diabetes Flashcards
Metformin
MOA:
Inhibits liver gluconeogenesis
- inhibiting mitochondrial glycerophosphate dehydrogenase, thereby preventing glycerol from contributing to gluconeogenesis
- inhibition of mGPD leads to accumulation of NADH in cytosol which inhibits conversion of lactate to pyruvate
Also has antilipolytic effect, decreasing substrate availability for gluconeogenesis.
- by activating AMP-activated protein kinase in hepatocytes
Increases insulin mediated glucose utilisation, particularly after meals.
SE:
- GI distress (metallic taste, nausea, vom, diarrhea, anorexia)
- Vitamin B12 deficiency
- Lactic acidosis (rare)
Acarbose
MOA
- inhibits alpha glucosidase on brush border of small intestine
- decreases formation of absorbable carbohydrate
- decreases post prandial glucose load and thereby need for insulin
SE: -GI distress -flatulence -diarrhoea hepatotoxicity
Thiazelidediones
Glitazone (Pio and Rosi)
MOA:
- bind to nuclear PPARs involved in transcription of insulin responsive genes
- increases sensitisation of insulin receptors
- inhibits gluconeogenesis
SE:
- allegies
- potentiates effect of alcohol
- hypglycaemia
- weight gain
- oedema
GLP-1
Exenatide
MOA:
- Binds to GLP-1 receptor on Beta islet cell and potentiates action of insulin, reducing blood glucose post prandially.
- Also slows gastric emptying and may decrease appetite and thus achieves weight loss
Side effects:
- nausea, vom, diarrhoea
- hypoglycaemia
- should not be used in severe kidney disease
DPP4
Sitagliptin
MOA:
inhibits dipeptidyl peptidase, thereby inhibiting inactivation of GLP-1
SE:
- headache
- nasopharyngitis
- URTI
- dose reduce kidney disease
SGLT2 inhibitor
empagliflozin, dapagliflozin
MOA
- SGLT-2 in proximal tubule resorbs 90% of filtered glucose load
- by blocking SGLT-2, empagliflozin increases urine excretion of glucose and lowers blood glucose
- also decrease cardiovascular morbidity and mortality
- also causes weight loss
SE:
- UTIs
- osmotic diuresis and hypotension
- increased risk of fractures
- caution in kidney dysfunction and drugs affecting kidney function
- euglycaemic DKA
Sulfonylureas
MOA
- bind to ATP-sensitive K channel on beta cell
- > block K efflux
- > depolisation -> voltage gated calcium entry
- > insulin release
- increases insulin responsiveness to stimuli
SE
- hypoglycaemia
- hypersensitivity
- dose reduce kidney disease
- nausea, rash
- transaminitis
Pharm strategy type 1 diabetes
Basal bolus:
basal
- subcut
- same time
- before bed time or breakfast and bed time
- 40% of insulin total
- long acting (eg. glargine) preferred to intermediate
- > onset = 1-6
- > no peak
- > 24-36 hour duration
bolus
- subcut
- 60% of insulin load
- rapid acting (eg. lispro) = 15 mins before meals
- short acting (eg. actrapid) = 30 mins before meals
- rapid prefered
- dosing adjusted by insulin:carbohydrate
- > determined by dietician
- > varies by individual and within individual
Supplemental
- determined by insulin sensitivity factor (drop in blood glucose per unit insulin
- > calculated by 100/total insulin load
Type 2 diabetes pharm
first line = lifestyle
add metformin
if no control, add -sulfonylurea -DPP4 -SGLT2 (SGLT2 or GLP1 if cardiovascular disease)
continue till three drugs
second line
- acarbose
- GLP1
- thiazelidedione
non pharm diabetes
Goals:
- Reducing HbA1c improves microvascular outcomes with no threshold effect, though returns are diminishing below 7%.
- Glycaemic control does not improve macrovascular outcomes.
- Addressing cardiovascular risk factors, blood pressure (!), weight loss/maintenance, smoking cessation, exercise, lipid levels, all improve macrovascular outcome.
Education
- comprehensive diabetes self-management education program
- including instruction on nutrition, physical activity, optomising metabolic control and preventing complications
- diabetes edu vs usual care has reduction in HbA1c
Nutrition
- should be referred to dietician.
- emphasis is on weight reduction, consistency in day-to-day carbohydrate intake and balanced nutritional intake
- avoid sugary beverages
- avoid artificial sweeteners (liver triglyceride synthesis, decrease insulin sensitivity, impairs satiety)
Weight loss or maintenance
- realistic goals
- improves insulin sensitivity and secretion
Exercise
- 30-60 mins a day, moderate to high intensity, aerobic and resistance
- improves insulin sensitivity
- improves outcome regardless of weight loss
Psychological
- psychotherapy to address diabetes distress association with many self care responsibilities and blood glucose monitoring
- is associated with small decrease in HbA1c
Intensive intervention
- significantly increases rate of diabetes remission, which is sustained overtime
- doesn’t improve macrovascular complications
- is associated with reduction in other complications such as urinary incontinence, sexual functioning, quality of life, depression
diabetes targets
Individualise targets and avoid hypoglycaemia
HbA1c:
- general = <7%
- short duration without medication = <6%
- with complications = 8%
Blood glucose:
- fasting = 4-8mmol/L
- post prandial = <10mmol/L
diabetes monitoring
Glycaemic control usually assessed by HbA1c.
Ketone monitoring is usually unnecessary, save SGLT-2 inhibitors when sick.
Blood glucose self monitoring (with a glucose strip and blood glucose monitor)
- used when treated with insulin or sulfonylureas.
- can be used in absence of these medications to educate about effect of dietary intake and exercise, to assist with reinforcement and motivation, when sick or pre-surgery, when taking drugs (eg. corticosteroids) or with major lifestyle changes
Continuous glucose monitoring can be used in patients using insulin.
Ongoing review of monitoring and screening for complications:
every 3-4 months
- HbA1c
- SMBG results
- hyperglycaemia symptoms
- hypoglycaemic episodes
- dietary intake
- exercise
- weight
- blood pressure
- foot exam
- injection sites
- diabetes distress
every 12 months
- vitamin B12 (if on metformin)
- peripheral neuropathy
- retinopathy (may be 2 years)
- lipid levels
- kidney function
- smoking
insulin
bolus short acting
- formulation
- > 100units/mL regular human = actrapid
- onset
- > 30mins
- peak
- > 4hrs
- duration
- > 7
bolus rapid acting
- formulations
- > aspart 100units/mL = novorapid
- > lispro 100 or 200 units/mL = humalog
- onset
- > 15mins
- peaks
- > 1.5hrs
- duration
- > 4hrs
bolus intermediate acting
- formulation
- > isophane 100units/mL = humulin
- onset
- > 2hrs
- peak
- > 6hrs
- duration
- > 18hrs
basal long acting
- formulation
- > glargine 100units/mL = lantus
- onset
- > 1.5hrs
- peak
- > nil
- duration
- > 24hrs
