Pharmacology - Endo

Front 1

How is glucose spread in the body?

Back 1

50% brain.
25% insulin independent- liver and GI.
25% insulin dependent- muscle and fat.

Front 2

Where is most endogenous glucose synthesized?

Back 2

Liver- 85% (half by breakdown of glycogen, half newlyformed).
The rest- kidney.

Front 3

How does insulin lower glucose levels in the blood?

Back 3

Shoves it into the cells and lowers synthesis of glucose in the liver.

Front 4

Where is glucagon synthesized?
What does it do?

Back 4

beta-cells in the pancreas, LIKE INSULIN.
Works mainly on the liver, to break down glycogen.

Front 5

How do insulin effect fat cells?

Back 5

Inhibits lipolysis- reduces FFA in plasma (FFA hurt insulin function).

Front 6

What does high glucose in the blood cause?

Back 6

1. Increase in free radicals in the cells it enters.
2. Glycosylation of protein on BV- causes damage to small BV and ischemia.
3. If the insulin isn't working, the cells starve.

Front 7

What is the mechanism of pancreatic control over glucose levels?

Back 7

When glucose in the blood is elevated, it enters the beta cells in the pancreas.
Krebs cycle etc.- more ATP.
ATP BLOCKS ATP-dependent K-channels -> depolarization -> release of insulin.
Elevated ATP also activates transcription factors to synthesize more insulin.

Front 8

Overall, how does glucose effect insulin?

Back 8

- Causes release of insulin (fast).
- Causes production of insulin (slow).

Front 9

What does insulin do the membrane glucose transporters?

Back 9

Changes the amount of time they are expressed.
Does not affect their production.

Front 10

Stages of development of DM2?

Back 10

1. Insulin resistance- d/t the high levels of insulin, it binds to other receptors as well. Can cause high blood pressure and atherosclerosis.
2. Impaired glucose tolerance- the pancreas gets tired and can't keep up.
Insulin levels may still be high, just not sufficient.
3. High glucose levels after a meal.
4. Diabetes..

Front 11

When do you test for insulin levels?

Back 11

Morning.

Front 12

How do FFA affect insulin activity?

Back 12

They cause phosphorylation of IRS on serine residue instead of Tyrosine, which inhibits it.

Front 13

What do small fat cells secrete?
Large?

Back 13

Small fat cells are more differentiated, and secrete adiponectin that lowers insulin resistance.

Large fat cells release Resistin, that causes insulin resistance.

Front 14

What does Adiponectin do?

Back 14

Lowers insulin resistance.
Beneficial effect on cardiovascular system.
Inhibits inflammatory reactions- Macrophages, release of adhesion molecules, etc.

Increased by weight loss!

Front 15

What does SulfonylUrea do?

Back 15

Imitate glucose- block ATP-dependent K channels, thus cause release of insulin (without increasing production).

These types of drugs still overwork the pancreas.

Front 16

Two types of SulfonylUrea?

Back 16

Glipizide- once a day. Danger of hypoglycemia.
Meglitinides - only block K channels when glucose is in the cell- enhance the effect of glucose.

Front 17

What are Insulin Secretagogues?

Back 17

Incretins (from GI)- elevate levels of insulin secreted from the pancreas.
Require working beta-cells.
Increase release AND production of insulin.

GLP1, GIP- working via GPCR.

Front 18

Who inhibits Insulin Secretagogues?

Back 18

DPP4.

Front 19

How do Insulin Secretagogues work?

Back 19

GLP1, GIP:
Cause increase of cAMP- that causes release of Ca from ER and activation of PKA, that in the presense of glucose blocks the ATP-dependent K channel (like Meglitinides).

They also increase the transcription factors for insulin and protect cells from apoptosis.

Front 20

What is Metformin?
Side effects?

Back 20

Most common DM drug.
Does NOT affect the pancreas, but lowers glucose formation in the liver and increase activity of Glut4- SIMILAR TO INSULIN.
Side effect: can cause acidosis.

Front 21

What does Metformin do?

Back 21

Similar to insulin- increase Glut4 and decrease glucose synthesis in liver.

Also: Work on adipocytes to inhibit production of FFA.
Also: Increase activity of AMP Kinase, that increases ATP.

Front 22

When in DM can you use Metformin?

Back 22

It can lower insulin levels at the first stages (when there is only insulin tolerance).
At later stages- can prevent elevation of glucose, maybe.

Front 23

What does Acarbose do?

Back 23

Inhibit the enzymes that breakdown amylan/sucrose - slower absorption of glucose.
WON'T HELP DURING CONSUMPTION OF GLUCOSE.

Front 24

What do Thiazolidinediones do?

Back 24

Significantly lowers insulin resistance (patients require less insulin than helathies).
Work through the PPAR-gamma receptor, that increases AMP Kinase.

Cause creation of new small fat cells (so weight gain is a side effect).

Cannot help much at the later stages (like Metformin can't).

Front 25

What are the positive properties of estrogen?
Negative?

Back 25

+ Lower lipids.
+ Good for bones.
+ Increase in cognitive ability.

- Induces hyperplasia- breast and endometrium.

Front 26

What is Tamoxifen?

Back 26

SERM - Selective Estrogen Receptor modulator.
Lowers risk of breast cancer, strengthens bones, lowers LDL.
Also causes hypercoagulation, increases hyperplasia of endometrium.

Front 27

What is Raloxifene?

Back 27

Against osteoporosis.
Lower spontaneous breast cancer, relapse.

Advantage over tamoxifen- does not cause hyperplasia of endometrium.

Front 28

What is Clomiphene?

Back 28

Not used for cancer- slightly toxic.

Used for fertility. When there are low LH levels, this one inhibits the negative feedback.

Front 29

What happens when fertile women receive Tamoxifen treatment?

Back 29

No negative feedback in peripheral receptors- increase is estradiol.

Front 30

When do you use aromatase inhibitors?

Back 30

- Preventive treatment.
- When tamoxifen alone will not work, or fertile women with high levels of estrogen.

Front 31

What does aromatase do?

Back 31

Cause production of estrogen EVERYWHERE-
* Estradiol in the ovary (pre-menopausal).
* Estron peripherally by fat tissue.
* Estron in tumor.

Front 32

Can you give GNRH directly?

Back 32

No- too short T1/2.

Front 33

How long does it take for GNRH treatment to lower levels of GH?

Back 33

6-8 weeks.
Until then, there is an increase.

To block that increase you can use tamoxifen/aromatase inhibitor, or non-steroidal-anti-androgen for men.

Front 34

Does GNRH affect testosterone production in the adrenal?

Back 34

Nope.

Front 35

What is the problem with androgen antagonists (for prostate cancer- like tamoxifen for women)?

Back 35

- They bind to many other receptors and cause side effects.
- Androgen receptors tend to mutate.

Front 36

What do GC cause?

Back 36

- Temporary increase in glucose, due to temporary insulin resistance- brings on side effects of hyperglycemia, like glaucoma.
- Adipocytes move around- fat stommaccchh.
- Stops growth.
- Inhibit immune system.

Front 37

Who is the main GC?

Back 37

Cortisol.

Front 38

What type is the GC receptor?

Back 38

Steroid receptor, type I.

Front 39

What does cortisol do?
Side effects?

Back 39

- Involved in natural inhibition of inflammation (all eicasinoids- including leukotrienes).
- Fetal growth- lung maturation.
- Inhibit release of cytokines.

Side effects: high blood pressure (in high doses), GI, osteoporosis.

Front 40

What is the difference between NSAIDs and steroids?

Back 40

NSAIDs only work on prostaglandins.
Steroids work on everybody.

Front 41

Who has a longer half life- cortisol or dexamethazon?

Back 41

Dexa.

Front 42

What does cortisol do to the hypophisa?

Back 42

Inhibit production of ACTH, TSH, GH, MC and more.

Front 43

What is the main danger of GC treatment?

Back 43

Stopping quickly will cause lack of GC d/t slow recovery- no GC at ALL for that patient!

Front 44

What happens to cortisone in the body?

Back 44

It is the inactive form.
The enzyme 11beta-FSB, that turns Cortisol -> Cortisone in the kidney, works backwards! Turns Cortisone -> Cortisol in the periphery.