Diabetes/Lipid Disorders Flashcards
How do biguanides work?
Inhibit hepatic gluconeogenesis by increasing AMPK activity
Give an example of a biguanide
Metformin
What are the advantages and disadvantaged of metformin?
ADV: Weight loss, low cost, long track record
DISADV: GI side effects
In which cases can metformin cause lactic acidosis?
- Renal impairment
- Heart failure
- Liver disease
How is metformin administered?
Give with meals 2/3x a day
How do sulphonylureas work?
Increase insulin secretion by binding to and depolarising beta cell
Give an example of a sulphonylurea
Gliclazide
Glimepiride
What are the advantages and disadvantages of sulphonylureas?
ADV: low cost, long track record
DISADV: weight gain, risk of hypoglycaemia
How are sulphonylureas administered?
Give with meals 2/3x a day
How do thiazolidinodiones work?
Enhance lipogenesis and decrease lipolysis by altering gene transcription
Give an example of a thiazo
Pioglitazone
What are the advantages and disadvantages of thiazos?
ADV: ‘insulin sensitizers’ - improve beta cell function
DISADV: weight gain!!!!!!! fluid retention, fracture risk
How do SGLT2 inhibitors work?
Prevent renal glucose reabsorption by inhibiting SGLT2 in proximal tubule
Give an example of an SGLT2 inhibitor
Gliflozin
What are the advantages and disadvantages of gliflozin?
ADV: weight loss, reduced risk of diabetic nephropathy
DISADV: UTI (from glucose), costly
How do DDP-IV inhibitors work?
Inhibition of enzyme that breaks down GLP-1 (an incretin)
Give an example of a DDP-IV inhibitor
-gliptin
What are the advantages and disadvantages of DDPIV inhibitors?
ADV: oral, use in renal disease
DISADV: uncertain long term effects, costly
How do GLP-1 mimetics work?
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
Give an example of a GLP-1 mimetic
Exenatide
What are the advantages and disadvantages of GLP-1 mimetics?
ADV: weight loss, no hypos
DISADV: SC injection, GI, costly
What are the 3 insulin regimens?
- Mealtime - rapid acting
- Basal-bolus - rapid acting at meals + one long acting
- Mixed
Name 2 rapid acting insulins
Humalog, Novorapid
Name 2 long acting insulins
Glargine, Detenir
How does an insulin pump work? (CSII)
Gives a constant infusion of rapid-acting insulin analogue at basal rate with meal time boluses
What is the main risk of insulin pumps?
Increased risk of DKA
Why do diabetic patients often take lipid lowering drugs?
Increased risk of CVD - especially effective in people over 40
How do statins work?
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.
Give an example of a statin
Atorvastatin
Simvastatin
What are the side effects of statins?
- Hepatic injury (monitor LFTs)
- Myalgia/myositis (monitor CK)
- Peripheral neuropathy
Which drugs do statins interact with?
- Antibiotics (replace statins with fibrates when on abx)
- Antihypertensives (CCBs)
- Grapefruit
These are all CYP3A4 inhibitors so cause increased levels of statin
How do fibrates work?
Activate PPARa receptors to facilitate lipid metabolism
Much less effective than statins
What are the side effects of fibrates?
Same as statins
How does ezelimibe work, and when is it indicated?
Inhibits NPC1L1 to reduce cholesterol production, used in secondary prevention in combo with statins
How do PCSK9 inhibitors work?
Monoclonal IgG abs promote intracellular degradation of LDL
What is the therapeutic algorithm for diabetes? treatment
- Conservative
- Metformin
- Sulphonylurea
- Others
- Insulin
What drug could give you a CK in the 1000s?
Statins - due to myositis (5% of pts on statin have a raised CK)
How is diabetes diagnosed in a symptomatic patient?
Fasting glucose >7
Random glucose>11
Only one reading required
How is diabetes diagnosed in an asymptomatic patient?
Fasting glucose>7
Random glucose>11
Two readings required
