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Systemic Pharmacology > Diabetes > Flashcards

Diabetes Flashcards

1
Q

Which glucose transporter is found at the pancreatic beta cells?

A

GLUT 2

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2
Q

How does an increase in glucose level stimulate insulin release?

A

Increased intracellular glucose leads to increased production of ATP, and an increase in the ATP/ADP ratio (1); the increased ATP/ADP ratio leads to closing of the potassium channels and depolarization of the cell (2); and cell depolarization opens voltage gated calcium channels (3) which leads to exocytosis of insulin containing vesicles(4).

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3
Q

How does insulin regulate blood glucose levels?

A

1.Facilitating cellular glucose uptake, 2.Regulating carbohydrate, lipid and protein metabolism (How?) and
3.Promoting cell division and growth

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4
Q

How is exogenous insulin mainly cleared?

A

Kidneys

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5
Q

When is insulin therapy indicated?

A

In all Type 1 diabetes patients, and in
Type 2 diabetes patients with
1. Severe hyperglycaemia or
2. When glycemic targets are not reached with 2 or more oral hypoglycaemic agents (OHAs)

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6
Q

What are the main types of insulins?

A

Rapid acting, short acting, intermediate acting and long acting
Degludec can be called ultra long acting

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7
Q

Which of the insulin types has the longest peak duration of action?

A

NPH (Intermediate acting insulin)

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8
Q

Which of the insulins are commonly used in an emergency to rapidly lower blood glucose levels?

A

Short acting regular human insulin
Note: It is administered intravenously

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9
Q

Which of the insulins have the highest risk for hypoglycaemia?

A

NPH (Intermediate acting insulin)

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10
Q

Which insulins cannot be mixed with any other insulin in a single syringe?

A

Glargine, detemir

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11
Q

What adverse effects are associated with insulin use?

A

Hypoglycaemia and lipodystrophy

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12
Q

How is insulin commonly administered?

A

Subcutaneous injection

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13
Q

What factors affect the absorption of insulin?

A

Site of injection, Depth of injection, Volume and concentration of the dose injected, exercise, heat (e.g. sitting in a sauna), massage of insulin site

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14
Q

How does corticosteroids or an acute infection affect insulin demands?

A

It is likely to increase insulin demands as it can cause an increase in blood glucose levels (likely due to insulin resistance)

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15
Q

Which oral hypoglycaemic agent is commonly used as the first line of treatment in the absence of any contraindications?

A

Metformin

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16
Q

What is metformin’s mechanism of action?

A

Metformin decreases hepatic glucose production, increases the density of insulin receptors at the tissues and reduces intestinal glucose absorption

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17
Q

What factors could contraindicate the use of metformin?

A

Renal dysfunction, lactic acidosis, hepatic dysfunction

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18
Q

What is thiazolidinedione’s mechanism of action?

A

Primary mechanism of action is via the activation of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ ligands are known to regulate glucose metabolism, adipogenesis, and improve insulin sensitivity at adipose tissues, liver and skeletal muscles.

19
Q

What are the key adverse effects associated with the use of thiazoldinediones?

A

Weight gain, peripheral edema, increased risk of heart failure (fluid retention) and bone fractures

20
Q

Will an obese patient be suitable for thiazolidinediones?

A

Ideally not recommended as the drug can cause weight gain

21
Q

What is sulfonylurea’s mechanism of action?

A

Sulfonyureas (SU) bind to the SU receptor proteins subunits of the KATP channels. Drug binding inhibits KATP channel mediated K+ efflux, triggering a calcium-dependent exocytosis of insulin granules from the pancreatic β-cells.

22
Q

Name a sulfonylurea with a long duration of action

A

Glibenclamide - High risk of hypoglycaemia compared to the others

23
Q

What are the key adverse effects associated with the use of sulfonylureas?

A

Weight gain, hypoglycaemia

24
Q

What patient profile may have a higher risk of hypoglycaemia with sulfonyureas?

A

Elderly, poor renal function, or hepatic dysfunction, people with irregular eating habits

25
Q

What is meglitinide’s mechanism of action?

A

Meglitinides bind and close the ATP-dependent potassium (KATP) channels on the pancreatic beta cells in a glucose-dependent manner stimulating insulin release

26
Q

Why are meglitinides commonly used at meal times?

A

They have a rapid onset and short duration of action

27
Q

What is acarbose’s mechanism of action?

A

The α-glucosidase inhibitors reversibly inhibit membrane-bound α-glucosidase in the intestinal brush borders slowing down the rise in glucose levels after a meal

28
Q

What are some side effects associated with the use of acrbose?

A

Flatulence, GI discomfort

29
Q

In which groups of patients will acarbose be contraindicated?

A

Gastrointestinal diseases like Inflammatory bowel disease, severe renal and hepatic disease

30
Q

What are the 2 classes of drugs that work by incretin based therapy?

A

Dipeptidyl peptidasae-4 inhibitors, GLP-1 receptor agonist

31
Q

What are the mechanisms of action of DPP-4 inhibtors?

A

DPP-4 inhibitors binds and inhibits DPP-4 thus prolonging the action of the endogenous incretins, which then stimulate pancreatic β-cells to increase glucose-stimulated insulin release, and suppress α-cell mediated glucagon release and hepatic glucose production.

32
Q

Name 3 DPP-4 Inhibitors

A

Sitagliptin, Linagliptin and Vildagliptin

33
Q

Which of the DPP-4 inhibitors can be used without any dose adjustment in patients with chronic kidney disease?

A

Linagliptin does not need dose adjustment, the rest will need dose adjustment

34
Q

Name 2 examples of glucagon-like 1 peptide 1-receptor agonist

A

Exenatide, Liraglutide

35
Q

How are GLP-1 receptor agonists administered?

A

Subcutaneous injection

36
Q

What are the mechanisms of action of glucagon-like 1 peptide 1-receptor agonist?

A

They activate the GLP-1 receptor, a membrane-bound cell-surface receptor in pancreatic beta cells to increase insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia.

37
Q

What are the potential adverse effects associated with the use of DPP-4 inhibitors and GLP-receptor agonist?

A

GI related issues, pancreatitis (not recommended for patients with a history of pancreatitis

38
Q

Other benefits of GLP-1 receptor agonists

A

Weight loss, improved cardiovascular outcomes

39
Q

What are examples of sodium glucose co-transporters?

A

Dapagliflozin, empagliflozin, canaglifloziin

40
Q

What is SGLT-2’s mechanism of action?

A

SGLT2, expressed in the proximal renal tubules, is responsible for 90% of the reabsorption of filtered glucose from the tubular lumen. By inhibiting SGLT2, reabsorption of filtered glucose is reduced and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

41
Q

What other benefits does SGLT-2 have?

A

Favourable cardiac outcomes - including reduced risk of hospitalizaton due to heart failure and reduced risk of worsening renal function

42
Q

What are some of the key adverse effects associated with the use of SGLT-2 inhibtors?

A

Urinary tract infection, and increased urination, female genital mycotic infections, increased risk of lower limb amputation (Canagliflozin), diabetic ketoacidosis

43
Q

Which hypoglycaemic agents are associated with weight gain?

A

sulfonyureas, thiazolidinediones, meglitinides

44
Q

Which hypoglycaemic agents are associated with more favourable cardiovascular disease outcomes?

A

Metformin, SGLT-2 inhibitors, GLP-1 receptor agonist

Systemic Pharmacology (8 decks)

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