ICL 4.2: Medical care and Pharmacological Agents of Diabetes

Question 1

how do you diagnose diabetes?

Answer 1

AIc over 6.5

FPG over 126

casual plasma glucose over 200

2 hr plasma glucose over 200

Question 2

how do you diagnose prediabetes?

Answer 2

A1c 5.7-6.4

impaired fasting glucose 100-125

impaired glucose tolerance

Question 3

what int he genetic risk of DMI?

Answer 3

identical twins is 30-60%

risk in family members is 5% if a sibling has it, 3% if mom and 6% if dad

Question 4

what int he genetic risk of DMII?

Answer 4

50-90% in twins

lifetime risk of DM2 is 40$ in offspring of one diabetic parents and 70% if both parents

Question 5

what are the goals of therapy for DM in non pregnant adults?

Answer 5

A1c under 7%

fasting 70-130

postprandial under 180

Question 6

what are the goals of therapy for DM in elders?

Answer 6

A1C under 8% but over 7

Question 7

what are the goals of therapy for DM in GDM pregnant adults?

Answer 7

fasting less than 95

post prandial in 1 hr is under 140 and 2 hr is under 120

Question 8

what is the goal in DM in the hospital?

Answer 8

critically ill surgical patients: 140-180 and treat with insulin

critically ill nonsurgical patients: 140-180 and also insulin treatment

noncritlcally ill patients: fasting under 140 but treat with insulin basal, nutritional and correct preferred

Question 9

what are the classes of DM drugs?

Answer 9

1. sensitizers
2. insulin secretagogues
3. insulin analogs
4. others

Question 10

which drugs are sensitizers?

Answer 10

1. biguianides like metformin

2. TZs like glitazones

Question 11

what is the MOA of biguanides?

Answer 11

biguanidesreducehepaticglucose output and increase uptake of glucose by the periphery, including skeletal muscle

reduces A1c 1.5-2%

among common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain

Question 12

what caution do you have to take when giving biguanidse?

Answer 12

although it must be used with caution in patients with impaired liver or kidneyfunction,metformin a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers

metformin(Glucophage) may be the best choice for patients who also have heart failure, but it should be temporarily discontinued before any radiographic procedure involving intravenousiodinatedcontrast, as patients are at an increased risk oflactic acidosis.

Question 13

what is the first line medication for treating DMII?

Answer 13

metformin is usually the first-line medication used for treatment of type 2 diabetes. In general, it is prescribed at initial diagnosis in conjunction with exercise and weight loss

there is an immediate release as well as an extended-release formulation, typically reserved for patients experiencinggastrointestinalside-effects

it is also available in combination with other oral diabetic medications

Question 14

what is the MOA of thiazolidinediones?

Answer 14

TZDs also known as “glitazones,” bind toPPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism

these PPARs act on peroxysome proliferator responsive elements (PPRE).

the PPREs influence insulin-sensitive genes, which enhance production of mRNAs of insulin-dependent enzymes. The final result is better use of glucose by the cells

so basically they increase insulin sensitivity and also reduce A1c by 1.5-2% like metformin

Question 15

what are the concerns with TZDs?

Answer 15

multiple retrospective studies have resulted in a concern about rosiglitazone’s safety, although it is established that the group, as a whole, has beneficial effects on diabetes

the greatest concern is an increase in the number of severe cardiac events in patients taking it

one large prospective study, PROactive, has shown thatpioglitazonemay decrease the overall incidence of cardiac events in people with type 2 diabetes who have already had a heart attack.

Question 16

which drugs are KATP secretagogues?

Answer 16

aka K+ATP sulfonylureas

1st generation: Acetohexamide · Carbutamide · Chlorpropamide · Metahexamide · Tolbutamide · Tolazamide

2nd generation: Glibenclamide · Glyburide# · Glibornuride · Glipizide · Gliquidone · Glisoxepide · Glyclopyramide · Glimepiride · Gliclazide

Question 17

what is the MOA of KATP secretagogues?

Answer 17

they areinsulinsecretagogues, triggering insulin release by inhibiting theKATPchannel of the pancreaticbeta cells

sulfonylureaswere the first widely used oral anti-hyperglycemic medications

sulfonylureas bind strongly toplasma proteins

reduce A1c by 1-2%

Question 18

which type of DM are KATP secretagogues used in?

Answer 18

sulfonylureas are useful only in type 2 diabetes, as they work by stimulating endogenous release of insulin

they work best with patients over 40 years old who have had diabetes mellitus for under ten years

they cannot be used with type 1 diabetes, or diabetes of pregnancy. They can be safely used with metformin or glitazones. The primary side-effect ishypoglycemia.

Question 19

which drugs are KATP non-sulfa drugs?

Answer 19

Meglitinides/”glinides” Nateglinide · Repaglinide · Mitiglinide

Question 20

what is the MOA of KATP non-sulfa drugs?

Answer 20

meglitinideshelp the pancreas produce insulin and are often called “short-acting secretagogues.”

they act on the same potassium channels as sulfonylureas, but at a different binding site

by closing the potassium channels of the pancreatic beta cells, they open the calcium channels, thereby enhancing insulin secretion

they are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped

.5-1% decrease in A1c

Question 21

what is the side effects of KATP non-sulfa drugs?

Answer 21

weight gain and hypoglycemia

Question 22

what are the GLP-1 agonist drugs?

Answer 22

Exenatide · Liraglutide · Taspoglutide† · Albiglutide† · Lixisenatide · Dulaglutide† · Semaglutide

Question 23

what is the MOA of GLP-1 agonist drugs?

Answer 23

incretins are insulinsecretagogues – the two main candidate molecules that fulfill criteria for being an incretin areglucagon-like peptide-1(GLP-1) andgastric inhibitory peptide(glucose-dependent insulinotropic peptide, GIP)

noth GLP-1 and GIP are rapidly inactivated by the enzymedipeptidyl peptidase-4(DPP-4)

glucagon-like peptide (GLP) agonists bind to a membrane GLP receptor – therefore, insulin release from the pancreatic beta cells is increased

endogenous GLP has a half-life of only a few minutes, thus an analogue of GLP would not be practical

typical reductions inA1C values are 0.5–1.0%

Question 24

what are GLP-1 agonists used to treat?

Answer 24

Exenatide(Byetta) was the firstGLP-1agonist approved for the treatment oftype 2 diabetes

Exenatide is not an analogue of GLP but rather a GLP agonist

Exenatide has only 53% homology with GLP, which increases its resistance to degradation by DPP-4 and extends its half-life

Liraglutide, a once-daily human analogue (97% homology), has been developed byNovo Nordiskunder the brand nameVictoza. Lixisenatide (Lyxumia) and Semaglutide (Ozempic) are now also available.

Question 25

what are the side effects of GLP1 agonists?

Answer 25

these agents may also cause a decrease in gastric motility, responsible for the common side-effect of nausea, and is probably the mechanism by which weight loss occurs.

Question 26

which drugs are DPP4 inhibitors?

Answer 26

Alogliptin · Anagliptin · Gemigliptin · Linagliptin · Saxagliptin · Sitagliptin · Teneligliptin · Vildagliptin

Question 27

what int he MOA of DPP4 inhibitors?

Answer 27

• DPP-4 inhibitorsincrease blood concentration of theincretinGLP-1 by inhibiting its degradation bydipeptidyl peptidase-4

GLP-1 analogs result in weight loss from more gastrointestinal side-effects, while in general DPP-4 inhibitors were weight-neutral and increased risk for infection and headache, but both classes appear to present an alternative to other antidiabetic drugs.

A1c lowered by .74%

Question 28

which drugs are alpha glucosidase inhibitors?

Answer 28

Acarbose · Miglitol Voglibose

Question 29

what is the MOA of alpha glucosidase inhibitors?

Answer 29

alpha-glucosidase inhibitorsare “diabetes pills” but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity

these agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin

these agents are effective by themselves only in the earliest stages ofimpaired glucose tolerance but can be helpful in combination with other agents intype 2 diabetes.
response or sensitivity

A1c resudeced by .5-1% BUT not used often because severe side effects of flatulence and blaoting

Question 30

what is the MOA of amylin analog pramlintide?

Answer 30

amylinagonist analogues slow gastric emptying and suppressglucagon

they have all the incretins actions except stimulation of insulin secretion

as of 2018,pramlintideis the only clinically available amylin analogue.
– like insulin, it is administered bysubcutaneous injection

the most frequent and severe adverse effect of pramlintide isnausea, which occurs mostly at the beginning of treatment and gradually reduces

Question 31

which drugs are SGLT2 inhibitors?

Answer 31

SGLT2 inhibitors Canagliflozin · Dapagliflozin · Empagliflozin · Remogliflozin§ · Sergliflozin§ · Tofogliflozin†

Question 32

what is the OMA of SGLT2 inhibitors?

Answer 32

SGLT-2 inhibitorsblock the re-uptake of glucose in the renal tubules, promoting loss of glucose in the urine

this causes both mild weight loss, and a mild reduction in blood sugar levels with little risk of hypoglycemia

Question 33

what are the side effects of GFLT2 inhibitor?

Answer 33

the side effects of SGLT-2 inhibitors are derived directly from their mechanism of action; these include an increased risk of:ketoacidosis,urinary tract infections,candida vulvovaginitis, andhypoglycemia

Question 34

which drugs are insulin analogs?

Answer 34

fast-acting (Insulin lispro · Insulin aspart · Insulin glulisine) ·

short-acting (Regular insulin) ·

long-acting (Insulin glargine · Insulin detemir · NPH insulin)

ultra-long-acting (Insulin degludec) · inhalable Exubera · Afrezza

Question 35

what is the MOA of insulin analogs?

Answer 35

insulin is usually givensubcutaneously, either by injections or by aninsulin pump and by inhalation.

in acute-care settings, insulin may also be given intravenously

in general, there are three types of insulin, characterized by the rate which they are metabolized by the body –> they are rapid acting insulins, intermediate acting insulins and long-acting insulins

most anti-diabetic agents are contraindicated in pregnancy in which insulin is preferred!

Question 36

which drugs would you give to DM with CVD if metformin isn’t enough?

Answer 36

1. GLP1 agonist

2. SGLT1 inhibitors

Question 37

which drugs would you give to DM with CKD if metformin isn’t enough?

Answer 37

SGLT1 inhibitors

Question 38

which drugs would you give to DM who want weight loss if metformin isn’t enough?

Answer 38

1. GLP1 agonist

2. SGLT1 inhibitors

Question 39

how do you treat DKA?

Answer 39

IV fluids!!

IV hydration: normal saline 500 cc+/hr initially, if after 1-2 hrs, BP is stable and urine output established, change to 1/2 NS and decrease to 250cc/hr

when glucose is < 200-mg/dl, change fluid to D5 1/2NS

once they’re stable give IV insulin and keep the glucose around 200 until acidosis resolves – DO NOT STOP INSULIN INFUSION IT WILL STOP BY ITSELF