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MBChB YR2 Endocrine > Pharmacology: Antidiabetic Drugs > Flashcards

Pharmacology: Antidiabetic Drugs Flashcards

1
Q

Why should SGLT2 inhibitors be used with caution in patients on other diuretics or with low blood pressure?

A

Diuretic effect

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2
Q

Name the indications for DPP4 inhibitors

A

Most effective in the early stages of type 2 diabetes, when insulin secretion is relatively preserved

Can be used as a monotherapy when metformin not tolerated/contraindiated, or as an addon

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3
Q

Describe the cardiac benefit of SGLT2 inhibitors

A

Glucose reduction → decreased insulin and increased glucagon → increase in lipolysis → increase in FFA which also increases ketone body production

FFA and ketones are a fuel to cardiac myocytes

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4
Q

Name the indications for thiazolidinediones

A

Follow on to metformin where cost is a major issue

Particularly potent in obese women

Generally avoided in patients 65+ due to side effects

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5
Q

Why do sulphonylureas cause weight gain?

A

Insulin concentrations increased, insulin is anabolic and stimulates appetite

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6
Q

How are SGLT2 inhibitors beneficial in terms of gout and CVD?

A

Urate excretion increased so plasma urate concentration reduced

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7
Q

Name the anti diabetic drugs which have cardiovascular benefit

A

Metformin, TZDs, GLP-1 receptor antagonists, SGLT2i

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8
Q

What is the mechanism of action of SGLT2 inhibitors?

A

Specific inhibitors of renal sodium glucose transporter 2

Lower the renal threshold for glucose, which increases urinary glucose excretion

Removes glucose and calories from circulation - lowers blood glucose and facilitates weight loss

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9
Q

What is a basal-bolus insulin regimen?

A

Long-acting insulin 1-2 times a day and short-acting insulin before each meal

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10
Q

Why are short-acting analogue insulins preferred over short-acting soluble insulins?

A

Short-acting analogue insulins disappear from circulation more rapidly compaired to soluble insulin which tends to persist after meals, predisposing to hypoglycaemia

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11
Q

What is metformin associated lactic acidosis (MALA)?

A

Metformin increases lactate production which is normally cleared by the liver and the kidneys

In acute kidney injury (often in the context of sepsis), metformin is associated with greater risk of lactic acidosis

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12
Q

Give an example of a sulphonylurea

A

Gliclazide

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13
Q

Name two examples of GLP-1 antagonists

A

Liraglutide, semaglutide

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14
Q

Describe the action of analogue basal insulins

A

Have a longer duration of action with less peak activity, may be given once or twice a day

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15
Q

Name the side effects of SGLT2 inhibitors

A

Genital candiasis

Fournier gangrene

Hypovolaemia and hypotension

Dehydration

DKA

Slight increase in LDL and HDL cholesterol

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16
Q

How do SGLT2 inhibitors increase ketosis and risk of ketoacidosis?

A

Increase in FFA increases ketone body production

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17
Q

Name the factors which increase risk of hypoglycaemia in patients prescribed insulin

A

Increased age, diabetes duration, impaired renal function, lower HbA1c

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18
Q

In which patient group is the risk of fractures due to thiazolidinediones doubled?

A

Elderly patients

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19
Q

Name two side effects of insulin

A

Weight gain, risk of hypoglycaemia

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20
Q

Which type of insulin is intermediate to long acting with a peak action around 4-6 hours?

A

Isophane ‘basal’ insulins, e.g. Insulatart, Humulin

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21
Q

How can thiazolidinediones precipitate heart failure?

A

Fluid retention

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22
Q

What is the mechanism of action of thiazolidinediones?

A

Increase insulin sensitivity by interaction with PPAR-𝛾

Main effect is on adipocytes and the mechanism involves increasing fat mass in subcutanous depots promoting ‘lipid steal’ - fat removed from liver and muscle which increases adiponectin

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23
Q

How do SGLT2 inhibitors cause genital candiasis?

A

Secondary to glycosuria

24
Q

How do SGLT2 inhibitors cause hypovolaemia and hypotension?

A

Due to diuretic effect

25
Q

Name the indications for GLP-1 receptor antagonists

A

Diabetic patients with atherosclerotic CVD (e.g. previous MI) should be given metformin + GLP-1 receptor antagonist Diabetic patients with heart failure or chronic kidney disease where SGLT2i are contraindicated/not tolerated should be given metformin + GLP-1 receptor antagonist Valuable in diabetic patients who need to loose weight

26
Q

Name the side effects of thiazolidinediones

A

Weight gain, fracture risk, mild anaemia

27
Q

Name the indications for SGLT2i

A

Diabetic patients with heart failure or chronic kidney disease should be given metformin + an SGLT2i as first line

Valuable in diabetic patients who need to loose weight

28
Q

Name 3 short-acting insulin analogues

A

Insulin aspart (NovoRapid), lispro (Humalog) and glulisine (Apidra)

29
Q

Name the only avaliable biguanide

A

Metformin

30
Q

Name two examples of DDP4 inhibitors

A

Sitagliptin, alogliptin

31
Q

Name two examples of SGLT2 inhibitors

A

Empagliflozin, dapagluflozin

32
Q

What is the mechanism of action of sulphonylureas?

A

Bind to the sulphonylurea receptor on the β-cell membrane, which closes ATP-sensitive K+ channels and promotes calcium influx which stimulates insulin release

33
Q

Why do sulphonylureas cause hypoglycaemia?

A

SUs are glucose independent and act via the triggering pathway, which means insulin release will occur whatever the blood glucose level of the patient is

34
Q

Why should SGLT2 inhibitors be omitted in prolonged fasting or acute illness?

A

Hypovolaema and DKA risks

35
Q

Name the side effects of GLP-1 receptor antagonists

A

GI - nausea, vomiting, bloating, diarrhoea

Small increase in incidence of gallstones

36
Q

Name the side effects of sulphonylureas

A

Weight gain, hypoglycaemia

37
Q

Name the side effects of DDP4 inhibitors

A

Nausea, increased risk of acute pancreatitis, may increase risk of HF

38
Q

Give two examples of intermediate insulin

A

Insulatart, Humulin

39
Q

Why is metformin contraindicated in renal impairment, cardiac failure and hepatic failure?

A

Due to the risk of lactic acidosis

40
Q

Why do GLP-1 receptor antagonists and DDP4 inhibitors come with no risk of hypoglycaemia?

A

Incretin drugs act via the amplifying pathway - glucose-dependent mechanism

41
Q

How do thiazolidinediones increase fracture risk?

A

Fat accumulation in bone marrow and reduction in bone density

42
Q

Why will patients with reduced eGFR will see little benefit if prescribed SGLT2 inhibitors in terms of glucose lowering?

A

Relies on renal glucose function

43
Q

How do SGLT2 inhibitors benefit diabetic patients with chronic kidney disease?

A

Increased Na+ delivery to DCT causes increased Na+ uptake by Na/K/Cl transporter at macula densa → increase in adenosine secretion → reduction in renal afferent vasodilation → renal protection

44
Q

What are the two methods of insulin administration?

A

Intermittent SC injection and continuous subcutaneous insulin infusion pump

45
Q

Name the indications for metformin

A

First line in all patients with type 2 diabetes

46
Q

Name the side effects of metformin

A

GI - anorexia, nausea, abdominal discomfort and diarrhoea

Metformin associated lactic acidosis (MALA)

47
Q

What is the mechanism of action of GLP-1 receptor antagonists?

A

Enhance the incretin effect by activating the GLP-1 receptors They are modified to avoid breakdown by DPP4

48
Q

How do SGLT2 inhibitors benefit diabetic patients with heart failure?

A

Na+ reabsorption reduced and glucose loss results in osmotic diuresis → mild diuretic action

49
Q

Why are SGLT2 inhibitors valuable in patients who want to loose weight?

A

Increases urinary glucose excretion so removes calories from circulation

50
Q

What is the mechanism of action of DDP4 inhibitors?

A

Inhibit DPP4 , which usually inactivate GLP-1 (incretin effect)

This in turn increases insulin secretion and reduces glucagon secretion

51
Q

Name the only currently avaliable thiazolidinedion (TZD)

A

Pioglitazone

52
Q

Name the indications for sulphonylureas

A

Alternative first line treatment of type 2 diabetes where cost is a major issue (developing countries, private healthcare if no insurance)

53
Q

Why are GLP-1 receptor antagonists especially useful in diabetic patients who want to loose weight?

A

Act in the hypothalamus to reduce appetite and intestines to reduce gastric empyting

54
Q

What is the mechanism of action of metformin?

A

Unclear but may involve the activation of AMP kinase, which regulates cellular energy metabolism

It reduces gluconeogenesis, and increaes gut glucose utilisation and metabolism

55
Q

Give two examples of analogue basal insulins

A

Lantus (glargine), levemir (dertermir)

56
Q

How do thiazolidinediones cause weight gain?

A

Increase in fat mass and fluid retention

57
Q

Why should patients rotate their insulin injection site?

A

To avoid lipohypertrophy

MBChB YR2 Endocrine (23 decks)

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