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Pharmacology > Hypothalamic and Pituitary Pharm > Flashcards

Hypothalamic and Pituitary Pharm Flashcards

1
Q

Describe the control of anterior pituitary hormone release

A
  1. Release of hypothalamic hormones (releasing factors) under CNS control via neurotransmitters (NE, DA, GABA, 5HT, ACh)
  2. Release of anterior pituitary hormones (trophic hormones) is controlled by hypothalamic hormones (either releasing or inhibiting factors) that are synthesized in and released from peptidergic neurons. They are then delivered via portal circulation to the pituitary gland for release into the systemic circulation where they act on endocrine glands to regulate production of hormones that perform ultimate regulatory functions
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2
Q

Describe the control of anterior pituitary hormone release

A
  1. released of hypothalamic HR under CNS control via neurotransmitters (DA, NE, GABA, 5HT, ACh)
  2. Release of ant. pit. HR is controlled by HYPOTHALAMIC HRs
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3
Q

Describe what anterior and posterior pit. hormones act on

A

Ant: ON ENDOCRINE glands to regulate production of hormones that perform ultimate regulatory fxn

Post: act DIRECTLY ON TARGET TISSUES to perform regulatory fxns

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4
Q

Another name for GH

A

Somatropin

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5
Q

What is the PK of GH including form, peak level time, and duration of action

A

Form: SC or IM
Peak levels: 2-4 hrs
Active level persist 36 hrs

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6
Q

GH release is increased by:

A
  1. GHRH**
  2. Hypoglycemia
  3. DA, I-DOPA
  4. Exercise
  5. Arginine (and Ghrelin)
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7
Q

GH produces __ and __ effects including:

A

Anabolic and metabolic effects

  1. Positive nitrogen balance
  2. Stimulate lipolysis
  3. Increase FFA and blood glucose*
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8
Q

At pharmacologic doses GH works indirectly to stimulate synthesis of ___ promoting ___ and __

A

Insulin-like growth factors (IGF-1, IGF-2 in growth plate cartilage and liver)

linear and skeletal muscle growth

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9
Q

Uses of GH (aka Somatropin)

A
  1. Replacement therapy in children w/ deficiency
  2. Poor growth due to Turner Syndrome, Prader-Willi Syndrome, CRI
  3. GH def. in adults
  4. Wasting and cachexia in AIDS pt
  5. Short bowel syndrome dependent on TPN
  6. idiopathic short stature is controversial
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10
Q

How is GH administered for GH deficiency in children

A
  1. SC daily injections at bedtime

2. 3x a week IM

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11
Q

recombinant IGF-1 (Mecasermin) creates concern for

A

hypoglycemia, so carb intake prior to injection

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12
Q

What are illicit uses of GH

A
  1. athletes to increase muscle mass and improve performance (lack control studies)
  2. healthy elderly for anti-aging
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13
Q

GH side effects when misued in atheletes

A
  1. acromegaly
  2. arthropathy
  3. visceromegaly
  4. extremity enlargement
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14
Q 
A 3-year-old boy with failure to thrive and metabolic disturbances was found to have an inactivating mutation in the gene that encodes the growth hormone receptor. Which of the following drugs is most likely to improve his metabolic function and promote growth? 
A.  Dopamine 
B.  Bromocriptine 
C.  Mecasermin 
D.  Octreotide 
E.  Somatropin
A

C.  Mecasermin

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15
Q

A 3-year-old girl was referred to the genetic counselor by her pediatrician. She presents with short stature (3 standard deviations below norm) and appears to have loose skin on her neck. Cytogenetic testing reveals an XO karyotype (e.g., Turners syndrome). Which of the following drugs will allow her to achieve a higher adult height?
A.  Growth hormone releasing hormone (GHRH)
B.  Somatropin
C.  Insulin-like growth factor
D.  Somatostatin
E.  Bromocriptine

A

B.  Somatropin

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16
Q

What are SE of GH used in healthy elderly for anti-aging

A
  1. Edema
  2. Joint pain
  3. muscle pain
  4. carpal tunnel syndrome
  5. skin numbness and tingling
  6. increase growth of premalignant cells
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17
Q

Describe effects of Somatotstatin

A
  1. Inhibits release of GR via GPCR coupled to Gi/o
  2. Decrease secrtion of gastric enzymes and acid
  3. decrease GI motility
  4. decrease release of serotonin and gastroenteropancreatic peptides
  5. Reduce insulin and glucagon release
  6. interferes w/ TRH ability to release TSH
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18
Q

Describe the PK of Octreotide including form and half life

A

SC every 6-12 hrs, t1/2= 90 minutes

IM every 4 weeks

19
Q

Uses of somatostatin Analogs

A
  1. GH excess (acromegaly in adults and gigantism in children)–> surgery preferred
  2. Control bleeding from esophgeal varices and GI hemorrhage (constrict splanchnic arterioles)
  3. Carcinoid tumors, VIP-secreting tumors, glucagonoma, gastrinoma
  4. Sx of WDHA (water diarrhea, hypokalemia, achlorhydria)
20
Q

When is Bromocriptine-cabergoline used?

A

Dopamine agonists may inhibit GH secretion in some patients, but not as effective as SST analogs.

-Cabergoline is preferred agent for adjuvant management of acromegaly with advantage of oral administration

21
Q 
All of the following drugs may be beneficial in the treatment of patients with acromegaly EXCEPT: 
A.  Lanreotide 
B.  Octreotide 
C.  Pegvisomant 
D.  Somatostatin
E.  Somatropin
A

E.  Somatropin

22
Q

Adverse reactions of Somatostatin and analogs

A
  1. Transient deterioration in glucose tolerance (Hyperglycemia)
  2. abdominal cramps and loose stools
  3. Cardiac (bradycardia 25% and conduction distrubances 10%)
23
Q

Regarding treatment of deficiencies and excesses of growth hormone:
A.  Risk of Creutzfeldt-Jacob disease must be considered when using currently available GH preparations
B.  Patients receiving cabergoline for acromegaly must be monitored for parkinsonian symptoms
C.  For patients who choose not to have surgery for acromegaly, long-acting SST analogs are preferred over dopamine agonists
D.  Patients initiating GH replacement therapy should be monitored for hypoglycemia
E.  Use of GH for its antiaging properties has approval by the FDA

A

C.  For patients who choose not to have surgery for acromegaly, long-acting SST analogs are preferred over dopamine agonists

24
Q

Prolactin release is under ___ control by ____

A

inhibitory

hypothalamic dopamine at D2 receptors

25
Q

the main stimulus for release of prolactin is

A

suckling (causes a 10-100 fold increase within 30 min)

26
Q

Prolactin stimulates ____ and inhibits ____

A

Stimulates: proliferation and differentiation of mammary tissue during preg.

Inhibits: gonadotropin (FSH/LH) release and/or ovarian response to these hormones (lack of ovulation during breastfeeding)

27
Q

Uses of Prolactin

A
  1. Hyperprolactinemia (prolactinomas)— most amendable to pharmacotherapy— dopamine agonist that decreases secretion and reduces tumor size

** No preparation available for prolactin deficiency (hypoprolactinemia)

28
Q

Compare and contrast Bromocriptine and Cabergoline in its use for hyperprolactinemia

A

Caber: preferred agent

  • more selective for D2 receptors and more effective in reducing prolactin secretion
  • better tolerated

Bromo: long standing use
-mores SE

*both oral preparations

29
Q

SE of Bromocriptine

A
  1. N/V
  2. HA
  3. postural hypotension
  4. Rare: pscyhosis or insomnia
30
Q

Adverse effects of Cabergoline

A
  • *better tolerated than bromocriptine
    1. some hypotension and dizziness
    2. concern w/ HDs and valvular heart disease
31
Q 
A 27-year-old woman with amenorrhea, infertility, and galactorrhea was treated with a drug that successfully restored ovulation and menstruation. Before being given the drug, the woman was carefully questioned about previous mental health problems (which she had none). She was advised to take the drug orally. Which of the following drugs is most likely to be the drug given to this patient? 
A.  Desmopressin 
B.  Dopamine 
C.  Octreotide 
D.  Bromocriptine 
E.  Prolactin
A

D.  Bromocriptine

32
Q

What hormones are released from the anterior and posterior pituitary

A

Ant: (FLAT PiG)
FSH, LH, ACT, TSH, Prolactin, GH

Posterior:
Oxytocin, ADH (aka vasopressin)

33
Q

Describe the PK of Vasopressin (aka ADH, Desmopressin) including forms and t1/2

A

Forms: must be administered parenterally (IM, IV, IN)

  • T1/2= 20 min
  • Desmopressin t1/2= 1.5-2.5 hrs
34
Q

What stimulates and inhibits ADH release

A

Stimulates: rising blood osmolality, decrease in circulating BV

Inhibit: alcohol

35
Q

ADH has a critical role in control of water content throughout body via actions on cells in __ and __ in kidney. Released from supraoptic nuclei of hypothalamus

A

distal nephron and collecting tubules

36
Q 
A 42-year-old woman developed a syndrome of polyuria, thirst, and hypernatremia after surgical removal of part of her pituitary gland. These signs and symptoms can be treated with which of the following? 
A.  Bromocriptine 
B.  Desmopressin 
C.  Octreotide 
D.  Somatropin 
E.  Vasopressin
A

B.  Desmopressin

37
Q

Describe how ADH works (Pharmacodynamic actions at V1 and V2 receptors)

A
  • Renal: mediated by V2 receptors (GPCRs coupled to Gs)
  • -> increase rate of insertion of water channels= increased permeability antidiuretic effects

At V1 receptors (GPCRs coupled to Gq) mediates vasoconstriction of vascular SmM. at HDs

38
Q

Non-V2 renal actions of ADH include

A
  1. release of coagulation factor VIII and von Willebrand’s factors
39
Q

What are the clinical uses of vasopressin at V2 receptors

A
  • *use Desmopressin
    1. Central (neurogenic) diabetes insipidus
    2. nocturnal enuresis
    3. Von Willebrand dz (increase factor)
    4. Moderate hemophilia A (elevates factor VIII)
40
Q

Forms of Desmopressin (DDAVP)

A
  1. SC-IV
  2. nasally 1-2x/day
  3. orally 2-3x/day—- useful in pts w/ sinusitis form nasal preps
41
Q

What are side effects of ADH/Desmopressin (SC-IV)

A
  1. HA
  2. Nausea
  3. abdominal cramps
  4. allergic rxn
  5. water intoxication
42
Q

What are side effects of Desmopressin nasally and orally

A

nasal: nasal irritation

orally:

  1. GI sx
  2. asthenia
  3. mild elevation of liver enzymes
43
Q

What are clinical uses of ADH at V1 receptor

A
  • *use vasopressin, Pitressin
    1. attenuates pressure and bleeding in esophageal varices (Octreotide better tolerated and now preffered w/ or w/o endoscopy)
    2. vasopressor for severe septic shock
    3. Alternative to Epi for ACLS shock-refractory VT/VF
44
Q

Side effects of Vasopressin

A
  1. HA
  2. nausea
  3. abdominal cramps
  4. allergic reactions
  5. water intoxication

Pharmacology (31 decks)

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