Endocrine Pharm Flashcards

1
Q

What are the two forms of insulin that can be given IV?

A

Lispro and regular - these are the only solution-form of insulin (others are suspension)

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2
Q

Which insulins have the fastest onset?

A

Lispro and regular, when given IV work within 2-4 min

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3
Q

What is unique about glargine?

A

It has no peak activity → used for basal glucose control & no risk of hypoglycemia

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4
Q

What kind of receptor does insulin bind? What happens next?

A

Tyrosine kinase → autophosphorylation of receptor → allows binding of IRS-1, which becomes phosphorylated → allows binding of SH2 domain proteins, which become phosphorylated → lots of enzyme activity, especially phosphatases → enzymes dephosphorylated to be activated/inactivated, some changes in gene expression (lipoprotein lipase, FA synthase, glucokinase) – SEE BIOCHEM SECTION

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5
Q

What are 3 ketoacids in DKA?

A
  1. acetoacetate
  2. β-hydroxybutyrate
  3. acetone → fruity breath (no E-delivering activity)
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6
Q

What energetic molecules can β-OHbutyrate give rise to? Where are these molecules used?

A

1x NADH
2x Acetyl-CoA
- used mainly by muscle tissue (e.g. heart), renal cortex, brain (only if period of prolonged starvation)

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7
Q

What energetic molecules can acetoacetate give rise to?

A

2x Acetyl-CoA

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8
Q

What is the treatment for DKA?

A
  1. regular insulin
  2. glucose
  3. fluid and electrolytes (esp. watch for hypokalemia)
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9
Q

What is the effect of insulin on K+ in the body?

A

insulin drives K+ into cells

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10
Q

What type of glucose transporters are on β cells in the pancreas? What is significant about the pharmacodynamics of this receptor?

A

GLUT 2 - has very high Km (thus low affinity for glucose) so it is only active when high glucose in blood (e.g. after meals)

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11
Q

How does elevated glucose → insulin release in β cells?

A

Glucose → gets in cell through GLUT 2 → ↑ ATP → closes K+ channel → depolarization → open voltage-gated Ca2+ channel → ↑ Ca2+ in cell → exocytosis of insulin

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12
Q

What do sulfonureas do? Do they work in T1DM?

A

block the K+ channel in β cells, mimicking the effect of ↑ ATP; don’t work in T1DM b/c these patients don’t have β cells

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13
Q

What drugs work oppositely to sulfonureas?

A

diazoxide and minoxidil: direct acting vasodilators that open ATP-dependent K+ channels → hyperpolarization → ↓ insulin release → drug-induced diabetes

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14
Q

What is acetohexamide? What is unique about it?

A

A first generation sulfonurea; it has an active metabolite → very long duration of action → be careful with renal function

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15
Q

What is tobutamide? What is unique about it?

A

A first generation sulfonurea; can use in kidney patients b/c no renal tox

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16
Q

What is chlorpropamide? What is unique about it?

A

A first generation sulfonurea; causes disulfaram-like reaction and SIADH (like carbamazepine)

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17
Q

What are the second generation sulfonureas and their side effects?

A

GLYburide - ↓ dose in renal pt. or will cause hypoglycemia

gLIPizide - ↓ dose in hepatic pt.

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18
Q

What are the general side effects for sulfonureas?

A
  1. hypoglycemia in fasting state (e.g. at 2-3 AM)
  2. weight gain
  3. hypersensitivity (SULFONureas have a sulfur group)
  4. drug interactions (highly plasma protein bound, p450 processed)
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19
Q

What drugs would interact with sulfonureas?

A
  1. p450: cimetidine
  2. hypoglycemia: insulin
  3. compete for protein binding sites → hypoglycemia: salicylates, sulfonamides
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20
Q

What drug is thought to bypass insulin receptors in cells? How? What are the side effects? What is a notable exception?

A

Metformin - thought to stimulate PPAR transcription factors directly; since it burns glucose can cause lactic acidosis (rare; contraindicated in renal failure for this reason), GI distress is most common side effect; does not cause hypoglycemia

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21
Q

What is the mechanism of action of acarbose and miglitol?

A

inhibit α-glucosidase → ↓ breakdown of sugars → ↓ absorption → ↓ post-prandial hyperglycemia and ↓ demand for insulin (may improve insulin sensitivity)

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22
Q

What are the side effects of thiazolidinediones?

A
  1. thia = hypersensitivity, lipid sol → hepatotox
  2. azol = potentiate effects of EtOH
  3. weight gain
  4. edema
  5. heart failure
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23
Q

What do the thiazolidinediones (glitazones) do?

A

bind to PPAR-gamma → mimic actions of insulin:

  1. ↓ gluconeogenesis via: ↑ PFK2 → ↑ fructose 2,6- bisphosphate → dephosphorylation/inactivation of fructose-1,6-bisphosphatase (rate limiting step)
  2. ↑ insulin receptors
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24
Q

What are 2 ways glitazones and metformin ↓ blood glucose?

A
  1. enhance uptake in skeletal mm. through ↑ GLUT 4 receptors

2. inhibit glucose production by liver (↓ gluconeogenesis)

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25
Q

What is exenatide? What is a similar drug?

A

A GLP-1 receptor agonist (incretin) that ↑ insulin release from β cells and ↓ glucagon produciton from α cells; liraglutide

26
Q

What is sitagliptin? What other drugs share its mechanism of action?

A

inhibits dipeptidyl peptidase (DPP-4) → prevents GLP-1 inactivation; linagliptin, saxagliptin

27
Q

When is hypercoagulability an issue with estrogen therapy?

A

at high doses or if patient is predisposed

28
Q

When is endometrial cancer an issue in estrogen therapy?

A

it is a real risk of unopposed E therapy; use progestin to eliminate risk

29
Q

What is DES (diethylstilbestrol)?

A

A synthetic estrogen that, when taken by pregnant ♀ → increased risk of clear cell vaginal adenocarcinoma in offspring

30
Q

What is premarin?

A

conjugated equine estrogens: natural estrogen isolated from the urine of pregnant mares (hence premarin) - this is the only estrogen without -est- in name

31
Q

What is norethindrone?

A

a progestin - the only that’s not obvious by the name

32
Q

What’s unique about Desogestrel?

A

it’s a synthetic progesterone without androgenic or anti-estrogenic effects

33
Q

What effect do progestins have on lipids?

A

↑ LDL and ↓ HDL (ok when preg b/c need more cholesterol, but not good for later → athero)

34
Q

What effect do progestins have on glucose metabolism?

A

cause glucose intolerance

35
Q

What effect do progestins have on androgen hormones?

A

36
Q

What is mefepristone?

A

blocks glucocorticoid and progestin receptors; used with prostaglandins as morning after pill

37
Q

What is the main hormonal purpose of oral contraceptives?

A

suppress the LH surge that causes ovulation

38
Q

Side effects of OCTs?

A

these are mostly progestin, so:

  1. ↑ androgens → acne, hirsutism
  2. ↑ LDL, ↓ HDL
  3. weight gain, tiredness, depression
39
Q

What is the most important point to remember about OCT drug interactions?

A

p450 inducers (e.g. phenytoin, rifampin) → ↓ levels of OCT → ↑ chance of unwanted pregnancy

40
Q

What are the additional benefits of OCTs (besides avoiding pregnancy)?

A
  1. ↓ risk of endometrial and ovarian cancer (antag. E)
  2. ↓ dysmenorrhea
  3. ↓ endometriosis (can be used in tx of chocolate cysts)
  4. ↓ PID (change pH of cervical/vaginal area)
  5. ↓ osteoporosis (if there is some estrogen in pill)
41
Q

Can OCTs cause tumors?

A

Yes, liver adenocarcinoma which is benign but highly vascularized → can cause retroperitoneal bleed in highly active ♀; tend to regress when stop taking OCT

42
Q

Explain the synthesis of thyroid hormones

A
  1. active accumulation of iodide into thyrocyte
  2. organification/oxidation of iodide to iodine by thyroid peroxidase
  3. iodination of tyrosine resides on thyroglobulin to MIT or DIT
  4. coupling of MIT/DIT + DIT = T3/T4
  5. proteolysis → release of thyroglobulin
  6. goes into bloodstream and converted to active T3 form by deiodinase
43
Q

What do thioamides do?

A

inhibit thyroid peroxidase (oxidation, iodination, coupling, and at high doses proteolysis step)

44
Q

What drug inhibits deiodinase in the periphery?

A
propylthiouracil 
propranalol (the only β blocker that does this)
45
Q

What drug is used for a thyroid storm (thyrotoxicosis)?

A

propranolol - improves symptoms (tachycardia, central ↓ response to NE/E → calms pt.) and blocks conversion of T4 to T3

46
Q

What are the two thioamides used for hyperthyroidism? Which is safer in pregnancy (i.e. won’t cause hypothyroidism)?

A

Propylthiouracil (safer because 90% albumin bound)

Methimazole (<10% albumin bound)

47
Q

What is Lugol’s preparation? When could it be used?

A

Potassium iodide + iodine

  • Could be used preoperatively in thyrotoxicosis to ↓ gland size, fragility, and vascularity (via negative feedback)
  • Not used for long-term b/c thyroid escape after 10-14 d
48
Q

When is radioactive iodine 131 used?

A

imaging of thyroid gland to check the activity of cancer nodules, and as therapeutic way to kill thyroid cancer

49
Q

Can GH be given to patients with hypopituitarism?

A

No, it’s a large peptide → doesn’t solubilize easily in IV and is digested if given orally; have to give analogs

50
Q

What are the GH analogs?

A

somatran and somatropin (soma = body, tropin = growth agent)

51
Q

What are GH analogs used for?

A
  1. pituitary dwarfism

2. osteoporosis

52
Q

What drug is used for acromegaly? What are some other uses for this drug?

A

octreotide, a somatostatin analog

other uses: carcinoid, gastrinoma, glucagonoma, esophageal varices

53
Q

What is the analog hormone for ACTH? When is it used?

A

cosyntropin, used for infantile spasms (which seem to be due to hypoglycemia; ACTH → cortisol → gluconeogenesis)

54
Q

Which drugs are GnRH analogs?

A

Leuprolide

Nafarelin

55
Q

What are GnRH analogs useful for?

A
  1. advanced prostate cancer
  2. endometriosis
  3. hypogonadal state (pulsatile delivery)
56
Q

What is prolactin inhibiting factor (PIH)?

A

dopamine

57
Q

What do we give to agonize dopamine? What do we use these for?

A

bromocriptine
pergolide
used for hyperprolactinemia

58
Q

What are the side effects of bromocriptine or pergolide?

A

Dyskinesias, nausea, vomiting, psychosis

59
Q

When do we use desmopressin?

A
  1. central DI
  2. hemophilia A and vWD (↑ vWF which also ↑ factor VIII)
  3. primary nocturnal enuresis
60
Q

What drug is a PTH analog? What is it used for? What considerations should be made?

A

Teriparatide - if given in bursts (e.g. 1xd) → stim. osteoblast → new bone growth, as tx. for some forms of osteoporosis
Considerations:
1. Continuous dose would → ↑ osteoclast activity
2. Can not use for > 2 years because ↑ risk of osteosarcoma