Chapter 6: Endocrine system Flashcards
What is the advice from the DVLA regarding insulin dependent diabetic drivers?
- Should always carry a glucose meter and test strips when driving
- check your glucose less than 2 hours before the start of the first journey and every 2 hours after driving has started.
- Blood glucose should always be above 5 mmol/L whilst driving
-Always keep an emergency supply of fast-acting carbohydrate such as glucose tablets or sweets
- If get hypo, stop car, have sugary beverage and then drive after 45mins if BMs in range
- If blood glucose is <4 mmol/L, should NOT drive
- This may also be the case in patients taking oral antidiabetic drugs (sulfonylureas, nateglinide, repaglinide), in particular, those that cause hypoglycaemia
True or false:Alcohol can cause delayed hyperglycaemia
False- can cause delayed HYPOglycaemia
What is a non diabetic HbA1c?
Prediabetic HbA1C
Type 2 diabetes HbA1C
WHO: HbA1c below 42 mmol/mol (6.0%): Non-diabetic
HbA1c between 42 and 47 mmol/mol (6.0–6.4%): Impaired glucose regulation or Prediabetes
HbA1c of 48 mmol/mol (6.5%) or over: Type 2 diabetes
Is HbA1c used for monitoring glycaemic control in Type 1 diabetes, Type 2 diabetes, or both?
HbA1c is used to Monitor glycaemic control in both type 1 and type 2. Diagnose type 2.
Should not be used for diagnosis of Type 1, during pregnancy, women up to 2 months postpartum and children
How often should HbA1c be measured in diabetes?
Monitor type 1 patients every 3-6 months
If type 2 then also 3-6 months however when stable, can be every 6 months
What is the recommended HbA1c target in Type 1 diabetes?
48mmol/mol or lower
How many times a day should blood glucose be measured in Type 1 diabetes?
At least 4 times a day (including before each meal and before bed)
What are the blood glucose aims in Type 1 diabetes for:
a) Waking up / fasting
b) Before meals / random
c) 90 minutes after eating
d) Driving
a) 5-7mmol/L on waking
b) 4-7mmol/L before meals
c) 5-9mmol/L at least 90 mins after eating
d) at least 5mmol/L when driving
What is a basal BOLUS insulin regimen?
Regimen type 1-
rapid acting insulin before meal times Insulin Lispro or Aspart
Basal =long acting (insulin detemir BD or Insulin Glargine OD ) at bedtime
Regimen type 2- soluble insulin +(humulin M3) intermediate acting
Or
Regiment type 3- Rapid insulin + intermediate acting- humalog/ Mix 25/ Novomix 30
What is a mixed (biphasic) insulin regimen?
One, two, or three insulin injections a day before meals, of short-acting insulin (soluble or rapid) mixed with intermediate-acting insulin
What insulin regimen is first choice for Type 1 diabetics?
Basal bolus
1) Insulin detemir (Levemir) BD (has a plataeu effect over 24hrs hence BD) should be offered as the long insulin therapy
2) Insulin glargine (Lantus) OD if dosing issues
3) Insulin detemir (Levemir) OD
In a basal bolus regimen for Type 1 diabetes, what BASAL insulin would be first choice?What would be the second choice?
Insulin determir (Levemir) BD - can also be offered as once daily
Once daily insulin glargine (Lantus)
Are non-basal bolus regimens recommended in newly diagnosed Type 1 diabetics?
No Should only be considered after trying basal bolus regimen
In basal bolus regimen in Type 1 diabetes, what type of insulin is recommended for the bolus aspect?
Rapid acting insulin (LAG - Lispro - Humalog, Aspart - novorapid, Glulisine - apidra) (Rather than soluble human or animal insulin)
Continuous subcut insulin infusion therapy (insulin pump) should only be offered to what group of people?
- adults suffering from disabling hypoglycaemia or high HbA1c of 69 or above with multiple daily injection therapy
What situations can cause an INCREASE in required insulin dose?
Infection- high blood sugar levels
Stress - liver releases more glucose
Accidental or surgical trauma
Pregnancy (2nd /3rd trimester)
What situations can cause an DECREASE in required insulin dose?
Physical activity
Vomiting
Reduced food intake
Impaired renal function
(The kidney is responsible for about 30 to 80 % of insulin removal)
Certain endocrine disorders (Addison’s disease -The adrenal gland is damaged in Addison’s disease, so it does not produce enough cortisol or aldosterone. Steroids cause hyperglycaemia so Addison’s disease does the opposite, hypoglycaemia)
Patients’ awareness of hypoglycaemia should be assessed annually using what score tools?
Gold or Clarke score
What cardiac class of drug can blunt hypoglycaemia awareness?
Beta blockers reduce warning signs such as tremor
Alcohol masks signs of hypo (confusion, hunger, rapid heart beat)
What is an impaired awareness of hypoglcyaemia?
Can occur when the ability to recognise usual symptoms of hypoglycaemia is lost, or when the symptoms are blunted or no longer present
What are the 3 types of insulin sources?
Human insulin- lab made
Human insulin analogues- produced same way as human insulin but modified to be absorbed faster or longer duration
Animal insulin -bovine /porcine
Which area of the body has the fastest absorption rate for insulin?
Abdomen
What can occur if you repeatedly inject insulin into the same area without rotating?
Lipohypertrophy
Can cause erratic absorption of insulin
How much time before meals do you administer short acting soluble insulin?
30 minutes before
What is the most appropriate form of insulin to use in diabetic emergencies e.g. DKA
Soluble insulin IV
Give Na/K 0.9% iv infusion if Bp low
Monitor blood glucose and ketones ever hour
Continue long acting insulin analogues (detemir and glargine) during treatment of DKA
What are the 3 types of rapid acting insulin?
Insulin Glulisine
Insulin Aspart
Insulin Lispro
How much time before meals do you administer rapid acting insulin?
5-15 mins before food
What are the advantages of rapid acting insulin over soluble acting insulin?
Rapid acting insulins (aspart and lispro) are better than soluble acting because there are fewer episodes of Hypo
Is injecting short acting insulins post meals recommended?
No
What type of insulin is isophane?
Intermediate - designed to mimic the effect of endogenous basal insulin
What are biphasic insulins?
Pre-mixed insulin preparations containing various combinations of short-acting insulin (soluble insulin or rapid-acting analogue insulin) and an intermediate-acting insulin.
What are the long acting insulins?
Insulin detemir (levemir) OD/BD
Insulin glargine (Lantas/toujeo/abasaglar) OD
Insulin degludec (Tresiba) OD
Rarely prescribed:
Protamine zinc insulin
Insulin zinc suspension
Does metformin cause hypoglycaemia?
Low risk
If standard release metformin is not tolerated e.g. GI side effects, what should be given?
Modified release metformin
By mouth using modified-release medicines
Initially 500 mg OD, then increased if necessary up to 2 g OD, dose increased gradually, every 10–15 days, dose to be taken with evening meal, alternatively increased to 1 g BD, dose to be taken with meals, alternative dose only to be used if control not achieved with once daily dose regimen.
Give examples of sulfonylureas
Glibenclamide
Gliclazide
Glimeprimide
Glipizide
Tolbutamide
Give examples of meglitinides
Nateglinide
Repaglinide
Drivers need to be particularly careful to avoid hypoglycaemia and should be warned of the problems.
Give examples of DPP-4 inhibitors
Alogliptin
Linagliptin
Sitagliptin
Saxagliptin
Vildagliptin
What is an advantage of DPP-4 inhibitors over sulphonylureas in terms of side effects?
Not associated with weight gain and have less incidence of hypoglycaemia
Give examples of SGLT2 inhibitors
Canaglifozin
Dapaglifozin
Empaglifozin
Give examples of GL P -1 receptor agonists- slow gastric emptying
Dulaglutide
Exenatide
Liraglutide
Lixisenatide
What should be the target HbA1c in a Type 2 diabetic that is managed by lifestyle/ a single antidiabetic agent that is NOT associated with hypoglycaemia?
48 mmol/mol
What should be the target HbA1c in a Type 2 diabetic that is managed with one or more antidiabetic drugs that cause hypoglycaemia?
53 mmol/mol
In terms of HbA1c, when should treatment in a Type 2 diabetic on ONE antidiabetic drug be intensified?
58 mmol/mol or higher
What should be the target HbA1c in a Type 2 diabetic that is managed with 2 or more antidiabetic drugs?
53 mmol/mol
What is first line drug treatment in Type 2 diabetes and why?
Metformin-
No effect on weight
-Reduced risk of hypoglycaemia
-Long term cardiovascular benefits
Which sulphonylurea would you recommend in Elderly patients /Renal impairment
Elderly and Renally impaired are at particular risk of hypoglycaemia
Use Short acting e.g. gliclazide or tolbutamide
If a Type 2 diabetic with no CVD disease, is not adequately controlled on metformin and requires intensification of treatment, what are the add in options?
Option 1) Metformin + dpp 4i /pioglitazone/ sulfonylurea / SGLT2
Option 2) or switch to another drug
Use SGLT2 if patient has CVD risk or disease
Type 2 diabetes:
Dapagliflozin is not recommended in a triple therapy regimen with what drug?
Dapagliflozin + Pioglitazone
Both Dapagliflozin and Pioglitazone can increase the risk of hypoglycaemia.
Type 2 diabetes: If first line therapy is unsuccessful, what are second line options?
Switch or add
Dpp4 inhibitor (gliptin) / pioglitazone / sulfonylurea (gliclazide)
SGLT2 I (dapagliflozin) may also be an option in dual therapy if CVD
When is GLP-1 receptor agonists (exenatide, litaglutide, dulaglutide) preferred in Type 2 diabetes?
If triple therapy with metformin hydrochloride and two other oral drugs is tried and is not effective, or is not tolerated or contra-indicated, a glucagon-like peptide-1 (GLP-1) receptor agonist may be considered as part of a triple therapy regimen by switching one of the other drugs for a GLP-1 receptor agonist.
These should only be considered for patients who have a BMI of 35 kg/m2 or above (adjusted for ethnicity) and who also have specific psychological or medical problems associated with obesity; or for those who have a BMI lower than 35 kg/m2 and for whom insulin therapy would have significant occupational implications or if the weight loss associated with GLP-1 receptor agonists would benefit other significant obesity-related comorbidities.
If started on a GLP-1 receptor agonist for Type 2 diabetes, when should this be reviewed and how do you know it is okay to continue?
After 6 months, the GLP-1 receptor agonist should be reviewed and only continued if there has been a beneficial metabolic response (a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body-weight).
If metformin is contraindicated or not tolerated, what should be used for initial treatment?
If metformin is contra-indicated or not tolerated, SGLT2 inhibitor (canaglifozin) with proven cardiovascular benefit should be offered as first-line treatment for patients who have chronic heart failure or established atherosclerotic cardiovascular disease. An SGLT2 inhibitor should also be considered for patients who are at high risk of developing cardiovascular disease.
For all other patients, consider a dipeptidylpeptidase-4 (DDP-4) inhibitor (gliptin), or pioglitazone, or a sulfonylurea (glipizide) as first-line drug treatment if metformin is contra-indicated or not tolerated. An SGLT2 inhibitor may be considered as an alternative option to a DDP-4 inhibitor, if neither a sulfonylurea or pioglitazone are appropriate.
What is the problem with using repaglinide monotherapy in Type 2 diabetes?
Repaglinide is also an effective alternative option for single therapy, but it has a limited role in treatment because, should an intensification of treatment be required, it is not licensed to be used in any combination other than with metformin hydrochloride; it would therefore require a complete change of treatment in those patients who have started it due to intolerance or contra-indication to metformin.
Which GLP-1 receptor agonist has proven CVD benefit?
liraglutide should be considered in patients with established cardiovascular disease.
🧹🧹🧹If a patient is on dual therapy for Type 2 diabetes, and metformin is contraindicated/not tolerated, what should be considered?
Insulin
In Type 2 diabetes, if insulin therapy is required, what should happen to their other antidiabetic drugs?
Continue
In Type 2 diabetics, what insulin regimens can you use?
- Isophane OD/BD
-Isophane + short acting (either separate or pre-mixed) - particularly appropriate if HbA1c is 75 or higher -Insulin detemir or glargine can be an alternative to isophane
In Type 2 diabetics, at what HbA1c would the following insulin regimen be particularly appropriate:Isophane + short acting insulin (separate or pre-mixed)
75 or higher
In type 2 diabetics requiring insulin therapy, when would long acting insulin (glargine or detemir) be preferable?
If require OD dosing, if recurrent hypo restricting lifestyle, if require BD isophane plus oral antidiabetics
When starting insulin therapy in Type 2 diabetes, when should the first BASAL insulin be given and how do you adjust the dose?
Bedtime basal insulin should be initiated and the dose titrated against fasting glucose in the morning
Providing there are no contraindications, what should you give for diabetic nephropathy that is causing proteinuria or established microalbuminuria?
Blood pressure should be reduced to the lowest achievable level to reduce the glomerular filtration rate. ARB or ACEi to be started even if the blood pressure is normal
What is the potential problem with ACEis in diabetics if the patient is on insulin or oral antidiabetic drugs?
Can potentiate the hypoglycaemic effect
More likely in the first few weeks of combined treatment and in patients with renal impairment
The management of DKA involves what? What should happen to their basal insulin?
What should be monitored and how often?
Replacement of fluid and electrolytes, potassium chloride in the fluids unless anuria (lack of urine production) is suspected
Administration of SOLUBLE Insulin in sodium chloride 0.1 units/kg/hr
Long acting insulin (basal) should be continued in the background
If blood glucose falls below 14, give glucose 10%
Monitor ketones and glucose hourly Monitor BP Blood pH
During DKA treatment when the patient is on an insulin infusion, when should you recommence the short acting subcut insulin and stop the infusion and how is this done?
Continue insulin infusion until patient is able to eat and drink; ideally give s/c fast-acting insulin and a meal, and stop the insulin infusion 1 hour after meal
In the management of HHS, are lower or higher rates of insulin infusion usually required compared to DKA?
Lower rates usually required
During DKA management, what rate should you give the insulin infusion?
0.1 units/kg/hr
Diabetic women who are planning on becoming pregnant should aim to keep their HbA1c to what?
Below 48 if possible without causing any problematic hypoglycaemia
What is the folic acid supplementation recommendation in diabetic patients planning on becoming pregnant?
High dose - 5mg daily as classed in the high risk group of neural tube defects
“”””””What is the treatment recommendation for diabetic patients when they become pregnant? What about during breastfeeding?
All antidiabetic drugs APART from metformin should be stopped and substituted with insulin therapy
For breastfeeding, the options are:- Insulin continued- Metformin continued- Glibenclamide is fine to restart if originally on it
However, all other antidiabetic agents should be avoided during breastfeeding
What is the first choice for long acting insulin therapy during pregnancy?
Isophane insulin
However in women who have good blood-glucose control before pregnancy with the long-acting insulin analogues (insulin detemir or insulin glargine), it may be appropriate to continue using them throughout pregnancy.
What is the patient advice regarding insulin therapy during pregnancy?
Should be aware of the risk of hypoglycaemia and should always carry a fast-acting form of glucose
It is recommended that pregnant women with Type 1 diabetes should be prescribed what just in case of hypoglycaemia?
Glucagon
Women with pre-existing diabetes treated with insulin during pregnancy are at an increased risk of what?
Hypoglycaemia during the postnatal period
Should reduce their insulin immediately after birth and blood glucose levels monitored
If a diabetic patient is on an ACEi or ARB for diabetic complications, however wishes to become pregnant, what would be the most appropriate action?
ACEi or ARB should be discontinued and an alternative antihypertensive suitable in pregnancy should be used(Preferably before conception if pregnancy is planned)
If a diabetic patient becomes pregnant but is on a statin, what would be the most appropriate action?
Discontinue the statin during pregnancy (Preferably before conception if pregnancy is planned)
True or false:A patient with gestational diabetes should continue their hypoglycaemic treatment after birth
False - should discontinue hypoglycaemic treatment immediately after giving birth
How would you manage an insulin dependent diabetic patient with good glycaemic control due for an elective minor procedure?(Day before surgery and during the operative period)
On the day before surgery, give the usual insulin dose
However, once daily long acting insulins should be given at 80% of normal dose
Then their usual insulin regimen can be adjusted accordingly during the operative period
On the day before a minor op in an insulin dependent diabetic with good glycaemic control, you can give their usual insulin dose as normal. With what insulin would you not give the full dose?
Long acting insulin
You give 80% of normal dose
How would you manage an insulin dependent diabetic due for major elective surgery or in patients pre-op who have poor glycaemic control?
(Day before surgery, day of surgery, during the operative period)
VRII - Continued until the patient is eating/drinking and stabilised on their previous diabetes medication
Day before surgery - Give normal insulin dose (Apart from once daily long acting insulin is given at 80% usual dose)
Day of surgery and during the operative period:- Once daily insulin given at 80% usual dose. All of the other patient’s insulin should be stopped until the patient is eating and drinking again- Start IV infusion of potassium chloride with glucose and sodium chloride AND a variable rate insulin infusion of soluble human insulin in 0.9% sodium chloride
Blood glucose monitored hourly for at least the first 12 hours
In patients that are on VRII during an operative period, what would you do if their blood glucose drops below 6?What about if it drops before 4?
<6 - Give IV glucose 20% and check blood glucose hourly
<4 - Give IV glucose 20% and check blood glucose every 15 mins
After surgery, if a patient is on VRII, they must not restart their subcut insulin until when?
They are eating/drinking without nausea or vomiting Note- their insulin dose may need adjusting due to altered food intake/post-op stress/infection
After surgery, a patient is ready to stop their VRII and go back to their BASAL-BOLUS regimen when would you stop the VRII and restart their subcut insulin?
Should be restarted when the first post-op meal is due
Give the first short-acting insulin first and then stop VRII 30-60 mins after Note- the long acting insulin is continued in the background of VRII at 80% dose - should continue at that dose until the patient leaves hospital
After surgery, a patient is ready to stop their VRII and go back to their TWICE DAILY MIXED insulin regimen when would you stop the VRII and restart their subcut insulin?
Should be restarted before breakfast or evening meal (not at any other time) Stop VRII 30-60 mins after
In type 2 diabetes, when would you consider VRII for surgery?
- When the fasting period requires more than one missed meal - major elective surgery - Patients with poor glycaemic control- Risk of renal injury- If on insulin as part of their treatment anyway -
If VRII is required for surgery in a type 2 diabetic, what antidiabetic drugs should be stopped?
When should they be restarted?
- Acarbose- Sulfonylureas- DPP-4 inhibitors- Pioglitazone- Meglitinides- SGLT-2 inhibitors
Should not be restarted until the patient is eating and drinking normally
If VRII is required for surgery in a type 2 diabetic, can GLP-1 receptor agonists be continued?
Yes
If a type 2 diabetic requires a minor surgical period, what should you do about their antidiabetic treatment?
If it requires a short fasting period (one missed meal), it may be possible to adjust antidiabetic drugs to avoid a switch to VRII
SGLT2 (fozins) inhibitors are associated with an increased risk of DKA, particularly the case in what situations?
Dehydration, stress, surgery, trauma, acute medical illness or any other catabolic state
What is the maximum licensed daily dose of standard release metformin?
Standard release- 2g/day
Initially 500 mg once daily for at least 1 week, dose to be taken with breakfast, then 500 mg twice daily for at least 1 week, dose to be taken with breakfast and evening meal, then 500 mg 3 times a day, dose to be taken with breakfast, lunch and evening meal; maximum 2 g per day.
What are the side effects of metformin?
Gastrointestinal side-effects are most frequent during treatment initiation and usually resolve spontaneously. A slow increase in dose may improve tolerability.
lactic acidosis (discontinue) symptoms include dyspnoea, muscle cramps, abdominal pain, hypothermia, or asthenia occur.
skin reactions, taste altered
vitamin B12 deficiency especially in those receiving a higher dose or longer treatment duration and in those with risk factors for vitamin B12 deficiency. Patients should continue taking metformin unless they are advised to stop.
At what eGFR should you avoid metformin?
<30
What are the risk factors for lactic acidosis?
Chronic heart failure
Concomitant use of drugs that acutely impair renal function
What is the patient advice with metformin?
Should be informed of the risk of lactic acidosis and told to seek immediate medical attention if symptoms such as dyspnoea, muscle cramps, abdominal pain, hypothermia, or asthenia (weakness/lack of energy) occur
Take with meals
MR gliclazide is equivalent to what standard release gliclazide dose?
30mg MR = 80mg standard release
What are the main side effects of sulphonylurea gliclazide to warn your patient about?
Sulphonylurea: IDE
Weight gain
Hypoglycaemia
What is the important safety information regarding Pioglitazone?
heart failure
bladder cancer
Patients should be advised to report promptly any haematuria, dysuria, or urinary urgency during treatment.
Bone fracture
weight increased
discontinue if jaundice occurs
DKA
What is the MHRA advice surrounding SGLT2 (fozins) inhibitors?
Risk of DKA Inform patients to be aware of signs e.g. rapid weight loss, sweet smell to breath, different odour in urine/sweat
Reports of Fournier’s gangrene (necrotising fasciitis of the genitalia or perineum
Canagliflozin - risk of lower-limb amputation
What is the MHRA advice surrounding the use of canagliflozin?
Risk of lower-limb amputation
Which antidiabetic class can cause pancreatitis?
DPP-4 inhibitors (gliptins)
GLP1 receptor agonists (Exenatide)
Which antidiabetic drug class commonly causes UTIs?
SGLT2 inhibitors, flozins
Can you use nateglinide as monotherapy in diabetes?
No - only with metformin
With what antidiabetic drug would it not be suitable in those with hernias or GI obstructions?
Acarbose Contra-indications
Disorders of digestion or absorption; hernia (condition may deteriorate); inflammatory bowel disease; predisposition to intestinal obstruction
What is the dose frequency of the different GLP-1 receptor agonists?
Once Weekly= semaglutide, duaglatide + MR exenatide
What is the important safety information regarding insulin pen devices?
Insulin should not be extracted from insulin pen devices.The strength of insulin in pen devices can vary by multiples of 100 units/mL. Insulin syringes have graduations only suitable for calculating doses of standard 100 units/mL. If insulin extracted from a pen or cartridge is of a higher strength, and that is not considered in determining the volume required, it can lead to a significant and potentially fatal overdose.
What is the name of the ultrarapid acting insulin?
Fiasp (aspart)
What are the types of soluble insulin (short acting)?
Humulin S
Actrapid
Insuman rapid
Hypurin neutral (povine/porcine)
What insulins can be used for VRII or in DKA as in infusion?
Soluble insulin
Humulin S
Actrapid
Is Actrapid classed as a rapid acting insulin?
No- it is a short acting insulin
What insulins are classed as rapid acting?
Apidra (glulisine)
Novorapid (aspart)
Humalog (lispro)
What insulins are classed as intermediate acting?
Insulatard
Humulin I (isophane)
Insuman basal
Hypurin isophane
Isophane can be otherwise known as NPH
What insulins are classed as long acting?
Levemir (detemir)
Lantus/Absalgar (glargine)
Tresiba (degludec)
Toujeo (glargine)
What insulins are classed as biphasic (pre-mixed)?
Novomix 30 Humalog Mix 25 or 50 Humulin M3 Insuman Combo 15 or 25 or 30
What does the 30 mean in Novomix 30?
The suspension contains rapid-acting and intermediate-acting insulin aspart in the ratio 30/70
What is recommended for the treatment of acute hypoglycaemia and the patient is conscious?
Treat with fast acting carbohydrate by Fast-acting carbohydrates include Lift® glucose liquid (previously Glucojuice®), glucose tablets, glucose 40% gels (e.g. Glucogel®, Dextrogel®, or Rapilose®), pure fruit juice, and sugar (sucrose) dissolved in an appropriate volume of water. Oral glucose formulations are preferred as absorption occurs more quickly. Orange juice should not be given to patients following a low-potassium diet due to chronic kidney disease, and sugar dissolved in water is not effective for patients taking acarbose which prevents the breakdown of sucrose to glucose. Chocolates and biscuits should be avoided if possible, as they have a lower sugar content and their high fat content may delay stomach emptying.
If necessary, repeat treatment after 15 minutes, up to a maximum of 3 treatments in total. Once blood-glucose concentration is above 4 mmol/litre and the patient has recovered, a snack providing a long-acting carbohydrate should be given to prevent blood glucose from falling again (e.g. two biscuits, one slice of bread, 200–300 mL of milk (not soya or other forms of ‘alternative’ milk, e.g. almond or coconut), or a normal carbohydrate-containing meal if due). Insulin should not be omitted if due, but the dose regimen may need review.
What is recommended for the treatment of acute hypoglycaemia and the patient is UNconscious?
IM Glucagon is given by family if unsuitable or no response after 10 mins then give IV glucose 20% or glucose 10% intravenous infusion needs to be given
Can glucagon be used for chronic hypoglycaemia?
No
What is given for chronic hypoglycaemia?
Diazoxide
What is used in diabetes insipidus?
Desmopressin or vasopressin
Is desmopressin or vasopressin more potent?
Desmopressin is more potent and has a longer duration of action Desmopressin is an analogue of vasopressin
Has no vasoconstrictor effect compared to vasopressin
What is vasopressin used for?
Diabetes insipidus
Initial control of oesophageal variceal bleeding
What is demeclocycline used for?
Treatment of hyponatraemia resulting from inappropriate secretion of antidiuretic hormone (if fluid restriction does not work)
What is tolvaptan used for?
Treatment of hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion
What mineralocorticoid can be used for postural hypotension in autonomic neuropathy?
Fludrocortisone
True or false:
High dose steroids should be used in the management of septic shock
High-dose corticosteroids should be avoided for the management of septic shock. However, there is evidence that administration of lower doses of hydrocortisone and fludrocortisone acetate is of benefit in adrenal insufficiency resulting from septic shock.
What is the MHRA advice surrounding corticosteroids?
MHRA/CHM advice:
Corticosteroids: rare risk of central serous chorioretinopathy with local as well as systemic administration
Patients should report any blurred vision/visual disturbances
What are the side effects of mineralocorticoids?
With which mineralocorticoid is this most present with?
hydrocortisone, corticotropin,
fludrocortisone, tetracosactide
Fludrocortisone
HYPERtension
Na retention + H2O retention
K loss +Ca loss
What are the side effects of GLUCOcorticoids apart from avascular necrosis of the femoral head in high doses?
psychiatric reactions may occur
For corticosteroid replacement therapy, what combination is usually given?
Hydrocortisone and fludrocortisone
Hydrocortisone alone is not sufficient as it does not provide sufficient activity
In Addision’s Disease or following adrenalectomy, what is usually given?How is it given?
Hydrocortisone
This is given in 2 doses, the larger in the morning and the smaller in the evening, mimicking the normal diurnal rhythm of cortisol secretion.
In acute adrenocorticol insufficiency, what is given?
IV hydrocortisone
What are the side effects of corticosteroids?
ADULTS:In what patients would you want a gradual withdrawal of systemic corticosteroids?
What is the physiological daily dose equivalent of prednisolone?
7.5mg daily
True or false:During corticosteroid withdrawal the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily)
TRUE
CHILDREN:In what patients would you want a gradual withdrawal of systemic corticosteroids?
- Received more than 40 mg prednisolone (or equivalent) daily for more than 1 week or 2 mg/kg daily for 1 week or 1 mg/kg daily for 1 month- Been given repeat doses in the evening- Received more than 3 weeks’ treatment- Recently received repeated courses (particularly if taken for longer than 3 weeks)-Taken a short course within 1 year of stopping long-term therapy- Other possible causes of adrenal suppression.
Prednisolone 5mg is equivalent to how much beclomethasone?
750 micrograms
Prednisolone 5mg is equivalent to how much dexamethasone?
750 micrograms
Prednisolone 5mg is equivalent to how much hydrocortisone?
20mg
Prednisolone 5mg is equivalent to how much methylprednisolone?
4mg
What is the most commonly used steroid for long-term disease suppression?
Prednisolone
What is the MHRA advice surrounding the methylprenisolone injectable preparation Solu-Medrone 40mg?
Contains lactose- not suitable for those with a cow’s milk allergy
If a newly diagnosed type 1 diabetic weighing 60kg was to be started on a basal bolus regime, what would their starting daily insulin unit dose be?How would you split this between basal bolus?
Starting at 0.5 units/kg/day
So 30 units Half basal and half bolus 15 units basal e.g. Lantus And split the other 15 into 3 for meal times, so 5 units TDS of rapid acting insulin
- What is first line for postmenopausal osteoporosis?2. What would be alternatives if this is not appropriate?
First line = Oral bisphosphonates: alendronic acid or risedronate as they have a broad spectrum of anti-fracture efficacy
- IV bisphosphonate (Ibandronic acid, zolendronic acid)
Denosumab, Raloxifene
What is teriparatide used for?
Reserved for postmenopausal women with severe osteoporosis at very high risk for vertebral fractures. Its duration of treatment is limited to 24 months.
- What would be first line for glucocorticoid-induced osteoporosis?
- First line Oral bisphosphonates- alendronic acid or risedronate sodium
Alternatives- IV zolendronic acid or denosumab, teripartide
Men who are receiving androgen deprivation therapy for prostate cancer have an increased risk of what?
Fractures
Fracture risk should be assessed at the start of therapy
- What would be first line in men with osteoporosis?
- Oral bisphosphonates- alendronic acid or risedronate sodium
Alendronic acid 10mg daily
Swallow whole and oral solution swallowed as single 100mg dose
Take with plenty of water sitting or standing
Take on empty stomach at least 30mins before breakfast / other oral meds
Stand/ sit upright for at least 30 minutes after administration
Or
By mouth Adult (male) 35 mg once weekly risedronate
Alt: IV zolendronic acid or denosumab
Bisphosphonate treatment should be reviewed after how many years?
5 years of treatment of alendronic acid, risedronate sodium or ibandronic acid
3 years of treatment with zolendronic acid
Which patient groups can continue their bisphosphonate therapy after 5 years?
Patients over 75 years of age, or with a history of previous hip or vertebral fracture, or patients who have had one or more fragility fractures during treatment, or who are taking long-term glucocorticoid therapy
What is the warnings surrounding the use of bisphosphonates?
- Risk of atypical femoral fractures
report any thigh/hip/groin pain Review treatment after 5 years - Risk of osteonecrosis of the jaw Dental check up and any necessary work is needed before therapy report non-healing sores, swelling, pain
If the patient wears dentures, need to ensure they fit properly before starting therapy - Risk of osteonecrosis of external auditory canal, report ear infections, ear discharge, ear pain
- Severe oesophageal reactions (oesophagitis, oesophageal ulcers, oesophageal stricture and oesophageal erosions) have been reported; patients should be advised to stop taking the tablets and to seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, new or worsening heartburn, pain on swallowing or retrosternal pain
What are the side effects of bisphosphonates?
- Anaemia
- Severe oesophageal reactions (ulcers, strictures, erosions)
- Risk of atypical fracture- Osteonecrosis of jaw or auditory canal
- Altered taste
-Joint swelling - Hypophosphatemia
NB- absorption is affected by other meds e.g. iron, so needs to be taken 30 mins before food and other meds
Is estradiol a natural or synthetic oestrogen?
Natural
Is ethinylestradiol a natural or synthetic oestrogen?
Synthetic
If long term oestrogen therapy is needed for women who still have a uterus, what should be added and why?
Progesterone to reduce the risk of hyperplasia of endometrium and cancer
HRT increases the risk of what?
Venous thromboembolism,
stroke,
endometrial cancer (reduced by a progestogen),
breast cancer,
ovarian cancer;
there is an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause.
What is the treatment for hyperthyroidism? Low TSH + high T4
HYPERthyroidism skinny needs Carbs
Carbimazole
Propylthiouracil
What is the important safety information regarding carbimazole?
The MHRA/CHM advice: Carbimazole: increased risk of congenital malformations; females of childbearing potential should use effective contraception during treatment.
Neutropenia and agranulocytosis
recognise bone marrow suppression induced by carbimazole and the need to stop treatment promptly.
Report symptoms and signs suggestive of infection, especially sore throat. A white blood cell count should be performed if there is any clinical evidence of infection.
Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia.
Carbimazole is associated with an increased risk of congenital malformations when used during pregnancy, especially in the first trimester and at high doses (daily dose of 15 mg or more).
MHRA/CHM advice: Carbimazole: risk of acute pancreatitis (February 2019)
acute pancreatitis reported during treatment with carbimazole. It should be stopped immediately and permanently if acute pancreatitis occurs.
Carbimazole should not be used in patients with a history of acute pancreatitis associated with previous treatment—re-exposure may result in life-threatening acute pancreatitis with a decreased time to onset.
What is the patient advice regarding Propylthiouracil?
Severe hepatic reactions have been reported
Recognise signs of liver disorder
seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, jaundice, dark urine, or pruritus develop.
How should a thyroid storm be treated? Rapid heartbeat/ high temp/ diarrhoea and vomiting/ jaundice/ loss of consciousness
Emergency situation:
IV fluids
propranolol
hydrocortisone
oral iodine /carbimazole/propylthiouracil
What is first line for hypothyroidism?What is an alternative?
Levothyroxine
Liothyronine
What is the patient advice regarding the administration of levothyroxine?
Dose to be taken preferably at least 30 minutes before breakfast, caffeine-containing liquids (e.g. coffee, tea), or other medication
What is tibolone used for?
For women
Short term treatment of oestrogen deficiency
Osteoporosis prophylaxis
Is norethisterone an oestrogen or progesterone?
Progesterone
What is the advice regarding missing a dose of progesterone only pill for contraception?
Take it as soon as you rememberHowever if it is not taken within 3 hours of the normal time of taking the pill- additional precautions should be used and for 2 days after
What is the advice regarding vomiting if taking a progesterone only pill?
If vomiting occurs within 2 hours of taking an oral progestogen-only contraceptive, another pill should be taken as soon as possible. If a replacement pill is not taken within 3 hours of the normal time for taking the progestogen-only pill, or in cases of persistent vomiting or very severe diarrhoea, additional precautions should be used during illness and for 2 days after recovery (but still keep taking the pill as usual)
True or false:You should take the progesterone only pill (for contraception) at the same time every day
True If delayed longer than 3 hours, then the contraceptive effect may be lost
When starting a progesterone only pill for contraception, what is the advice surrounding when to start during the menstrual cycle and if additional contraceptive cover is needed?
Should ideally start taking on day 1 of the cycle
Additional contraceptive precautions are not required if norethisterone is started up to and including day 5 of the menstrual cycle; if started after this time, additional contraceptive precautions are required for 2 days.
If you are changing from a combined oral contraceptive pill to the progesterone only, when should this happen?
Start on the day following completion of the combined oral contraceptive course without a break (or in the case of ED tablets omitting the inactive ones)
When starting a progesterone only pill for contraception AFTER CHILDBIRTH, what is the advice surrounding when to start and if additional contraceptive cover is needed?
Can be started up to and including day 21 postpartum without the need for additional contraceptive precautions. If started more than 21 days postpartum, additional contraceptive precautions are required for 2 days.
If on a progesterone only pill for contraception, in what situations would you need emergency contraception?
If one or more progestogen-only contraceptive tablets are missed or taken more than 3 hours late and unprotected intercourse has occurred before 2 further tablets (2 days worth) have been correctly taken.
Which antidiabetic drug can cause lactic acidosis and B12 deficiency?
Metformin
If a pregnant patient diagnosed with gestational diabetes what can be done?
1) diet and exercise
2) metformin
3) add insulin if metformin ineffective
If a pregnant patient diagnosed with gestational diabetes presents with a fasting glucose of >7mmol/L, what should be done?
Should be treated with insulin immediately, with or without metformin hydrochloride, in addition to a change in diet and exercise
What are the complications of gestational diabetes?
Hydramnios- a condition in which excess amniotic fluid accumulates during pregnancy
Macrosomia- larger than normal baby
If a pregnant lady presents with complications of gestational diabetes, how should this be managed?
Discontinue Ace/ARB and replace with methyldopa or labetalol in pregnancy
Discontinue statin
What is the advice surrounding patients on metformin who is going to have contrast media administered as part of radiologic studies?
Can lead to nephrotoxicity
If patient’s eGFR >60 and only missing one meal, then there is no need to stop metformin
If eGFR < 60:Metformin should be discontinued prior to, or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable
What is the advice surrounding metformin during surgery?
Stop all anti diabetic drugs once insulin infusion is commenced (Acarbose/sulfonylureas/ pioglitazone/ meglintinide/ SGLT2/ Gliptins)
Continue metformin and GLP-1 agonists once infusion insulin is commenced
If a patient is on 500mg OD metformin, due for surgery and the metformin needs to be stopped beforehand, would you give VRII?
No, only give VRII if their usual metformin dose is more than once daily OR if their blood glucose is >12 on 2 consecutive occasions
What is the risk of continuing metformin during surgery?
Renal impairment may lead to accumulation and lactic acidosis
What is the advice surrounding sulphonylureas and surgery?
Sulfonylureas are associated with hypoglycaemia in the fasted state and therefore should always be omitted on the day of surgery until the patient is eating and drinking again. Monitor blood glucose and give insulin if necessary
If a patient does not require VRII, what antidiabetic drugs can be continued during surgery?
Pioglitazone, dipeptidylpeptidase-4 inhibitors (gliptins) and glucagon-like peptide-1 receptor agonists can be taken as normal during the whole peri-operative period.Metformin- depends on AKI risk, eGFR, how many doses they are missing
Do gliptins or sulphonylureas have a higher incidence of hypoglycaemia?
Sulphonylureas
A HbA1c alone at what level would indicate diabetes?
48
HbA1c should not be used for diagnosis in what patients groups?
Those with suspected type 1 diabetes, in children, during pregnancy, or in women who are up to two months postpartum
Also should not be used in the following:-
Symptoms for less than 2 months
- Treatment with medication that may cause hyperglycaemia
- Acute pancreatic damage
- HIV
- End stage CKD
Zoledronic acid is contraindicated in what patient group?
Women of child bearing potential
For DKA, what strength glucose do you give?
10%
For hypoglycaemia when glucose is needed, what strength do you give?
20%
A high TSH level with a low FT4 and FT3 level indicates what?
Hypothyroidism
A LOW TSH level with a high T4 level and a high T3 level indicates what?
HYPERthyroidism
How do you manage hyperthyroidism during pregnancy?
Carbimazole is associated with congenital defects, including aplasia cutis of the neonate, therefore
propylthiouracil = first trimester of pregnancy.
Second trimester= carbimazole
because of the potential risk of hepatotoxicity with propylthiouracil
Why should you avoid rapid correction of sodium in SIADH?
Can cause serious CNS effects and demyelination of neurones
What effect can corticosteroids have on potassium levels?
Can cause hypokalaemia
If chicken pox develops in a person taking corticosteroids, what is recommended?
Seek urgent medical attention as they are immunocompromised
Passive immunisation with varicella zoster immunoglobulin is important
When would you issue patients with a steroid card?
Taking long term steroids > 3 weeks
High dose ICS
What is macrosomia?
Larger than average foetus- usually a complication for pregnant women with diabetes
What class of antidiabetic drugs can cause volume depletion, DKA, weight loss, constipation?
SGLT2 inhibitors
What kind of cancer must you rule out if irregular bleeding continues after stopping continuous HRT?
Endometrial cancer
What is a severe side effect of Exenatide (GLP1)?
Which other group of drugs also causes this side effect?
Severe pancreatitis
DPPi - gliptins (linagliptin… Alogliptin)
What is the advice if a patient is on levothyroxine and iron tablets?
Iron can decrease the absorption of levothyroxine, so separate administration by at least 4 hours
Name the 3 rapid acting strong insulins
Can you think of their brand names?
Insulin GlulisineApidra®
Insulin AspartNovorapid®
Insulin LisproHumalog®
That GAL is RAPID!
When should the rapid acting insulins be injected?
0- 15 mins before food
How long is the duration of action of rapid acting insulins?
2 - 5 hours
Whattype of insulins aresoluble insulins?
When should soluble acting insulins be injected?
15 - 30 mins before food
Must eat food within 30 mins of injecting to avoid hypoglycaemia
They start working after 30 mins
Can you think of any brands of Intermediate acting insulins?
When should intermediate acting (isophane) insulins be injected?
They usually need to be injected twice daily, sometime once daily in eldery
No need to inject with meals
They have a peak action at 4 - 12 hour and last for around 21 hours
What are the three types of long- acting insulins? Do you know their brand names?
Insulin DetemirLevemir ®
Insulin GlargineLantus ®
Insulin DegludecTresiba®
How long do the long-acting insulins usually work for?Which one works for up to 42 hours?
Degludec tresiba
NovoMix is a Biphasic insulin (intermediate acting). It contains a mixture of which insulins?
Insulin aspart rapid acting
Insulin aspart protamine (long acting) Together it becomes intermediate acting- injected twice daily
What electrolyte disturbance can insulins cause?
HypoKaleamia
How do Sulfonylureas work?
Increase insulin secretion from the pancreas
What side effects can sulphonylureas cause?
Weight gain
GI disturbance: Diarrhoea, dyspepsia, nausea, vomitting
Allergic dermatitis (usually in first 6- 8 weeks)
Jaundice (avoid in severe liver impairment)
What is Metformins Mechanism of Action?
It is a Biguanide: Decreases gluconeogenesis (production of new glucose) and increases peripheral utilisation of glucose
Remember: metformin produce normoglycemia rather than hypoglycaemia It does not increase insulin secretion like other oral antidiabetics, therefore it does not cause weight gain!
Main side effects of Metformin?
GI upset- take with food, use MR if intolerable
Taste disturbance
Lactic acidosis
What enzyme do the Dipeptidylpeptidase-4 inhibitors inhibit?How does this help lower glucose?
Linagliptin
Sitagliptin
Vildagliptin
Saxagliptin
Inhibit an enzyme called Dipeptidylpeptidase-4. This enzyme breaks down incretins, incretins trigger insulin secretion and lower glucagon secretion, therefore they are good at helping control glucose, so by inhibiting the enzyme that breaks them down, gliptins increase incretin levels.Gliptins.. incretins… gliptins…. incretins!
What are the side effects of the gliptins (dipeptidylpeptidase 4 inhibitors)?
Discontinue if symptoms of acute pancreatitis occur such as persistent, severe abdominal pain
Abdominal pain; gastrooesophageal reflux disease; headache; increased risk of infection; skin reactions
Which oral antidiabetics can cause acute pancreatitis? What are the symptoms of this?
Dipeptidylpeptidase-4 inhibitors (gliptins- sitagliptin, Linagliptin etc)
Glucagon-like peptide-1 receptor agonists (Exenatide, Liraglutide, Lixisenatide)
Exenatide especially can cause SEVERE PANCREATITIS
Symptoms: Persistent and severe abdominal pain, Nausea and vomitting
What is the mechanism of action of the Thiazolidinediones?(Only one licensed in UK is pioglitazone)
Reduces peripheral insulin resistance
Which oral antidiabetics must care be taken with in Heart Failure? And what cancer can it possibly increase risk of?
Pioglitazone:Incidence of HF increased when pioglitazone is combined with insulin
Also small risk of BLADDER cancer
Signs of bladder cancer: blood in urine, pain on urination, urinaryurgency
Can oral anti-diabetic drugs cause headaches?
Yes- alot of them cause a headache, particularly pioglitazone and the DDPi gliptins
Can you name any oral anti-diabetic drugs that can cause liver toxicity?
Pioglitazone
DDP4i - Vidagliptin
What are GLP-1 agonists? How do they work?
Glucagon-like peptide-1 receptor agonists Examples: Exenatide Liraglutide Lixisenatide
These are given by SUBCUTANEOUS INJECTION- not oral (apart from semaglutide). These work by binding to the GLP-1 receptor causing: Increase in insulin secretion suppression of glucagon secretion (glucagon gets converted in glucose usually) Slow gastric emptying
If given with sulfonylureas or insulin, their dose may need to be reduced as increased risk of hypoglyceamia!
Which anti diabetics do we have to be particularly vigelant for symptoms such as persistent and severe abdominal pain, nausea and vomitting?
(GLP-1 agonist)
These are symptoms of pancreatitis- exanatide can cause severe pancreatitis- discontinue permanently
Also DDP4i gliptins can cause pancreatitis
What are the SGLT2 inhibitors?
3 examples? How do they work?
Sodium Glucose Co-transporter 2 inhibitors, Gliflozins Examples:Canagliflozin, Dapagliflozin, Empagliflozin
The sodium glucose transporter is found in the kidneys: by inhibiting this they stop glucose being re-absorbed in the renal tubule and therefore more glucose is excreted
What important Side effect can the SGLT2 inhibitors (Canagliflozin, dapagliflozin, empagliflozin) cause?
What concomitant drugs/ conditionscould increase the risk of this?
Volume depletion
Think floz= flow
Think: these are inhibiting glucose reabsorption into the renal tubules. Water usually follows the glucose- less reabsorbed= less water follows= more weeing etc
Patients need to report signs of this: Dizzy, postural hypotension
Side effects: Thirst
Constipation (less water in stools)
Increased risk: things that also decrease fluid volume
Antihypertensives Elderly diarrhoea
What condition, other than diabetes, can metformin be used in Unlicensed?
Poylcystic ovary syndrome
It helps to normalise the menstrual cycle on ovulation
What are the contraindications of sulfonylureas?
Especially gliclazide
For all SULFONYLUREAS:
Presence of ketoacidosis
For GLICLAZIDE:
Avoid where possible in Acute porphyrias
Metformin in pic incorrect- weight neutral
What is the name of the thiazide diuretic that is used in chronic intractable hypoglyceamia in Neonates/ children?
Diazoxide
(remember diuretics can cause hyperglyceamia)
Which bisphosphonate needs to be discontinued if a skin rash develops?
Strontium ranelate
Severe allergic reaction:
Symptoms known as DRESS ‘Drug rash with eosinophilia and systemic symptoms’
Starts with: fever, rash, swollen glands, high WCC
What is the side effect we need to be vigilant about with Bisphosphonate treatment?
Osteonecrosis of the Jaw
The risk is higher with IV therapy for cancer treatment than it is with oral. Patients have a dental check up before starting and need to maintain good oral hygiene and attend regular check ups. They should report any oral symptoms: Pain, inflammation, difficulty swallowing
Elevated ketones are a sign of DKA
What are the Symptoms of DKA?
Rapid weight loss
Abdominal pain
Nausea and vomiting
Rapid and deep breathing?
Sweet smelling breath
Altered odour of urine/sweat
Sleepiness
Who requires gradual withdrawal of systematic corticosteroids?
Steroid with very high glucocorticoid activity and insignificant mineralocorticoid activity?
Betamethasone and Dexamethasone
Corticosteroid with moderate glucocorticoid activity and high mineralocorticoid activity - good for topical use because side-effects are less marked?
HYDROCORTISONE
Side effects of glucocorticoids?
Side effects of mineralocorticoids
Metformin causes vitamin b12 deficiency, what are the signs and symptoms?
Do corticosteroids cause hyper/hypoglycaemia ?
What is the topical strength of Synalar fluocinolone 0.025% ?
Potent? Moderate?
Hypothyroidism vs hyperthyroidism
Metformin interaction with cimetidine
How do you apply topical corticosteroids with other topical preparations?
Side effects of topical corticosteroids
How do you counsel on applying topical corticosteroids
Corticosteroid counselling
Mometasone -potent / moderate?
Hydrocortisone butyrate- potent/moderate potency?
Do corticosteroids cause hyper /HYPOkalaemia?
Which corticosteroids mineral/ gluco have high anti inflammatory effects?
Which antidiabetic drugs are contraindicated in ketoacidosis?
Diabetes numbers
Which drugs exacerbate Aki?
Which antidiabetic drugs cause weight gain?
????? In which 3 anti diabetics is DKA contraindicated in?
Sulphonylureas
SGLT2
DPP4i ????
