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ENDOREPRO MODULE > ENDO Pharm > Flashcards

ENDO Pharm Flashcards

0
Q

What are hormones that counter insulin?

A

Cortisol
Epi and NE
Glucagon
GH

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1
Q

Insulin regulates glucose uptake and metabolism in all tissues except…

A 
CNS
Peripheral Neurons (including retina)
Renal medullary cells
cells lining the blood vessels
liver cells (but insulin does affect glucose metabolism)
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2
Q

What type of receptor does insulin act on?

A

tyrosine kinase.

Insulin receptor autophosphorylates on tyrosine residues and phosphorylates IRS-1 on multiple tyrosine residues.

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3
Q

In type 1 DM, what hormones are unopposed?

A

cortisol
Epi and NE
Glucagon
GH

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4
Q

What insulin preparation has no peak of activity?

A

Insulin glargine

Maintains glucose at 130 mg/dL for about 20 hr.

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5
Q

Which insulin preparation has the quickest onset?

A

Insulin lispro

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6
Q

What are the two short acting insulin preparations?

A 
insulin aspart (duration 3-5 hr)
insulin glulisine (duration 1-2.5 hr)
both have an onset of 0.-0.25 hr
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7
Q

How can you give insulin?

A

NOT orally

Subcutaneous injection, portable pen injectors, nasal spray, insulin pumps, powdered insulin that is inhaled.

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8
Q

How do you treat type II diabetes?

A

DIET AND EXERCISE

Oral hypoglycemics and euglycemics

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9
Q

Name five sulfonylureas, to include the 2nd generation sulfonylureas. What do they treat?

A

Oral hypoglycemics for Type II DM
Tolbutamide (1st generation)
Glyburide, glipizide, gliclazide, glimepiride (2nd generation)

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10
Q

What is the mechanism of action of sulfonylureas?

A

“Bind to K+ channels of B cells, depolarize cells, release insulin”
Bind to the same K+ channel on membrane of pancreatic B cells that is regulated by glucose metabolism.
K+ channels close -> membrane depolarizes -> Causes Ca2+ channels to open -> helps release of insulin

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11
Q

Adverse effects of sulfonylureas?

A

Prolonged and severe hypoglycemia -> can be fatal!

Symptoms: sweating, hunger, paresthesis, tremor, anxiety

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12
Q

What is a drug that is not a sulfonylurea but acts just like one on the K+ channels?

A

repaglinide

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13
Q

What is Metformin mechanism of action?

A

Reduces hepatic glucose output by inhibiting gluconeogenesis

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14
Q

What is the benefit of using Metformin to help Type II DM patient’s hyperglycemia?

A

It never causes hypoglycemia!

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15
Q

What are some adverse effects of Metformin?

A 
Lactic Acidosis (seen in patients with renal failure or CHF)
2% patients experience diarrhea
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16
Q

What is Acarbose mechanism of action?

What does is treat?

A

Acts by inhibiting carbohydrate breakdown in the intestine (alpha-glucosidase inhibitor)
Reduces glucose uptake from intestine -> reduces postprandial spike in blood glucose
Helps with hyperglycemia in DM Type II

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17
Q

Adverse effects of acarbose?

A

Alone will not cause hypoglycemia, but if taken with sulfonylurea and hypoglycemia occurs-> take GLUCOSE and not SUCROSE
Adverse effects: abdominal bloating, diarrhea, flatulence.

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18
Q

Name three thiazolidinediones.

What are they known asn for type II DM?

A

Pioglitazone, rosiglitazone, ciglitazone

AKA “glitazones”

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19
Q

Pioglizazone
MOA:?
SE:?

A

MOA: selective PPARy agonists; increase insulin sensitivity, possibly by inc. glucose transporters (GLUT4) in muscle & adipose, also decreases gluconeogenesis in liver.
SE: does NOT cause hypoglycemia; no liver toxicity. can be combined with sulfonylureas or metformin.

20
Q

What drugs that help with hyperglycemia never cause hypoglycemia?

A

Pioglitazone
Metformin
Sitagliptin

21
Q

What endogenous compound does Exenatide mimic?

A

Glucagon-like-peptide-1 (GLP-1): a peptide released from the GI tract when food enters

22
Q

GLP-1 stimulates what cells to release what hormone?

A

GLP-1 travel via the blood to B cells where it stimulates insulin release and inhibits glucagon release.

23
Q

What compound is an orally active “dipeptidyl peptidase-4” inhibitor? MOA?

A

Sitagliptin
Prevents breakdown of endogenous glucagon-like peptide-1 (GLP-1).
Also reduces hemoglobin A1C
does NOT cause hypoglycemia

24
Q

What is GLP-1’s function?

A

It is a potent stimulator of insulin release in a glucose-dependent manner, and inhibits glucagon release.

25
Q

Canagliflozin
What does it treat?
MOA:

A

Type II DM
MOA: Sodium-glucose-co-transporter-2 inhibitor (SGLT2)
Since almost 100% of glucose is reabsorbed back into blood in proximal tubules by SGLT2, canagliflozin causes some glucose to be lost in the urine by inhibiting SGLT2

26
Q

What are some benefits of using canagliflozin after 26 weeks of treatment?

A
  • 1% reduction in HbA1c
  • reduction of fasting glucose
  • loss of ~2.5 kg
27
Q

What were some adverse effects of canagliflozin?

A

~10% inc. in genital mycotic infections (male and female)
-inc UTI
diuretic effect with volume depletion
some reports say hyperkalemia, hypermagnesemia and hyperphosphatemia

28
Q

What factors stimulate GH release?

A 
Hypoglycemia
Amino Acids (arginine most potent)
Deep sleep
exercise
Dopamine agonists (DA normally stimulates GH release by inhibiting SST release, but in acromegaly DA inhibits GH release)
29
Q

What recombinant hGH form causes mild allergies in 50% of patients?

A

Somatrem

30
Q

Growth hormone therapy for hypopituitary dwarfism

A

Dose 0.3mg/kg/wk, three IM or subcut. injections of 0.1 mg/kg
Start treatment ASAP
require T3 and T4 for GH to increase growth
will need to increase dose over time because there is a decrease in response.

31
Q

What is Hypersomatotrophic dwarfism?

A

“Laron Syndrome”
Defect in GH receptor (GH cannot stimulate IGF-1 synthesis and release.
Occurs in: jews of oriental origin, african pygmies, toy poodles.

32
Q

Whats another name for Somatomedin C?

A

IGF-1

33
Q

Laron Syndrome:
GH high or low?
IGF-1 high or low?

A

GH high

IGF-1 Low

34
Q

Mecasermin:
What is it?
What does it treat?

A

Recombinant human IGF-1 combined with rhIGF-BP-3 to increase IGF-1 stability.
Increasing drowth in Laron Dwarfs.

35
Q

What is the usual cause of acromegaly?

A

Adenoma of somatotroph

36
Q

Features of acromegaly

A

Broadening of nose, elongation of mandible, severe narrowing of joints, carpal tunnel syndrome, glucose intolerance, hypertension, hypertrophy of organs (heart -> congestive failure)

37
Q

How can you treat a GH secreting adenoma of the anterior pituitary?

A 
Surgical removal
Bromocriptine
Cabergoline
Ocreotide
Pegvisomant
38
Q

Dopamine agonists work best in patients whose tumors secrete what two things?

A

GH and Prolactin

39
Q

Somatotroph and Lactotroph stem from the same progenitor cell. What receptors are expressed on the progenitor cell?

A

GHRH, SST, Dopamine 2

40
Q

Which drug is a dopamine agonist?

A

Bromocriptine

Cabergoline is also a very long acting D2 agonist (t1/2 = 65 hr)

41
Q

Octreotide:

Description

A

Long acting somatostatin agonist.

Peptide so it MUST be injected.

42
Q

Pegvisomant:
Gen:

A

Gen: GH receptor antagonist
has PEG polymers attached to it and decreases antigenicity -> causes GH receptors to dimerize but not activate
Effective but costs a SHIATTTT ton (50000-100K a year!)

43
Q 
Pasireotide
General:
Use:
MOA:
SE:
A

Gen:Somatostatin analog
Use: Treat’s Cushing’s Disease that persists after surgical removal of an ACTH-secreting pituitary tumor.
MOA: Binds to somatostatin receptor, esp subtype 5 which is often overexpressed on corticotroph adenomas that secret ACTH
SE: diarrhea, nausea, cholelithiasis, ab pain, fatigue, hyperglycemia

44
Q

Pasireotide inhibits insulin release from the pancreas (SST receptors) which will cause what in patients who are being treated for Cushing Disease?
How can you fix this issue?

A

hyperglycemia

Co-treat with sitagliptin, drug that prolongs activity of endogenous insulin secretagogue (GLP-1)

45
Q

Where is prolactin produced?

A

Lactotrophs in anterior pituitary.

Stimulates milk production in women who have given birth.

46
Q

What are four causes of hyperprolactinemia?

A

Lack of sufficient dopamine
Adenoma of lactrotrophs
Hypothyroidism (excess TRH stimulates lactrotrophs)
Antipsychotic (most antipsychotics block D2 dopamine receptors)

47
Q

Treatment of hyperprolactinemia

A

Bromocriptine (long acting D2 dopamine agonist)
Cabergoline (long acting D2 dopamine agonist)
both reduce prolactin levels and shrink adenomas.

48
Q

Side effect of cabergoline?

A

Can cause valvular heart disease

ENDOREPRO MODULE (11 decks)

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