Drugs Flashcards
What is type 2 diabetes characterised by?
Characterised by increased insulin resistance of peripheral tissue
Impaired insulin release by beta cells in the pancreas
Decrease in number of or efficient insulin receptors
Key symptoms of type 2 diabetes
Polyuria
Polydipsia
Fatigue
Weight loss
Which organ do each of the diabetes drug target?
Pancreas (insulin release)
Sulfonlyureas
Insulin secretagogues
DPP-4 inhibitors (gliptins)
GLP-1 agonists
Muscle (increase glucose uptake) &
Liver (reduce glucose production)
metformin
pioglitazone
Pancreas (decrease glucagon release)
DPP-4 inhibitors (gliptins)
GLP-1 agonists
Kidney (reduce glucose absorption)
SGLT-2 inhibitors
Metformin Type 2 diabetes
Metformin is still generally considered the gold standard for type 2 diabetes
It has no direct effect on the pancreas
Works by
• reducing hepatic glucose production
• inhibiting intestinal absorption of glucose
• increasing glucose utilisation by enhancing the action of insulin at peripheral receptors • increasing glucose uptake by muscles
Needs to be taken with meals
Metformin advantages and disadvantages and other considerations
Advantages:
• No weight gain
• Has cardiovascular-protective effects
• Reduces risk of MI and death
• Does not usually cause hypoglycaemia
• Cost-effective & long-term evidence
Disadvantages:
Starting dose is 500mg daily & needs to be titrated up gradually over a period of weeks
Dose is often limited by gastrointestinal side effects
Care if eGFR < 45, avoid if <30 ml/ min/ 1.72m
Risk of lactic acidosis (avoid in renal impairment, shock, severe infection, acute, MI, heart failure, resp failure)
Other considerations:
Withhold if administering contrast dye
Have to stop metformin for quite a lot of things ie surgery
Metformin cautions and contra indications
• Elective surgery involving anaesthesia- Should be stopped 48 hours prior, and restarted 48 hours after surgery.
ØRisk factors for lactic acidosis
Ø Caution in chronic stable heart failure (monitor cardiac function)
• concomitant use of drugs that can acutely impair renal function
• avoid in conditions that can acutely worsen renal function, or cause tissue hypoxia.
• Monitor renal function- once a year in normal people ,twice a year in people with risk factors for renal function deteriorations.
Sulfonylureas
• Examples
• Short acting: gliclazide (eg high blood sugar caused by steroids)
• Long acting: glimepiride, glibenclamide
• Work by:
• stimulating insulin secretion by acting directly on pancreatic beta cells
• increasing tissue sensitivity to insulin
• requires residual beta cell function
• Place in therapy
• first line for patients who are not overweight or in whom metformin is contra-indicated or where a rapid response to therapy is required because of hyperglycaemic symptoms
Sulfonylureas side effects and contra indications
Side effects
Weight gain
Generally well tolerated, however can cause GI disturbances.
Liver function impairment
Increased risk of hypoglycaemia
Contraindications:
Severe renal/hepatic impairment
Sulfonylureas advantages and disadvantages
Eg gliclazide
Advantages
• Choice of agents on the market
• Cost effective & long-term data
• Better than metformin at bringing blood sugars down initially especially of the patient is symptomatic (brings blood sugar down rapidly)
Disadvantages
• Risk of hypoglycaemia (advice patient, driving considerations)
• Care in the elderly, renal & hepatic impairment
• Can cause weight gain
Driving advice for diabetics
Tell the DVLA
• on insulin or
• on oral agents and have had 2 episodes of severe hypos in 12 months where you have required someone else to treat you,
• or you have had a disabling hypo whilst driving,
• or are unable to recognise a hypo when it starts.
Examples of DPP- 4 inhibitors (gliptins)
linagliptin, saxagliptin, sitagliptin, vildagliptin, alogliptan
• linagliptin is the only renal friendly gliptin and is licensed for monotherapy
Action of DPP- 4 inhibitors (gliptins)
Work by:
• inhibiting dipeptidylpeptidase-4 which acts on the GLP1 pathway to increase insulin secretion & lower glucagon secretion
DPP- 4 inhibitors advantages and disadvantages
Advantages
• Low risk of causing hypoglycaemia
• Weight neutral
Disadvantages
• Expensive & lack of long-term data
• MHRA reports of pancreatitis & liver toxicity (stop drug if abdo pain occurs)
• Hypersensitivity reactions reported (SJS)
• Dose adjustments in renal impairment
• except linagliptin (excreted in bile)
Side effects:
Sneezing and headaches
GLP-1 Agonists examples
exenatide, liraglutide, lixisenatide,semaglutide
Subcutaneous injection (looks like insulin pen)
GLP-1 agonists
Binds to and activates the GLP- 1 receptor
GLP-1 receptor
• Increase insulin secretion
• Decreases glucagon secretion
• Slow gastric emptying
GLP-1 AGONISTS advantages and disadvantages
Advantages
• promotes some weight loss
• minimal hypoglycaemia
• good option for certain occupations (e.g. HGV drivers) as don’t need to stop driving
Disadvantages
• subcutaneous administration
• store in fridge (can be kept at room temp once in use)
• administer one hour before food (exenatide & lixisenaditide)
• nausea and vomiting
• pancreatitis
• caution in renal impairment
GLP-1 agonists place in therapy line
• Place in therapy
• 3rd line
• Combination therapy (with metformin and/or sulphonylurea)
• Combination with insulin upon specialist advice
• NICE:
• BMI ≥ 35 if European (or > 30 in other ethnic groups) and has weight related medical problems
• BMI < 35 but are not able to take insulin (i.e., for occupational reasons) or have co- morbidities that would benefit from weight loss
• Only continue if HbA1c concentration is reduced by 1% and weight loss of at least 3% is achieved within 6 months
THIAZOLIDINEDIONES “GLITAZONES”
Examples
Action
Side effects
Contraindications
• Pioglitazone
• Agonist of a receptor called PPAR-gamma which enhances
the action of insulin on liver, fat and skeletal muscle by:
• increasing glucose uptake into muscle cells
• reducing insulin resistance
• decreasing hepatic glucose production
Side effects:
• Fluid retention
• Weight gain
• ↑ risk of fractures
Contraindications:
• Heart failure
• Active bladder cancer
• Hepatic impairment
THIAZOLIDINEDIONES “GLITAZONES” advantages and disadvantages
Advantages
• a third line option if a patient has not tolerated or had a poor response to the DPP-4 inhibitors
• low hypoglycaemia risk
Disadvantages
• fluid retention therefore weight gain and contra-indicated in heart failure
• slow onset of action
• fracture risk
• bladder cancer risk
• liver toxicity - monitor LFTs
THIAZOLIDINEDIONES place in therapy line
• Pioglitazone should only be continued if HbA1c concentration is reduced by 0.5 percentage points within 6 months of starting treatment
• Place in therapy:
• 2nd or 3rd line
• may be useful if hypos a concern (e.g. driving, falls, occupational hazards)
• combination therapy (with metformin and/or sulphonylurea)
SLT-2 inhibitors “flozins”
Examples
Action
Example: dapagliflozin, canagliflozin, empagliflozin
Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2)
• reduces glucose re-absorption
• increases urinary glucose excretion
Licensed as monotherapy but NICE suggest dual therapy
• Dapagliflozin can be used as dual therapy or as add on to insulin but not for triple oral therapy
• Canagliflozin can be used as dual/triple therapy and as add on with insulin
SGLT-2 INHIBITORS advantages and disadvantages
Advantages
• Promotes weight loss
Disadvantages
• Need good renal function
• Withhold in AKI/GI illness
• Risk of UTIs and candidiasis due to osmotic diuretic seeing out glucose
Insulin in type 2 diabetics
Advantages
Disadvantages
Other considerations
Advantages
• established effective drug
Disadvantages
• hypoglycaemia
• weight gain
• subcutaneous dosing
Other considerations
• may be suitable for patients in whom HbA1c is particularly high and/or are on maximum oral hypoglycaemic therapy
• patient suitability for insulin
What diabetes treatment should be given to a patient recently diagnosed however has GI upset?
Modified release metformin
