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Module 308 > Drugs in Endocrinology and Diabetes > Flashcards

Drugs in Endocrinology and Diabetes Flashcards

1
Q

target blood glucose before meals

A

4-7mmol/l

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2
Q

target blood glucose after meals

A

<10mmol/l 2hrs after the meal

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3
Q

When is HbA1C unreliable? (5)

A 
in pregnancy
for T1DM
diabetes symptoms for less than 2m
in acute pancreatic damage
haemolysis
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4
Q

Mechanism of Metformin/Biguanides? inhibits hepatic gluconeogenesis
opposes glucagon action

A

inhibits hepatic gluconeogenesis

opposes glucagon action

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5
Q

side effects of metformin (6)

A 
Anorexia
Nausea
Diarrhea
Weight Loss 
Vitamin B12 Deficiency 
Lactic Acidosis
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6
Q

what is the most common initiation drug in T2DM?

A

Metformin

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7
Q

examples of sulfonylureas

A

glipizide
gliclazide
tolbutamide
glimepiride

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8
Q

mechanism of sulfonylureas

A

Close K+ channel in beta-cell membrane so cell depolarizes = insulin release via Ca2+ influx

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9
Q

Side effects of sulfonylureas

A

hypoglycaemia
diarrhoea
weight gain
deranged LFTs

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10
Q

which is the only glitazone licensed in the UK?

A

pioglitazone

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11
Q

Mechanism of glitazones/thiazolidinediones

A

They bind avidly to peroxisome proliferator-activated receptor gamma in adipocytes to promote adipogenesis and fatty acid uptake

modulates genes increasing insulin sensitivity

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12
Q

Onset of pioglitazone

A

takes about 4 weeks to start working, 8 for full effect

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13
Q

side effects of pioglitazone (7)

A 
weight gain
oedema
headache
anaemia
hypoglycaemia
altered lipids
risk of atypical fractures and heart failure
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14
Q

GLP-1 agonists

A

Exenatide, liraglutide

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15
Q

Mechanism of GLP-1 agonists

A

increases glucose dependent insulin secretion, suppresses glucagon secretion

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16
Q

Route of GLP 1 Agonists?

A

subcutaneous injection

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17
Q

Side effects of GLP-1 agonists (6)

A

nausea, vomiting, weight loss, pancreatitis, hypoglycaemia, AKI

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18
Q

DPP-4 inhibitors

A

alogliptin
sitagliptin
vildagliptin

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19
Q

Side effects of DPP-4 inhibitors (3)

A

pancreatitis
peripheral oedema
GI side effects

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20
Q

SGLT2 inhibitors - list 3

A

Canagliflozin
Dapagliflozin
Empagliflozin

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21
Q

Mechanism of SGLT2 inhibitors

A

block glucose reabsorption in PCT

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22
Q

Side effects of SGLT2 inhibitors (5)

A 
weight loss
dyslipidaemia
dehydration
hypotension
hypoglycaemia (in combos)
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23
Q

which diabetes drugs come with increased risk of lower limb amputation?

A

sglt2 inhibitors

Canagliflozin
Dapagliflozin
Empagliflozin

24
Q

Alpha-glucosidase inhibitors example

A

acarbose

25
Q

Mechanism of alpha glucosidase inhibitors

A

inhibit glucosidases so reduced glucose absorption from gut after carbohydrate meal

26
Q

Side effects of alpha-glucosidase inhibitors (3)

A

flatulence, diarrhea, abdominal pain (often poor adherence)

27
Q

mechanism of meglitinides

A

closing the ATP-dependent K+ channel in beta cells, stimulating insulin release - basically same as sulfonylureas

28
Q

benefit of meglitinides

A

very rapid onset so could be taken just before eating, good for irregular eating

29
Q

stepwise therapy for T2DM (4)

A

metformin 1st
dual therapy
triple therapy
consider insulin

30
Q

Prevalence of gestational diabetes

A

2-12% of pregnancies

31
Q

what drug can be used for gestational diabetes?

A

metformin, all the others to be avoided

32
Q

driving with diabetes

A

need to test blood sugar less than 2hrs before start of journey and every 2hrs whilst driving

33
Q

HbA1c target if on metformin

A

48mmol/mol

34
Q

at what HbA1c would you start another drug if patient is on metformin?

A

58mmol/l

35
Q

which drug should be added if HbA1c rises to 58?

A

either a sulfonylurea, a gliptin, pioglitazone or SGLT2 inhibitor

36
Q

when is triple therapy considered in T2DM?

A

if HbA1c rises or remains above 58mmol/l on 2 drugs

37
Q

triple therapy combos in T2DM

A
  1. metformin, gliptin, sulfonylurea
  2. metformin, pioglitazone, sulfonylurea
  3. metformin, SGLT2i, sulfonylurea
  4. metformin, pioglitazone, SGLT2i
    OR start insulin
38
Q

criteria for starting a GLP-1 agonist e.g. exenatide in T2DM

A

triple therapy not working

39
Q

what needs to happen within 6 months for a patient to continue on exenatide?

A

need to see effect on HbA1c or at least 3% weight loss

40
Q

What is considered the first-line hypoglycaemic agent for the treatment of type 2 diabetes mellitus?

A

Metformin is considered the first-line hypoglycaemic agent for the treatment of type 2 diabetes mellitus.

41
Q

Metformin has been one of most prescribed medications worldwide over the last decade.

The typical starting dose for adults is … mg daily, which can be increased to a maximum dose of 2 g daily. The most common adverse-effect is gastrointestinal upset (i.e. nausea, abdominal pain, diarrhoea), although rarely metformin can result in lactic acidosis.

A

Metformin has been one of most prescribed medications worldwide over the last decade.

The typical starting dose for adults is 500 mg daily, which can be increased to a maximum dose of 2 g daily. The most common adverse-effect is gastrointestinal upset (i.e. nausea, abdominal pain, diarrhoea), although rarely metformin can result in lactic acidosis.

42
Q

Metformin is considered the first-line hypoglycaemic agent for the treatment of type 2 diabetes mellitus. It can be used in combination with other hypoglycaemic agents and with insulin.
Indications include:

A

Treatment of type 2 diabetes mellitus - Monotherapy or in combination with other anti-diabetic agents
Polycystic ovarian syndrome (PCOS) - to help reduce symptoms of hyperandrogenism (unlicensed indication)

43
Q

Metformin reduces hepatic glucose production and acts systemically to increase glucose uptake.

A

Metformin is a biguanide, which is a compound formed by two guanidine molecules. Despite its global use, the exact mechanism of action remains incompletely understood.

Metformin has multiple sites of action. Metformin reduces hepatic glucose production and acts systemically to increase glucose uptake. Metformin does not affect insulin secretion.

44
Q

Metformin is a…

A

Metformin is a biguanide,

45
Q

Suppression of hepatic gluconeogenesis

A

Within the liver, metformin inhibits the mitochondrial electron transport chain. This leads to activation of the enzyme AMP-activated protein kinase (AMPK). Through other downstream mechanisms, this enhances insulin sensitivity and reduces hepatic glucose output.

Metformin also acts through AMPK-independent pathways by inhibition of the enzyme fructose-1,6-bisphosphatase, which is required for gluconeogenesis. However, risk of hypoglycaemia is minimal as some gluconeogenic activity remains.

46
Q

GLP-1 is important in glucose homeostasis through numerous mechanisms, including: (4)

A

GLP-1 is important in glucose homeostasis through numerous mechanisms, including:

Increased insulin secretion
Decreased glucagon secretion
Decreased hepatic glucose output
Increased insulin sensitivity

47
Q

Dosing of metformin

A

The general starting dose for adults in 500 mg daily, which can be increased to a maximum of 2g daily.
Metformin should not be used in patients with significant renal impairment (eGFR < 30).

48
Q

Metformin - most serious adverse effect?

A

Commonly metformin can cause gastrointestinal upset (i.e. nausea, abdominal pain, diarrhoea). The most serious and well recognised adverse effect, albeit rare, is lactic acidosis.

49
Q

Absolute contraindications to metformin include…

A

acute metabolic acidosis.

50
Q

Metformin should not be used in patients with acute metabolic acidosis (i.e. DKA, lactate acidosis). In addition, metformin should be used with caution in the elderly, particularly those with poor renal function (see below).

A

Metformin should not be used in patients with acute metabolic acidosis (i.e. DKA, lactate acidosis). In addition, metformin should be used with caution in the elderly, particularly those with poor renal function (see below).

51
Q

Metformin should not be used in patients with an estimated glomerular filtration rate (eGFR -  mL/minute/1.73 m2) or calculated creatinine clearance (CrCl - ml/min) < …

A

Metformin should not be used in patients with an estimated glomerular filtration rate (eGFR -  mL/minute/1.73 m2) or calculated creatinine clearance (CrCl - ml/min) < 30.

52
Q

Metformin + pregnancy ?

A

Metformin can be used in diabetes but should be guided by a specialist diabetologist/endocrinologist

53
Q

Which cells are important for the secretion of the incretin GLP-1?

A	K cells
B	M cells
C     L cells 
D	D cells
E	S cells
A

Incretin hormones are gut peptides that are secreted after nutrient intake.
The key incretin secreted in response to a meal is Glucagon-like-peptide 1 (GLP-1), which is secreted by intestinal L cells.

  • K cells: secrete gastric inhibitory peptide (GIP)
  • M cells: Specialised epithelial cells of mucosa-associated lymphoid tissue (MALT)
  • D cells: Secrete somatostatin
  • S cells: Secrete Secretin
54
Q 
Aside from diabetes mellitus, metformin can be prescribed in which other condition?
A	Migraine
B	Chronic obstructive pulmonary disease
C	Hypertension
D    Polycystic ovarian syndrome (PCOS)
E	Alcoholic liver disease
A

D = Polycystic ovarian syndrome (PCOS)

Metformin is prescribed in the treatment of polycystic ovarian syndrome to help reduce symptoms of hyperandrogenism

55
Q

Which of the following medications can metformin be co-prescribed with?

A	Liraglutide
B	Sitagliptin
C	Gliclazide
D	Canagliflozin
E	All of the above
A

Metformin is the first-line hypoglycaemic agent used in the treatment of type 2 diabetes, which can be prescribed with all other hypoglycaemic agents.

  • Liraglutide: GLP-1 agonist (multiple downstream effects)
  • Sitagliptin: DPP-IV inhibitor (inhibis breakdown of GLP-1)
  • Gliclazide: short acting sulfonylurea (stimulates release of insulin)
  • Canagliflozin: sodium-glucose transport protein 2 (increases urinary glucose excretion)
56
Q

Metformin may be prescribed as an immediate-release or modified-release preparation.

Which of the following is a common reason for conversion to a modified-release preparation?

A	Patient choice
B	Other hypoglycaemic agent use
C	Pill burden
D	Poor absorption
E	GI side-effects
A

Modified-release preparations of metformin can be used in patients with GI side-effects
In patients with persistent GI side effects on standard immediate-release preparations of metformin, a trial of modified-release metformin may be used before switching to a different hypoglycaemic agent.

Module 308 (17 decks)

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