Insulin and Oral antidiabetics

Question 1

Routes of administration of insulin?

Answer 1

subcutaneous, intramuscular, intravenous

Question 2

Clinical uses of Insulin?

Answer 2

T1 Diabetes, Hyperglycemic diabetes emergencies (DKA/HHS), chronic T2 DM, gestational DM (not so impt to know) + hyperkalemia at late stages

Question 3

Adverse effects of Insulins?

Answer 3

1. Hypoglycemia (extreme opposite of the intended effect)
2. Rebound hyperglycemia (Somogyi effect)
3. Allergy due to anti-insulin IgE antibodies (body creates antibodies towards insulin)
4. Insulin resistance (down regulation of insulin receptors)

Question 4

What is the drug class related to Insulin secretagogues?

Answer 4

Sulfonylureas

Question 5

What are the 2 drug class of Insulin sensitisers?

Answer 5

Biguanides (Metformin) and Thiazolidinediones (Rosiglitazone, Pioglitazones**) –> the -zones

Question 6

What are the few drug class related to insulin sparing agents?

Answer 6

SGLT2 inhibitors, Alpha-glucosidase (Acarbose), GLP-1 receptor agonists (Exenatide, -glutides like Liraglutides), DPP-4 inhibitors (Sitagliptins, -gliptins)

Question 7

What’s the indication of Sulfonylureas? Explain MOA of Sulfonylureas simply and give examples of them

Answer 7

Indication: T2 DM

1. increase insulin release/secretion from pancreatic beta cells
2. reduction of serum glucagon concentrations

Some examples: (-amides)
Glibenclamide, Tolbutamide, Chlorpropamide

Question 8

Adverse effects of Sulfonylureas

Answer 8

Hypoglycemia,
Gastrointestinal irritations/upsets, weight gain, Allergic skin rash, bone marrow damage, increase in CVS death

Question 9

what is an example of Biguanides? what is it often called in toxicity? (x-toxic) –> what is X?

What is its indications?

Answer 9

Metformin.

Nephrotoxic since its excreted by the kidneys

T2 DM, insulin resistance

Question 10

MOA of Biguanides?

Answer 10

1. Increases insulin sensitivity by increasing insulin receptor density
2. direct stimulation of glycolysis in tissues, with increased glucose removal from blood
3. decreased hepatic and renal gluconeogenesis
4. slowing glucose absorption from the GIT
5. decrease in plasma glucagon levels

Question 11

Contraindications of biguanides?

Answer 11

Anorexia
hepatic and renal disease
alcoholicism patient
conditions r/t tissue anoxia

Question 12

Side effects of biguanides?

Answer 12

Anorexia (low BMI patients), GI effects (nausea, vomitting, abdominal pain, diarrhoea), decreased vitamin B12 absorption

Question 13

Indications of Thiazolidinediones (Tzds)? Give the examples of them

Answer 13

T2 DM. Rosiglitazone, Pioglitazone (-zones)

PPAR-gamma heterodimerise w another transcription factor (Retinoid X receptor (RXR)),
Tzds bine to PPAR-gamma- Rxr complex so complex binds DNA and promotes several genes transcriptions

Question 14

MOA of thiazolidinediones

Answer 14

1. Decrease hepatic glucose output
2. increase glucose uptake into muscle tissues and adipocytes
3. decrease triglyceride levels in blood, and enhancing uptake of fatty acids and glucose, + lipogenesis.

Question 15

Side effects of Thiazolidinediones??

Who should not use Tzds?

Answer 15

Hypoglycemia (w. sulfonylurea and insulin), weight gain, fluid retention (edema), hepatotoxicity

Contra: liver disease, heart failure patients

Question 16

Give the indication of Alpha-glucosidase inhibitors and an example of this class of drug.

Answer 16

Used for T2 DM. Acarbose, a pseudo, tetrasaccharide

Question 17

MOA of alpha-glucosidase?

How should a patient take this drug?

Answer 17

delay digestion of specific polysaccharides (carbohydrates) and absorption of sugars into the gut.

Take it before meals.

Question 18

Side effects of alpha glucosidase?

Answer 18

GI Sx: Flatulence, diarrhoea, increased liver enzymes*

Question 19

Give examples of GLP-1 Receptor agonists and DPP-4 Inhibitors.

Indicated for?

Answer 19

GLP1: Exenatide, and -glutides (Liraglutides, Dulaglutides, Albiglutides)

DPP4 Inhibitors: -gliptins (Sitagliptin, Linagliptin, Alogliptin, saxagliptin, vildagliptins) –> remember the first 2 and the suffix if u cant remember the rest

Used for T2 DM

Question 20

MOA for DPP4 inhibitors and GLP1 receptor agonists??

Answer 20

GLP1: increases incretin action, increasing GLP1 and GIP hormones,
1. increasing insulin release, increased cellular glucose uptake
2. decreased glucagon release, decreased glucose production hence decreased hepatic glucose output

DPP4:
increases incretin action
DPP4 enzyme deactivates GLP1 and GIP,

MOA:
- decreased glucagon release –> decrease glucose production –> decreased hepatic glucose output
- decreased gastric emptying

Both drugs work on the same pathway

Question 21

Side effects for GLP1 and DPP4?

Answer 21

GLP1: Weight loss, GI problems, risk of pancreatitis (?)

DPP4: GI and flu Sx (headaches, runny nose, sore throat, nasopharyngitis, nausea, stomach pain, diarrhoea)

Question 22

Indications for Sodium Glucose Cotransporter 2 inhibitors?

Give example of such drugs.

Answer 22

Indicated for t2 DM, but good for diabetic patients with CVS disorders (Chronic heart failure)

-Gliflozin drugs
(e.g. Dapagliflozin, Empagliflozin, Canagliflozin)

Question 23

MOA of SGLT2 inhibitors?

Answer 23

Blocks the reabsorption of glucose in the proximal convoluted tubule (PCT) in the kidneys by blocking the sodium-glucose cotransporter pump. Hence, increased glucose excretion (in the urine) and decreased blood glucose levels

Other mechanisms:
-increased insulin sensitivity and uptake of glucose in muscle cells
-decrease gluconeogenesis
-improved first phase insulin release

Question 24

Drawbacks/ Adverse effects of SGLT2 inhibitors?

Answer 24

increased genital infections and increased urinary tract infections