Type 2 Diabetes Therapeutics Flashcards Preview

Endocrinology > Type 2 Diabetes Therapeutics > Flashcards

Flashcards in Type 2 Diabetes Therapeutics Deck (99):
1

Metformin dosages

500, 850 and 1000mg tablets,

Usually start with 500mg od or bd

Little evidence for > 1g bd

XR tablets 500, 750mg, 1g

liquid formulation: 500mg in 5 ml

2

Metformin and insulin

Lowers insulin resistance "insulin sensitiser"

3

By how much does metformin lower HbA1c?

Lowers by 15-20mmol/L

4

Metformin and weight?

Often lowers weight

5

Metformin and micro & macrovascular complications

Reduces both (UKPDS)

6

UKPDS and metformin?

Metformin reduces microvascular and macrovascular complications

7

Metformin and LDL and triglycerides?

Reduces triglycerides and LDL

8

Is metformin safe in pregnancy?

Yes:
-pre-existing T2DM
-GD

9

Metformin and PCOS

Metformin often prescribed to try and prevent diabetes

10

NAFLD and metformin

You could give metformin in NAFLD. Probably helps because of its insulin sensitising effect etc

11

Metformin side effects

GI side effects:
Anorexia, nausea, vomiting, diarrhoea, abdo pain, taste disturbance
GI side effects in up to 25%; only 5% cannot tolerate the drug
Interference with vitamin B12 and folic acid absorption (anaemia is rare)
Lactic acidosis
- 1 case per 100,000 treated patients
- Can be fatal
Liver failure
Rash (jennifer lawrence lol)

12

Metformin and vitamin B12 and folic acid

Metformin can reduced vitamin B12 and folic acid absorption
Other effects:
Lactic acidosis (hyperventilation, confusion, coma)
Rash
Liver failure

13

Which patients are at high risk of lactic acidosis?

high pre-existing risk eg acute heart failure, sepsis, acute MI, respiratory failure, hypotension for any cause

14

Metformin and the Liver

-may cause liver failure
-Liver toxicity:
Discontinue if advanced cirrhosis/liver failure
Discontinue if risk of lactic acidosis eg encephalopathy, alcohol excess
May be beneficial in Non-alcoholic fatty liver disease (NAFLD)

15

Metformin and the kidneys

-Avoid or stop if eGFR 150μmol/l
Half dose if eGFR 30-45 ml/min
Temporarily withhold if IV contrast being used eg. Angiography, CT scan

16

Which OHA should you temporarily avoid when using contrast? (i.e. angiography, CT scan)

Metformin

17

At which eGFR value should you half dose of metformin?

30-45ml/min
Stop when below 30ml/min or if serum creatinine >150µmol/L

18

Sulphonylureas and HbA1c?

Reduce by 15-20mmol/mol by increasing insulin secretion
More rapid reduction in hyperglycemia than insulin sensitizers
Concern re acceleration of beta cell demise

19

Which reduced hyperglycemia more quickly: metformin or SU's?

SU's

20

Do SU's reduce micro and macrovascular complications?

Just microvascular
UKPDS and ADVANCE

21

Which sulphonylureas have the greatest risk of hypoglycaemia?

Older agents e.g. chlorpropramide or glibenclamide
Particular care in elderly/frail, alcohol excess, liver disease

22

Which types of people should you be especially careful with sulphonylureas?

Elderly/frail people
Alcohol excess
(probably because of increased risk of hypoglycaemia)

23

Side effects of sulphonyureas?

Hypoglycaemia (be carfeful in oldies, liver disease, alcoholics)
Weight gain
GI upset, headache

24

Why would Gillian not want to take sulphonylureas?

weight gain mothafukas
lol probably also because of hypersensitivity, blood dyscrasias and liver dysfunction
and hypoglycaemia
and headaches
and GI upset

25

When should you avoid sulphonylureas?

In severe hepatic and renal failure
(metformin should be discontinued in advanced cirrhosis/liver failure, and when eGFR<30ml/min, lactic acidosis, encephalopathy, IV contrast)

26

Why was rosiglitazone taken off the market?

Increased risk of MI (this was in red in lecture)

27

Dosage of pioglitazone?

15-45 mg

28

What receptor do PPAR-gamma agonists bind to? (pioglitazone)

Nuclear receptors
-transcription of certain insulin sensitive genes

29

Where are PPAR-gamma receptors found?

Mainly adipose tissue but also skeletal tissue and liver

30

Are TZDs lipophiylic or lipophobic?

Lipophiylic,
don't even know if lipophobic is a thing lol

31

Hypoglycaemia with TZDs?

Not if used without SU's

32

What is the absolute worse thing about TZDs?

Weight gain almost inevitable
-This is due to increase in subcutaneous fat and fluid retention
REMEMBER OMG this fluid retention almost doubles risk of admission with heart failure
-risk still low if no heart failure pre-existing

33

TZD's and heart failure?

Fluid retention results in near doubling of risk of admission with heart failure (risk still low in non-elderly without pre-existing HF)

34

Prevention of microvascular and macrovascular complications with TZD's?

No :( but improvement in microalbuminuria :)
Prevention of macrovascular complications:
No, but composite endpoint of all-cause mortality and non-fatal MI reduced (PROactive trial)

35

Glitazone drugs and risk of hip fracture

Glitazone drugs increase risk of fracture by 20% per year of use

36

Incretins and blood glucose level?

Incretins decrease the blood glucose level by increasing the amount of insulin released from beta cells

37

What is dapagliflozin?

SGLT2 inhibitor, also known as Forxiga

38

Name an SGLT2 inhibitor

Dapagliflozin (Forxiga)

39

The incretin effect

The incretin effect: Oral glucose load produces a greater insulin response than that of an isoglycemic intravenous infusion

40

What would you do if you have risk of lacic acidosis (i.e encephalopathy, alcohol excess) and you are on metformin?

Discontinue metformin
-Also discontinue in advanced liver failure/cirrhosis
-temporarily withold if iv contrast is being used e.g. angiogram, CT scan

41

TZDs and hip fractures?

Increases risk of hip fractures by 20%

42

How are gliptins cleared?

Kidneys

43

Where are gliptins secreted?

The intestines

44

Risk pancreatitis with which diabetes drugs?

GLP-1 agonists
DPP-IV inhibitors
(1/200 risk unless liraglutide 1/100)

45

Why is a very low energy diet not recommended?

Because after 12 months, change is not very different to just going on a normal diet

46

Bariatric surgery recommended at which BMI?

BMI>35 is recommendation for surgery in diabetes
-But, need to demonstrate at least 5-10% weight loss before the surgery over 6-12 months

47

Side effects of GLP-1 agonists

Nausea
Injectable :(
(pancreatitis, pancreatic cancer??)

48

Why are DDP-IV inhibitors not quite as good as GLP-1 agonitsts?

Less potent than GLP-1 mimetics – can only work on what’s there and GLP-1 levels are low in T2DM

49

Weight loss in GLP-1 agonists/DPP-IV inhibitors?

Weight loss in GLP-1 agonists but not DPP-IV inhibitors

50

By how much does an SGLT2 inhibitor reduce sugar uptake?

Reduces sugar uptake by about one quarter

51

Possible side effects of SGLT2 inhibitors? (because of more sugar in urine)

Thrush
Possible increase in urinary infections

52

Normal insulin regime for type TWO diabetes

o.d. NPH
If that doesn't work: b.d. NPH or humulin M3

53

Which T2DM drug can cause oedema?

Thiazolidinediones

54

Which molecule binds to SUR-1 subunits to open the KATP channel?

ADP-Mg2+

55

Tolbutamide, glibenclamide, glipizide

Sulphonylureas
-displace binding of ADP-Mg2+

56

When do you take glinides?

Just before meals. They prevent the post-prandial rise in blood glucose

57

Exenatides mimic which type of drug?

GLP-1 agonists

58

Actions of GLP-1 and GIK

-GLP-1 decreases release of glucagon
-GLP-1 and GIK both increase insulin secretion and delay gastric emptying

59

Which receptor does exenatide (an incretin analogue) bind to?

Binds to GPCR GLP-1 receptors that increase intracellular cAMP concentration

60

Exenatide and weight loss?

Modest weight loss, reduces hepatic fat accumulation

61

How is exenatide administered?

Subcutaneously, twice daily
(liraglutide longer lasting, once daily)

62

Side effects of exenatide?

May cause nausea, hypoglycaemia and much more rarely, pancreatitis

63

Gliptins

(DPP-4 inhibitors)

64

What is alpha-carbosidase?

A brush border enzyme that breaks down dissacharides and starch into absorbable glucose

65

Side effects of acarbose?

Adverse effects occur in the G.I. tract – flatulence, loose stools, diarrhoea, abdominal pain, bloating – undigested carbohydrate is welcomed by colonic bacteria!
ON THE PLUS SIDE, NO HYPOGLYCAEMIA fatt

66

Which cells are predominantly associated with PPARɣ?

Adipocytes

67

PPARɣ becomes associated with which receptor?

PPARɣ becomes associated with the retinoid receptor (RXR)

68

Name some of the proteins expressed through PPARɣ-RXR?

Lipo-protein lipase
Fatty acid transport protein
GLUT 4

69

Lipo-protein lipase, fatty acid transport protein and GLUT 4

PPARɣ-RXR

70

Insulin independent drugs used in diabetes?

-SGLT2 inhibitors
-alpha carbosidase inhibitors

71

Insulin dependent drugs?

GLP-1 agonists
DPP-IV inhibitors
Biguanides

72

Which part of the kidney tubule do SGLT2 inhibitors act upon?

Proximal tubule

73

Why might blood glucose levels fluctuate widely in a person with diabetes? (nerve)

Autonomic nerve damage
Gastroparesis: persistant nausea and vomitting, bloating and loss of appetite can make blood glucose levels fluctuate widely due to ABNORMAL FOOD DIGESTION

74

Treatment for gastroparesis?

Metoclopramide, domperidone, erythromycin
Gastric pacemaker

75

Gustatory sweating

Autonomic neuropathy can affect the nerves that control sweating- prevents the sweat glands from working properly.
The body cannot regulate its temperature as it should. Nerve damage can also cause profuse sweating at night or while eating.
"Gustatory sweating"

76

Autonomic neuropathy in diabetes and its effect on the heart and blood vessels

Blood pressure may drop sharply after sitting or standing, causing a person to feel light-headed/ faint.
Heart rate may stay high, instead of rising and falling in response to normal body functions and physical activity

77

Autonomic neuropathy and the eyes (pupil)

Autonomic neuropathy can affect the pupils of the eyes, making them less responsive to changes in light.

A person may not be able to see well when a light is turned on in a dark room or may have trouble driving at night.

78

Bladder and diabetes?

Bladder might not empty completely etc and other diabetic related problems. You can do an ultrasound of the bladder to double check structure and whether it empties or not etc

79

Where does amyotrophy usually occur?

Pelvic girdle and thigh

80

Kimmelsteil- Wilson Syndrome or Nodular Glomerulosclerosis??

Lol, other names for diabetic nephropathy

81

Consequences of diabetic nephropathy?

Development of hypertension
Relentless decline of renal failure (reduction in GFR of 1ml/min/month)
Accelerated vascular disease

82

Screening for nephropathy

Use urinary albumin creatinine ratio (ACR) to screen for diabetic kidney disease
Screen all patients aged 12 or over
At diagnosis & annually
May use RANDOM rather than 1st pass urine sample as initial check
Confirm abnormal result with EMU
Dipstick test at point of care
Don’t forget U&E’s (eGFR)

83

How often do you screen for nephropathy?

At diagnosis and annually

84

From which age should you screen for nephropathy?

From age 12

85

Why do you check U&E's in nephropathy?

Show if kidney is filtering etc (eGFR)

86

Normal albumin:creatinine ratios in men and women?

<3.5mg/mol creatinine (women)

87

Measuring microalbumin

Microalbuminuria: 30-300mg/ml
Macroalbuminuria: >300mg/ml

88

How could you check for nitrites/leucocytes/blood in urine?

Mid-stream urine sample

89

False positives for micro-albuminuria

Vaginal discharge
Pregnancy
Menstruation
UTI
"other illnesses"
on-diabetic renal disease

90

Which eye problems do people with diabetes develop?

Cataracts
Glaucoma (increase in fluid pressure in eye leading to increased pressure on optic nerve)
Retinopathy
Acute hyperglycemia (blurring)

91

How much more common is glaucoma in people with diabetes vs people without diabetes?

Glaucoma is twice as common in people with diabetes

92

How could you check for maculopathy?

Optical coherence tomography

93

Treatment for maculopathy? (/retinopathy)

Laser
Vitrectomy
Anti-VGEF injection

94

Causes of erectile dysfunction

Diabetes
Chronic renal failure
Hepatic failure
Multiple Sclerosis
Severe depression
Other (vascular disease, low HDL, high cholesterol, hormonal deficiency)
Other risk factors:
Spinal cord injuries
Pelvic and urogenital surgery and radiation
Substance abuse
Alcohol: >600ml/wk
Smoking amplifies other risk factors
Medications may be responsible for ~25% of cases of ED
Bicycle riding

95

Medications which can cause erectile dysfunction

Anti-hypertensive drugs
All capable
Common: thiazides and beta blockers
Uncommon: calcium channel blockers, alpha-adrenergic blockers, and ACE inhibitors
CNS drugs:
Antidepressants, tricyclics, SSRIs
Tranquilizers
Sedatives
Analgesics

96

Contraindications for PDE inhibitor treatment (for erectile dysfunction)

nitrates/ nicorandil medication
Recent stroke/Myocardial infarction within 3 months.
Hypotension (BP less than 90/50mmHg).
Severe hepatic dysfunction.
Hereditary degenerative retinal disorders.
Concomitant treatment for ED (except counselling).

97

PDE inhibitors used to treat erectile dysfunction

Sildenafil
Tadalafil
Vardenafil

98

Sildenafil
Taladafil
Vardenafil are PDE inhibitors, what could they be used for?

Treatment of erectile dysfunction

99

Which organ filters out lactate?

Liver