Diabetes Medications

Question 1

Biguanides

Answer 1

Metformin and Phenformin (no longer on market - liver tox)

• Stop gluconeogenesis / glucose production in the liver
• increase glucose sensitivity
• decreases intestinal absorption of glucose

AEs: GI issues, Risk of lactic acidosis! (particularly w/ renal impairment)

Question 2

Sulfonylureas

Answer 2

1st gen: Glyburide, glipizide, gliclazide, glimepiride
2nd gen (inc 10-100x potency):  micronase, glucotrol, diabend, amaryl

• Increases pancreatic insulin production by binding/closing K+ channel (depolarizing) which opens the Ca channel, causing an increased release of insulin
• inc insulin sensitivity by inc glucose uptake
• may decrease insulin metabolism by liver
• extensively protein bound!

AEs: Hypoglycemia, lose effect after long term tx

Question 3

Thiazilideniodes “itazones”

Answer 3

Pioglitazone, Rozeglitazone (BBW), Troglitazone (w/drawn for liver toxicity)

• Binds PPAR gamma receptor, increasing cell sensitivity to insulin
• inc glucose transport into muscles

AEs: Weight gain, edema, CV risk

Question 4

Human recombinant insulin

Answer 4

Humulin and Novolin

Question 5

Lispro, Aspart, Glulisine Insulin

Answer 5

Pro –> Lys/Asp/Glu, doesn’t form Zn hexamer ie exist as monomers = faster onset, shorter half life/duration of action

Question 6

Glargine and Detemir Insulin

Answer 6

Altered Isoelectric Points (soluble at acidic pH)

• -> precipitate when neutralized at body pH = longer acting/slow absorption
• -> low peak insulin (decreases chance of nocturnal hypoglycemia)

Question 7

Degludec Insulin

Answer 7

conjugated to hexadecanedioic acid = allows hexamer formation subcutaneously

acts like an insulin reservoir –> NO PEAK, slow absorption

Can be mixed with other insulins

Question 8

Short acting vs intermediate acting insulin

Adjustments?

Answer 8

short acting = regular/human insulin
intermediate = NPH and Lente insulins

• *Short acting = gets you through meal directly administration
• *intermediate gets you through time between breakfast and lunch and through the night

** ie glucose too high before lunch/bedtime = adjust regular insulin, glucose too high before dinner/breakfast = adjust NPH

Question 9

NPH and Lente insulins

Answer 9

Intermediate insulins

• NPH = neutral, protamine, hagedorn
• Lente = Zn insulin crystals (discontinued in favor of NPH)

Question 10

Most common cause of hypoglycemia? Treatment?

Answer 10

Insulin overdose, give glucose (NOT insulin)

vs. Ketoacidosis = hyperglycemic, give insulin

Question 11

HbA1c recommendations, level for dx of diabetes?

Answer 11

Normal: 6.4%

Recommended = keep diabetics below 6.4%! …> 8% not good …>10% dangerous

Question 12

Meglitinides

Answer 12

Repaglinide, Nateglinide

• similar to sulfonylurea MOA = inc insulin secretion, but not related structure
  (benzoic acid derivative)
• RAPID GI absorption — before meals to control post prandial glucose level

AEs: hypoglycemia

Question 13

Acarbose and Miglitol

Answer 13

Alpha glucosidase inhibitors! –> dec intestinal starch/disaccharide absorption by brush border

Often used with insulin/other hypoglycemic drugs

AEs: hypoglycemia

Question 14

Octreotide and Diazoxide

Answer 14

**tx for Insulinomas

Octreotide/Somatostatin = inhibits TSH and GH secretion form pituitary + inhibit Insulin and glucagon release form pancreas
**uses: insulinomas, GH excess ie acromegaly, glucagonomas

Dizoxide = inhibit insulin SECRETION (not synthesis) from pancrease
**used for insulinomas! or other causes of hypoglycemia

Question 15

Incretin Analogs

Answer 15

Exenatide, Liraglutide, Dulaglutide

• • increases glucose dependent insulin secretion
• inhibits glucagon synthesis/glucagon stimulated glycogenolysis
• slows gastric emptying
• decreases apetite

also cardioprotective/increases cardiac output

Question 16

DPP-4 inhibitor “GLiPtins”

Answer 16

Sitaglipitin, saxagliptin, linagliptin

• xDPP-4 which inactivates incretins ie potentiates incretin action

Question 17

Pramlinitide (and symlin)

Answer 17

Amylin analog

• released by Beta cells w/ insulin
• deficient in type I DM
• slows gastric emptying (dec onslaught of glucose)
• increases satiety
• inhibits inappropriate glucagon secretion

*symlin = approved for type II diabetics using insulin – decreases insulin dose needed

Question 18

SGLT2 inhibitors

MOA and AEs

Answer 18

Cinagliflozin
(SGLT1 (GI) and SGLT2 (renal prox tubule) increased in diabetics)

MOA: decreases reabsorption of glucose in kidney – DOES NOT INCREASE SECRETION (glucose is never secreted in nephron)

AEs: hypotension, hyperkalemia, hypoglycemia, increased LDL

Question 19

Who are SGLT inhibitors contraindicated with?

Answer 19

Pts w/ severe renal impairment, end stage renal disease, or on dialysis

Question 20

Bile acid sequestrants

Answer 20

Colesevelam hydrochloride

Uses: lowers LDL and HbA1c ~ 1.5% (assumed to interupt enterohepatic cycling/lower Farnesoid X receptor activation)

AEs: gastrointestinal problems

Question 21

Glyburide, glipizide, gliclazide, glimepiride

Answer 21

1st generation sulfonylureas

Question 22

micronase, glucotrol, diabend, amaryl

Answer 22

2nd generation sulfonyureas (more potent)

Question 23

Pioglitazone, Rozeglitazone

Answer 23

Thiazilideniodes — PPAR

PPAR = nuclear receptor that plays a role in adipocyte differentiation – activation of PPAR gamma increases secretion/synthesis of adiponectin (adipokine that increases insulin sensitivity)! …vs. other adipokines released with FFAs that dec insulin sensitivity

Question 24

Humulin and Novolin

Answer 24

hInsulin