Endocrine and Reproductive systems Flashcards
Name some examples of bisphosphonates
Alendronic acid, disodium pamidronate, zoledronic acid
What are bisphosphonates indicated for?
- Alendronic acid is used as the first-line drug treatment option for patients at risk of osteoporotic fragility fractures
- Pamidronate and zoledronic acid are used in the treatment of severe hypercalcaemia of malignancy after appropriate IV rehydration
- For patients with myeloma and breast cancer with bone metastases, pamidronate and zoledronic acid reduce the risk of pathological fractures, cord compression and the need for radiotherapy or surgery
- Bisphosphonates are used as first-line treatment of metabolically active Paget’s disease, with the aim of reducing bone turnover and pain
How do bisphosphonates work?
They reduce bone turnover by inhibiting the action of osteoclasts, the cells responsible for bone resorption
As bone is resorbed, bisphosphonates accumulate in osteoclasts, where they inhibit activity and promote apoptosis
The net effect is reduction in bone loss and improvement in bone mass
What are the important adverse effects of bisphosphonates?
Common side effects include oesophagitis (when taken orally) and hypophosphataemia
A rare but serious adverse effect is osteonecrosis of the jaw, which is more likely with high-dose IV therapy
Another rare AE is atypical femoral fracture
What are the warnings for bisphosphonate prescription?
They are renally excreted and should be avoided in severe renal impairment. They are contraindicated in the context of hypocalcaemia.
Oral administration is contraindicated in patients with active upper GI disorders. Because of the risk of jaw osteonecrosis, care should be exercised in prescribing bisphosphonates for smokers and dental disease patients
What are the important interactions with bisphosphonates?
They bind with calcium, therefore their absorption is reduced if taken with calcium (inc milk), as well as antacids and iron salts
How are bisphosphonates prescribed?
For osteoporosis, alendrinic acid is prescribed orally, 70mg once weekly
For severe hypercalaemia and bone mets, pamidronate or zoledronic acid are prescribed as slow IV infusions, in single or divided doses. Calcium-lowering effects may not become apparent for 3-4 days and are maximal at 7-10 days, so re-prescription should not be considered before 1 week
For Paget’s disease, risedronate is given orally and pamidronate as an IV infusion
How are bisphosphonates administered?
Alendronic acid tablets should be swallowed whole at least 30 mins before breakfast or other medications, and taken with plenty of water (it is poorly absorbed)
The patient should remain upright after taking to reduce oesophageal irritation
How are bisphosphonate medications monitored?
In osteoporosis, check and replace calcium and vit D before treatment. Monitor efficacy using DEXA scans every 1-3 years to check whether bone density is stable or increasing
For hypercalcaemia, monitor efficacy by symptom enquiry and reduction in calcium levels
In the treatment of myeloma, bone metastases and Paget’s disease, enquire about symptoms e.g. bone pain and bone complications e.g. pathological fracture
Be alert for symptoms of oesophagitis, osteonecrosis of the jaw and atypical fractures, and monitor CA and phosphate
Which of the bisphosphonates is the cheapest?
Alendronic acid (£1 a month) Others are around £200 a month
Can bisphosphonates be prescribed without a DEXA scan?
Yes, you can assume a diagnosis of OP in women aged >75 who have had a fragility fracture
Bisphosphonates reduce recurrent fracture by 50%
Name some examples of systemic corticosteroids
Prednisolone, hydrocortisone, dexamethasone
What are systemic corticosteroids indicated for?
- To treat allergic or inflammatory disorders e.g. anaphylaxis, asthma
- Suppression of autoimmune disease e.g. IBD, inflammatory arthritis
- In the treatment of some cancers as part of chemotherapy or to reduce tumour-associated swelling
- Hormone replacement in adrenal insufficiency or hypopituitarism
How do systemic steroids work?
They exert mainly glucocorticoid effects, and are commonly prescribed to modify the immune response
They upregulate anti-inflammatory genes and downregulate pro-inflammatory genes e.g. cytokines, TNF-a). Direct actions on inflammatory cells include suppression of circulating monocytes and eosinophils.
Their metabolic effects include increased gluconeogenesis from increased circulating amino and fatty acids, released by calabolism (breakdown) of muscle and fat. These drugs also have mineralocorticoid effects, stimulating Na- and water retention K+ excretion in the renal tubule
What are the important adverse effects of steroids?
- Infection risk from immunosuppression
- Metabolic effects include diabetes mellitus and osteoporosis
- Increased catabolism causes proximal muscle weakness, skin thinning with easy bruising and gastritis
- Mood and behavioural changes include insomnia, confusion, psychosis and suicidal ideas
- Hypertension, hypokalaemia and oedema can result from mineralocorticoid actions
- Steroid treatment suppresses ACTH secretion, which can cause adrenal atrophy in prolonged treatment. If treatment is stopped suddenly, an acute Addisonian crisis with CV collapse may occur.
- Symptoms of chronic glucocorticoid deficiency that occur during treatment withdrawal include fatigue, weight loss and arthralgia
What are the warnings for prescribing systemic steroids?
They should be prescribed in caution in people with infection and in children
What are the important interactions for steroid treatment?
They increase the risk of peptic ulceration and GI bleeding when used with NSAIDs and enhance hypokalaemia in patients taking B2-agonists, theophylline, loop or thiazide diuretics
Their efficacy may be reduced by cytochrome P450 inducers e.g. phenytoin, carbamazepine, rifampicin
Corticosteroids reduce the immune response to vaccines
How are the potencies different for systemic steroids?
They have different potencies-
Dexamethasone is the most potent- with a dose of 750mcg being equivalent to prednisolone 5mg and hydrocortisone 20mg
Systemic corticosteroid treatment can be given orally or by IV or IM injection
How are steroids prescribed in emergencies/ short-term treatment?
In emergencies (e.g. treatment of the vasogenic oedema that may surround brain tumours), dexamethasone is prescribed at a high dose e.g. 8mg BD orally or IV), then weaned slowly as symptoms improve
In acute asthma, prednisolone is usually prescribed at a dose of 40mg orally daily
When oral administration is appropriate (e.g. IBD flares, anaphylaxis), IV hydrocortisone may be used
How are steroid prescribed in long-term treatment?
In inflammatory arthritis, use the lowest dose or oral prednisolone that control disease while limiting adverse effects. This may require co-prescription of a steroid-sparing agent (e.g. azathioprine methotrexate)
Consider bisphosphonates and PPIs to mitigate adverse effects
When should systemic corticosteroids be administered?
Once-daily corticosteroid treatment should be taken in the morning, to mimic the natural circadian rhythm and reduce insomnia
How should steroids be monitored?
Depends on the condition being treated e.g. peak flow in asthma, blood inflammatory markers for RA
Monitor for adverse effects in prolonged treatment by HBA1C and glucose, and a DEXA scan (to measure bone density)
How should steroid treatment be changed in acute illness?
Dose should be doubled, as atrophic adrenal glands may be unable to increase cortisol secretion in response to stress
Name some examples of Dipeptidylpeptidase-4 (DPP-4) inhibitors
Sitagliptan, linagliptan, saxagliptin
What are DPP-4 inhibitors used for?
T2DM
Used in combination with metformin (and/or other hypoglycaemic agents) where blood glucose is not adequately controlled on a single agent
OR as a single agent to control BG and reduce complication where metformin is CI’d or not tolerated
How do DPP4 inhibitors work?
The incretins (GLP1 and GIP) are released by the intestine throughout the day, but particularly in response to food. They promote insulin secretion and suppress glucagon release, lowering blood glucose. They are rapidly inactivated by the enzyme DPP4. DPP4-inhibitors (the 'gliptins') therefore lower blood glucuse by preventing integrin degredation.
The actions of integrins are glucose dependent, so they do not stimulate insulin secretion at normal blood glucose conc or suppress glucagon release in response to hypoglycaemia, therefore they are less likely to cause hypos than sulphonylureas, which stimulate insulin secretion irrespective of blood glucose
What are the important adverse effects of DPP4 inhibitors?
Generally well tolerated. Patients may experience GI upset, headache, nasopharyngitis, or peripheral oedema
Hypoglycaemia can occur, particularly where DPP4 inhibitors are prescribed in combination with sulphonlyureas and insulin
There is a small risk of acute pancreatits, affecting 0.1-1% patients. This should be suspected in patients experiencing persistent abdo pain and ususally resolves on stopping the drug
What are the warnings for DPP4 inhibitors?
They are contraindicated in people with a history of hypersensitivity to the drug class and should not be used in the treatment of T1DM or ketoacidosis
They should not be used pregnancy or breastfeeding
Use with caution in over 80s and people with a history of pancreatitis
As they are renally excreted, a dose reduction may be required for patients with moderate-to-severe renal impairment
What are the important interaction for DPP4 inhibitors?
Risk of hypoglycaemia increased by co-prescription of other anti-diabetic drugs e.g. sulphonylureas and insulin and by alcohol
(beta blockers may mask symptoms of hypoglycaemia)
The efficacy of DPP4 inhibitors is reduced by drugs that elevate blood glucose e.g. prednisolone, thiazide and loop diuretics
How are DPP4 inhibitors prescribed?
Orally, usually OD, with or without food
e.g. sitagliptin 100mg daily, linagliptin 5mg daily, saxabliptin 5mg daily
They are also formulated in fixed-dose combinations with metformin
As metformin needs to be taken 2-3 times daily, these fixed dose combinations contain half the daily dose of the DPP4 inhibitor (e.g. sitagliptin 50mg with metformin 1g) and are prescribed twice-daily
+ves- combined preparations include reduced tablet burden and improved treatment adherence
-ves- limited dose options, culprit of AEs more difficult to identify
