Antidiabetics II

Question 1

Insulin Secretagogues

Answer 1

Sulfonylureas & Meglitinides

Question 2

Sulfonylureas are effective at reducing ___ and ___

Answer 2

Sulfonylureas are effective at reducing fasting plasma glucose and HbA_1C

Question 3

Sulfonylureas bind to ____ subunit and block the ATP-sensitive ___ channel in the B cell membrane stimulating ___ release

Answer 3

Sulfonylureas bind to SUR1 subunit and block the ATP-sensitive K⁺ channel in the B cell membrane stimulating insulin release

Question 4

sulfonylureas end in “__”

Answer 4

“ide”

Question 5

1st generation Sulfonylurea

Answer 5

Chlorpropamide

Question 6

Chlorpropamide has a ___ half life

AE’s?

Answer 6

• Long half-life
• Hypoglycemia, particularly in elderly
  
  • Contraindicated in elderly patients
• Hyperemic flush with alcohol
  
  • d/t inhibition of aldehyde dehydrogenase
• may potentiate vasopressin
  
  • ​elicit an apparent SIADH
  • ​hyponatremia

Question 7

list 2nd generation Sulfonylureas

compare them to Chlorpropamide

Answer 7

• Glyburide (Glibenclamide)
• Glipizide
• Glimepiride
• much more potent than 1st gen drugs
• lack some of the adverse effects and drug interactions of 1st gen drugs
• replaced 1st gen drugs

Question 8

compare hypoglycemic actions between 2nd gen sulfonylureas

Answer 8

Glimepiride < Glipizide < Glyburide

Question 9

Sulfonylurea & Meglitinide AEs

Answer 9

• Hypoglycemia
• Weight gain

Question 10

list Meglitinides

Glinides have the same MOA as ___

Answer 10

• Repaglinide, Nateglinide
• same MOA as Sulfonylureas
  
  • stimulate insulin release by binding to SUR1 and inhibiting ATP-sensitive K+ channel

Question 11

Sulfonylureas vs. Meglitinides

• effect
• onset and duration of action

Answer 11

Sulfonylureas = more effective in reducing FPG and HbA1C levels

Meglitinides = more rapid onset and shorter DOA

Question 12

Glinides are ____ glucose regulators.

Must be taken ____; if the meal is missed the drug must be omitted

Answer 12

Glinides are postprandial glucose regulators

Must be taken before each meal; if the meal is missed the drug must be omitted

Question 13

Comparing the Meglitinides, ___ has a less risk of hypoglycemia than ___

Answer 13

Comparing the Meglitinides, Nateglinide has a less risk of hypoglycemia than Repaglinide

Question 14

Biguanides

Answer 14

Metformin

Question 15

Metformin does not cause ____

does not cause ___ (even in large doses)

___ efficacy to sulfonylureas in reducing FPG and HbA_1C levels

Answer 15

Metformin does not cause insulin secretion

does not cause hypoglycemia (even in large doses)

Equal efficacy to sulfonylureas in reducing FPG and HbA_1C levels

Question 16

Metformin reduces glucose levels primarily by inhibiting ___ by reducing ____ of gluconeogenic enzymes

Answer 16

Metformin reduces glucose levels primarily by inhibiting gluconeogenesis by reducing gene expression of gluconeogenic enzymes

• increases insulin-mediated glucose utilization in muscle and liver
• As a result of the improvement in glycemic control, serum insulin concentrations decline slightly

Question 17

Metformin actions are mediated by activation of ____

Answer 17

Metformin actions are mediated by activation of AMPK

Question 18

other effects of metformin

Answer 18

• Reduces plasma TG by 15-20%
• weight LOSS

(sulfonylureas / glinides = weight gain)

Question 19

1^st line agent for treating T2 DM

Answer 19

Metformin

• high insulin sensitivity
• associated w/ weight loss
• rarely causes hypoglycemia
• does not depend on B-cells

Question 20

Metformin AE and contraindications

Answer 20

• Largely GI: anorexia, nausea, vomiting, abdominal discomfort, diarrhea
• Long term use: B12 deficiency
• Fatal lactic acidosis
• Contraindicated: renal disease, hepatic disease, hypoxia, alcoholism

Question 21

list the TZDs

Answer 21

• Pioglitazone
• Rosiglitazone

Question 22

Pioglitazone and Rosiglitazone decrease insulin ____

___ agonist found in muscle, fat and liver

Answer 22

Pioglitazone and Rosiglitazone decrease insulin resistance

Peroxisome proliferator-activated receptor-y (PPAR-y) agonist found in muscle, fat and liver

Question 23

Glitazones promote glucose uptake and utilization in adipose tissue by ___

__ effective than Sulfonylureas/Metformin in decreasing FPG and HbA_1C

MOA involves ___

Answer 23

Glitazones promote glucose uptake and utilization in adipose tissue by increasing insulin sensitization

Less effective than Sulfonylureas/Metformin in decreasing FPG and HbA_1C

MOA involves gene regulation

Question 24

Glitazones have a slow onset and offset of activity taking ____

Answer 24

Glitazones have a slow onset and offset of activity taking weeks to months

Question 25

\_\_\_\_ effects on **lipids** are more favourable than \_\_\_ associated with significant improvements in:

Answer 25

**pioglitazone** effects on lipids are more favourable than **rosiglitazone** **pioglitazone** is associated with significant improvements in: **HDL, TG, LDL particle concentration, LDL particle size**

Question 26

TZD AE's

Answer 26

* **fluid retention, weight gain, edema** * **cause or exacerbate CHF** * contraindicated: Class III or IV heart failure * **Troglitazone:** 1st TZD approved, caused severe hepatotoxicity → withdrawn * FDA requires monitoring of liver function with TZD * so far pioglitazone or rosiglitazone have not been associated with hepatotoxicity

Question 27

a-Glucosidase Inhibitors

Answer 27

Acarbose

Question 28

Acarbose: MOA

Answer 28

* competitive inhibitor of intestinal a-glucosidases * reduces postprandial digestion of starch and disaccharides * minimizes upper intestinal carb absorption and **defers absorption to distal SI** * **decreases postprandial hyperglycemia and hyperinsulinemia** * modest drop in HbA_1C and FPG levels

Question 29

Acarbose AEs

Answer 29

* Flatulence, diarrhea, abdominal pain * **Contraindicated** in IBS or any intestinal condition worsened by gas and distension * associated with reversible hepatic enzyme elevation * **Periodical liver function monitoring is required with acarbose therapy**

Question 30

Incretin Analog: \_\_\_\_ DDP-4 inhibitor: \_\_\_\_ both ___ insulin secretion

Answer 30

GLP-1 analog: **Exenatide** DDP-4 inhibitor: **Sitagliptin** (oral) both **increase** insulin secretion

Question 31

Incretin secretion & action on the B cell

Answer 31

Question 32

Exenatide effects

Answer 32

* Resistant to **dipeptidyl peptidase IV (DPP-IV)** * **increases insulin secretion** * Suppresses postprandial glucagon release * **Slows gastric emptying** * **Decreases appetite** * May stimulate β-cell proliferation

Question 33

Exenatide and Sitagliptin AEs

Answer 33

* Both: **Pancreatitis** * Exenatide * **GI:** Nausea, vomiting and diarrhea * **not used in patients w/ gastroparesis** * Sitagliptin * **urticaria, angioedema**, anaphylaxis, skin reactions (Stevens-Johnson syndrome)

Question 34

Amylin Analog

Answer 34

* **Pramlintide** * Peptide co-secreted with insulin from pancreatic β-cells * **Inhibits food intake, gastric emptying, and glucagon secretion**

Question 35

Bile-acid Sequestrants and Use

Answer 35

**Colesevelam** used to **lower LDL cholesterol** Approved for treatment of **type 2 DM** Mechanism unclear. Given orally

Question 36

SGLT2 Inhibitor

Answer 36

* **"-Gliflozin"** (canagliflozin) * blocked SGLT2 leads to **decreased glucose reabsorption in proximal tubule, increased glucose excretion, and decreased blood glucose levels** * Given orally

Question 37

-gliflozin AE

Answer 37

* Increased risk of **genital and urinary tract infections** * osmotic diuresis: **volume depletion, increased serum creatinine levels, hyperkalemia, hypermagnesemia, hyperphosphatemia and hypotension** * Contraindicated in patients with **renal insufficiency**

Question 38

Answer 38

Question 39

Question 40

INITIAL DRUG THERAPY FOR T2 DM \_\_\_\_ is the preferred first agent if lifestyle intervention does not achieve HbA1c goals

Answer 40

INITIAL DRUG THERAPY FOR T2 DM **Metformin** is the preferred first agent if lifestyle intervention does not achieve HbA1c goals

Question 41

Patients with **HbA_1c ≥9.0%** are unlikely to achieve HbA1c goals with \_\_\_\_ what do we give them?

Answer 41

Patients with **HbA_1c ≥9.0%** are unlikely to achieve HbA1c goals with **monotherapy** ## Footnote **combination of 2 noninsulin agents or with insulin itself**

Question 42

If **monotherapy** does not achieve HbA_1C goal over**∼3 months,** the next step is to add a second agent:

Answer 42

oral agent, **exenatide** or **insulin** (the higher the HbA_1C, the more likely insulin will be required)

Question 43

If 2-drug combination fails to achieve the glycemic target a third agent can be added - many patients will eventually need to be on \_\_\_ when HbA1c ≥ 8.5% we should transition to \_\_\_

Answer 43

If 2-drug combination fails to achieve the glycemic target a third agent can be added - many patients will eventually need to be on **insulin** when HbA1c ≥ 8.5% we should transition to **insulin**

Question 44

Describe Insulin Therapy

Answer 44

1. Begins with a **single** **low** **dose** injection of **basal** **insulin** * NPH, Glargine, Detemir 2. Dose is then **uptitrated** 3. If there is **postprandial** **hyperglycemia**, add **prandial insulin** * lispro, aspart, glulisine

Question 45

\_\_\_ is the most effective of diabetes medications in lowering glycemia

Answer 45

**Insulin** is the most effective of diabetes medications in lowering glycemia * decreases any level of elevated HbA1C to therapeutic goal * no maximum dose of insulin beyond which a therapeutic effect will not occur * Large doses of insulin may be necessary to overcome the insulin resistance of type 2 diabetes

Question 46

when is insulin warranted as **initial** **therapy** for patients with type 2 diabetes?

Answer 46

* **severe hyperglycemia** * Significant hyperglycemic symptoms * Ketonuria * HbA_1c \> 10% * random glucose \> 300 mg/dL

Question 47

what is the preferred drug for **Gestational DM?**

Answer 47

**Insulin** (does not cross the placenta) * start with a single dose of bedtime **NPH insulin** * If postprandial glucose control is required injections of **lispro** or **aspart** can be added

Question 48

which insulin drugs should not be given in Pregnancy

Answer 48

**Glulisine, Glargine, Degludec** (Category C)

Question 49

DM + **HTN** should be given:

Answer 49

ACEi **(pril)** or ARB **(sartan)**

Question 50

what should be monitored in a patient on an ACEi?

Answer 50

K⁺ and creatinine

Question 51

DM + **Dyslipidemia** should be given... Potential AE of this drug?

Answer 51

**Statins** **AE:** AST/ALT elevations, rhabdomyolysis * With overt CVD * Aged \< 40 yr with CVD risk factors * Aged \> 40 yr with or without CVD risk factors

Question 52

DM + **increased CV risk** should be given...

Answer 52

**Aspirin** (antiplatelet agent) - 1° prevention strategy

Question 53

DM + **Albuminuria** patients should be given....

Answer 53

**ACE inhibitors or ARBs**

Question 54

Drugs used for neuropathic pain

Answer 54

* Imipramine * Amitriptyline * Pregabalin * Gabapentin * Duloxetine * Venlafaxine * Valproate * Opioids

Question 55

**Diabetic gastroparesis** (2)

Answer 55

**Metoclopramide** or **Erythromycin** (prokinetic agents) Potential AE of Metoclopramide: **Parkinsonism**

Question 56

**Contraindicated** in a patient with **gastroparesis**?

Answer 56

Exenatide, Sitagliptin, Pramlintide

Question 57

DM neuropathy + **erectile dysfunction**

Answer 57

Phosphodiesterase-5 inhibitor: **Sildenafil**

Question 58

\_\_\_\_ is used to treat severe hypoglycemia in diabetic patients treated with insulin

Answer 58

**Glucagon** is used to treat severe hypoglycemia in diabetic patients treated with insulin Also used for: * **Radiology of bowel** (relaxes intestine) * **B-blocker overdose** * **Glucagon C-peptide Test** (tests for residual β-cell function in diabetes)