B.18

Question 1

Pancreatic hormones and parenterally applied antidiabetic

Answer 1

Regular insulin,
Lispro insulin,
Aspart insulin,
Glargine insulin,
Isophan (NPH)-insulin,
Liraglutide

Question 2

Anti hyperglycemic therapy

Answer 2

1. Glycemic targets
2. Therapeutic options:
   a, Lifestyle modification
   b, Insulin (analogues)
   c, Oral antidiabetics and non-insulin injectable

Question 3

Insulin effects

Answer 3

-Gluconeogenesis, Glycogenolysis, Lipolysis, Ketogenesis, Proteolysis: Inhibition
-Glucose uptake in muscle and adipose tissue, Glycolysis, Glycogen synthesis, Protein synthesis, Uptake of ions (especially K+ and PO4-3): Stimulation

Question 4

Regular insulin

Answer 4

Kinetics: s.c/i.v. adm., short acting, onset:30min-1h, DOA: 5-6h, given in aqueous (transparent) solution; IND: diabetic ketoacidosis-emergency care (i.v. adm.), Preprandial (s.c. injection 60min before meal);
Dose: 40-100IU/mL insulin;
Extra: if given at time of meal→ prandial hyperglycemia→ postprandial hypoglycemia

Question 5

Lispro insulin, Aspart insulin

Answer 5

Kinetics: administered i.v/s.c, Rapid acting, fast absorption, onset: ~20-30min,
DOA: ~3-4h, given in aqueous (transparent) solution; Dose: 40-100IU/mL;
Structure: proline at B28 position is rather active in the formation of hexamer binding→ target of modifications→ no hexamer production→ rapid action→ to mimic normal post-prandial insulin spike; IND: emergency care- diabetic ketoacidosis (i.v.)

Question 6

Glargine insulin

Answer 6

Kinetics: adm. s.c, Ultralong acting, slow absorption, onset: ~1-3h,
DOA: ~24h, given in aqeous (transparent) solution; Dose: 40-100IU/mL insulin;
Structure: two Arginines after B30

Question 7

Isophan (NPH)-insulin

Answer 7

Kinetics: adm. s.c., intermediate acting (neutral protamine Hagedorn), onset of action ~4-5h,
DOA: ~12-14h, given in suspension (opaque solution); Dose: 40-100IU/mL insulin;
SEs: Protamine hypersensitivity is more common in males after vasectomy or in patients allergic to fish

Question 8

IND, SEs of insulin

Answer 8

IND:
Diabetes mellitus (type 1&2, in case of lack of insulin secretion); Gestational diabetes (pregnancy related→ pathomechanism is similar to T2DM, but oral antidiabetics are contra-IND);
Eemergency situations (DKA, Hyperosmolar hyperglycemic state);
Emergency care for hyperkalemia (insulin + glucose →insulin enhance K+ uptake into cells);
SEs:
Hypoglycemia!! (Fast onset: stimulation of vegetative nervous system;
Slow onset: CNS symptoms;
Therpy: glucose p.o/i.v, i.m glucagon (0.5-1mg)); Lipodystrophy; Edema; Skin reactions; Anaphylaxis (rare!); Hypokalemia

Question 9

Liraglutide

Answer 9

MOA: GLP-1 R agonist (inhibits glucagon release, increase insulin release→ ↓Plasma glucose);
Kinetics: adm x1/day;
IND: weight loss - even without diabetes;
SEs: Nausea, vomiting diarrhea, dizziness, headache, dehydration, tachycardia, Acute pancreatitis, Thyroid tumurs (?)

Question 10

Kinetics

Answer 10

T1/2<9min in plasma, degraded in the liver (50% is destroyed in a single passage without reaching the systemic circulation), kidney (filtration by the glomeruli→reabsorption by tubules→ degradation in tubules) and muscle (minor significance);
Clinical significance: insulin degradation can be diminished in renal/hepatic failure leading to increased risk of hypoglycemia

Question 11

Subcutaneous administration of Insulin

Answer 11

Injection→ dissolution to hexamers→ dimers→ monomers→ can cross via capillary membrane into the blood