Diabetes and Endocrine

Question 1

Aspart, Glulisine, Lispro are all examples of:

What is their Clincal use?

What is are some (-) side effects?

Answer 1

Aspart, Glulisine and Lispro are all rapid acting insulin preparations

Use: Type 1 or Type 2 DM for RIGHT after meansl

Sides: hypoglyema

Question 2

What is the MOA for all insulin drugs?

Answer 2

Binds insulin receptor (tyrosine kinase activity).

Liver: INCREASE ?glucose stored as glycogen.

Muscle:? INCREASE glycogen, protein synthesis;?

INCREASE K+ uptake.

Fat:?TG storage.

Question 3

What insulin drugs are intermediate (12 hr) acting?

Which provide Long acting 24 hour coverage?

Answer 3

NPH is Intermediate coverage

Detemir and Glargine are Long Acting

Question 4

Oral drug that is first-line therapy in type 2 DM, causes modest weight loss.

**Can be used in patients without islet function.

Answer 4

Metformin : oral hypoglycemic drug

Question 5

What is the Mechanism of Metformin?

What is a toxicity of metformin?

Answer 5

Exact mechanism unknown.
? Decrease gluconeogenesis, ? Increase glycolysis, ?Increase peripheral glucose uptake (?INCREASES insulin sensitivity).

Metformin sensitivity: GI upset; most serious adverse effect is
lactic acidosis (contraindicated in renal insufficiency )

Question 6

This drug has a risk for causing Lactic acidosis thus contraindicated in pts with renal fail

It’s first line with Type 2 DM and can be used in pts that don’t have islet cell function.

Answer 6

Metformin

Question 7

These drugs are used to treat T 2 DM and require islet cell fuction to stimulate release of endogenous insluin.

(Thus useless in Type 2 DM)

Answer 7

Sulfonylureas

First generation:Chlorpropamide, Tolbuta mide

Second generation:

Glimepiride, Glipizide, Glyburide

Question 8

What is the mechanism of action of the following drugs?

Glimepiride, Glipizide, Glyburide

What is their risk of toxicity?

Answer 8

Glimepiride, Glipizide, Glyburide are all sulfonylureas

Mech: Close K+ channel in B cell membrane–> cell depolarizes–> insulin release via Increase Ca++ influx:

thus stimulate release of endogenous insulin in type 2 DM

Sides = Hypoglycemia

Question 9

What types of drugs are Pioglitazone, Rosiglitazone?

What is the Mechansim of action?

Answer 9

Glitazones/ thiazolidinediones:

?Increased insulin sensitivity in peripheral tissue. Binds to PPAR-γ nuclear transcription regulator: Genes activated by PPAR-γ regulate fatty acid storage and glucose metabolism. Activation of PPAR-γ? INCREASES insulin sensitivity and levels of adiponectin.

Question 10

?Increase insulin sensitivity in peripheral tissue. Binds to PPAR-γ nuclear transcription regulator and activated by PPAR-γ regulate fatty acid storage and glucose metabolism. Activation of PPAR-γ will Increase ?insulin sensitivity and levels of adiponectin.

Answer 10

Pioglitazone, Rosiglitazone

Question 11

What side effect are we worried about with Pioglitazone or Rosigliotazone?

Answer 11

It’s causes weight gain, edema

Hepatotoxicity, HF and Increase risk of fractures

Question 12

MOA of Exenatide, Liraglutide

Answer 12

GLP-1 analogs : ?Increase insulin,? Decrease glucagon release.

For T2DM

Sides: Nausea, vomitting and pancreatitis

Question 13

Linagliptin, Saxagliptin, Sitagliptin

MOA?

Use?

Toxicities

Answer 13

DPP-4 inhibitors

Increase ?insulin,? Decrease glucagon release.

Type 2 DM.

Mild urinary or respiratory infections.

Question 14

MOA of Pramlintide

Uses?

?Side Effects?

Answer 14

Decrease gastric emptying,? Increase glucagon.

Uses: Type 1 DM, type 2 DM.

Sides; Hypoglycemia, nausea, diarrhea

Question 15

Decrease gastric emptying,? Increase glucagon.

Uses: Type 1 DM, type 2 DM.

Sides; Hypoglycemia, nausea, diarrhea

Answer 15

Pramlintide

Question 16

Block reabsorption of glucose in PCT.

Uses: Type 2 DM.

Sides: Glucosuria, UTIs, vaginal yeast infections

Answer 16

SGLT-2 inhibitors

Canagliflozin

Question 17

Inhibit intestinal brush-border α-glucosidases.

delayed carbohydrate hydrolysis and glucose absorption –> Increased postprandial hyperglycemia.

Answer 17

α-glucosidase inhibitors

Acarbose, Miglitol

Question 19

What is the mechanism of Propylthiouracil, methimazole

Answer 19

Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification (coupling) of iodine?–> inhibition of thyroid hormone synthesis. Propylthiouracil also blocks 5′-deiodinase–> DECREASE??peripheral conversion of T4 to T3.

Question 21

When would we prescribe Propylthiouracil, methimazole?

What is the toxicity seen with these drugs?

Answer 21

Hyperthyroidism. PTU blocks Peripheral conversion, used in Pregnancy (Methimazole isn’t safe).
Side: Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity (propylthiouracil).

Methimazole is a possible teratogen (can cause aplasia cutis).

Question 22

When would we presrcibe Levothyroxine (T4), triiodothyronine (T3)

What’s it’s use?

What sides do we see?

Answer 22

Thyroid hormone replacement.
Uses: Hypothyroidism, myxedema. Used off-label as weight loss supplements.

Sides: Tachycardia, heat intolerance, tremors, arrhythmias.

Question 23

What drug can we prescribe to a pt with SIADH?

What’s it’s mechanism?

Answer 23

ADH antagonists (conivaptan, tolvaptan)

SIADH, block action of ADH at V2-receptor.

Question 24

When would we prescribe GH to a pt?

When would we prescribe Oxytocin to a pt?

Answer 24

GH: GH deficiency, Turner syndrome.

Oxytocin: Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage.

Question 25

Drug used to tx Acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices.

Answer 25

Somatostatin (octreotide)

Question 26

When would we prescribe Demeclocycline

Toxicity?

Answer 26

ADH antagonist (member of tetracycline family).
Use: SIADH.
Toxicity: ​Nephrogenic DI, photosensitivity, abnormalities of bone and teeth.

Question 27

What type are the following drugs: Beclomethasone, dexamethasone, fludrocortisone (mineralocorticoid and glucocorticoid activity), hydrocortisone, methylprednisolone, prednisone, triamcinolone.

Answer 27

Glucocorticoids

Question 28

What is the MOA of Glucocorticoids?

Answer 28

Metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interactions with glucocorticoid response elements, inhibition of phospholipase A2, and inhibition of transcription factors such as NF-κB.

Question 29

Addison disease, inflammation, immunosuppression, asthma.

What drugs would you prescribe?

Answer 29

Beclomethasone, dexamethasone, fludrocortisone (mineralocorticoid and glucocorticoid activity), hydrocortisone, methylprednisolone, prednisone, triamcinolone.

Question 30

Toxicity associated with Glucocorticoids?

Answer 30

Iatrogenic Cushing syndrome (hypertension, weight gain, moon facies, truncal obesity, buffalo hump, thinning of skin, striae, osteoporosis, hyperglycemia, amenorrhea, immunosuppression), adrenocortical atrophy, peptic ulcers, steroid diabetes, steroid psychosis.

Adrenal insufficiency when drug stopped abruptly after chronic use.

Question 31

Sensitizes Ca2+-sensing receptor (CaSR) in parathyroid gland to circulating Ca2–> DECREASES +??PTH.

When would you prescribe this?

Answer 31

Cinacalcet

H_ypercalcemia due to 1° or 2° hyperparathyroidism._

Toxicity = Hypocalcemia