DMII Pharmacology

Question 1

Biguanides (Metformin)

1. Uses:
2. MOA:
3. End result:

Answer 1

Biguanides (Metformin)

1. Uses: Considered first choice for treatment ot T2DM if not contraindicated
2. MOA: Activates AMP- or so THEY say
3. End result: reduction in liver glucose production, improved insulin sensitivity leading to decreased postprandial and fasting blood glucose levels

Question 2

Metformin:

1. weight gain?
2. risk of hypoglycemia?
3. cost?

Answer 2

Metformin:

1. NO weight gain
2. Low risk of hypoglycemia
3. inexpensive

Question 3

Metformin- adverse drug reactions

1. GI
2. Black Box?
3. anemia?

Answer 3

Metformin- adverse drug reactions

1. GI: diarrhea (can be chronic)
2. Black Box: Lactic Acidosis
3. Megaloblastic anemia due to impaired absorption of B12

Question 4

Metformin- Contraindications:

Answer 4

Metformin- Contraindications:

1. Patients who are at a higher risk of developing acidosis
   
   1. renal disease/impairment
   2. history of metabolic acidosis
   3. decreased tissue perfustion or hemodynamic instability
      
      1. MI/septicemia/chronic cardiopulmonary dysfunction
   4. Use with caution in: hepatic disease or alcohol abuse and heart failure

Question 5

Sulfonylureas

1. MOA:
2. suffix:
   
   1. 1st generation
   2. 2nd generation

Answer 5

Sulfonylureas- insulin secretagogues

1. MOA: stimulate release of insulin from the pancreas by closing K_ATP channels on Beta cells, also reduces glucagon levels after long term use but the mechanism is unknown
2. suffix:
   
   1. 1st generation: “- amide”
   2. 2nd generation: “-ride” or “-zide”

Question 6

Sulfonylureas

Pros:

Answer 6

Sulfonylureas

1. Pros:
   
   1. decreases microvascular complications
   2. oral administration
   3. inexpensive
   4. can be used in pt with chronic renal failure

Question 7

Sulfonylurea

1. Cons
2. Most serious adverse reaction:
3. Contraindications:

Answer 7

Sulfonylurea

1. Cons:
   
   1. hypoglycemia risk
   2. weight gain
2. Most serious adverse reaction: hypoglycemia
   
   1. longer 1/2 lives: glipizide, pt. with impaired renal function
3. Contraindicated in patients with sulfa allergies

Question 8

Glitinide

1. Drug names:
2. MOA:
3. rate of onset:

Answer 8

Glitinide

1. Drug names: Repaglinide, Nateglinide
2. MOA: similar to sulfonylurea (closes the K_ATP channels) but has a weaker binding/faster dissociation
3. rate of onset: fast acting

Question 9

Glitinide

1. cost
2. route of administration:
3. can you use this in patients with a sulfa allergy?

Answer 9

Glitinide

1. cost: expensive
2. route of administration: oral
3. can you use this in patients with a sulfa allergy? Yes
4. similar risk of weight gain but lower risk of hypoglycemia compared to sulfonylureas

Question 10

Thiazolidinediones (TZDs)

1. suffix:
2. Drugs:
3. MOA:
4. End result:

Answer 10

Thiazolidinediones (TZDs)

1. suffix: “-zone”
2. Drugs: pioglitazone, rosiglitazone
3. MOA: peroxisome proliferator-activated receptor gamma agonist
4. end result is improved insulin sensitivity resulting in increased glucose useage and decreased production

**this drug is special because the PPAR-gamma receptor is on the adipose tissue (its a nuclear receptor) and increases adiponectin

Question 11

TZD

1. route of administration:
2. risk of hypoglycemia:
3. ____ TRG level
4. cost:
5. can you use this in a patient with renal disease?

Answer 11

TZD

1. route of administration: oral
2. risk of hypoglycemia: low
3. improve TRG level
4. cost: inexpensive
5. can you use this in a patient with renal disease? yes

Question 12

TZD: adverse drug reactions/concerns

1. effect on weight:
2. effect on bones:
3. Black Box:

Answer 12

TZD: adverse drug reactions/concerns

1. effect on weight: Gain
   
   1. partially due to fluid retention/peripheral edema caused by PPAR-gamma activation of Na reabsorption
2. effect on bones: loss of mineral density/increased fracture risk in women
3. Black Box: contraindicated in NYHA class III or IV heart failure

Question 13

Acarbose, Miglitol

1. MOA:
2. route of administration:
3. rate of onset:

Answer 13

Acarbose, Miglitol

1. MOA: competitive inhibitor of intestinal alpha-glucosidases (sucrase). Sucrose can not be broken down into a monosaccharide and will not be absorbed
2. route of administration: oral
3. rate of onset: rapid onset
   
   1. useful in decreasing postprandial hyperglycemia

Question 14

Acarbose, miglitol

1. Adverse effects:
2. what should you use in patients who do develop hypoglycemia?

Answer 14

Acarbose, miglitol

1. Adverse effects:
   
   1. Flatulence, diarrhea, abdominal pain
      
      1. Don’t use in pt with IBD or other GI problems
2. oral glucose must be used because sucrose can’t be absorbed

Question 15

What is the role of incretins?

what are they named?

Answer 15

Incretins are GI hormones that increase glucose-stimulated insulin secretion, suppress glucagon secretion, delay gastric emptying, and promote satiety

GLP-1 and GIP

Question 16

Exenetide, lixisenitide, liraglutide, albiglutide, dulaglutide

“-tides”

1. MOA:
2. route of administration:
3. cost
4. end result:

Answer 16

GLP-1 receptor agonist

“-tides”

1. MOA: they are modified peptides resistant to DPP-4 activity. They have the same effects as GLP-1 but can not be inactivated by DPP4.
2. route of administration: injection
3. cost: expensive
4. end result:
   
   1. decreased postprandial glucose levels
   2. increase beta cell mass/ improve function

Question 17

What does DPP4 do?

Answer 17

DPP4 inactivates GLP1/GIP so that they do not have an effect to increase insulin or decrease glucagon in the pancreas.

Question 18

GLP-1 receptor agonists adverse drug reactions/concerns

1. GI:
2. Black Box:
3. why does it have the potential for an immune response?
4. what other crazy things can this cause?

Answer 18

GLP-1 receptor agonists adverse drug reactions/concerns

1. GI: N/V- common
2. Black Box: thyroid tumors
   
   1. contraindicated for patients with family Hx of thyroid cancer or MEN2
3. Because it is derived from Gila Monster venum, obviously.
4. random things that this can cause:
   
   1. pancreatitis
   2. suicidal behavior
   3. exacerbation of renal disease

Question 19

“-liptin”

1. MOA:
2. route of administration:
3. cost:
4. effect on weight:

Answer 19

“-liptin”

1. MOA: Dipeptidyl peptidase-4 (DPP-4) inhibitor. This increases the circulating levels of GLP-1 and GIP by preventing their degradation
2. route of administration: oral
3. cost: expensive
4. effect on weight: NONE, they also dont’ cause hypoglycemia… but who really cares about that?

Question 20

What drug is also approved for chronic weight management?

Answer 20

Liraglutide

Question 21

DPP-4 inhibitor adverse reactions

Answer 21

Uticaria and other derm effects

increased risk of nasoharyngitis, UTIs and URI infections

pancreatitis

Question 22

“-flozin”

1. MOA:
2. route of administration:
3. cost:
4. effects on weight:

Answer 22

“-flozin”

1. MOA: SGLT2 inhibitor (prevents the reabsorption of glucose from the proximal tubule)
2. route of administration: oral
3. cost: expensive
4. effects on weight: may promote weight loss

Question 23

“-flozin”

adverse effects:

increases in ______ have been noted in ongoing trials.

Answer 23

Think about what effect an increased glucose would have in the urine:

polyuria, fungal vaginosis, UTIs- these can require hospitalization

(glucose IS bug food afterall)

can lead to hypotension because of the volume depletion

increased rate of leg and foot amputations in pations taking SGLT2 inhibitors