DM pt.2 and pt.3- Khan

based off sg

What is a PPAR agonist?

Thiazolidinediones (TZDs)

PPAR belongs to what receptor class?

nuclear receptor

What is the MOA of thiazolidinediones?

activate PPARy receptor

What are the effects of thiazolidinediones on adipose tissue, skeletal muscle, and the liver?

adipose tissue- adipocyte differentiation, uptake of FA into fat cells, shift lipid stores (increase insulin sensitivity)

skeletal muscle- increase insulin mediated glucose uptake (increase GLUT4)

liver- increase glucose uptake, decrease gluconeogenesis

What effect of pioglitazone is produced by PPAR alpha?

decreased TG

What are the ADRs of thiazolidinediones?

• weight gain

• edema

• cause/worsen HF

• increased risk of bone fracture

What is the cause of bone fracture by thiazolidinediones?

decrease osteoblast activity

What are the C/I and Boxed warnings of thiazolidinediones?

C/I- pts. with active bladder cancer or CHF

BW- CHF

What are the monitoring parameters of thiazolidinediones?

• LFTs

• HF signs

What are the names of DPP-4 inhibitors?

• sitagliptin

• linagliptin

• sitagliptin

• alogliptin

What is the brand name of sitagliptin?

januvia

What is the brand name of linagliptin?

tradjenta

What is the MOA of DPP-4 Inhibitors?

inhibit INACTIVATION of incretin hormones by DPP-4

What infections can be caused by DPP-4 Inhibitors?

• upper respiratory tract infections

• UTIs

• nasopharyngitis

• pancreatitis

Describe the GLP-1 receptor:

seven member transmembrane GPCR

What are the names of the Incretin memetics/GLP-1 analogs?

• exenatide

• liraglutide

• dulaglutide

What is the brand name of Exenatide?

byetta

What is the brand name of liraglutide?

victoza

What is the brand name of dulaglutide?

Trulicity

What is the MOA of incretin mimetics?

bind to and activate GLP-1 receptor

What are the effects of incretin mimetics?

• increase insulin synthesis/release

• lower glucagon release (reduce gluconeogenesis)

• slow gastric emptying

What is the boxed warnings of incretin mimetics?

W/ LIRAGLUTIDE AND DULAGLUTIDE: should not be used in pts. w/ personal and family history of medullary thyroid carcinoma and multiple endocrine neoplasia syndrome type 2

Can the incretin mimetics cause hyper or hypoglycemia?

hypoglycemia

What are the names of the SGLT2 Inhibitors?

empagliflozin

canagliflozin

What is the brand name of canagliflozin?

invokana

What is the brand name of empagliflozin?

jardiance

What is the MOA of SGLT2 Inhibitors?

inhibit SGLT2 and that inhibits reabsorption of glucose from the tubular lumen and increases urinary excretion of glucose

What are the ADRs of SGLT2 Inhibitors?

• thirst

• urination

• weight loss

Where is SGLT2 located in the nephron?

proximal tubule

What % of glucose is reabsorbed by SGLT2 vs. SGLT1?

SGLT2- 90%

SGLT1- 10%

What are the monitoring parameters for SGLT2 Inhibitors?

• infection (UTI, vulvovaginal candidiasis)

• renal function

• hypotension

• hyperkalemia

• ketoacidosis

What is the Boxed warning of SGLT2 Inhibitors?

CANAGAFLOZIN- increased risk of amputation

How is insulin classified?

according to duration

What insulins belong to the rapid-acting class?

• insulin gliusine

• insulin aspart

• insulin lispro

Think: “GAL”

What is the brand name of insulin aspart?

Novolog

What is the brand name of insulin lispro?

Humalog

What insulins belong to the short-acting class?

• regular insulin

• concentrated regular insulin

What is the brand name of regular insulin?

Humulin R

What is the brand name of concentrated regular insulin?

Humulin R U-500

What insulins belong to the intermediate-acting class?

NPH

What is the brand name of NPH?

Humulin N, Novolin N

What insulins belong to the long-acting class?

• insulin glargine

• insulin degludec

What is the brand name of insulin glargine?

Lantus

Which insulin formulation contains unmodified insulin?

regular insulin

What is concentrated insulin? What is it used for?

Concentrated insulin- like insulin but 5x as concentrated.

Used for insulin resistant patients.

Which insulin is conjugated with protamine and requires enzymatic degradation of protaine for absorption?

NPH

Which insulin provides background insulin replacement?

• insulin glargine

• insulin degludec

Which insulin is peakless?

• insulin glargine

• insulin degludec

What are the ADRs of insulin?

• hypoglycemia

• lipodystrophy

• weight gain

• hypokalemia

What is the cause of hypoglycemia from insulin injections? What can this hypoglycemia lead to?

Cause- delay in meal taking, excessive exercise, inadequate carb intake, high dose insulin

Leads to autonomic hyperactivity (tachycardia, palpitations, nausea, etc.) which can progress to coma or convulsions

What are the contraindications of inhaled insulin?

lung diseases, smokers

Is inhaled insulin rapid, short, intermediate, or long acting?

rapid

What’s amylin?

an amino acid that is co-secreted with insulin (almost like c-peptide)

What’s the difference between amylin and pramlintide?

pramlintide has amino acid substitutions to increase solubility and stability

In what form of diabetes is amylin deficient?

type 1

What are the effects of pramlintide?

• slows gastric emptying

• promotes satiety (fullness)

• prevents rise in plasma glucagon

• NOTE: NO EFFECT ON INSULIN

What are the ADRs of pramlintide?

• hypoglycemia

• GI

What are the contraindications of pramlintide?

• gastroparesis

• hypoglycemic unawareness

What is the BW of pramlintide?

pramlintide + insulin can cause severe hypoglycemia