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Exam 1 Pharm II > Endocrine pharma > Flashcards

Endocrine pharma Flashcards

1
Q

Why are synthetic analogs more potent?

A

Longer half-life

Greater receptor affinity.

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2
Q

Why are synthetic analogs more preferred?

A

Greater Specificity

Reduced antigenic effects

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3
Q

Name the Somatotrophic hormones of the ant. pituitary

A

Growth Hormone

Prolactin

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4
Q

Name the glycoprotein hormones of the ant. pituitary

A

LH, FSH, TSH

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5
Q

Name the pro-opiomelanocortin peptides of the anterior pituitary

A

ACTH

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6
Q

Name the 5 hormone producing cell types in the ant pituitary.

A 
Somatotroph
Lactotroph (memmotroph)
Thyrotroph
Gonadotroph
Corticotroph-lipotroph
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7
Q

What are the effects of hypopituitarism?

A

Absence of menses
atrophy of genital tract
thyroid hypofunction
adernal deficiency (may result in death)

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8
Q

What is hypopituitary dwarfism?

A

Failure of pituitary development causing slow growth.

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9
Q

What distinguishes hypopituitary dwarphism from cretinism?

A

Cretinism=Kid is mentally retarded. Doesn’t respond to exogenous hormones
Hypopituitary dwarfism= Kid is not mentally retarded. Responds wo exogenous hormones.

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10
Q

What is Hyperpituitarism? How does it manifest?

A

Excessive growth hormone secretion. Manifests as acromegaly.

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11
Q

Over production of ACTH (pituitary tumor) causes?

A

Cushing syndrome

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12
Q

Increased secretion of prolactin causes?

A

amenorrhea, galactorrhea and infertility. In men===> Impotence

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13
Q

Hypersecretion of gonadotropins in_________.

A

Think bigger sexual organs (precocious sexual development)

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14
Q

What does Growth hormone do?

A

Causes proportional growth of all organs in the body

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15
Q

How are hypopituitary dwarfs treated?

A

With GH

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16
Q

Name the 3 Growth hormone drugs

A

Somatropin
Somatrem( 1x daily)-More antigenic response capable.
Nutropin Depot (1X a month-Encapsulated somatropin)

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17
Q

What signal pathway is involved with the HG receptor?

A

Jak===>IP3K====> STAT and MAPK signaling

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18
Q

What IGF-1?

A

IGF-1 is a somatomedin and primary mediator of the actions of GH

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19
Q

Where are IGF-1 and IGF-2 produced mainly?

A

In the liver (source of cerfulating IGFs)

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20
Q

Type I IGF receptor binds?

A

IGF-1 and IGF-2 with high affinity.

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21
Q

Type II IGF receptor binds_____?

A

IGF-2 specifically

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22
Q

What binds IGFs in plasma?

A

IGF-Binding proteins. EX. IGFBP-3

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23
Q

What are some characteristics of GH deficiency?

A 
Short Stature
Adiposity (Fat) and hypoglycemia
Very low plasma IGF-1
Poor response to provocative hormone tests.
Reduced muscle mass.
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24
Q

How is GH deficiency diagnosed?

A

Usisng a provocative test like (Insulin-induced hypoglycemia)

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25
Q

What is GH hormone used to Tx?

A 
Idiopathic short stature
Prader-Willi Syndrome- Low sex hormones(Off label use)
Turner syndrome (off-label use)
Adults with GH deficiency
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26
Q

What are the side effects of GH in kids?

A

Type 2 diabetes mellitus (due to anti-insuline metabolic effects of GH.
Scoliosis due to rapid growth

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27
Q

What are the side effects of GH in adults?

A 
Periorbital edema
Arthralgias
carpal tunnel syndrome
Myalgias
Mild to moderate nausea and headache.
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28
Q

What is Mecasermin?

A

It contains recominant human IGF-1.

Mecasermin: Contains IGF-1 and IGFBP-3.

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29
Q

What is Laron-type dwarfism?

A

Defective/low amount of GH receptors. Low IGF-1 concentration. It is inheritable.

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30
Q

What does GH excess cause?

A

Acromegaly, Giantism

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31
Q

How is GF excess diagnosed?

A

Increased GH after oral glucose load.

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32
Q

What is somatostatin?

A

Secreted by pancreas and pituitary. It inhibits GH, flucagon, insulin and gastrin release.

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33
Q

Name the Somatostatin analogs

A

Octre(otide)

Lanre(otide)

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34
Q

What are the Dopamine receptor (D2) agonists?

A

Bromocriptine
Carbegoline
Thy inhibit GH secretion by Tumors.

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35
Q

What is Bromocriptine used to treat?

A

Inhibits prolactin release.

Also inhibits GH release from small pituitary tumors that develop from lactotrophs.

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36
Q

Name one GH recerptor antagonist?

A

Pegvisomant (Inhibits GH receptor)

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37
Q

What does pegvisomant treat?

A

Acromegaly

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38
Q

Where is prolactin synthesized?

A

Pituitary, Placenta

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39
Q

What hormones can bind prolactin receptors?

A

Prolactin
Placental lactogen
Growth hormone

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40
Q

What signal pathway is the prolactin receptor linked to?

A

The JAK and STAT pathway.

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41
Q

What causes hyperprolactemia?

A

Drugs Eg. Dopamine agonists
Disorders of they hypothalamus or pituitary that interfere with the actions of Dopamine on prolactin secretion
Prolactin secreting pituitary tumors

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42
Q

What are the effects of hyperprolactemia?

A

Glactorrhea
Amenorrhea
Infertility
Hypogonadism

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43
Q

How are prolactin tumors treated?

A

Dopamine agonists

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44
Q

Name the dopamine agonists

A

Bromocriptine
Cabergoline
Quinagoline (not in USA)

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45
Q

What does dopamine do to prolactin?

A

It inhibits prolactin secretion.

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46
Q

What characteristics fo glycoprotein hormones of the anterior pituitary share?

A

Are heterodimers with Alpha and beta subunits.

Alpha subunits are identical

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47
Q

What are the gonadotropic hormones?

A 
Lutenizing Hormone (LH)
Follicle-Stimulating Hormone (FSH)
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48
Q

Thyroid-Stimulating Hormone is a_______________

A

Thyrotropic hormone

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49
Q

In men, LH and FSH plasma levels are ______________ throughout the month and ________in women throughout the month.

A
  1. Constant

2. Higher and vary throughout the month.

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50
Q

Plasma LH and FSH are highest near____________ and after__________

A
  1. Ovulation

2. Menopause

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51
Q

Where is hCG produced?

A

in the fetal placenta (syncytiotrophoblasts)

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52
Q

When is hCG produced?

A

Early as 7days after sex.

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53
Q

What is the purpose of hCG?

A

To support luteal function

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54
Q

What suppresses LH secretion during pregnancy?

A

Increasing levels of progesterone

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55
Q

How are gonadotropic hormones drugs administered

A

Via IM or SubQ injection. They are resistant to degradation.

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56
Q

Name three, native preps. of gonadotropic hormone

A

Chorionic gonadotropin

Menotropins, Urofollitropin

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57
Q

Menotropins contains………..

A

Contains both LH and FSH (50:50)

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58
Q

Urofollitropin contains…….

A

Contains FSH

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59
Q

Chorionic gonadotropin contains……

A

Contains only LH activity

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60
Q

What are the therapeutic uses of gonadotropin preparations?

A

Femal infertility
Male infertility
Invitro fertilization

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61
Q

What is Follitropin?

A

Recombinant human FSH

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62
Q

When is recombinant human LH used?

A

To treat LH deficiency together with follitropin alpha.

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63
Q

What are the diagnostic uses of gonadotropins?

A

Pregnancy diagnosis
Ovulation prediction
Diseases of reproductive system
MH and FSH measurement helpd differentiate between gonadal and hypothalamo-pituitary failures.

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64
Q

Low levels of both LH and FSH indicate_______

A

hypogonadotropic hypogonadism (pituitary /hypothalamic failure)

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65
Q

High levels of FSH and LH indicates___________________

A

gonadal failure.

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66
Q

Toxicity ann contraindications of gonadotropin use?

A

Hyperstimulation in some women causes ovarian enlargement and abdominal pain.
Multiple pregnancies may result
Gynecomastia may occur in men (through testosterone)
Anti-estrogen (Clomiphene) can also cause ovarian hyperstimulation

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67
Q

What hormone regulates TSH secretion?

A

TRH

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68
Q

Role of TSH

A

Stimulate thyroid hormone synthesis and secretion by the thyroid gland.

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69
Q

What is Thyrogen (thyrotropin alpha)? Whenis it used?

A

It is s a recombinant human TSH.

Used in Iodine uptake by thyroid tests.

70
Q

What does GnRH do?

A

It causes a pulsitile release of LH and FSH. Synthetic GnRH is poorly absorbed from the guy. It is slowly degraded in blood.

71
Q

Name 6 GnRH preparations

A 
Gonadorelin
Leuprolide acetate
Hist(relin) acetate
Nafa(relin) acetate
Gose(relin) acetate
Tripto(relin)
72
Q

What are the therapeutic uses of GnRH ?

A

Pulsatile infusion causes gonadal activity stimulation. (Female and male fertility)
Used to suppress gonadal release of endogenous pituitary gonadotropins.
Treat fibroids
Supress estrogen in pts w/ endometriosis
Treat prostate cancer
Treats precocious puberty
Treats polycystic ovarian syndrome.

73
Q

What are the toxicities of GnRH analog use?

A

Symptoms of menopause (hot flashes, sweats, headache)
Reduced bone density and osteopososis
Hot flashes, sweats, gynecomastia, low libido, decreased hematocrit .

74
Q

Name 4 GnRH receptor antagonists

A

Ganirelix
Cetrorelix
Abarelix
Degarelix

75
Q

What 2 GnRH receptor antagonists are used to supress endogenous LH?

A

Ganirelix and Cetrorelix

76
Q

What GnRH receptor antagonists are used to treat advanced prostate cancer?

A

Abarelix and Degarelix

77
Q

What are the advantages of GnRH receptor antagonists over GnRH analogs?

A

Immediate effects

Complete inhibition of gonadotropin secretion

78
Q

What is the role of the hormone GHRH?

A

Regulates secretion of GH

79
Q

Name one GHRH synthetic drug

A

Sermorelin acetate

80
Q

What is Sermorelin used for?

A

Diagnostic purposes/ replacement therapy if pituitary can respond to GHRH

81
Q

What is Protirelin?

A

A syntheric TRH 9Stimulates secretion of TSH from ant. pituitary)

82
Q

What is somatostatin?

A

Pretty much inhibitor of the endocrine system. Produced in the hypothalamus and distributed widely outside the nervous system.

83
Q

What receptors brind Somatostatin?

A

SSTR (They increase cAMP, activate K+channels and increase tyrosine phosphorylation.
SSTR2 and SSTR5 mediate inhibitory effects of GH

84
Q

Name 3 somatostatin analog drugs

A

Octreotide acetate (Sandostatin)-more potent than somatostatin.
Snadostatin
Lanreotide
These drugs bind SSTR2 and SSTR5

85
Q

What are somatostatin analog drugs used for?

A

Treating metastatic carcinoid tumors.

Used to reduce of normalize GH and IGF-1 levels in patients with acromegaly

86
Q

What stimulates Vasopressin (ADH) release?

A

Increase in plasma Osmolarity (above setpoint)
Decreased blood volume
Chronic disease states affecting circulating volume

87
Q

How can AHD release be reduced?

A

Decrease in plasma osmolarity
Increase in blood volume
Alcohol, nicotine
Emotional stress

88
Q

What is central diabetes indipidus? How is it treated?

A

Caused by lack of ADH production and release.

Treated with ADH

89
Q

What is nephrogenic diabetes insipidus?

A

AKA (ADH insensitive)- Kidney collecting tubules can’t respond to ADH. These patients cant respond to ADH.

90
Q

Whatis SIADH?

A

Excessive production of AHD. Causes retention of H2O amd results in low solute levels (hyponatremia)

91
Q

How is SIADH reated?

A

With ADH antagonists: Ex. Antibiotic Demeclocycline

ADH receptor Antagonists Conivaptan, Tolvaptan

92
Q

What is conivaptan and Tolvaptan?

A

These are ADH receptor antagonists.

93
Q

How does Vasopresin work?

A

Enhances reabsorption of water from the collecting tubule of the nephron. (binds to V2 receptor)

94
Q

The ADH levels in a hydrated individual are___________and those in a dehydrated individual are __________

A
  1. Low

2. High

95
Q

What does ADH do in the thick ascending loop of Henry?

A

ADH stimulates active reabsorption of NaCl by the medullary thick ascending limb.

96
Q

V1 receptors have a __________affinity for ADH while V2 receptors have a _________affinity for ADH.

A
  1. Low

2. High

97
Q

What do V1 receptors do?

A

Mediate the pressor effects of AHD

98
Q

What do V2 receptors do? Where are they found?

A

Mediate the antidiuretic effects of ADH. They are on the basolateral membranes of the principal cells of the renal collecting tubule. (cAMP coupled)

99
Q

Prostaglandins especially (PGE)___________ADH’s anti-duiretic actions.

A

Inhibit.

100
Q

Name 3 substances that inhibit ADH

A

Prostaglandins
Lithium
Demeclocycline

101
Q

Name 3 ADH prepatations

A 
Vasopresin injection (Pitressin)
Desmopressin acetate (DDAVP, Minirin, Stimate)-Has only antidiuretic effect
Lypressin
102
Q

What is the pharmacological used of Vasopressin?

A

Tx of Neurogenic Diabetes Insipidus.
esophageal variceal bleeding
colonic diverticular bleeding

103
Q

What are the adverese effects of Vasopressin use?

A

Overdose may result in hyponatremia and seizures

Vasopressin must be used with care in patients with coronary heart disease.

104
Q

Name two vasopressin receptor antagonists.

A

Conivaptan (V1a and V2)
Tolvaptan (30X more V2 selective)
Are selective V1a and V2 antagonists

105
Q

Where is Oxytocin produced?

A

In the supraoptic and paraventricular nuclei of the hypothlamus.
Ovary of humans and mammals
In human amnion, choroid and decidua
In testis synthesized by ledig cells

106
Q

What does oxitocin do?

A

Oxytocin stimulates production of prostaglandins and LTEs in the uterus.
In low concentrations, oxytocin increases the frequency and force of uterine smooth muscle contration
At high concentrations it causes sustained uterine contration

107
Q

What is Oxytocin used for pharmacologically?

A 
To induce labor
Augment dysfunctional labor
Manage uterine atony or hemorrhage
Induce uterine contactin during surgery.
Oxytocin challenge test= Asseses fetal stress. Administer Oxytocin and monitor fetal HR. Reduced heart rate means fetal hypoxia.
108
Q

Name one oxytocin receptor antagonist

A

Atosiban

109
Q

What is Atosiban used for?

A

It is used to treat preterm/premature labor. (Not in USA)

110
Q

What induces Oxytocin production?

A

Suckling

111
Q

What increases uterine contration?

A

Increased plasma estrogen
Decreased plasma progesterone
Prostaglandin F2a
Increased oxitocin

112
Q

What steps are involved in thyroid hormone synthesis?

A
  1. Iodine uptake
  2. Oxidation of iodine and iodination of tyrosyl goups
  3. Condensation of iodotyrosyl residues
  4. Proteolysis
  5. Conversion to thyroxine and triiodothyronine in peripheral tissue
113
Q

How is majority of T3 produced?

A

By metabolism of T4 in peripheral tissues by Type 1, 2 and 3 deiodinases.

114
Q

Where are Types 1,2 and 3 deiodenases expressed?

A

Type 1= Liver, kidney and thyroid gland ( Produces T3 for all tissues)
Type 2= Heart, Skeletal musle, brain, hypothalamus, pituitary, brown adipose tissues. (Produces T3 for these tissue only)
Type 3=Metabolizes T4 to inactive reverse T3 (rT3)

115
Q

Name two factors that inhibit deiodenases.

A

Oral cholecystographic agents (iodinated contrast)
Propythiouracil (PTU)
Amiodatone
FATTY ACIDS

116
Q

Name 4 agents that increase metabolism of T4 and T3

A 
Rifampin
Phenobarbitol
Carbamazepin
Phenytoin
Rifabutin
117
Q

How is T3 and T4 transported in blood?

A

By Thyroxine binding globulins (TBGs). Have higher affinity for T4 than T3

118
Q

What is Transthyretin?

A

Thyroxine Binfinf Pre-Albumin or (TBPA)- Is in higher concentration than TBP and binds T4 and T3 with less affinity than TBG.

119
Q

What is goiter?

A

Enlargement of the thyroid. May be due to both hypo and hyperthyroid states

120
Q

What is simple goiter?

A

Thyroid enlargement without hyperthyroidism. TSH levels are very high due to decresed thyroid output of thyroid hormone. My be caused by iodine deficiency or goitrogen.

121
Q

What is hashimoto’s disease?

A

autoimmune destruction of the thyroid gland. Abs produced against thyroid peroxidase and thyroglobulin. Causes hypothyroidism

122
Q

What is Diffuse toxic goiter?

A

Thyroid enlargement with hyperthyroidism. (Graves’ disease)

123
Q

What is nodular goiter?

A

Thyroid enlargement with nodules.
Non-toxic= Without tyroid hormone production
Toxic=With thyroid hormone production (hyperthyroidism)

124
Q

Name 3 thryoid preparations

A 
Levothyroxine sodium (T4)
Lithyronine sodium (T3)
Liotrix (T3+T4)
125
Q

What are the therapeutic used of thyroid hormones?

A

Replacement therapy

Treating simple goiter (no hyperthyroid

126
Q

What precautions must you take prior to thyroid therapy?

A

Must never give a normal dose without priming especially in pats with heart disease.
Monitor TSH levels

127
Q

How is effectiveness of replacement therapy of simple goiter judged?

A

By return of TSH levels to normal levels.

128
Q

What are the adverse effects and precautions of thyroid hormone replacement therapy?

A

Myxedema
Be very careful when giving thyroid replacement therapy to pt’s with CAD!!!
Hypothyroidism treatment in preganat women requires a larger dose because dat baby needs it too.

129
Q

What is subclinical hypothyroidism?

A

Elevated TSH with normal levels of thyroid hormone.

130
Q

How are patients with subclinical hypothyroidism treated?

A

Levothyroxine

131
Q

What are the symptoms of hyperthyroidism (thyrotoxicosis)?

A

Patient is hot, thin, nervous, shoer of breath, flushed skin, bone and muscle turnover increased, muscle weakness and tremor, increased basal contractility of heart, increased HR, SV, CO, PP, arrythmia, angina.

132
Q

Name two diseases with hyprthyroidism

A

Graves’ disease (younger patients)

Plummer’s disease(Older patients)

133
Q

What is Graves disease

A

Autoimmune TSH receptor stimulating antibody activates the thyroid. Normally younger patients

134
Q

Name 3 categories of drugs that interfere with thyroid hormone synthesis

A

Thioamides
Aniline Derivatives
Polyhydric phenols

135
Q

Name 3 examples of thioamides. How do they work?

A

Propylthiouracil (PTU)
Methimazole
Carbimazole (not in USA)
Inhibit thyroid peroxidase enzyme.

136
Q

How do thioamides work?

A

They inhibit thyroid peroxidase enzyme.

137
Q

What is special about PTU?

A

PTU inhibits thyroid peroxidase and inhibits peripheral tissue conversion of T4 to T3.
It is used to treat prgnant women with hyperthyroidism.

138
Q

What is the treatment of choice of adults and childrean with hyperthyroidism?

A

Methimazole

139
Q

What are the toxicities associated with Thioamides?

A

Nausea, GI distress, rash, fever,
PTU=Causes hepatitis
Methimazole= Causes jaundice in some

140
Q

How do Anionic Inhibitors work

A

They interfere with Iodide uptake.

141
Q

Give two examples of Anionic inhibitors

A

Thiocyanate (SCN-)
Perchlorate (CIO4-)
Rarely used in clinical practice today

142
Q

How is Iodide used pharmacologically?

A

In high doses, it inhibits thyroid hormone production
High amounts may however cause hyperthyroidism (jodbasedow effect)
Iodine inhibits the release of thyroid hormone (MOST IMPORTANT CLINICALLY)

143
Q

What precaustions must be taken when usinf iodide therapy?

A

Give pt’s thiomides preceeding tx with iodine.

Minimize use in pregnant women as Iodide does cross the placenta and can cause fetal goiter.

144
Q

Name 3 preparations of iodine

A

Lugol’s solution
Potassium iodide
Sodium iodide

145
Q

Name two Iodinated contrast agents

A

Diatrizoate

lohexol

146
Q

How to iodinated contrast agents work? When are thy used?

A

Suppress thyroid hormone synthesis and secretion. They are relatively non-toxic and used when thioamides and iodides are contraindicated. Tx for hyperthyroidism

147
Q

Radioactive iodine uses __________to destroy paranchymal cells of the thyoid and ____________ for diagnostic scans.

A
  1. Beta-particles

2. Gamma rays

148
Q

Testosterone is a precursor for?

A

5 alpha-DHT

Estrogen

149
Q

Andreogens bing to a receptor located____________ and_______ which has a greater affinity for____________

A

In the nucleus
Plasma membrane
5a-DHT

150
Q

What proteins bind Testosterone?

A

Sex-hormone binding globulin (SHBG)

Albumin

151
Q

What hormones increase SHBG?

A

Estrogen

Thyroid hormone

152
Q

Why isn’t testosterone administered directly as replacement therapy?

A

It is quickly degraded if given via IV or orally. So the molecular structure is altered.

153
Q

What alterations are made to androgen preparations to minimize degradation?

A

Type A: Esterification of 17b-hydroxyl group
Type B: 17a-alkylation (slows doen breakdown in liver)
Type C:Ring structure changes.

154
Q

How is testosterone therapy delivered?

A

Transdermally (patch)

155
Q

When is Testosterone replacement therapy indicated?

A

In hypopituitarism/Pituitary dwarfism.
Protein anabolic agents
Osteoporosis
Stimulation of erythropiesis

156
Q

Side effects of Testosterone include:

A

Masculiinizing actions in women and prepubertal children.
17-alkyl-substituted synthetic androgens cause liver damage.
Achne, sleep apnea,erythrocytosis, gynecomastia, azoospermia

157
Q

What are the contraindications of androgenic steroid use?

A

DONT USE IN PREGNANT WOMEN
Men with prostate carcinoma or breast should not use them
Avoid use in infants

158
Q

Name 4 antiandrogens that inhibit androgen synthesis

A

GnRH
Abiraterone
Spironolactone
Ketokonazole

159
Q

Name 4 anti-androgens that block androgen action

A 
Cyproterone acetate
Flutamide
Bicalutamide
Nilutamide
Cimetidine
Finazteride
Dutasteride
160
Q

Finazteride and Dutasteride inhibit_____________

A

5a-reductase.

161
Q

Abiraterone inhibits______________and is used to treat_______

A
  1. 17a-hydroxylase enzyme

2. Metastatic prostate cancer.

162
Q

Spironolactone competitively inhibits_________ ___ by binding to it’s receptor and inhibits androgen synthesis by inhibiting____________

A
  1. Aldosterone

2. P-450

163
Q

________________competes with DHT and testosterone fo the androgen receptor.

A

Spironolactone

164
Q

What blocks adrenal and testicular androgen synthesis?

A

Ketoconazole (Inhibits activity of C17,20 Lyase and cholesterol side chain cleavage enzymes)

165
Q

Cyproterone Acetate is a _________________of testosterone. It competes _________with DHT and testosterone for androgen receptor.

A
  1. potent inhibitor

2. Competitively

166
Q

What does Cyproterone Acetate treat?

A

Achne, hirsutism, virilization, perecocious puberty

prostatic hypertrophy, inhibition of libido in men with severe deviations in sexual behavior.

167
Q

Flutamide is a non steroidal that competes with androgens for the receptor and used to treat_________

A

Prostatic cancer

168
Q

Bicalutamide is a non-steroidal that competes with androgens for the androgen receptor and is used to treat___________

A

Prostate prostate carcinoma

169
Q

Nilutamide

A

Non steroidal approved for use following surgical castration.

170
Q

Cimetatine is a ___________ antagonist and also competes with androgens for the androgen receptor. It is used to treat__________

A

Histamine H2 antagonist

Hirsutism

171
Q

Finazterise is a competitive inhibitor of ___________ and causes a dramatic decrease in plasma _________. It is used to treat_____________

A

5a-reducatase
DHT
BPH and male pattern baldness

172
Q

Dutasteride is a competitive inhibitot of ____________ it is used to treat benign prostate hyperplasia

A

5a-reductase.

Exam 1 Pharm II (8 decks)

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