Endorcine Flashcards
What is used to treat diabetes insipidus?
Vasopressin
What is desmopressin used for?
Nocturnal enuresis
Used to test fibrinolytic response
Used to treat mild-moderate haemophilia and VWD (a life-long bleeding disorder in which blood does not clot properly)
How do you treat hyponatraemia resulting from inappropriate secretion of antidiuretic hormone?
If fluid restriction alone does not restore sodium concentration or is not tolerable
- Treat with demeclocycline
- 2nd line: Tolvaptan
What would happen if rapid correction of hyponatraemia occurs during tolvaptan therapy?
Could cause osmotic demyelination leading to serious neurological events
- slowly monitor serum sodium concentration and balance fluid
Which drugs increase the secretion of vasopressin?
Tricyclic antidepressants = increases risk of hyponatraemia
What counselling is given for the treatment of nocturnal enuresis with desmopressin?
Hyponatraemic convulsions - avoid fluid overload (including during swimming) and stop taking drug during episodes of vomiting and diarrhoea until fluid balance normal
What is the risk associated with desmopressin and vasopressin in pregnancy?
oxytocic
How do you take tolvaptan?
Morning dose 30 minutes before food and second dose can be taken with or without food
What are the risk factors associated with osteoporosis?
Post-menopausal women
Men over 50
Patients taking long-term corticosteroids
What vitamins should patients with osteoporosis aim to increase?
Intake of calcium and vitamin D
How do you treat postmenopausal osteoporosis?
1st line: alendronic acid (10mg OD or 70mg weekly) or risedronate (5mg OD or 35mg weekly) due to broad spectrum of anti-fracture efficacy
Alternative - ibandronic acid
If intolerant of oral bisphosphonates = consider parenteral bisphosphonates or denosumab
More alternatives: raloxifene, strontium
HRT - restricted to younger postmenopausal women due to risk of adverse effects such as CVD and cancer
- Another option in younger women is tibolone
What is used in menopausal women at severe risk of osteoporosis at high risk of fractures?
Teriparatide
Romosozumab - who have previously experienced a fragility fracture and are at imminent risk of another (within 24 months)
Who should be considered for bone-protection treatment for patients who have glucocorticoid-induced osteoporosis?
Women:
- aged ≥ 70 OR
- had previous fragility fracture OR
- taking large doses of glucocorticoids (prednisolone ≥ 7.5mg daily or equivalent)
Men:
- aged ≥ 70 with a previous fragility fracture OR
- taking large doses of glucocorticoids
All men and women taking large doses of glucocorticoids (≥ 7.5mg daily prednisolone or equivalent) for 3 months or longer
What is the treatment for bone protection?
1st line: alendronic acid/ risedronate
If intolerant to oral bisphosphonates or unsuitable
- zoledronic acid
- denosumab
- teriparatide
How do you treat osteoporosis in men?
1st line: alendronic acid (10mg OD) or risedronate (35mg weekly)
2nd line: zoledronic acid or denosumab
3rd line: teriparatide or strontium
How long is the duration of biphosphonate treatment?
Reviewed after 5 years with alendronic acid, risedronate and ibandronic acid
Reviewed after 3 years with zoledronic acid
Continuation beyond this period recommended for patients over 70, have a history of previous hip or vertebral fractures, had 1 or more fragility fractures during treatment, or who are taking long-term glucocorticoid therapy
What are the MHRA warnings for biphosphonates?
- Atypical femoral fractures: report any thigh, hip or groin pain during treatment
- Osteonecrosis of the jaw: (most potent bisphosphonates = zoledronic acid) get regular dental check-ups and good oral hygiene
- Osteonecrosis of the auditory canal: report any ear pain, discharge from the ear or an ear infection during treatment
What are the common side effects of alendronic acid?
GI disorders
Joint swelling
Vertigo
Skin reactions
When should you avoid alendronic acid in renal impairment?
If CrCl less than 35ml/min
What is the caution for strontium?
Risk factors for CVD - assess every 6-12 months during treatment
Risk factors for VTE - discontinue in patients who become immobile
What are the MHRA warnings associated with denosumab?
- atypical femoral fractures
- osteonecrosis of the jaw
- osteonecrosis of the auditory canal
- rebound hypercalcemia up to 9 months after discontinuation of treatment for giant cell tumour of bone
- vertebral fractures after stopping (up to 18 months) or delaying ongoing treatment (60mg)
- do not use in under 18 due to severe risk of hypercalaemis
What corticosteroid is used for postural hypotension in autonomic neuropathy?
Fludrocortisone - mineralcorticoid activity
What corticosteroids are used for congenital adrenal hyperplasia?
Dexamethasone and betamethasone - glucocorticoid activity (long-acting)
What corticosteroid do you use to test for Cushing’s syndrome?
overnight dexamethasone suppression test
What is the MHRA warning for corticosteroids?
Rare risk of central serous chorioretinopathy with local and systemic administration - report blurred vision or visual changes
What are the side effects of mineralocorticoids?
Hypertension
Sodium retention
Water retention
Potassium loss
Calcium loss
These are most marked with fludrocortisone but also significant with hydrocortisone, corticotropin, and tetracosactide
What are the side effects of glucocorticoids?
Diabetes
Osteoporosis - danger in elderly
High doses associated with avascular necrosis of femoral head
Muscle wasting (proximal myopathy)
Weakly linked with peptic ulceration and perforation
Psychiatric reactions
What are the symptoms of adrenal insufficiency?
Fatigue
GI upset
Anorexia
Weight loss
Salt cravings
Dizziness/ syncope due to hypotension
Musculoskeletal symptoms
What are the symptoms of adrenal crisis?
Severe dehydration
Hypotension
Hypovolemic shock
Altered consciousness
Seizures
Stroke
Cardiac arrest - if left untreated
How do you treat adrenal insufficiency?
Physiological glucocorticoid replacement - mainly with hydrocortisone, prednisolone and rarely dexamethasone
Patients with primary adrenal insufficiency may also require mineralocorticoid replacement with fludrocortisone due to aldosterone deficiency
What should you advise patients with adrenal insufficiency to do during times of stress?
Double the dose of glucocorticoid
What are the sick day rules for glucocorticoids?
if unwell with moderate intercurrent illness (fever or infection requiring antibiotics) - double the dose
Patients with adrenal insufficiency on long-acting hydrocortisone should be switched to short-acting, more readily absorbed preparations during illness
During severe illness (vomiting and GI viral illness) - IM/IV hydrocortisone should be given
How do you manage adrenal crisis?
Prompt glucocorticoid replacement - hydrocortisone
Rehydration - using crystalloid fluid (sodium chloride 0.9%)
What are the MHRA warnings for corticosteroids?
- rare risk of central serous chorioretinopathy with local and systemic administration
- steroid emergency card
- paediatric steroid card for children with adrenal insufficiency
What is an important side effect to be aware of with high doses of corticosteroids?
Psychiatric reactions
What symptoms are associated with steroid withdrawal?
Fever
Myalgia
Arthralgia
Rhinitis
Conjunctivitis
Painful itchy skin nodules
Weight loss
When should gradual steroid withdrawal be considered?
- More than 40mg of prednisolone for more than 1 week
- Repeat doses in the evening
- Treatment more than 3 weeks
- Recent repeat courses
- Taken short-course within 1 year of stopping long-term therapy
Which steroid is associated with Stevens-Johnson syndrome?
Betamethasone
Other side effects of betamethasone:
- oedema
- hiccups
- myocardial rupture: following recent MI
Which steroid can cause hyperglycaemia?
Dexamethasone
Which steroid increases blood pressure and conjunctivitis?
Fludrocortisone
Which steroid has a common side effect of depressed mood?
Methylprednisolone
Which drugs are used to manage Cushing’s syndrome?
Metyrapone
Ketoconazole - for endogenous cushings syndrome
What is the safety warning associated with ketoconazole?
Administration of oral ketoconazole to treat fungal infections should be suspended - risk associated with hepatotoxicity is greater than the benefit
- oral ketoconazole for treatment of Cushing’s syndrome not affected by this warning
What should the minimum blood glucose concentration be while driving?
At least 5mmol/L
If 5mmol/L or below - have a snack
Driver treated with insulin should always ensure a fast-acting carb is in the vehicle
When should a driver with diabetes not drive?
When blood glucose is less than 4 mmol/L or there are warning signs of a hypo
- stop vehicle and wait 45 minutes for blood glucose to return to normal
If a diabetic patient is not taking insulin, what other drugs would you need to monitor blood glucose levels for when driving?
Sulfonylureas and meglitinides (‘glinide’)
what causes delayed hypoglycaemia or makes the symptoms of hypoglycaemia less clear?
Alcohol
What are the typical features of T1DM?
Blood glucose concentrations of above 11mmol/L
Ketosis
Rapid weight loss
BMI of less than 25kg/m2
Age younger than 50
Personal/ family history of autoimmune disease
What is the target fasting blood glucose concentration on waking?
5-7mmol/L
What is the target blood glucose concentration before meals?
4-7mmol/L
What is the target blood glucose concentration at least 90 minutes after eating?
5-9mmol/L
For a patient with T1DM, when would you consider metformin as add-on therapy?
When they have a BMI of 25kg/m2 or above (23kg/m2 or above for south asian and related ethnicities) who wish to improve their blood glucose control while minimising their effective insulin dose
What is a multiple daily injection basal-bolus insulin regimen?
One or more separate daily injections of intermediate-acting insulin or long-acting insulin analogue
Alongside multiple bolus injections of short-acting insulin BEFORE meals
What is a mixed (biphasic) regimen?
1-3 insulin injections per day of short-acting insulin mixed with intermediate-acting insulin
It may be mixed by the patient or a pre-mixed product can be used
Must always be taken 30 minutes before a meal
Not recommended for adults newly diagnosed with T1DM
What type of insulin is used for continuous subcutaneous insulin infusion?
Rapid-acting analogue or soluble insulin
What is the first line recommended insulin regimen?
Basal-bolus regimen
Long-acting insulin = twice daily insulin detemir
- alternative: once daily insulin glargine
Nocturnal hypoglycaemia concern = once daily insulin degludec (ultra-long acting)
Which insulin would you consider if the patient experiences nocturnal hypoglycaemia?
Once daily insulin degludec
What insulin would you consider if a patient requires help administering from a carer or HCP?
Once daily ultra-long acting insulin
- insulin degludec
- insulin glargine (300 units/ml)
What insulin is recommended as the mealtime insulin replacement?
Rapid-acting insulin analogue (rather than soluble human insulin or animal insulin)
Administered BEFORE meals
Who should the insulin pumps be offered to?
- Patients who suffer disabling hypoglycaemia while attempting to achieve target HbA1c
- Have high HbA1c levels: 69mmol/mol (8.5%) with multiple daily injection therapy
- children under 12 where multiple injection regimen is impractical
How do you test a patient’s awareness of hypoglycaemia?
The Gold score or the Clarke score
What class of drugs masks the symptoms of hypoglycaemia?
Beta blockers - by reducing warning signs such as a tremor
How do you restore the warning signs of hypoglycaemia?
By minimising episodes of hypoglycaemia
Why is insulin given subcutaneously and not orally?
Gastrointestinal enzymes inactivate insulin
What risk is associated with insulin injections in one site?
Lipohypertrophy - can causes erratic absorptions of insulin
Which insulins are soluble insulins?
Soluble insulins are short-acting insulins
Soluble insulins include: human and bovine or porcine
Which insulins are rapid-acting insulins?
Rapid-acting insulins are short-acting insulins
Rapid-acting insulins include:
- insulins aspart
- insulin glulisine
- insulin lispro
LAG - there is not lag with rapid-acting insulins
onset of action = 15 minutes
duration of action = 2-5 hours
Which insulin can be injected subcutaneously, IV and IM?
Soluble insulin
S/C: rapid onset of action (30-60 mins), peak action between 1-4 hours and duration of action of 9 hours
IV: short half-life (few minutes) but onset of action instantaneous –> used in diabetic emergencies e.g. diabetic ketoacidosis and peri-operatively
Which short-acting insulin is more advantageous?
Rapid-acting insulin is more advantageous than soluble insulin
- improved glucose control
- reduce HbA1c
- reduction in incidence of hypoglycaemia episodes including nocturnal
Name an intermediate-acting insulin
Isophane insulin
onset of action 1-2 hours
maximal effects: 3-12 hours
duration of action: 11-24 hours
How is intermediate-acting insulin used?
It can be used given OD, BD in basal-bolus regimen with separate short-acting mealtime insulins
OR
It can be mixed with short-acting insulin for biphasic regimens (administered before meals)
Also comes are pre-mixed
- biphasic isophane insulin
- biphasic insulin aspart
- biphasic insulin lispro
Name the long-acting insulins
- protamine zinc insulin
- insulin zinc suspension
- insulin determir (OD/BD)
- insulin glargine (OD)
- insulin degludec (OD)
duration of action: up to 36 hours
achieve steady-state level: after 2-4 days
What is the blood glucose targets in patients managing their T2DM with lifestyle changes and or with one antidiabetic drug not associated with hypoglycaemia?
48 mmol/mol (6.5%)
What is the target blood glucose level in T2DM on an antidiabetic associated with hypoglycaemia?
53 mmol/mol (7%)
What is the blood glucose target for patients with T2DM on 2 antidiabetic drugs?
53 mmol/mol (7%)
Which anti-diabetic non-insulin drug causes hypoglycaemia?
sulfonylureas
More associated with long-acting sulfonylureas e.g. glimepiride
Which anti-diabetic non-insulin drugs is associated with weight gain?
sulfonylureas
Pioglitazone
Which anti-diabetic drugs promote weight loss?
SGLT2s
GLP-1s “tide”
Which anti-diabetic drug has benefits when used in HF?
SGLT2s
Which anti-diabetic drug has renal benefit?
SLGT2s
Which anti-diabetic drug poses a risk of diabetic ketoacidosis?
SGLT2s
What is used in rescue therapy for patients who become symptomatically hyperglycaemia?
Insulin or Sulfonylureas
What is the initial treatment for T2DM?
1st line: standard release metformin - increase dose gradually to minimise risk of GI side effects (offer MR metformin if experiencing GI side effects)
if patient has chronic HF, or established atherosclerotic CVD (or at high risk of developing CVD) - offer SGLT2 as well
-> initiate as soon as tolerability to metformin established
2nd line: (monotherapy of metformin +) DPP4/ piogloitazone/ sulfonylureas
-> use SLGT2 instead of sulfonylureas if contraindicated or not tolerated or pt at significant risk of hypo’s
(after dual therapy, can consider insulin)
3rd line: (triple therapy) options:
-> metformin + sulfonylureas + SGLT2 (canagliflozin, empagliflozin/ dapagliflozine)
-> metformin + pioglitazone + canagliflozin/empagliflozin
-> metformin + DPP4 + ertugliflozin (if sulfonylureas or pioglitazone inappropriate)
What is the treatment option for T2DM if triple therapy ineffective?
Consider GLP-1 as part of triple therapy by swapping it with one of the other drugs
-> only consider in patients with BMI 35kg/m2 or above AND who have specific psychological or medical problems associated with obesity
-> OR have BMI <35kg/m2 and whom insulin therapy would have significant occupational implications
-> OR if weight loss associated with GLP-1 would benefit other obesity-related co-morbidities
Which sulfonylureas are short-acting and may be considered for elderly patients/ patients with renal imapirment?
Gliclazide or tolbutamide
Which class of drugs have proven CVD benefit?
GLP-1 - consider in patients with established cardiovascular disease
What are the conditions after starting a GLP-1?
Review after 6 months of starting
-> continue only if there has been at least 11 mmol/mol (1%) reduction in HbA1c AND weight loss of at least 3% of initial weight