66. Insulin And Oral Hypoglycaemic Agents. Glucagon

Front 1

List the groups of insulin prepasrations

Back 1

- Rapid-acting insulin

- Short-acting insulin

- Intermediate-aciting insulin

- Long-acting insulin

- Mixed insulin

Front 2

Name rapid-acting insulin

Back 2

Insulin lispro, insulin aspart

Front 3

Name short-acting insulin

Back 3

Soluble insulin

Front 4

Name intermediate-acting insulin

Back 4

NPH insulin

Front 5

Name long-acting insulin

Back 5

Insulin glargine, insulin detemir

Front 6

How are the different insulin preparations made so they can have different pharmacokinetic properties?

Back 6

They can be modified by changing a few amino acids or make a suspension like with NPH insulin which will crystallize and release insulin slowly from the crystal.

Front 7

What is mixed insulin?

Back 7

A mix between short-acting insulin and intermediate-acting insulin

Front 8

Duration of action of the different insulins?

Back 8

Rapid-acting insulin: 3-5 hours

Short-acting insulin: 4-24 hours

Intermediate-acting insulin: 14-24 hours

Long-acting insulin: 24 hours

Front 9

Indications of insulin preparations?

Back 9

- Type 2 diabetics who dont get desired effect with oral antidiabetic drugs

- Type 2 diabetics who get pregnant

- Type 2 diabetes with end-stage renal failure

- Type 1 diabetes

- Hyperglycemic emergency (given as IV)- Hyperkalemia together with glucose (so potassium enter the cell)

Front 10

Side effects of insulin preparations?

Back 10

- Hypoglycemia

- Lipodystrophy

- When the injection is performed at the same site and it results in a lump or skin atrophy, decreasing insulin absorption

- Allergic reactions (rare)

- Antibody formed against the modified insulin (rare)

Front 11

Name the groups of oral antidiabetic drugs

Back 11

Metformin (biguanide), sulfonylureas, meglitinides (sulphonylurea-ish), GLP-1 agonists/incretin mimetics, DPP-4 inhibitors (gliptins), thiazolidinediones (glitazones), SGLT-2 inhibitors (gliflozins), alpha-glucosidase inhibitors

Front 12

What are the contraindications for antidiabetics drugs?

Back 12

- Pregnancy

- Surgery

- Severe infections

- Renal failure

They should be replaced with insulin monotherapy when contraindicated

Front 13

What is metformin?

Back 13

A biguanide

Front 14

Indications for metformin?

Back 14

- First-line drug for type 2 diabetes

- PCOS

- Non-alcoholic fatty liver disease

Front 15

Mechanism of action of metformin?

Back 15

- Reduced gluconeogenesis

- Increased glucose uptake and utilization in skeletal muscle, decreasing insulin resistance- Reduced carbohydrate absorption from the intestine

- Increased B-oxidation

- Reduced LDL and VLDL

It inhibits mitochondrial oxidative phosphorylation, increasing intracellular level of AMP. This activates AMPK and AMPK stimulates release of GLP-1, which again stimulates insulin release

Front 16

How is the half-life of metformin?

Back 16

Short, only 3 hours

Front 17

Advantages and disadvantages of metformin?

Back 17

Advantages:

- Weight loss or weight stabilization

- No risk for hypoglycemia

- Cheap

Disadvantage:

- Cant be used in renal failure, which is common in 2DM.

Front 18

Side effects of metformin?

Back 18

- GI symptoms

- B12 deficiency

- Metallic taste

- Metformin-associated lactic acidosis, rare but can occur if given when contraindicated

Front 19

Contraindications of metformin?

Back 19

- Renal failure, end stage, because its excreted by kidneys.

- Severe liver failure - increase risk of lactic acidosis

- Heart failure

- Alcoholism

- Surgery

- Iodinated contrast medium

Front 20

Name sulfonylureas

Back 20

Glimepiride, glipizide

Front 21

Mechanism of action of sulfonylureas?

Back 21

They bind to a sulfonylurea receptor on ATP-gated K+ channels on pancreatic B-cells. This causes the channels to close, and the cells gets depolarized and releases insulin.

Front 22

Pros and cons for sulphonylureas?

Back 22

Pros:

- Acts quickly

Cons:

- High risk for hypoglycemia

- Risk for interactions due to plasma protein binding

- Weight gain

Front 23

What groups of drugs should not be taken together with sulfonylureas?

Back 23

Beta blockers. They mask the symptoms of hypoglycemia and sulfonylureas have a high risk of hypoglycemia

Front 24

Side effects of sulfonylureas?

Back 24

- Severe and prolonged hypoglycemia

- Weight gain due to increased appetite

- Disulfiram-like effect

Front 25

Name meglitinides

Back 25

Repaglinide, nateglinide

Front 26

Name GLP-1 (glucagon-like peptide) agonists

Back 26

Liraglutide, semaglutide

Front 27

Mechanism of action of GLP-1 agonists?

Back 27

They are incretin mimetics. Incretins are released from enteroendocrine cells in the GI-tract when there is food intake. They stimulate insulin release and inhibit glucagon release, resulting in a net reduction of blood glucose.

They get inactivated by DPP-4.

Front 28

Pros and cons of GLP-1 agonists?

Back 28

Pros:

- Weight loss due to decreased appetite

Cons:

- Long-term safety is not well known

- Must be injected

- Expensive

Front 29

Name Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins)

Back 29

Saxagliptin, linagliptin

Front 30

Side effects of DPP-4 inhibitors?

Back 30

Heart failire

Front 31

Name thiazolidinediones (glitazones)

Back 31

Pioglitazone, rosiglitazone

Front 32

Indications for glitazones?

Back 32

Often combined with metformin.Can be used as monotherapy in severe renal failure.

Front 33

Mechanism of action of glitazones?

Back 33

They activate PPAR-y which will increase transcription of genes involved in glucose and lipid metabolism:

- Lipoprotein lipase

- Fatty acid transporter protein

- GLUT4

- Adipocyte fatty acid binding protein

It results in increased lipogenesis and enhanced cellular uptake of fatty acids and glucose.

Front 34

Side effects of glitazones?

Back 34

- Fluid retention

- Risk of heart failure

- Weight gain- Increased risk of osteoporosis

- Risk of AMI with rosiglitazone

- Risk of bladder cancer with pioglitazone

Front 35

Name SGLT-2 inhibitors (gliflozins)

Back 35

Empagliflozin, dapagliflozin

Front 36

Indications of gliflozins (SGLT-2 inhibitors)?

Back 36

Treatment of young males since they are less prone to get UTIs and genital infections

Front 37

Mechanism of action of SGLT-2 inhibitors?

Back 37

SLGT-2 is a transport protein responsible for reabsorption of glucose in proximal tubule. When inhibited, where will be glucosuria, and 70 g of glucose is lost per day.

Acts as an osmotic diuretic due to all the glucose

Front 38

Pros and cons of SGLT-2 inhibitors?

Back 38

Pros:

- Weight loss

- Decreased BP

- Reduced cardiovascular mortality

Cons:

- Long-term safety is not known

Front 39

Side effects of SGLT-2 inhibitors?

Back 39

- UTIs

- Genital infections

- Dehydration

- Hypotension

Front 40

Name alpha-glucosidase inhibitors

Back 40

Acarbose, miglitol

Front 41

Mechanism of action of alpha-glucosidase inhibitors?

Back 41

Alpha-glucosidase is an enzyme of the brush border of the small intestine that cleaves disaccharides and increase their absorption.

By inhibiting it we can reduce carbohydrate absorption, and intestinal bacteria degrade them into gases.

Front 42

Side effects of alpha-glucosidase inhibitors?

Back 42

- Flatulence

- Abdominal pain

- Diarrhea

Front 43

Indications for glucagon?

Back 43

- Severe hypoglycemia

- Beta blocker overdose-related cardiogenic shock

Front 44

Mechanism of action of glucagon?

Back 44

It rapidly stimulates gluconeogenesis and glycogenolysis in the liver, raising the blood glucose.

By activating glucagon receptor, adenylate cyclase will increase the levels of cAMP, also in myocardial cells. This will give positve heart effects, reversing beta-blocking effects of the heart.