Lipid lowerers and hypoglycaemics

Question 1

Statins- half life?

Answer 1

Simvastatin = short, 1-4hr give at night
Atorvastatin = long, 20hrs, give any time!

Question 2

Statins- ADRs?

Answer 2

GI disturbance, increased AST/ALT, arthralgia, myopathy

Question 3

Statins-DDIs?

Answer 3

CYP inhibitors- increase chance of myopathy
CYP inducers- decrease efficacy
OATP2 inhibitors- decrease efficacy AND increase plasma levels (increase toxic effects!) e.g. Gemfibrizil (fibrate)

Question 4

Statins- monitoring?

Answer 4

Baseline LFTs

Question 5

Statins- when to give?

Answer 5

Low dose- Primary prevention of CVD if more than 10% risk (QRISK2 score) or have diabetes
High dose- patients with established CVD

Question 6

Cholesterol absorption inhibitors e.g. Ezetimibe

Answer 6

Block NPC1L1 transport protein-> decrease cholesterol absorption from GI tract, undergoes enterohepatic circulation, use instead of/with statin, in combination has less ADRs and is more effective

Question 7

Fibrates- mechanism?

Answer 7

Increase production of lipoprotein lipase (PPAR-a agonist) reduces TAGs, treat hypertriglyceraemia

Question 8

Biguanides e.g. Metformin- mechanism?

Answer 8

• increase insulin sensitivity
• increase glucose uptake by cells
• decrease gluconeogenesis

Question 9

Metformin- ADRs?

Answer 9

GI disturbance, lactic acidosis, B12 deficiency,

Question 10

Metformin- contraindications?

Answer 10

Don’t give if heart failure, resp disease or CKD (GFR

Question 11

Sulphonylureas e.g. Tolbutamide - mechanism?

Answer 11

Block K+/ATP transporter on beta cell -> increase K+ in cell -> depolarisation -> Ca2+ entry -> insulin vesicles released!

Question 12

Sulphonylureas- PKs?

Answer 12

HEAVILY protein bound!

Varying half lives- some short (tolbutamide), some long (glipizide)

Question 13

Sulphonylureas- ADRs?

Answer 13

GI disturbance, weight gain, hypoglycaemia

Question 14

TZDs e.g. Pioglitazone - mechanism?

Answer 14

PPAR-y agonists, decrease gluconeogenesis and increase glucose uptake

Question 15

TZDs e.g. Pioglitazone - PKs?

Answer 15

Heavily protein bound

Question 16

TZDs e.g. Pioglitazone - ADRs?

Answer 16

LOTS! Weight gain, heart failure, osteoporosis, bladder cancer!

Question 17

Gliptins- mechanism?

Answer 17

Inhibit DPP4 thus inhibit incretin (GLP-1) breakdown -> increased insulin secretion, decreased gluconeogenesis, decrease appetite, increased glucose uptake!

Question 18

Why are gliptins good?

Answer 18

Don’t cause weight gain or hypoglycaemia :)

Question 19

Statins- mechanism of action?

Answer 19

Inhibit HMG-CoA reductase -> reduced LDL synthesis and increased LDL receptor synthesis -> decreased LDLs!

Question 20

Nicotinic acid- mechanism?

Answer 20

Inhibit lipoprotein a production -> decrease vLDLs and increase HDLs -> decrease coronary risk

Question 21

Nicotinic acid ADRs

Answer 21

Flushing, headache, hepatotoxicity, GI disturbance

Question 22

Megaglitinides- mechanism?

Answer 22

Same as sulphonylureas!

Question 23

Megaglitinides ADRs compared with sulphonylureas?

Answer 23

Lower risk of hypoglycaemia than sulphonylureas, no weight gain :)

Question 24

Alpha glucosidase inhibitors- mechanism?

Answer 24

Delay carbohydrate absorption from GI tract

Question 25

Alpha glucosidase inhibitors ADRs?

Answer 25

Flatulance, diarrhoea, abdo pain

Question 26

Orlistat- mechanism and ADRs

Answer 26

Inhibits pancreatic and gastric lipase -> decreased conversion of lipids to fatty acids and glycerol BUT ADRs are fatty soft stools, farting and faecal incontinence!