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Metabolism > Oral Hypoglycaemic Agents > Flashcards

Oral Hypoglycaemic Agents Flashcards

1
Q

Chronic disturbed carbohydrate and lipid metabolism results from

A

absolute and relative lack of insulin

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2
Q

What is meant by ‘relative’ lack of insulin?

A

Insulin is present but doesn’t work as effectively (resistance)

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3
Q

T/F Insulin levels are always abnormal in T2D

A

False; early stages insulin levels can be normal or slightly elevated; they fall as the disease progresses

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4
Q

Early in T2D, insulin levels are __________ or _________; as the disease progresses, insulin levels __________ and can resemble T1D

A

normal, slightly elevated; decrease

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5
Q

What causes insulin resistance?

A

decreased numbers and/or impaired function of insulin receptors

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6
Q

Pharmacotherapy in T2D needs to target

A

impaired secretion of insulin and receptor responsiveness (dysfunctional)

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7
Q

How do sulphonylureas (oral hypoglycaemics) stimulate insulin release?

A

Inhibit ATP-sensitive K+ channel (normally hyperpolarizes B cell, powered by ATP from glucose metabolism in mitochondria) causing depolarization and Ca2+ influx that triggers exocytotic release of insulin

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8
Q

Sulfonylureas

A

chlorpropramide, glibenclamide, glipizide

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9
Q

What is the action of sulfonylureas?

A

Increase in insulin secretion from B cells by inhibiting Katp channels - restores phase 1 insulin secretion

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10
Q

What are the adverse effects of sulfonylureas?

A

hypoglycaemia and weight gain; cross BBB so can’t be used in pregnancy; nephropathy needs to be monitored bc excreted by kidney

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11
Q

What type of receptor is the insulin cell surface receptor?

A

Tyrosine kinase

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12
Q

What is the action of the insulin receptor?

A

Insulin binds the tyrosine kinase receptor that switch on protein and glycogen synthesis, glucose transport, and translocation of the GLUT4 transporter to cell surfaces to take up glucose for metabolic pathways

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13
Q

Metformin is what class of drug?

A

Biguanide

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14
Q

What are the actions of metformin for tx in T2D?

A

increase insulin-mediated peripheral glucose uptake; reduce hepatic glucose production; decrease carbohydrate absorption; reduce LDL and TAG levels

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15
Q

What is the mechanism of metformin?

A

Activation of AMP kinase

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16
Q

What are the adverse effects of metformin?

A

GI disturbances: diarrhoea, nausea, abdominal discomfort, anorexia; lactic acidosis; weight loss; contraindicated in impaired renal function

17
Q

In treatment of T2D, sulfonylureas target

A

insulin secretion - stimulate secretion from pancreas to restore phase 1 insulin spike

18
Q

In treatment of T2D, biguanides (metformin) target

A

insulin resistance - sensitize the body to insulin and/or control hepatic glucose production

19
Q

Acarbose

A

alpha-glucosidase inhibitors

20
Q

What is the mechanism of alpha-glucosidase inhibitors?

A

block the enzymes that digest and promote absorption of starches in the SI

21
Q

What are the adverse effects of alpha-glucosidase inhibitors?

A

flatulence, abdo discomfort, loose stools, abdo pain, contraindicated in IBD or cirrhosis

22
Q

In tx of T2D, alpha-glucosidase inhibitors target

A

glucose absorption

23
Q

Incretins target

A

insulin secretion and glucagon secretion

24
Q

Incretins __________ insulin and _________ glucagon

A

increase; decrease

25
Q

Dipeptidyl peptidase-4 inhibitors target

A

DPP4 which breaks down GLP-1

26
Q

What is the action of DPP4 inibitors?

A

Increase GLP-1 levels which increase insulin and decrease glucagon

27
Q

Sitagliptin

A

DPP4 inhibitor

28
Q

What are the adverse effects of DPP4 inhibitors?

A

URT infections; headaches; hypoglycaemia in combo with insulin; allergic/hypersensitivity reactions; pancreatitis

29
Q

Exenatide

A

GLP-1 receptor agonist

30
Q

How is exenatide administered?

A

subcutaneous injection

31
Q

What are the actions of exenatide?

A

potentiate glucose-mediated insulin secretion (GLP-1 action); suppress glucagon release; slow gastric emptying; decrease appetite

32
Q

What are the adverse effects of exenatide (GLP-1R agonist)?

A

Nausea, vomiting, diarrhoea; weight loss; Ab formation, immune reactions, pancreatitis; endocrine neoplasias

33
Q

In the tx of T2D, incretins, incretin mimetics and enhancers target

A

incretins - GLP-1, GIP; increase insulin and decrease glucagon

34
Q

In the tx of T2D, SGLT2 inhibitors target

A

sodium glucose cotransporter 2 to slow renal glucose reabsorption

35
Q

What is the treatment progression in T2D?

A

diagnosis; therapeutic lifestyle change; monotherapy (metformin); combo therapy - oral only (until renal effects; also SC exenatide soon); combo therapy - oral with insulin

36
Q

Target glucose homeostasis in diabetes treatment are

A

4-8mmol/L

37
Q

Target HbA1c levels in diabetes treatment are

A

6%

Metabolism (16 decks)

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