Pharmacology: Antidiabetic Drugs Flashcards
Why should SGLT2 inhibitors be used with caution in patients on other diuretics or with low blood pressure?
Diuretic effect
Name the indications for DPP4 inhibitors
Most effective in the early stages of type 2 diabetes, when insulin secretion is relatively preserved
Can be used as a monotherapy when metformin not tolerated/contraindiated, or as an addon
Describe the cardiac benefit of SGLT2 inhibitors
Glucose reduction → decreased insulin and increased glucagon → increase in lipolysis → increase in FFA which also increases ketone body production
FFA and ketones are a fuel to cardiac myocytes
Name the indications for thiazolidinediones
Follow on to metformin where cost is a major issue
Particularly potent in obese women
Generally avoided in patients 65+ due to side effects
Why do sulphonylureas cause weight gain?
Insulin concentrations increased, insulin is anabolic and stimulates appetite
How are SGLT2 inhibitors beneficial in terms of gout and CVD?
Urate excretion increased so plasma urate concentration reduced
Name the anti diabetic drugs which have cardiovascular benefit
Metformin, TZDs, GLP-1 receptor antagonists, SGLT2i
What is the mechanism of action of SGLT2 inhibitors?
Specific inhibitors of renal sodium glucose transporter 2
Lower the renal threshold for glucose, which increases urinary glucose excretion
Removes glucose and calories from circulation - lowers blood glucose and facilitates weight loss
What is a basal-bolus insulin regimen?
Long-acting insulin 1-2 times a day and short-acting insulin before each meal
Why are short-acting analogue insulins preferred over short-acting soluble insulins?
Short-acting analogue insulins disappear from circulation more rapidly compaired to soluble insulin which tends to persist after meals, predisposing to hypoglycaemia
What is metformin associated lactic acidosis (MALA)?
Metformin increases lactate production which is normally cleared by the liver and the kidneys
In acute kidney injury (often in the context of sepsis), metformin is associated with greater risk of lactic acidosis
Give an example of a sulphonylurea
Gliclazide
Name two examples of GLP-1 antagonists
Liraglutide, semaglutide
Describe the action of analogue basal insulins
Have a longer duration of action with less peak activity, may be given once or twice a day
Name the side effects of SGLT2 inhibitors
Genital candiasis
Fournier gangrene
Hypovolaemia and hypotension
Dehydration
DKA
Slight increase in LDL and HDL cholesterol
How do SGLT2 inhibitors increase ketosis and risk of ketoacidosis?
Increase in FFA increases ketone body production
Name the factors which increase risk of hypoglycaemia in patients prescribed insulin
Increased age, diabetes duration, impaired renal function, lower HbA1c
In which patient group is the risk of fractures due to thiazolidinediones doubled?
Elderly patients
Name two side effects of insulin
Weight gain, risk of hypoglycaemia
Which type of insulin is intermediate to long acting with a peak action around 4-6 hours?
Isophane ‘basal’ insulins, e.g. Insulatart, Humulin
How can thiazolidinediones precipitate heart failure?
Fluid retention
What is the mechanism of action of thiazolidinediones?
Increase insulin sensitivity by interaction with PPAR-𝛾
Main effect is on adipocytes and the mechanism involves increasing fat mass in subcutanous depots promoting ‘lipid steal’ - fat removed from liver and muscle which increases adiponectin
How do SGLT2 inhibitors cause genital candiasis?
Secondary to glycosuria
How do SGLT2 inhibitors cause hypovolaemia and hypotension?
Due to diuretic effect
Name the indications for GLP-1 receptor antagonists
Diabetic patients with atherosclerotic CVD (e.g. previous MI) should be given metformin + GLP-1 receptor antagonist Diabetic patients with heart failure or chronic kidney disease where SGLT2i are contraindicated/not tolerated should be given metformin + GLP-1 receptor antagonist Valuable in diabetic patients who need to loose weight
Name the side effects of thiazolidinediones
Weight gain, fracture risk, mild anaemia
Name the indications for SGLT2i
Diabetic patients with heart failure or chronic kidney disease should be given metformin + an SGLT2i as first line
Valuable in diabetic patients who need to loose weight
Name 3 short-acting insulin analogues
Insulin aspart (NovoRapid), lispro (Humalog) and glulisine (Apidra)
Name the only avaliable biguanide
Metformin
Name two examples of DDP4 inhibitors
Sitagliptin, alogliptin
Name two examples of SGLT2 inhibitors
Empagliflozin, dapagluflozin
What is the mechanism of action of sulphonylureas?
Bind to the sulphonylurea receptor on the β-cell membrane, which closes ATP-sensitive K+ channels and promotes calcium influx which stimulates insulin release
Why do sulphonylureas cause hypoglycaemia?
SUs are glucose independent and act via the triggering pathway, which means insulin release will occur whatever the blood glucose level of the patient is
Why should SGLT2 inhibitors be omitted in prolonged fasting or acute illness?
Hypovolaema and DKA risks
Name the side effects of GLP-1 receptor antagonists
GI - nausea, vomiting, bloating, diarrhoea
Small increase in incidence of gallstones
Name the side effects of sulphonylureas
Weight gain, hypoglycaemia
Name the side effects of DDP4 inhibitors
Nausea, increased risk of acute pancreatitis, may increase risk of HF
Give two examples of intermediate insulin
Insulatart, Humulin
Why is metformin contraindicated in renal impairment, cardiac failure and hepatic failure?
Due to the risk of lactic acidosis
Why do GLP-1 receptor antagonists and DDP4 inhibitors come with no risk of hypoglycaemia?
Incretin drugs act via the amplifying pathway - glucose-dependent mechanism
How do thiazolidinediones increase fracture risk?
Fat accumulation in bone marrow and reduction in bone density
Why will patients with reduced eGFR will see little benefit if prescribed SGLT2 inhibitors in terms of glucose lowering?
Relies on renal glucose function
How do SGLT2 inhibitors benefit diabetic patients with chronic kidney disease?
Increased Na+ delivery to DCT causes increased Na+ uptake by Na/K/Cl transporter at macula densa → increase in adenosine secretion → reduction in renal afferent vasodilation → renal protection
What are the two methods of insulin administration?
Intermittent SC injection and continuous subcutaneous insulin infusion pump
Name the indications for metformin
First line in all patients with type 2 diabetes
Name the side effects of metformin
GI - anorexia, nausea, abdominal discomfort and diarrhoea
Metformin associated lactic acidosis (MALA)
What is the mechanism of action of GLP-1 receptor antagonists?
Enhance the incretin effect by activating the GLP-1 receptors They are modified to avoid breakdown by DPP4
How do SGLT2 inhibitors benefit diabetic patients with heart failure?
Na+ reabsorption reduced and glucose loss results in osmotic diuresis → mild diuretic action
Why are SGLT2 inhibitors valuable in patients who want to loose weight?
Increases urinary glucose excretion so removes calories from circulation
What is the mechanism of action of DDP4 inhibitors?
Inhibit DPP4 , which usually inactivate GLP-1 (incretin effect)
This in turn increases insulin secretion and reduces glucagon secretion
Name the only currently avaliable thiazolidinedion (TZD)
Pioglitazone
Name the indications for sulphonylureas
Alternative first line treatment of type 2 diabetes where cost is a major issue (developing countries, private healthcare if no insurance)
Why are GLP-1 receptor antagonists especially useful in diabetic patients who want to loose weight?
Act in the hypothalamus to reduce appetite and intestines to reduce gastric empyting
What is the mechanism of action of metformin?
Unclear but may involve the activation of AMP kinase, which regulates cellular energy metabolism
It reduces gluconeogenesis, and increaes gut glucose utilisation and metabolism
Give two examples of analogue basal insulins
Lantus (glargine), levemir (dertermir)
How do thiazolidinediones cause weight gain?
Increase in fat mass and fluid retention
Why should patients rotate their insulin injection site?
To avoid lipohypertrophy
