Diabetes mellitus Flashcards
1
Q
Metformin
Common indications
A
- Type 2 diabetes mellitus- first-line medication for control of blood glucose, used alone or in combination with other oral hypoglycaemic drugs (e.g. sulphonylureas) or insulin
2
Q
Metformin
MOA
A
- Metformin (biguanide) lowers blood glucose by increasing the response (sensitivity) to insulin.
- It suppresses hepatic glucose production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilisation by skeletal muscle and suppresses intestinal glucose absorption
- It achieves this by diverse intracellular mechanisms, which are incompletely understood
- It does not stimulate pancreatic insulin secretion and therefore does not cause hypoglycaemia
- It reduces weight gain and can induce weight loss, which can prevent worsening of insulin resistance and slow deterioration of diabetes melitus
3
Q
Metformin
Adverse effects
A
- GI upset- N&V, taste disturbance, anorexia and diarrhoea
- This adverse effect may contribute to weight loss in patients taking metformin
- Lactic acidosis is a rare adverse effect associated with metformin use, which can be fatal if untreated
- It does not occur in stable patients, but can be precipitated by intercurrent illness that causes metformin accumulation (e.g. worsening renal impairment), increased lactate production (sepsis, hypoxia and cardiac failure) or reduced lactate metabolism (liver failure)
4
Q
Metformin
Warnings
A
- Severe renal impairment- contraindicated
- Moderate renal impairment- dose reduction required
- Withhold where there is AKI- sepsis, shock, dehydration
- Severe tissue hypoxia- cardiac or respiratory failure or MI
- Caution in hepatic failure- reduced clearance of lactate
- Acute alcohol intoxication- when it may precipitate lactic acidosis
- Chronic alcohol overuse
5
Q
Metformin
Interactions
A
- Metformin must be withheld before and 48 hours after injection of IV contrast media (CT scan, coronary angiogram)
- Drugs which impair renal function- ACEI, NSAIDs, diuretics)
- Prednisolone, loop diuretic, thiazide- they increase Blood glucose
6
Q
Metformin
Communication
A
- Take tablet with a whole glass of water with or after food
- Tablets are not a replacement for lifestyle measures (diet and exercise)
- Urgent medical attention- If they get vomiting, stomach ache, muscle cramps, SOB, severe tiredness- symptoms of lactic acidosis
- Tell doctors before surgery or X-ray may need to be stopped
7
Q
Metformin
Monitoring
A
- Assess blood glucose control by measuring glycated Haemoglobin (HbA1C)- the target should be <58mmol/mol)
- BG monitoring is not routinely required
- For safety, measure renal function before starting treatment, then at least annually
- Renal function should be measured more frequently (at least twice per year) in people with deteriorating renal function or at increased risk of renal impairment
8
Q
Insulins (General)
Common indications
A
- Insulin replacement for T1DM and control of BG in people with T2DM where oral agents are inadequate
- Given IV, in the treatment of diabetic emergencies such as diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome and perioperative glycaemic control is selected, diabetic patients
- Alongside glucose to treat hyperkalaemia while other measures are initiated
9
Q
Insulins (General)
MOA
A
- Functions the same as endogenous insulin
- It stimulates glucose uptake from the circulation into tissues, including skeletal muscle and fat, and increases the use of glucose as an energy source
- Insulin stimulates glycogen, lipid and protein synthesis and inhibits gluconeogenesis and ketogenesis
- For the treatment of hyperkalaemia, insulin drives K+ into cells, reducing Serum K- once insulin is stopped the K goes back into the blood (Short term while other agents are initiated)
- Rapid-acting insulin- insulin aspart- Novorapid
- Short acting- actrapid
- Immediate-acting- isophane insulin (NPH) e.g. Humulin I
- Long-acting- insulin glargine (Lantus)
- Biphasic- novomix (aspart/protamine)
10
Q
Insulins (General)
Adverse effects
A
- Hypoglycaemia- severe enough for coma and death
11
Q
Insulins (General)
Warnings
A
- renal impairment- insulin clearance is reduced, so there is an increased risk of hypoglycaemia
12
Q
Insulins (General)
communication
A
- When starting a patient with diabetes mellitus on insulin, explain that insulin will help to control blood sugar levels and prevent complications
- This is not a replacement for lifestyle changes
- Risk of hypoglycaemia, advising them of symptoms to watch out for (dizziness, agitation, nausea, sweating and confusion)
- Explain that if hypoglycaemia develops, they should take something sugary then something starchy
13
Q
Insulins (General)
Monitoring
A
- HbA1C
14
Q
Sulphonylureas (Gliclazide)
Common indications
A
- T2DM- as a single agent to control blood glucose and reduce complications where metformin is contraindicated or not tolerated
- In combination with metformin where blood glucose is not adequately controlled on a single agent
15
Q
Sulphonylureas (Gliclazide)
MOA
A
- Sulphonylureas lower BG by stimulating pancreatic insulin secretion
- They block ATP-dependent K channels in pancreatic B-cell membranes, causing depolarisation of the cell membrane and opening of voltage-gated Ca channels
- This increases intracellular Ca concentrations, stimulating insulin secretion.
- SU is only effective in patients with residual pancreatic function
- As insulin is an anabolic hormone, stimulation of insulin secretion by SU is associated with weight gain
- Weight gain increases insulin resistance and can worsen diabetes mellitus in the long term
16
Q
Sulphonylureas (Gliclazide)
Adverse effects
A
- GI upset is usually mild and infrequent
- Hypoglycaemia is a potentially serious adverse effect, which is more likely with high treatment doses, where drug metabolism is reduced or where other hypoglycaemic medications are prescribed
- SU-induced hypoglycaemia may last for many hours and if severe, should be managed in hospital
- Rare hypersensitivity reactions: Hepatic toxicity (cholestatic jaundice), Rash, fever, Haematological abnormalities (agranulocytosis)
17
Q
Sulphonylureas (Gliclazide)
Warnings
A
- Half-life 10-12 hours
- Unchanged drug and metabolites are excreted in the urine
- A dose reduction may, therefore, be required in patients with hepatic impairment, and BG should be monitored carefully in patients with renal impairment
- SU should be prescribed with caution for people at increased risk of hypoglycaemia including those with hepatic impairment, adrenal, or pituitary insufficency
18
Q
Sulphonylureas (Gliclazide)
Interactions
A
- Risk of hypoglycaemia is increased by co-prescription of other antidiabetic drugs including metformin
- The efficacy of sulphonylureas is reduced by drugs that elevate BG e.g. prednisolone, thiazide or loop diuretics
19
Q
Sulphonylureas (Gliclazide)
Communications
A
- Not a replacement for lifestyle
- Warn patients about hypoglycaemia, advising them to watch out for symptoms, such as dizziness, nausea, sweating and confusion
- If this develops they should take sugar then something starchy
20
Q
Thiazolidinediones (pioglitazone)
Common indications
A
- T2DM- as a single agent in overweight patients where metformin is contraindicated or not tolerated
- Added as a 2nd agent to metformin or SU where BG control is inadequate on one drug and the metformin/SU combo is contraindicated or not tolerated
- Added as a third agent with metformin and su where BG control is adequate as an alternative to starting insulin
21
Q
Thiazolidinediones (pioglitazone)
MOA
A
- Thiazolidinediones are insulin sensitisers- they lower BG by activating the gamma subclass of nuclear peroxisome proliferator-activated receptors (PPARy)
- This induces genes which enhance insulin action in skeletal muscle, adipose tissue and the liver, with increased peripheral glucose uptake and utilisation and hepatic gluconeogenesis
- Thiazolidinediones do NOT stimulate pancreatic insulin secretion, hence do not cause hypoglycaemia
- However, they CAUSE WEIGHT GAIN, which can increase insulin resistance
22
Q
Thiazolidinediones (pioglitazone)
Adverse effects
A
- GI upset, anaemia
- Neurological effects- headache, dizzieness and disturbed visions
- More serious side effect include oedema and cardiac failure, particularly where pioglitazone prescribed with insulin
- Pioglitazone increased risk of bladder cancer and bone fracture in women
-
Severe liver toxicity
*
23
Q
Thiazolidinediones (pioglitazone)
Warnings
A
- HF, bladder cancer
- Caution in cardiovascular disease
- Careful consideration in elderly patients, who tend to have increased risk of cardiac disease and bone fractures
- extensively metabolised in liver and can cause liver toxicity, so should be used in caution in hepatic impairment
24
Q
Thiazolidinediones (pioglitazone)
Interactions
A
- Other antidiabetic drugs- severe hypoglycaemia
25
Thiazolidinediones (pioglitazone)
Communication
* **lifestyle measures are the same as other**
* **unexpected side effects**
* Nausea, loss of appetite, lethargy, dark urine (liver toxicity), ankle swelling and difficulty breathing (HF), pain, blood passing urine (Bladder cancer)
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Thiazolidinediones (pioglitazone)
Monitoring
* **Glycated Haemoglobin** (HbA1C) before and 3-6 months after commencing treatment
* Treatment should be stopped if there is no fall in HbA1C
* LFT should be measured prior to and during therapy
* If transaminase levels are increased, may need to be discontinued if values are persistently elevated during treatment
27
DPP4-i (sitagliptin)
common indications
* Type 2 diabetes mellitus as monotherapy (if metformin inappropriate), or in combination with other antidiabetic drugs (including insulin) if existing treatment fails to achieve adequate glycaemic control
28
DPP4-i (Sitagliptin)
MOA
* Inhibits Dipeptidylpeptidase enzyme which increases insulin secretion and decreases glucagon secretion
29
DPP4-i (Sitagliptin)
Adverse effects
* Ketoacidosis
* GI dysmotility
* Risk of pancreatitis
* Bowel cancer risk
30
SGLT2 inhibitors (Canagliflozin)
Common indications
* Type 2 diabetes mellitus as monotherapy (if metformin inappropriate)
* Type 2 diabetes mellitus in combination with insulin or other antidiabetic drugs (if existing treatment fails to achieve adequate glycaemic control)
31
SGLT2 inhibitors (Canagliflozin)
MOA
* Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
32
SGLT2 (Canagliflozin)
Adverse effects
* Life-threatening diabetic ketoacidosis- Rapid weight loss, ab pain, sleepiness
* Hypoglycaemia- escpeically if also on insulin
*
33
SGLT2 (Canagliflozin)
Warnings
* Fournier's gangrene
* Fournier’s gangrene, a rare but serious and potentially life-threatening infection, has been associated with the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors. If Fournier's gangrene is suspected, stop the SGLT2 inhibitor and urgently start treatment (including antibiotics and surgical debridement).
* Patients should be advised to seek urgent medical attention if they experience severe pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise—urogenital infection or perineal abscess may precede necrotising fasciitis
* Risk of lower limb amputation
* Stop if patients develop siginificant skin ulcers
* Cardiovascular disease (risk of hypotension); elderly (risk of hypotension); elevated haematocrit; history of hypotension
34
SGLT2 (Canagliflozin)
Monitoring + Communication
* Determine renal function before treatment and at least annually thereafter, and before initiation of concomitant drugs that reduce renal function and periodically thereafter.
* Patients should be advised to report symptoms of volume depletion including postural hypotension and dizziness.
Patients should be informed of the signs and symptoms of diabetic ketoacidosis, see MHRA advice.
35
GLP-1 Antagonist
Common indications
* T2DM
36
GLP-1 Antagonist
MOA
* Semaglutide binds to, and activates, the GLP-1 (glucagon-like peptide-1) receptor to increase insulin secretion, suppress glucagon secretion, and slow gastric emptying
37
GLP-1 Antagonist
Adverse effects
* Pancreatitis
* WEIGHT LOSS- this can aid insulin resistance
*
38
GLP-1 Antagonist
Warnings
* Severe congestive heart failure
* Diabetic ketoacidosis
* Retinopathy
*
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