Diabetes/Lipid Disorders

Question 1

How do biguanides work?

Answer 1

Inhibit hepatic gluconeogenesis by increasing AMPK activity

Question 2

Give an example of a biguanide

Answer 2

Metformin

Question 3

What are the advantages and disadvantaged of metformin?

Answer 3

ADV: Weight loss, low cost, long track record
DISADV: GI side effects

Question 4

In which cases can metformin cause lactic acidosis?

Answer 4

• Renal impairment
• Heart failure
• Liver disease

Question 5

How is metformin administered?

Answer 5

Give with meals 2/3x a day

Question 6

How do sulphonylureas work?

Answer 6

Increase insulin secretion by binding to and depolarising beta cell

Question 7

Give an example of a sulphonylurea

Answer 7

Gliclazide

Glimepiride

Question 8

What are the advantages and disadvantages of sulphonylureas?

Answer 8

ADV: low cost, long track record
DISADV: weight gain, risk of hypoglycaemia

Question 9

How are sulphonylureas administered?

Answer 9

Give with meals 2/3x a day

Question 10

How do thiazolidinodiones work?

Answer 10

Enhance lipogenesis and decrease lipolysis by altering gene transcription

Question 11

Give an example of a thiazo

Answer 11

Pioglitazone

Question 12

What are the advantages and disadvantages of thiazos?

Answer 12

ADV: ‘insulin sensitizers’ - improve beta cell function
DISADV: weight gain!!!!!!! fluid retention, fracture risk

Question 13

How do SGLT2 inhibitors work?

Answer 13

Prevent renal glucose reabsorption by inhibiting SGLT2 in proximal tubule

Question 14

Give an example of an SGLT2 inhibitor

Answer 14

Gliflozin

Question 15

What are the advantages and disadvantages of gliflozin?

Answer 15

ADV: weight loss, reduced risk of diabetic nephropathy
DISADV: UTI (from glucose), costly

Question 16

How do DDP-IV inhibitors work?

Answer 16

Inhibition of enzyme that breaks down GLP-1 (an incretin)

Question 17

Give an example of a DDP-IV inhibitor

Answer 17

-gliptin

Question 18

What are the advantages and disadvantages of DDPIV inhibitors?

Answer 18

ADV: oral, use in renal disease
DISADV: uncertain long term effects, costly

Question 19

How do GLP-1 mimetics work?

Answer 19

More potent synthetic form of endogenous GLP-1 which has the following effects:

• Promotes satiety
• Reduces hepatic glucose output
• Slows rate of gastric emptying
• Enhances insulin secretion
• Suppresses glucagon secretion

Question 20

Give an example of a GLP-1 mimetic

Answer 20

Exenatide

Question 21

What are the advantages and disadvantages of GLP-1 mimetics?

Answer 21

ADV: weight loss, no hypos
DISADV: SC injection, GI, costly

Question 22

What are the 3 insulin regimens?

Answer 22

1. Mealtime - rapid acting
2. Basal-bolus - rapid acting at meals + one long acting
3. Mixed

Question 23

Name 2 rapid acting insulins

Answer 23

Humalog, Novorapid

Question 24

Name 2 long acting insulins

Answer 24

Glargine, Detenir

Question 25

How does an insulin pump work? (CSII)

Answer 25

Gives a constant infusion of rapid-acting insulin analogue at basal rate with meal time boluses

Question 26

What is the main risk of insulin pumps?

Answer 26

Increased risk of DKA

Question 27

Why do diabetic patients often take lipid lowering drugs?

Answer 27

Increased risk of CVD - especially effective in people over 40

Question 28

How do statins work?

Answer 28

Inhibit HMG-CoA reductase, an enzyme involved in cholesterol synthesis. This stimulates upregulation of LDL receptor in the liver so that less LDL is in the bloodstream.

Question 29

Give an example of a statin

Answer 29

Atorvastatin | Simvastatin

Question 30

What are the side effects of statins?

Answer 30

- Hepatic injury (monitor LFTs) - Myalgia/myositis (monitor CK) - Peripheral neuropathy

Question 31

Which drugs do statins interact with?

Answer 31

- Antibiotics (replace statins with fibrates when on abx) - Antihypertensives (CCBs) - Grapefruit These are all CYP3A4 inhibitors so cause increased levels of statin

Question 32

How do fibrates work?

Answer 32

Activate PPARa receptors to facilitate lipid metabolism | Much less effective than statins

Question 33

What are the side effects of fibrates?

Answer 33

Same as statins

Question 34

How does ezelimibe work, and when is it indicated?

Answer 34

Inhibits NPC1L1 to reduce cholesterol production, used in secondary prevention in combo with statins

Question 35

How do PCSK9 inhibitors work?

Answer 35

Monoclonal IgG abs promote intracellular degradation of LDL

Question 36

What is the therapeutic algorithm for diabetes? treatment

Answer 36

1. Conservative 2. Metformin 3. Sulphonylurea 4. Others 5. Insulin

Question 37

What drug could give you a CK in the 1000s?

Answer 37

Statins - due to myositis (5% of pts on statin have a raised CK)

Question 38

How is diabetes diagnosed in a symptomatic patient?

Answer 38

Fasting glucose >7 Random glucose>11 Only one reading required

Question 39

How is diabetes diagnosed in an asymptomatic patient?

Answer 39

Fasting glucose>7 Random glucose>11 Two readings required