulin depleted
62
How is methimazole degraded?
it is iodinated and degraded within the thyroid gland
63
(blank) directly interferes with the first step in thyroid hormone biosynthesis in the thyroid gland.
Methimazole
64
Methimazole acts as a substrate for the (blank), methimazole inhibits the incorporation of iodide into the thyroid hormone precursor, thyroglobulin.
catalyst thyroid peroxidase
65
What causes this:
| Oxidized iodine is diverted away from thyroglobulin, which effectively diminishes the biosynthesis of thyroid hormone.
methimazole
66
Methimazole can inhibit the coupling of (blank) to form thyroglobulin. Methimazole may interfere with the oxidation of the iodide ion and iodotyrosyl groups. Eventually, thyroglobulin is depleted and circulating thyroid hormone levels diminish.
iodotyrosyl residues
67
What does methimazole do to thyroxine (T4) and triiodothyronine (T3) in the circulation or stored in the thyroid gland?
It does not alter their action
| additionaly, does not effect exogenously administered thyroid hormones
68
```
What does this:
blocks peripheral conversion of T4 to T3
Bind and inactivate peroxidase
enzyme which is responsible for
oxidation of iodine and iodotyrosyl
groups.
```
Propylthiouracil
69
Can you use propylthiouracil in pregnant women?
should be used with caution in pregnant or breast feeding women (less neg effects that methimazole)
70
What are the toxic effects of propylthiouracil?
skin rash (common) and severe immune reactions (rare)
71
What do you use for well differentiated thyroid cancer (papillary and follicular)?
surgical thyroidectomy, radioiodine and levothyroxine to suppress TSH
72
What do you use for low risk patients with stage 1 or 2 thyroid cancer?
maintain TSH just below reference range
73
Most well differentiated thyroid carcinomas accumulate very little (blank). Stimulation of iodine uptake with (blank) is required to treat metastases effectively.
How do you do this?
iodine
| TSH
74
How do you treat thyroid carcinoma after a patient has a thyroidectomy with or without radioactive ablation of residual thyroid tissue?
You stop thyroid hormone therapy and give thyrogen (recombinant human TSH) to test the capacity of thyroid tissue (normal or malignant)
i.e tells you if the thyroid is taken up iodine and secreting thyroglobulin
75
Why is thyroglobulin a good drug to use when treating thyroid carcinoma?
because you can use it to assess thyroid function without having to stop suppressing thyroglobulin and thus prevents patients from becoming hypothyroid.
76
TSH suppressive therapy with (blank) is indicated in all patients after treatment with thyroid cancer.
levothyroxine.
77
What are the 2 most important minerals for cellular function?
calcium and phosphate
78
Where do you find 98% of the calcium and 85% of phosphorous>
in the bone
79
There are complex mechanisms that regulate calcium and phosphate homeostasis with a dynamic exchange b/w what 2 things
bone and the mineral in extracellular fluid
80
Abnormalities in bone metabolism can lead to a wide variety of cellular dysfunction resulting in (blank X 3), defects in structural support resulting in (blank), and loss of hematopoietic activity (blank)
muscle weakness, coma and tetany
osteoporosis
infantile osteopetrosis
81
What will decreased calcium cause?
| What will this hormone do?
an increase in parathyroid hormone
- conversion of calcifediol to calcitriol
- decreased exretion of calcium by kidney, increased calcium absorption in the intestin and mobilization of calcium from bone which causes a rise in plasma calcium concentration
82
PTH is an (Blank) amino acid peptide. Amino acids (blank) of PTH confer activity.
1-34
83
How do you regulate PTH?
- a calcium-sensitive protease cleaves intact hormone into fragments which limits production of PTH
- a calcium-sensing receptor in the parathyroid gland is stimulated by calcium to reduce PTH production and secretion
- PTH gland contains Vit D receptor and CYP27B1 to produce active metabolite of vit D to suppress PTH production
84
The parathyroid gland contains the (blank) receptor and (blank) to produce the active metabolite of vitamin D to suppress PTH production.
vitamin D
| CYP27B1
85
What are the synthetic human parathyroid drugs?
parathar or teriparatide
86
What does PTH do?
- mobilizes bone calcium
- decreases renal excretion of calcium
- stimulates Vit D3 synthesis
- promotes phosphate excretion
87
Do you use PTH often clinically?
no, D3 and calcium are preferred
88
What is the biosynthesis of vit D?
7-dehydrocholesterol + heat-> D3 (cholecalciferol)-> 24,25 (OH)2D3 (secalciferol)-> 1,25(OH)2D3 (calcitriol)
89
Calcitriol is derived from the diet and generated in the skin as (blank). Calcitriol is formed by hydroxylation steps that take place in the (blank and blank)
pro-vitamin D3
| liver and kidney
90
Formation rom calcifediol is increased by (blank)
PTH
91
Vit D and its metabolites circulate in the blood bound to (blank) and is rapidly cleared by (blank) from the blood
vit D binding protein
| liver
92
Calcitriol (vit D) stimulates the absorption of calcium and (Blank) in the (blank) and the mobilization of calcium from (blank)
phosphate
intestine
bone
93
What do you use calcitriol (vit D) to treat?
osteomalacia and hypocalcemia associated with hypoparathyroidism
94
Calcitonin is a (blank) hormone made up of (blank) amino acids produced by the thyroid gland
protein
| 32
95
What is calcitonin regulated by?
| What does it do?
plasma calcium
| inhibits osteoclasts and decreases reabsorption of both calcium and phosphate
96
What is the overall effect of calcitonin?
lower plasma calcium
97
Is there a synthetic form of calcitonin?
yes!
98
When do you use calcitonin?
in the tx of hypercalcemia associated with some neoplasms
99
(blank) is characterized by a reduced quantity of bone
osteoporosis
100
(blank) is characterized by a lack of mineralization
osteomalacia
101
(blank) is characterized by the production of abnormal bone
Pagets disease
102
Pagets disease affects app. (blank) percent of the population over age 60
3
103
Pagets disease of the bone presents with what symptoms?
bone pain
skeletal deformity
neurological complications or fractures
104
Where is Pagets disease common?
| Where is it rare?
- Central Europe, UK, australia, new zealand, and USA
| - Rare in Africa, Middle east, scandinava
105
What is the pathology of Pagets disease?
excessive bone resorption and formation in 3 phases
Phase 1: osteolytic
Phase 2: osteoblastic
Phase 3: quiescent
(may be present in the same patient at the same time)
106
(blank) is caused by decreased mineralization of new bone matrix
Osteomalacia
107
How will osteomalacia affect children?
lack of calcification results in growth failure and deformity of Rickets
108
How will osteomalacia affect adults?
adults will present with bone pain, proximal myopathy or fractures with minor trauma
109
Osteomalacia is commonly caused by (blank) defiency. Biomarkers include (Blank X 3)
Vit D
| hypocalcemia, secondary elevation in PTH, low plasma 25-hydroxyvitamin D.
110
What are the causes of osteomalacia?
- insufficient exposure to sunlight
- malnutrition
- renal tubular acidosis
- malnutrition during pregnancy
- malabsorption syndrome
- hypophosphatemia
- chronic renal failure
- tumor induced osteomalacia
- long term anti-convulsive therapy
- coelaic disease
- cadmium poisoning
111
What is this:
| a common disorder in post-menopausal women that may result in hip, forearm, and spinal fractures
Osteoporosis
112
What is osteoporosis caused by?
| What is it accelerated by?
thinning of the bone with aging
- premature or surgical loss of ovarian function
- drugs (e.g corticosteroids)
- Lifestyle (alcohol or smoking)
113
How do you treat osteoporosis?
estrogen replacement therapy (ERT) at the time of menopause inhibits the effect of osteoclasts on bone resportion and increases bone density
114
What are the drugs used in hormone replacement therapy?
- oral estrogens (equine estrogen, estrone sufate and miconized estradiol-20b)
- widely prescribed to treat postemenopausal osteoporosis
115
HRT results increased (blank) events especially women with a history of (blank and blank)
CV
| heart disease and breast cancer
116
(blank) can be considered for hormone resplacement therapy in patients that have not had a hysterectomy
Progesterone
117
What was first approved as a treatment for osteoporosis?
Selective estrogen receptor modulator
| Raloxifen
118
```
Raloxifene has (blank) activity but not on all sensitive tissues. What does it increase?
What does it decrease?
```
estrogenic
increases bone density and appears to decrease number of fractures
decreasese cholesterol
119
Long term clinical trials with (blank) mg/day of raloxifene shows improvements in (blank) of the hip and lumbar spine
60
| bone density
120
Patients takes raloxifene for the TX of osteoporosisi were followed for cancer and found to have a (blank) in overall cancer incidence
50% decrease
121
What are the adverse effects of raloxifene?
increased risk of thromboembolic events similiar to estrogen. Some women report hot flashes and leg cramps
122
What are bisphosphates?
| What is there structure?
enzyme-resistant analogs of pyrophosphate (designed to mimic pyrophosphate)
POP structure replaces by PCP
123
What is the results of bisphosphonates? How long do they take to work?
reduces turnovver of bone by preventing the number and activity osteoclasts.
-Takes 48 hours to block bone resorption
124
How do bisphosphonates work?
blocks transformation of calcium phosphate into hydroxyapatite thus inhibiting the formation, aggregation, and dissolution of hydroxyapatite crystals in bone
125
What are bisphosphonates used for?
osteoporosis and pagets disease
126
Studies have shown what three bisphosphonates increase bone density by 4-9% over the first 3 years of tx and reduces vertebral fractures by (blank)?
etidronate, alendronate and risedronate
| 50%
127
(blank) should not be given continuously as it can cause osteomalacia. Dosing is normally intermittent over 2 weeks with periods off the drugs.
Etidronate
128
(blank) 10mg/day or (blank) 5mg/day reduce the incidence of single vertebral fractures by 50% and by 90% for multiple vertebral fractures
Alendronate
| Risedronate
129
Bisphosphates should not taken with (blank X 3) as this inhibits drug absorption
milk products, food or Ca2+ supplements
130
What are the adverse effects of bisphosphonates?
GI (heartburn, nausea, and abdominal pain), incidence of gastric ulcers and erosive oseophagitis.
131
How should you take bisphosphonates?
with water and avoid lyng in supine position for at least 30 minutes
132
What is this:
a human monoclonal antibody against RANKL
What does it do?
Denosumab
Treats osteoporosis, bone loss and bone metastasis, rheumatoid arthritis, multiple myeloma and giant cell tumor of the bone
133
Precursors of (blank) express RANK (receptor activator of nuclear kappa B), a member of the TNFR family. RANK is activated by RANKL present on the surface of (blank) which converts pre-osteoclasts to osteoclasts to resorb bone.
osteoclasts
| oesteoblasts
134
Denosumab inhibits the maturation of (blank) into osteoclasts and therefore prevents bone resorption.
pre-osteoclasts
135
What is osteoprogenin?
An endogenous RANKL inhibitor
136
Denosumab mimics that actions of (blank), an endogenous RANKL inhibitor that is decreased in patients with osteoporosis.
osteoprogenin
137
Clinical trials showed Denosumab reduced (blank) in women aged 60 to 90 yeas by 35%
fractures
138
What are the adverse effects of denosumab?
increased urinary and respiratory tract infections, rashes, joint pain, eczema
139
What are the contraindications of denosumab?
hypocalcemia
140
Calcium supplements have a small beneficial effect in preventing (blank)
bone loss
141
(blank) analogs facilitate calcium absorption from the (blank) and may have an effect on bone formation and reabsorption.
Vit D
| GI tract
142
(blank) is a synthetic C-19 steroid with weak hormonal properties. What does it do?
Tibolone
| increase bone mass in the spine and prevention of bone loss from the forearm in postmenopausal women
143
What is Teriparatide? How do you use it and what is it for?
PTH analog
used in cyclic doses
effective in tx of osteoporosis
144
How do you treat Hashimotos?
levothyroxine
