Diabetes

Question 1

Indications for insulin use

Answer 1

1. DM 1
2. DM 2 → failure of oral drugs OR stress conditions (pregnancy, infection, surgery)
3. DKA emergency IV regular insulin
4. Hyperkalemia - insulin + IV glucose since insulin potassium shift into tissue

Question 2

Treatment of insulin resistance

Answer 2

1. Underlying cause - stress or infection
2. Metformin - ↑ insulin sensitivity and ↓ intestinal glucose absorption
3. Insulin sensitizers thiazolidinediones
4. Change site of injection local insulin resistance

Question 3

Adverse effects of insulin

Answer 3

1. Hypoglycemia (most common and dangerous)
2. Hypokalemia
3. Insulin resistance
4. Hypersensitivity reaction - urticaria, angioedema and anaphylactic shock
5. Local effects
   - Lipodystrophy - atrophy or hypertrophy
   - Allergy at site of injection
   - Local infection

Question 4

Metabolic syndrome

Answer 4

Central obesity + hypercholesterolemia + heart disease + IR + DM 2

Question 5

Insulin drug interactions

Answer 5

Hypoglycemia
Abs FM
1. Alcohol - ethanol inhibtis glucneogeneiss
2. Beta blockers - inhibit glycogensolysis and glucose release from liver and muscle + mask hypoglecmia
3. Salicylates
4. Fenfluramine - SSRI anorexic drugs ↑ serotonin in brain causing ↓ calorie intake + uptake of glucose into striated muscle
5. MAO - inhibit gluconeogenesis

Question 6

Oral antidiabetic drugs

Answer 6

BTS ∝ M
1. Biguanides - metformin
2. Thiazolidinediones - pioglitazone and rosiglitazone
(pio and ros glitazone)
3. Sulfonylurea
4. ∝ glucosidase inhibitors- acarbose - miglitol
5. Meglitinides - repaglinide and nateglinide (me, repa, nate glinide)

Question 7

Sulfonylurea

Answer 7

• amide - zide - ide

1st gen - amide
1. Chlorpropamide (long acting)
2. Tolbutamide
3. Acetohexamide

2nd gen -amide -zide
1. Glibenclamide
2. Glyclazide
3. Glipizide

3rd gen -ide
1. Glimepiride

CAT - amide
G
2nd gen - amide + zide
3rd gen - ide

30 minutes before breakfast

Question 8

Mechanism of action of sulfonylureas

Answer 8

Pancreatic
1. ↑ insulin secretion - inhibits K+ ATP dependant channels
2. ↓ serum glucagon

Extrapancreatic
1. ↑ insulin receptor sensitivity
2. ↓ glucose hepatic output - gluconeogenesis

Question 9

Adverse effect of sulfonylurea

Answer 9

1. Hypoglycemia
   - Chlorpropamide (long acting)
   - Elderly patients with hepatic or renal dysfunction
2. Increased appetite and weight gain
3. Pharmacological failure is common
   - Primary 15-30%
   - Secondary 6-7 yrs 90%
4. Hepatoxicity
5. Allergic reactions
6. Teratogenicity
   Chlorpropamide
7. Disulfiram like reaction in patients that consume alcohol
8. Dilutional hyponatremia SIADH

Question 10

Sulfonylurea contraindications

Answer 10

1. DM 1
2. Renal, hepatic and liver failure
3. Pregnancy “gestational diabetes” - fetal hypoglycemia
4. Sulfa drug hypersensitivity - use meglitinide

Question 11

Meglitinide

Answer 11

• glinide
  1. Repaglinide
  2. Nateglinide

Repa/nate glinide

• Just before meals to prevent postprandial hyperglycemia - very fast onset and short duration of action
• ORAL

Question 12

Mechanism of action of Meglitinide

Answer 12

↑ insulin secretion - similar to sulfonylurea different binding site on beta cells

Question 13

Adverse effects of meglitinide

Answer 13

Hypoglycemia

Question 14

Contraindications

Answer 14

Use with caution in patients with renal and hepatic dysfunction

Question 15

Biguanides

Answer 15

Metformin

• Oral x3 with meals
• Well absorbed from GIT
• Does not bind to plasma proteins
• Excreted unchanged

Question 16

Mechanism of action of biguanides

Answer 16

Increases
1. Insulin receptor sensitivity
Decreases
2. Intestinal glucose absorption
3. Hepatic gluconeogenesis

DOES NOT CAUSE HYPOGLYCEMIA since it does not increase insulin secretion

Question 17

Therapeutic uses of metformin (biguanides)

Answer 17

1. DM 2 - alone if mild or combination
2. Weigh loss (decreases glucose absorption)
3. PCOS - decreases androgen levels + restores normal menstrual cycle and ovulation

Question 18

Adverse effects of metformin (biguanides)

Answer 18

1. GIT upset - anorexia, diarrhea and vomiting
2. Lactic acidosis ↑ anaerobic glycolysis
3. ↓ absorption of B12

Question 19

Contraindications of metformin (biguanides)

Answer 19

Lactic acidosis
1. Patients with history of lactic acidosis
2. Renal or hepatic dysfunction
3. Chronic lung disease

Question 20

Thiazolidinediones

Answer 20

• glitazone
  1. Pioglitazone
  2. Rosiglitazone

Slow onset + prolonged duration of action → gene regulation

Question 21

Mechanism of action of thiazolidinediones (pioglitazone and rosiglitazone)

Answer 21

Nuclear gene PPAR γ (peroxisomal proliferator activated receptor gamma) in muscles, adipose tissue and liver
Increase
1. Insulin receptor sensitivity + ↓ insulin resistance
2. GLUT transporters ↑ glucose uptake
Decrease
3. TGs

DOES NOT CAUSE HYPOGLYCEMIA

Question 22

Thiazolidinediones (pioglitazone and rosiglitazone) therapeutic use

Answer 22

Improve insulin resistance in DM 2

Question 23

Adverse effects of thiazolidinediones (pioglitazone and rosiglitazone)

Answer 23

1. Hepatoxicity
2. Fluid retention - edema and weight gain (contraindicated in CHF)

Question 24

Contraindications of thiazolidinediones (pioglitazone and rosiglitazone)

Answer 24

CHF

Question 25

α glucosidase inhibitors (starch blockers)

Answer 25

Acarbose - miglitol >90% elimination by kidney (contraindicated in patients with kidney disease)

Question 26

Mechanism of action of α glucosidase inhibitors

Answer 26

Competitive blocking of intestinal α glucosidase enzyme - ↓ digestion and absorption of glucose DOES NOT CAUSE HYPOGLYCEMIA

Question 27

Adverse effect of α glucosidase inhibitors

Answer 27

GIT - fluctuance, diarrhea and abdominal pain

Question 28

Contraindications of α glucosidase inhibitors

Answer 28

IBD