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Pharm > Block 3 review > Flashcards

Block 3 review Flashcards

0
Q

Anterior Pituitary Hormones share a common alpha subunit structure:

A

TSH, LH, FSH, and HCG

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1
Q

Hypothalamic/Pituitary Hormones

A

Peptides Hormones
Not stored in granules
Released into Hypothalamic portal system

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2
Q

ACTH is derived from:

A

POMC

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3
Q

Growth Hormone (GH) is structurally similar to

A

Prolactin and chorionic somatomammotropin (HPL)

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4
Q

Hormones of the hypothalamus

A 
CRH
GHRH
GnRH (LHRH)
PIH
TRH
PRH
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5
Q

Hormones of the anterior pituitary

A 
GH
ACTH
LH
FSH
TSH
Prolactin
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6
Q

Functions of homones released by Anterior Pituitary

A

GH–––liver–––insulin-like growth factor
ACTH–––adrenal cortex–––glucocorticoids, mineralocorticoids, + androgens
LH (female)–––ovary–––estrogen + progesterone
LH (male)–-–testes–––testosterone
FSH–––ovary–––estrogen
TSH–––thyroid–––thyroxine
Prolactin–––breast

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7
Q

GnRH (LHRH) ANALOGUES

A

Are Used to treat sex hormone responsive cancers by decreasing gonadal stimulation and preventing release of steroid sex hormones
Stimulate the LHRH receptor in a non-pulsatile fashion causing downregulation of receptors
Inhibit release of FSH and LH

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8
Q

Examples of GnRH (LHRH) ANALOGUES

A 
Gonadorelin –  GnRH (LHRH)
Goserelin  - Synthetic GnRH superagonist
Histrelin  - Synthetic LHRH agonist
Leuprolide – Synthetic LHRH analogue
Nafarelin – Synthetic LHRH analogue
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9
Q

Side Effects of GnRH ANALOGUES

A

Hot flashes, sweating, diminished libido, ovarian cysts (women), gynecomastia (men), initially causes a rise in testosterone.

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10
Q

OCTREOTIDE

A 
Somatostatin analogue
Longer half-life
Used to treat acromegaly
Somatostatin inhibits release of GH, TSH, IGF-1, Insulin, Glucagon and Gastrin
Lanreotide is a long acting analogue
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11
Q

Side Effects of Octreotide

A

diarrhea, abdominal pain, flatulence, nausea, steatorrhea (delays bile secretion)

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12
Q

CRH

A

Stimulates the synthesis of POMC
Used diagnostically to differentiate between Cushing’s disease and Cushing’s syndrome
Also Dexamethasone is used for this purpose

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13
Q

ANTERIOR PITUITARY

A 
Urofollitropin – Purified FSH derived from urine
Follitropin alpha - FSH alpha subunit
Follitropin beta – FSH beta subunit
Menotropin – LH and FSH derived from menopausal women
Somatropin - GH
Pegvisomant – GH receptor antagonist
Corticotropin - ACTH
Cosyntropin – synthetic ACTH analogue
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14
Q

ACTH

A

Peptide hormone derived from POMC
Stimulates the adrenal cortex
Necessary for synthesis of adrenocortical hormones including cortisol, aldosterone, and sex hormones produced in the adrenal cortex
Stimulates Desmolase
Stress stimulates secretion, cortisol is a negative feedback regulator of ACTH
Cosyntropin is an analogue of the 24 a.a. amino terminus. Used to diagnose adrenal insufficiency

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15
Q

Adverse Effects of ACTH

A

Since ACTH stimulates cortisol, the adverse effects of high concentrations would be similar to Cushing’s syndrome side effects: osteoporosis, gastric ulcers, hypertension, peripheral edema, hypokalemia, immunosuppression, glaucoma, cataracts, etc.

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16
Q

Cushing Syndrome

A

is seen with any elevation in cortisol levels (endogenous or exogenous)

17
Q

Cushing’s Disease

A

Cushing’s Disease is a specific type of Cushing’s Syndrome specifically caused by high levels of ACTH produced by the pituitary gland
Elevated ACTH caused by ectopic tumors is not considered Cushing’s Disease
Since only the Anterior Pituitary contains receptors for CRH, this will respond to CRH stimulation

18
Q

SOMATOTROPIN

A

Growth Hormone is a protein produced by somatotroph in the anterior pituitary
Highest secretion occurs during sleep
Inhibited by Somatostatin
Induced by GHRH
Effects of GH are mediated through Somatomedins (IGF-1, IGF-2)
Protein synthesis, Cell proliferation, Bone growth, cartilage synthesis, myocyte proliferation, GFR, adipocyte proliferation, lipolysis, etc.

19
Q

Side Effect of SOMATOTROPIN

A

hyperglycemia, joint swelling

20
Q

Growth Hormone (GH)

A

is used to treat GH deficiency (hypopituitarism) or growth failure in children from other causes
Used in Prader-Willi syndrome

21
Q

Pegvisomant

A

is a GH receptor blocker used to treat acromegaly. Its use is limited to inefficacy of somatostatin analogues. Protein that is administered parenterally (SQ)

22
Q

FSH

A

Used to stimulate the follicles used to treat infertility
Glycoproteins that share the same alpha subunit
Effects: ovarian maturation, spermatogenesis
Ovulation when HCG

23
Q

FSH ANALOGUES

A

Urofollitropin – purified FSH
Follitropin alpha - Recombinant
Follitropin beta – Recombinant
Menotropin – LH and FSH

24
Q

PROLACTIN

A

Peptide produced by anterior pituitary lactotrophs
Stimulates and maintains lactation
Also decreases libido and inhibits ovulation
Prolactin secretion is inhibited by Dopamine acting at D2 receptors
Hyperprolactinemia can be treated by Bromocriptine, Pergolide and Cabergoline

25
Q

Hormones of the POSTERIOR PITUITARY

A

Vasopressin
Desmopressin (DDAVP)
Oxytocin

26
Q

Desmopressin

A

is a synthetic analogue (of ADH) used for Diabetes Insipidus and nocturnal enuresis
Desmopressin only has activity at V2 receptors
Longer half-life
Administered intranasally

27
Q

ADH

A

Vasopressin is a nonapeptide that affects expression of aquaporins in the renal collecting ducts (V2 mediated)
Also has vasopressor effects (V1 mediated)
Released in response to plasma osmolarity changes (and hypovolemia)

28
Q

Side effects of ADH

A

water intoxication and hyponatremia

29
Q

OXYTOCIN

A

Peptide hormone that acts on the pregnant uterus to stimulate contraction
Used to induce labor
Also plays a role in milk let-down
Causes contraction of myoepithelial cells around mammary alveoli

30
Q

THYROID FUNCTION Meds

A

Levothyroxine
Liothyronine
Liotrix

Methimazole
Propylthiouracil
Iodine

31
Q

Functions of thyroid gland

A
  1. Uptake of iodide ion
  2. Synthesis of thyroglobulin
  3. Iodination
  4. Condensation
  5. Proteolytic release of hormones
32
Q

THYROID GLAND

A 
Under control of Pituitary gland
Stimulated by TSH
Iodine Uptake
Synthesis of thyroglobulin
Iodination of tyrosine residues
Condensation
Release of T3 and T4
T3 is more potent than T4, but more T4 is synthesized and released.  Conversion occurs in the periphery.

Thyroid gland also secretes Calcitonin (parafollicular cells)

33
Q

HORMONE REGULATION

A

TRH is released by hypothalamus and stimulates TSH production in the anterior pituitary
TSH stimulates thyroid hormone production and secretion
Thyroid Hormone feedback regulates TRH and TSH secretion

Dopamine, somatostatin and glucocorticioids also can inhibit TSH secretion

34
Q

PROTEIN BINDING

A

Thyroid hormone is hydrophobic so it is transported in the bloodstream attached to various plasma transport proteins:
Albumin – lowest affinity but highest capacity
Transthyretin – intermediate affinity and capacity
Thyroglobulin – highest affinity but low capacity

In equilibrium with free fraction which is pharmacologically active
Increased protein-binding extends half-life but decreases free fraction
Decreased protein-binding increases free fraction

35
Q

Treatment of Hyperthyroidism

A

Treatment of Hyperthyroidism is accomplished by using drugs that inhibit synthesis and release of thyroid hormones:
Propylthiouracil
Methimazole
Iodine preparations
Inhibit iodination and condensation reactions
PTU also inhibits conversion of T4 to T3
PTU is more toxic: Hepatotoxicity
Other side effects: Agranulocytosis, rash, edema

36
Q

STEROID SEX HORMONES

A

Produced in the gonads
Necessary for development of primary and secondary sexual characteristics, conception, fertility, and embryonic maturation
Replacement therapy is used when there is a blockage in hormone production, antagonists are used in treatment of sex hormone responsive neoplasias

37
Q

SEX HORMONE ANALOGUES

A 
SEX HORMONE ANALOGUES
ESTROGENS
Estradiol
Estrone
Ethinyl Estradiol
Mestranol
PROGESTINS
Desogestrol
Drosperinone
Levonorgestrol
Medroxyprogesterone
Norethindrone
Norgestrel
Progesterone
ANTIPROGESTINS
Mifepristone
ANDROGENS
Danazol
Fluoxymesterone
Oxandrolone
Testosterone
ANTIANDROGENS
Bicalutamide
Dutasteride
Finasteride
Flutamide
Nilutamide
SERMs
Clomiphene
Tamoxifen
Raloxifene
38
Q

ESTROGEN EFFECTS

A

Estrogen binds to an intracellular receptor
Estrogen affects may organs and molecular processes:

  • Increased bone mass
  • Positive effects on Lipid Profile
  • Increased biliary cholesterol secretion
  • Increase plasma levels of CBG, TBG, SHBG
  • Increase coagulation factors but decrease proteins S, C and Antithrombin III
  • Increase induction of NO Synthase
  • Induction of Progestin Receptors in endometrium
  • Increases thrombosis
  • Stimulates the development of sexual organs, breast development, shaping the skeleton, epiphyseal closure
  • Affects secondary sex characteristics in puberty
  • Vasodilation and positive effects on blood pressure and cardiovascular system
  • Feedback inhibition of LHRH, LH and FSH
  • Stimulate of cell proliferation of many tissues (breasts)
39
Q

MENSTUAL CYCLE

A

At the start of the menstrual cycle, FSH levels increase due to LHRH, stimulating Estrogen production
Estrogen produced by the growing follicle feedback inhibits FSH secretion and sensitizes the endometrium for proliferation and progesterone receptor expression
At midcycle, an LH/FSH surge stimulates ovulation
The corpus luteum secretes both estrogen and progesterone, maintaining the endometrium.

40
Q

ESTROGEN

A

Prescribed as oral contraceptive, hypogonadism, hormonal replacement therapy

Oral Contraceptive - Estrogens inhibit pituitary hormone secretion and prevent ovulation. However unopposed estrogen has been linked to the development of uterine cancer

Hypogonadism – Estrogens are prescribed for the development of secondary sexual characteristics in Turner’s Syndrome and enzyme deficiencies

Hormonal Repalcement Therapy - used in post-menopausal women to treat vasomotor symptoms, osteoporosis, cardiovascular disease including lipid profile, vaginal and urogenital atrophy. Unopposed estrogen replacement in postmenopausal women leads to uterine cancer. Hysterectomy can be performed or progestins must be added.

41
Q

SERMs

A

Selective Estrogen Receptor Modulators are drugs that exert tissue specific action on estrogen receptors
Different types of Estrogen receptors:
GPCR
Intracellular receptors
ERα
ERβ
The receptors form homo- and heterodimers once bound to ligands: (αα) (ββ) (αβ) The effects seen on transcription depend on which dimers are formed.

Pharm (8 decks)

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