Hypoglycaemic Agents Flashcards
Name the 2 insulin sensitizers:
- Biguanide - Metformin
- Thiazoldinediones - Pioglitazone
Name the 2 Meglitinides.
- Repaglinide
- Nateglinide
Name the 2 naturally occurring incretin hormones.
- Glucose-dependent insulinotropic polypeptide (GIP)
- Glucagon-like peptide-1
- increases insulin secretion when there is an increase in glucose levels
Why do Incretin hormones have a short half life?
- due to rapid inactivation by dipeptidyl peptidase-4
(So in incretin based therapy, we inhibit dipeptidyl peptidase-4, so that incretin hormones will exist for longer and more insulin is secreted)
Name the 3 SGLT2 inhibitors.
- Empaglifozin
- Canagliflozin (increases risk of lower limb amputation)
- Dapaglifozin
SGLT2 inhibitors have what effect?
- cardiorenal protective effects
List out the 5 types of Hypoglycaemic Agents.
- Insulin sensitisers
- Insulin secretagogues
- α glucosidase inhibitors
- Incretin based therapy
- Sodium-glucose co-transporter 2 inhibitors
What are the 2 types of hypoglycaemic agents that cause weight gain?
- Thiazoldinediones - Pioglitazone
- Sulfonylureas e.g. Gibenclamide
- better not give in obese patients
Which Hypoglycaemic agents are preferred for obese patients?
- GLP-1 receptor agonist
- incretin mimic, promotes secretion of insulin + feeling of satiety - Sodium-Glucose co-transporter 2 inhibitors
- prevents reabsorption of glucose, glucose gets excreted
What is the main difference between sulfonylureas and meglitinides? + implications
Dependency on glucose levels
Sulfonylureas NOT dependent, Meglitinides DEPENDENT
Sulfonylureas have a higher risk for hypoglycaemia as it is not glucose dependent
Meglitinides diminish at low glucose concentrations => reduces risk of hypoglycaemia
What are some negative side effects of incretin mimetics?
- GIT issues: nausea, vomiting, diarrhea, indigestion
- Use w caution in patient w renal problems.
=> contraindicated in patients w severe renal impairment - Increased risk of Vit B12 malabsorption => vit b12 deficiency, can worsen symptoms of neuropathy
TLDR: git, renal, vit b12
Simply put, what do Sulfonylureas do?
- bind to potassium channel => cause insulin to be released whether or not glucose is present
Side effects of Sulfonylureas?
- Weight gain
- High risk for hypoglycemia
- esp in elderly n those w renal/hepatic impairment
- renal impairment=> metabolism impaired=> sulfonylurea stays in system for longer
Name all the Sulfonylurea drugs:
- Gibenclamide
- longest acting sulfonylurea, highest risk of hypoglycemia
- 50% renal 50% faecal excretion - Glipizide
- shortest duration of action
- excreted in urine - Glimepiride (2nd gen)
- Gliclazide
- Tolbutamide (1st gen)
What are insulin secretagouges and which are the 2 classes of insulin secretagouges?
Insulin secretagouges: gets pancreatic β-cells to secrete insulin
- Sulfonylureas
- independent of glucose levels => higher risk of hypoglycemia
- side effect: weight gain - Meglitinides
- dependent on glucose levels, diminishes at low glucose concentrations => reduced risk of hypoglycemia
- more rapid onset + shorter duration than sulfonylureas
Name the 3 DPP-4 inhibitors:
- Sitagliptin
- Vildagliptin
- Linagliptin*
- suitable for px w renal impairment!!
-> no dose adjustment in patients w chronic kidney disease cuz it is excreted 80% thru faeces (other 2 are excreted via renal)
Which DPP-4 inhibitor is suitable in patients w renal impairment?
Linagliptin
- no dose adjustment in patients w chronic kidney disease cuz it is excreted 80% thru faeces (other 2 are excreted via renal)
What are the glucose-dependent hypoglycaemic drugs?
Glucose-dependent: works only in presence of hyperglycemia)
1. Incretin based therapy
- DPP-4 inhibitors (Sitagliptin, Vildagliptin, Linagliptin)
- GLP-1 receptor agonists (Exanatide, Liraglutide)
2. Meglitinides (insulin secretagouges)
- Nateglinide
- Repaglinide
What do α-glucosidase inhibitors do? Mechanism of action?
TLDR: prevent absorption of glucose in intestine
Mechanism:
1. Reversibly inhibits α-glucosidase in intestinal brush borders
2. Slow down increase in glucose levels after a meal => inhibit postprandial hyperglycaemia
3. Bacteria breaks down remaining carbs
- α-glucosidase hydrolyse oligosaccharide to glucose & other sugars
- stronger affinity to α-glucosidase than carbs (inhibitor + α-glucosidase > carbs + α-glucosidase)
Name the hypoglycaemic drugs that can be orally administered
All hypoglycaemic drugs except GLP-1 receptor agonists(subcutaneous injection).
Aka.
1. Biguanide - Metformin
2. Thiazoldinediones - Pioglitazone
3. Sulfonyureas
4. Meglitinides
5. α-glucosidase inhibitor
6. DPP-4 inhibitors
7. SGLT2 inhibitors
Name the hypoglycaemic drug that blocks glucose reabsorption at the kidneys.
SGLT2 inhibitors
Sodium-Glucose Co-Transporter 2 inhibitors
Mechanism of action for SGLT2 inhibitors?
- Inhibits SGLT2
- decreases reabsorption of filtered glucose
- decreases renal threshold for glucose (cannot hold as much glucose => pee out) - Increases urinary glucose excretion
What is unique adverse effect of Canagliflozin?
Increased risk of lower limb amputation
Adverse effects of SGLT2 inhibitors?
- Urinary tract infection (due to increased glucose in urine, which bacteria will feed on)
- Increased urination (cuz water leaves w the glucose)
- Female genital mycotic infections (fungal)
- Diabetic ketoacidosis (even if blood glucose normal)
+ - Canagliflozin: increased risk of lower limb amputation
