Endocrine - High Flashcards
Is thyroid stimulating hormone (TSH) elevated or decreased in hypothyroidism?
Elevated due to the loss of negative feedback from thyroxine (T4) on the pituitary
What are some signs and symptoms of hypothyroidism?
- fatigue
- weight gain
- constipation
- intolerance of the cold
- depression
- dry skin
- reduced body and scalp hair
- menstrual irregularities
What is meant by “Primary hypothyroidism”?
Primary hypothyroidism refers to when the condition arises from the thyroid gland and may be caused by iodine deficiency, autoimmune disease, radiotherapy, surgery or drugs, rather than due to a pituitary or hypothalamic disorder (secondary hypothyroidism)
Is hypothyroidism more common in males or females?
Females
What are the classifications of primary hypothyroidim, and how do they differ?
Primary hypothyrodism is characterised as either overt or subclinical, both of which may or may not symptomatic.
Overt is characterised as TSH levels being above the normal reference range and T4 levels being below the reference range.
Subclinical hypothyroidism is characterised as TSH levels above the reference range and T3 and T4 levels within the reference range.
How should secondary hypothyroidism be managed?
Th patient should be urgently referred to an Endocrinologist so the underlying cause of the issue can be assessed
How long can it take for patients who have had very high TSH levels before being initiated on levothyroxine treatment to see a return of levels to the reference range?
Up to 6 months
How is hypothyroidism defined in pregnancy?
In pregnancy hypothyroidism is always defined as overt using trimester specific reference ranges regardless of T4 levels
What is the first line treatment for overt hypothyroidism?
Levothyroxine
How often and in what form should thyroid function tests be measured in patients started on levothyroxine in both overt and subclinical hypothyroidism?
TSH levels should be measured every 3 months until stable levels within the reference range have been reached and then annually thereafter. T4 levls should also be measured in those who continue to be symptomatic.
When should levothyroxine be considered in a patient with subclinical hypothyroidism?
Patients with a TSH of 10mlU/L or higher on 2 separate occasions 3 months apart regardless of symptoms
When should a 6-month trial of levothyroxine be initiated for a patient with suspectd subclinical hypothyroidism?
In symptomatic patients under 65 years of age with a TSH above the reference range but less than 10mlU/L on 2 separate occasions within 3 months
What advice should be offered to a female patient with thyroid function tests outside of the reference range who is planning on getting pregnant?
Delay conception until established on levotyroxine and TFTs are stable within reference range
When is levothyroxine contra-indicated
Thyrotoxicosis
What drug class does thyrotropin alfa belong to?
Thyroid stimulating hormones
What is the primary cause of hyperthyroidism?
Graves Disease
What are the main symptoms of hyperthyroidism?
- hyperactivity
- disturbed sleep
- fatigue
- palpitations
- anxiety
- unintentional weight loss
- intolerance of heat
- increased appetite
What does “Primary hyperthyroidism” refer to?
The condition arises from the thyroid gland rather than due to a pituitary or hypothalmic disorder
What are the 2 classifications of hyperthyroidism and how are they defined?
Overt and subclinical
Overt - TSH levels are below he reference range and T4 and/or T3 are above the reference range
Subclinical - TSH levels are below the reference range but T4 and/or T3 levels are within the reference range
What is the first line recommendation for the treatment of hyperthyroidism?
Carbimazole
What is the alternative to carbimazole for the teatment of hyperthyroidism?
Propylthiouracil (where carbimazole is unsuitable)
What tests need to be performed before a patient is initiated on anti-thyroid medication such as carbimazole?
Full blood count and liver funcion tests
What is the first line treatment for Graves’ disease?
Radioactive iodine
How should carbimazole be prescribed for the treatment of Graves’ disease when the use of radioactive iodine has been deemed unnecessary?
Carbimazole should be offered as a 12-18 month course of block and replace regimen (with levothyroxine) OR as a titration regimen
What drug class does carbimazole belong to?
Sulphur-containing imidazole
What is the clinical indication for carbimazole?
Hyperthyroidism as a single agent
OR
Hyperthyroidism in combinatio with levothyroxine as part of a blocking-replacement regimen
Which antithyroid medication should be considered where the patient has experienced side effects with carbimazole, is pregnant, or is trying to conceive in the next 6 months, or has a history of pancreatitis?
Propylthiouracil
Over how long is a course of carbimazole typically given?
12-18 months
What dose of propylthiouracil is equivalent to 1mg of carbimazole?
10mg of propylthiouracil is equialent to 1mg of carbimazole
What are the MHRA warnings associated with carbimazole?
- Increased risk of congenital malformations: strengthened advice on contraception (February 2019)
- Risk of acute pancreatitis (February 2019)
What other important safety information is given by the manufacturer regarding the use of carbimazole?
Importance of recognising bone marrow suppression (neutropenia and agranulocytosis) caused by carbimazole:
- Patient should be asked to report any signs suggestive of infectition such as sore throat
- A white blood cell count should be performed if there are any signs of infection
- Carbimazole should be immediately stopped if there are laboratory signs of inection
When is the use of carbimazole contraindicated?
In severe blood disorders
What drug class does propylthiouracil belong to?
Thiouracils
Which medications are used in the treatment of pituitary (cranial) diabetes insipidus?
Vasopressin and Desmopresin
Which between vasopressin and desmopressin is more potent and has a longer duration of action?
Desmopressin
What is an unlicensed use of carbemazepine?
Treatment of partial pituitary diabetes insipidus - acts to sensitise the renal tubules to the action of remaining endogenous vasopressin
Which between vasopressin and desmopressin has vasoconstrictor effects
Vasopressin
In simple terms what is diabete insipidus?
Diabetes insipidus is a rare condition in which the kidneys are unable to retain water, which results in increased thirst, urination, and appetite
What is the mechanism of action of vasopressin and desmopressin?
Vasopressin, an endogenous hormone, and desmopressin, its analogue, have an antidiuretic effect on the kidney encouraging the retention of fluid
What are some of the indications for desmopressin?
- Diabetes insipidus (treatment and diagnosis)
- Primary nocturnal enuresis
- Polyuria and polydipsia
- Renal function testing
- Haemophilia and von Willebrand’s disease
How is desmopressin used for the diagnosis of diabetes insipidus?
After receiving a dose of desmopression IM or IN, restoration of the ability to concentrate urine after water deprivation conforms the diagnosis of diabetes insipidus
What is the most common side effect of desmopressin?
Hyponatraemia - as serum sodium levels are diluted
When is the use of desmopressin contraindicated?
- Cardiac insufficiency
- Conditions being treated with diuretics
- History of hyponatraemia
- Alcohol dependence
Which class of medications can increase the secretion of endogenous vasopressin and should therefore be avoided in concomitant use with desmopresin and exogenous vasopressin?
Tricyclic antidepressants
What monitoring should be performed for a patient being treated with desmopressin for nocturia?
Weight and blood pressure checks to ensure the patient is not becoming fluid overloaded
Which drug class/classes do vasopressin and desmopressin belong to?
Antidiuretic hormones and analogues
Can antidiuretic hormones be used during pregnancy and breastfeeding?
Pregnancy - Yes, but oxytocic effect in the third trimester
Breastfeeding - Yes, not known to be harmful
What are the clinical indications for the use of vasopressin?
- Pituitary diabetes insipidus
- Initial treatment of oesophageal variceal bleeding
What class of drug is Tolvaptan?
Vasopressin V2-receptor antagonist
What are the clinical indications for tolaptan and what brand names are licensed for each?
- SAMSCA - Hyponatraemia secondary to inappropriate antidiuretic hormone secretion
- JINARC - Autosomal dominant polycystic kidney disease in adults with CKD 1 to 4 at initiation of treatment wih evidence of rapidly progressing disease
When is tolvaptan contraindicated?
- Hypernatraemia
- Hypovolaemic hyponatraemia
- Impaired perception of thirst
- Volume depletion
Can tolapstan be used in pregnancy and breastfeeding?
No
When should caution be exercised for a patient prescribed tolvapstan for the treatment of hyponatraemia secondary to inapropriate secretion of antidiuretic hormone?
Patients at risk of demyelination syndromes such as in alcoholism, hypoxia, and malnutrition
In what patient demographics is osteoporosis most prevalent?
Post-menopausal women, men > 50yo, and those taking long term oral corticosteroids
How often should bisphosphonate treatment be reviewed?
5 years for alendronic acid, risedronate sodium, and ibandronic acid
3 years for zoledronic acid
What are the first line choices for the treatment of osteoporosis inpost-menopausal women, men over the age of 50, and those with glucocorticoid induced osteoporosis?
Alendronic acid and risedronate
What are the alternative treatments if alendronic acid and risedronate are not suitable for osteoporosis in post-menopausal women?
- Ibandronic acid
- Parenteral bisphosphonates (where oral is unsuitable)
- Denosumab (where oral is unsuitable)
What is recommended over oral bisphosphonates to treat osteoporosis in post-menopausal women who are at either a very high risk of fractures or in those that have severe osteoporosis and have experienced fractures in the past?
Teriparatide
OR
Renosozumab
What is an alternative to oral bisphosphonates in those with glucocorticoid induced osteoporosis?
- Zoledronic acid
- Denosumab
- Teriparatide
What is an alternative to oral bisphosphonates in men over the age of 50 with osteoporosis
- Zoledronic acid
- Denosumab
- Teriparatide
- Strontium ranelate
What are the MHRA warnings assocaited with bisphosphonate use?
- Atypical femoral fratures (June 2011)
- Osteonecrosis of the jaw (July 2015)
- Osteonecrosis of external auditory canal (December 2015)
When is th use of alendronic acid contraindicated?
- Abnormaliies of the oesophagus
- Hypocalcaemia
- Other factors which delay emptying
When should alendronic acid be used in caution?
- Dysphagia
- GI and oesphageal issues such GI bleeds, ulcers, or gastritis
- Femoral fractures
What are the key points when counselling a patient on the use of oral bisphosphonates?
- Sit up or stand to take
- Remain upright and do not eat or take any other medication for at least 30 minutes after taking
- Take on an empty stomach and swallow whole with a glass of water
- Take on the same day once a week
- Stop taking if you develop signs of oesophageal irritation
- Maintain good oral health and visit the dentist peiodically
Can alendronic acid be used in renal impairment?
It should be avoided if CrCl is <35 ml/minute
What are the clinical indications for ibandronic acid?
- Reduction of bone damage in bone metastases in breast cancer
- Hypercalcaemia of malignancy
- Post-menopausal osteoporosis
Can ibandronic acid be used in renal impairment?
If being used for the treatment of post-menopausal osteoporosis - avoid <30 ml/minute
How often is ibandronic acid administered typically and at what dose for the treatment of post-menopausal osteoporosis?
150mg ONCE a month PO
OR
3mg every 3 months IV
How is pamidronate disodium typically administered?
Intravenously
What are the clinical indications for pamidronate sodium?
- Hypercalcaemia in malignancy
- Osteolytic lesions and bone pain in bone metastases asociated with breast cancer or multiple myeloma
- Paget’s disease of bone
Can pamidronate sodium be given in either pregnancy or breastfeeding?
No
What are the clinical indications for the use of risedronate sodium?
- Paget’s disease of bone
- Treatment of post-menopausal osteoporosis
- Prevention of post-menopausal osteoporosis
- Treatment of osteoporosis in men at high risk of fractures
Can risedronate sodium be used in renal imapirment?
Avoid if CrCl <30 ml/minute
Can risedronate sodium be used in pregnancy or breastfeeding?
No
What are the non-specialist clinical indications fro the use of zoledronic acid?
- Osteoporosis (including glucocorticoid induced) in post-menopausal women, and men
- Fracture prevention in osteopenia
How is zoledronic acid administered?
Intravenously
In which patient demographic is zoldronic acid conra-indicated?
Women of cild bearing potential
Can zoledronic acid be used in either pregnancy or breatfeeding?
No
What is the most common side effect of zoledronic acid?
Flushing
What class of medication does calcitonin belong to?
Bone resorption inhibitors
What are the clinical indications for calcitonin?
- Hypercalcaemia for malignancy
- Paget’s disease of bone
- Prevention of bone loss due to sudden immobility
When is the use of calcitonin contraindicated?
Hypocalcaemia
Can calcitonin be used in either pregnancy or breastfeeding?
No
What drug class does strontium ranelate belong to?
Calcium resorption inhibitors
What is the general mechanism of action of strontium ranelate?
Strontium ranelate stimulates bone formation and inhibits calcium resorption
When is the use of strontium ranelate contraindicated?
- Cerebroascular disease
- Thromboembolic event
- Ischaemic heart disease
- Peripheral arterial disease
- Uncontrolled hypertension
- Permanent immobilisation
What is the clinical indication of strontium ranelate?
Treatment of severe osteoporosis in men and women at increased risk of fractures
What drug class does teriparatide belong to?
Parathyroid hormones and analogues
What are the clinical indications for the use of teriparatide?
- The treatment of osteoporosis in both men and women at increased risk of fractures
- Treatment of corticosteroid induced osteoporosis
What drug class does denosumab belong to?
Monoclonal antibodies
What drug class does renosozumab belong to?
Monoclonal antibodies
What are the MHRA warnings associated with denosuma?
- Atypical femoral fractures (February 2013)
- Osteonecrosis of the jaw (July 2015)
- Osteonecrosis of the external auditory canal (June 2017)
- For giant giant cell tumour of the bone: Risk of clinically significant hypercalcaemia following discontinuation (June 2018)
- New primay malignancies reported more frequently compared to zoledronic acid (June 2018)
- Increased risk of multiple vertebral fractures after stopping or delaying ongoing treatment (August 2020)
What are the clinical indications for denosumab?
- Treatment of osteoporosis in post-menopausal women and men at an increasedrisk of bone fractures
- Bone loss asociated with hormone ablation in men with prostate cancer at increased risk of fractures
- Bone loss associated with long term use of glucocorticoid therapy in patients at increased risk of bone fracture
- Prevention of skeletal related events in patients wit bone metastases
- Giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity
What is the use of denosumab contraindicated in?
Hypocalcaemia
Unhealed lesions from oral or dental surgery
What information regarding contraception and conception is relevant for the use of denosumab?
Ensure effective contraception is being used in women of child-earing potential durin treatmen and for at least 5 months after discontinuation
What are the typical symptoms of hypocalcaemia?
- muscle spasm
- twitches
- cramps
- numbness or tingling in the fingers, toes, or around the mouth
What should happen when a patient misses a dose of denosumab for the treatment of osteoporosis in post menopausal women (Prolia)?
Make sure that the dose is administered within 1 month of the scheduled date
How often is denosumab administred for the treatment of osteoporosis across the majority of patient demographics and at what dose?
60mg every 6 months
What is the general mechanism of action of denosumab?
Denosumab inhibits osteoclast formation, function, and survial and therefore decreases bone resorption
What is the clinical indication of romosozumab?
Severe osteoporosis in postmenopausal women at increased risk of fractures (specialist use only)
What is the general mechanism of action of romosozumab?
Romosozumab inhibits sclerostin, thereby increasing bone formation and decreasing resorption
What is bone resorption?
Bone resorption is the process where bones are absorbed and broken down by osteoclasts
When is the use of romosozumab contraindicated?
- Myocardial infarction
- Stroke
Can romosozumab be used in renal impairment?
The manufacturer advises that serum calcium concentrations are monitored in patients with severe renal impairment as the are at an increased risk of hypocalcaemia, but otherwise yes, it can be used in mild and moderate renal impairment
What is the brand name for romosozumab?
Evenity
What is the relevant safety information associated with the use of both denosumab and romosozumab?
- Be aware of, and report and signs of atypical femoral fratures
- Maintain good oral hygeine and see a dentist routinely
- Be aware of, and report any symptoms of hypocalcaemia
What are the brand names of different preparaions of denosumab?
- Prolia
- Xgeva
Do corticosteroids cause more side adverse effects when used orally or when inhaled?
Orally
What is meant by adrenal insufficieny?
Adrenal insufficien is the result of the inadequate production of steroid hormones in the adrenal cortex. These hormone are involved in a number of systems such as metabolic actiity, water and electrolyte balance, and the body’s response to stress
What are the two main types of hormone produced in the adrenal cortex?
Glucocorticoids (e.g. cortisol) and mineralocorticoids (aldosterone)
How is adrenal crisis treated?
Glucucorticoid replacement using hydrocortisone, and rehydration using crystalloid fluid (e.g. NaCl 0.9%)
What should happen to a patient taking long-acting hydrocortisone if they are admitted to hospital with acute intercurrent illness?
They should be switched onto a short-acting preparation of hydrocotisone.
If the illness is severe (vomiting or GI upset) then hydrocortisone should be administered either IV or IM
Which corticosteroid is the motsimilar to endognous cortisol?
Hydrocortisone
What are the first line treatments for adrenal insufficiency?
Hydrocortisone, prednisolone, and rarely dexamethasone
Which corticosteroid also has the most marked mineralocorticoid effects?
Fludrocortisone acetate
Name an endogenous mineralocorticoid
Aldosterone
Name an endogenous glucocorticoid
Cortisol
Which type of corticosteroid has the most marked anti-inflammatory effects?
Mineralocorticoid or Glucocorticoid
Glucocorticoid
Why is the anti-inflammatory effect of fludrocortisone not clinically relevant?
Because it has such a high mineralocorticoid effect
Why is hydrocortisone unsuitable for long term disease suppression?
Because of its high mineralocorticoid activity and therefore results in fluid retention
What should always be supplied alongside a prescription of a corticosteroid?
A steroid card
Which corticosteroid is predominantly used topically due to its moderate anti-inflammatory effects?
Hydrocortisone
Which corticosteroid is predominantly used for long term disease suppression?
Prednisolone
Which corticosteroids have predominantly glucocorticoid effects and very little mineralocorticoid effects, making them especially useful in conditions where fluid retention would be a disadvantage?
Betamethasone and dexamthasone
What causes Cushing’s syndrome
Elevated levels of cortisol
Can corticosteroids be used during pregnancy and breastfeeding?
Yes, and corticosteroid cover is required during labour
Does hydrocortisone have higher glucocorticoid or mineralocorticoid activity?
Its glucocorticoid and mineralocorticoid activity are the same
What is meant by mineralocorticoid activity?
Mineralocorticoids regulate water and salt balances; promoting Na and K transport followed by changes to water balance.
Treatment with aldosterone causes an increase in the reabsorption of sodium and and increase in the extretion of potassium and hydrogen in the renal tubule.
What drug class doe deflazacort belong to and what is it derived from
Corticosteroids - prednisolone
What is an unlicensed use for dexamethasone?
Bacterial meningitis
What is type 1 diabetes and what causes it?
Typ 1 diabetes is an absolute insulin deficiency in which there is little to no endogenous insulin secretory capacity due to the destuction of insulin-producing beta cells in thepancreatic islets of Langerhans.
What complications can arise as a result of poorly treated type 1 diabetes?
- Retinopathy
- Nephropathy
- Premature cardiovascular disease
- Peripheral arterial disease
How does type 1 diabetes present in adults?
- Hyperglycaemia (random plasma glucose >11mmol/L)
- Ketosis
- Rapid weight loss
- BMI <25
Which drug class are the (suffix) “gliptins”
DPP-4 inhibitors
Which drug class are the (suffix) “glutides”
GLP-1 agonsists
Which drug class are known as the (suffix) “glitazones”
Thiazolidinediones
Which drug class are known as the (suffix) “ides” (sort of)
Sulphonylureas
What is the most commonly prescribed sulphonulurea?
Gliclazide
Name the GLP-1 agonists
- Semaglutide
- Dulaglutide
- Liraglutide
- Exenatide
- Lixisenatide
What is the MHRA warning associated with the use of GLP-1 agonists?
Reports of diabetic ketoacidosis when concomitant insulin was rapidly reduced or discontinued (June 2019)
How does prednisolone interact with Beta2-antagonists?
Increased risk fo hyperkalaemia
What is the target fasting blood glucose range for a diabetic patient upon waking?
5 - 7 mmol/l
What is the target blood glucose range for a dibetic patient before meals?
4 -7 mmolL
What is the target blod glucose range for a diabetic person up to 90 minutes after eating?
5 - 9 mmol/L
What is the target blood glucose of a diabetic patient when diving?
> 5 mmol/L
What is the first line regimen for treatment of type 1 diabtes?
Patients should be offered a multiple daily injection basal-bolus insulin regimen with BD detetmir as the first line choice of long acting insulin, along side a rapid acting insulin analogue
What is the alternative to BD detemir as the basal insulin therapy for the treatment of type 1 diabetes?
OD insulin glargine may be used if detemir is not tolerated or he patientdoes not want to use a BD basal insulin
What is an alternative to both basal insulin detemir and glargine in the treatment of type 1 diabetes when there is a particular concern regarding nocturnal hyperglycaemia?
Insulin degludec
Are non-basal “twice daily” biphasic insulin regimens recommended for patients with newly diagnosed type 1 diabetes?
No
When should the bolus rapid acting insulin be injected in a basal-bolus regimen?
Before meals and not after
Can biphasic twice daily insulin regimens be used in type 1 diabetes?
Yes
What is lipohypertrophy and how can it be prevented?
Lipohypertropy is the formation of scar tissue or lumps of fat at the site of repeated insulin injection and can cause irraticinsulin absorption and poor glycaemic control. It can be avoided by rotating sites on insulin injection.
How long does it take to reach steady-state levels using long acting insulins?
2 - 4 days
Typicaly how long is the duration of action of long acting insulins?
36 hours
Typically how long is the duration of action of intermediate acting insulins?
11 - 25 hours
What is type 2 diabates mellitus?
Type 2 diabetes mellitus is a chronic metabolic disorder charactrised by insulin resistance, where insufficient pancreatic insulin production occurs over time leading to hypoglycaemia
What is the target HbA1c when type 2 diabetes is being treated with lifestyle measures or with just a single agent not associatd with hypoglycaemia (metformin)?
48 mmol/L
What is the target HbA1c when type 2 diabetes is being treated with a single agnt associated with hypoglycaemia (sulphonylureas), or two or more antidiabetic drugs used in combination?
53 mmol/L
WHat HbA1c reading would prompt you to intensify a antidiabetic treatment in a patient with type 2 diabates?
58 mmol/L
What is the first line antidiabetic drug for the treatment of type 2 diabetes?
Metformin hydrochloride
(Alongside modification of diet and lifestyle)
When is insulin treatment typically initiated in patients with type 2 diabetes?
It is typically started at the second intensfication of treatment
What are the treatment options available for the first intensification of type 2 diabetes?
(2x antidiabetic drugs) Metfomin combined with the use of either:
- Sulphonylurea
- Pioglitazone
- DPP-4 inhibitor
- SGLT2 inhibitor (only where sulphonylureas are contraindicate or the patient is at a high risk of hypoglycaemia)
What are the reatment options available for the second intnsification of treatment of type 2 diabetes?
(3x antidiabetic drugs) The use of metformin and a sulphonylurea combined with the use of:
- DPP-4 inhibitor
- Pioglitazone
- SGLT2 inhibitor
OR
The use of metformin, pioglitazone and an SGLT2 inhibitor
OR
Insulin-based treatment
If triple therapy of metformin combined with two other antidiabetic medications is not successful, not tolerated or contraindicated what is the next available option?
Besides the initiating insulin-based treatment
The use of an GLP-1 agonist in combination with metform and a sulphonylurea
Only when should GLP-1 agonists be prescribed for the treatment of type 2 diabates?
BMI >35 an specific medical problems associated with obesity
OR
BMI<35 but for whom insulin therapy would have significant occupational complications
OR
The weight loss associated with the use of GLP-1 agonists would benefit other obesity-related comorbidities
Where metformin is not tolerated or contraindicated, what are the alternative first line therapies fo the treatment of type 2 diabetes?
Monotherapy using:
- Sulphoylurea
- DPP-4 inhibitor
- Pioglitazone
- SGLT2 inhibitor (only if a DPP-4 inhibitor would otherwise be precribed, and neither the use of a sulphonylurea or pioglitazone is appropriate)
How can the cardiovascular risk in patients with type 2 diabetes be further reduced beyond the use of antidiabetic medication?
The use of:
- ACEi or ARB
- lipid-regulating drugs
How should the blood pressure of a patiet with type 2 diabates and nephropathy be managed?
Blood pressure should be lowered to he lowest possible level to slow the rate of decline of glomerular filtration and reduce proteinuria
What should diabetic patients with confirmed neophropathy be given?
ACEi or ARB regardless of their blood pressure
What should patients with type2 diabetes and CKD who are being treated with aACEi or ARB be given?
SGLT2 inhibitor
What effect can ACE inhibitors have on the action of insulin and other oral antidiabetic drugs, and in which patient demgraphic is this more common?
ACEi’s can potentiate the hypogycaemic effects of insulin and oral anti-diabetic drugs. This is more common in patients with renal impairment and those in the first weeks of combined therapy.
How is diabetic diarrhoea managed in patients with autonomic diabetic neuropathy?
Tetracycline
OR
Codeine
How can neuropathic postural hypotension be managed in a patient with type 2 diabetes?
Increased salt intake and the use of fludricortisone acetate
Which drugs can be used to manage painful diabetic peripheral neuropathy?
Monotherapy with:
- Tricyclic antidepressants such as amutriptyline, imipramine, duloxetine, and venlafaxine
- Antepileptics such as ganapentin and pregabalin
- Opioid analgesics in combination with gabapentin or pregabalin (if monotherapy ineffetive)
What are the two medical emergencies associated with type 2 diabetes?
Diabetic ketoacidosis (DKA) and Hyperosmolar hyperglycaemic state (HHS)
What are some precipitating factors for DKA and HHS?
- Infection
- Myocardial infarction
- Inadequate insulin therapy
- Pancreatitis
- Stress/ physical trauma
What is the initial drug management for DKA?
- IV fluids
- IV insulin (patients who use long-acting insulin should continue to take their usual doses throughout treatment
Potasium and glucose may be needed later to preven hypokalaemia and hypoglycaemia
Is DKA more common in type 1 or 2 diabetes?
Type 1
How does DKA typically present?
- Develops over just a few hours
- Hyperglycaemia (>11 mmol/L)
- Ketonaemia (blood ketones >3mmol/L or ketonuria of >2+)
- Acidosis (bicarbonate <15 mmol/L or venous pH <7.3
- Dehydration
- Weight loss
- Tiredness
- Nausea and vomiting
- Abdominal pain
What is the initial drug management for HHS?
- IV fluids
- IV insulin
- Potassium replacement
How does HHS typically present?
- Hypovolaemia
- Marked hyperglycaemia (>30 mmol/L) without increased ketone levels or acidosis
- Hyperosmolarity
- Dehydration
- Weakness
- Weight loss
- Tachycardia
- Dry mucous membranes
- Poor skin tugour
- Shock
When should basal-bolus inulin be restarted when converting back to SC insulin therapy after using a VRII?
Basal-bolus insulin should be restarted when the first post-operative mealtime dose of insulin is due, and the VRII should continue until 30-60 minutes after the meal.
When should twice-daily mixed regimens inulin be restarted when converting back to SC insulin therapy after using a VRII?
Twice-daily mixed insulin therapy should be restarted before breakfast or evening meal after the operation, and the VRII should be maintained for 30-60 minutes after the meal.
At what % of the usual dose, should insulin be given on the day before and day of a major operation in a patient with type 2 diabetes?
80%
Which class of antidiabetic drug can be continued as normal during an insulin infusion during surgery?
GLP-1 agonists
Which oral antidiabetic medications can be continued into pregnancy?
Metformin
Insulin
Which antidiabetics drugs can be used when breastfeeding?
Metformin
Which type of insulin is the first line choice long-acting insulin during pregnany?
Isophane isulin (despite being intermediate), though i he patient had good blood-glucose control using detemir or glargine these may be continued
What should pregnant women wih type 1 diabetes be prescribed in case it is necessary?
Glucagon
What should happen with regards to ACEi/ARB’s and other cardiovascular medications in a patient with type 2 diabetes at the confirmation on pregnancy?
ACEi’s and ARBs should be replaced with alternate antihypertensives that are suitable for use in pregnancy.
Statins
What is the first line treatment for gestational diabtes in woemn with blood glucose of 7 mmol/L at diagnosis?
Try to manage blood glucose wih diet and exercise initially, and then if target levels are not met then metormin may be started
What is the first line treatment for gestational diabetes in women who have a blood glucose of >7 mmol/L at diagnosis
Treatment with insulin with or without metformin
When should women with gestational diabetes discontinue antihyperglycaemic therapy?
Immediately after giving birth
What drug clas is acarbose?
Acarbose is a Alpha glucosidase inhibitor
What drug class does metformin belong to?
Biguanides
What is the basic mechanism of action of GLP-1 agonists?
They augment glucose-dependent insulin secretion and slow gastric emptying
Do GLP-1 agonists cause hypoglycaemia?
No, their mechanism of action is seemingly dependent on ambient glucose levels so they do not cause hypolycaemia when used concurrently with metformin or thiozolidinediones
Which drug is sold under the brand name Truliciy
Dulaglutide
Which drug is sold under the brand names Saxenda and Victoza?
Liraglutide
What causes diabetic ketoacidosis?
Diabetic ketoacidosis is caused by a severe lack of insulin, which results in the body breaking down fat instead of glucose. The breakdown of fats (ketosis) releases ketones which can accumalate to toxic levels and lower the pH of the blood.
What advice is offered by the MHRA for the use of SGLT2 inhibitors regarding the increased risk of diabetic ketoacidosis?
- Stop treatment with SGLT2 in acute illness
- Inform patients about the signs and symptoms of DKA
- Tests for raised ketones in patients with signs and symptoms of DKA
- Discontinue use if DKA is suspected
- Do not restart the use of any SGLT2 in patients who have experienced DKA during their use
Name the sulphonylureas
- Gliclazide
- Glimepiride
- Glipizide
- Tolbutamide
What is the MHRA warning associated with the use of insulins?
Risk of cutaneous amyloidosis at injection site (September 2020)
What drug class does pioglitazone belong to?
Thiozolidinediones
In the presence of what condition is the use of most oral antidiabetic medications contraindicated in?
Ketoacidosis
What is the basic mechanism of action of the thiozolidinediones?
Thiozolidinediones such as pioglitazone reduce peripheral insulin resistance
Which antidiabetic drugs are unlikely to cause hypglycaemia when prescribed without insulin or sulphonylureas?
- Metformin
- DPP-4 inhibitors
- Pioglitazone
- GLP-1 agonists
- SGLT2 inibitors
When using which antidiabetic drug is it not appropriate to give a patient sugar dissolved in water as a treatment for a hypoglycaemic episode and why?
Acarbose, as it inhibits the conversion of sucrose into glucose
In which patient demographics is the use of glucagon ineffective and why?
Patients with depleted glycogen stores in the liver
- Patients who been on a prolonged fast
- Alcohol induced hypoglycaemia
- Adrenal insufficiency
- Chronic hypoglycaemia
Should a regular dose of insulin be omitted in a patient having an episode of hypoglycaemia?
No, but the dose may need to be adjusted
Which drug is used to treat chronic hypolycaemia?
Diazoxide
What are some side effects to diazoxide use?
- Loss of appetite
- GI disturbance (N+V)
- Hyperglycaemia
- Hypoension
- Tachycardia
What is the risk of starting combined HRT more than 10 years after menopause?
Increased risk of coronary heart disease
Which prepaeration type of HRT, combined or oestrogen-only, has an associated higher risk of breast cancer?
Combined oestrogen-progestrogen prepartions
What benefit is there to adding a progestrogen cyclically to a HRT regimen?
Reduced risk of endometial cancer
The risk of endometrial cancer is eliminated completely when progestrogens are given continuously, but the risk of breast cancer is increased
What are the risks associated with using any type of HRT preparation?
(oestrogen-only or combined)
Increased risk of:
- Cancer
- Endometrial cancer
- Ovarian cancer
- VTE
- Stroke
Does HRT need to be stopped prior to surgery?
Yes, at least 4 - 6 weeks before surgery
List some reasons to stop HRT therapy
- Sudden severe chest pain
- Sudden breathless
- Unexplained swelling and pain of the calf
- Severe stomah pain
- Serious neurological effects
- Hepatitis, jaundice, or liver enlargement
- BP above 160/95
- Prolonged immobility
- Detction of any conditions in which the use is contraindicated
What are the two main groups of progestrogens, and list some examples
Progesterone and its analogues (dydrogesterone and medroxyprogesterone acetate)
Testosterone analogues (norethisterone and norgestrel)
Desogestrel, norgestimate, and gestodene are derivatives of which progestrogen?
Norgestrel
What is the first line drug treatment for endometriosis?
A 3-month trial of paracetamol and/or an NSAID, followed and a combined oral contraceptive or a progestrogen
What is the first line drug treatment for a patient with heavy menstrual bleeding?
Levonorgestrel-releasing intrauterine device (IUD)
What are the second line treatment options when an IUD has been unsuccessful for the treatment of heavy menstrual bleeding?
Tranexamic acid
OR
NSAID
OR
Combined hormonal contraceptive
OR
A cyclical oral progestrogen
What is the MHRA warning associated with HRT?
Further information on the known increased risk of breast cancer with HRT and its persistence after stopping (September 2019)
Which drug class does raloxifene belong to?
Calcium resorption inhibitor
What is raloxifene indicated for?
Treatment of postmenopausal osteoporosis
What is the name of the hormone sold under the brand name Elleste solo?
Estradiol
Which progestrogens are used in combined, and progrestrogen-only contraceptives?
- Desogestrel
- Norethisterone
- Gestodene
- Norgestimate
- Levonorgestrel
To which drug class does cyproterone acetate belong to?
Anti-androgens
What kind of hormone is testosterone?
Androgen
What is the MHRA warning associated with cyproterone acetate?
New advice to reduce the risk of meningioma (June 2020)
What are Dipeptidylpeptidase-4 inhibitors indicated for?
Type 2 Diabetes: In combination with metformin (or other hyperglycaemic agents) where blood glucose is inadequately controlled.
As a single agent where metformin is contraindicated or not tolerated.
What is the mechanism of action for DPP-4 inhibitors?
Incretins and glucose-dependent insulinotropic peptide are released by the intestine throughout the day, and particularly in response to food - these promote the secretion of insulin and suppress glucagon release, thus lowering blood glucose. Incretins are rapidly inactivated by the enzyme DPP-4. DPP-4 inhibitors therefore prevent the degradation of incretins and increase plasma concentrations of their active forms, lowering blood glucose concentrations.
Which are less likely to cause HYPOglycaemia, DPP-4 inhibitors or sulphonylureas ?
DPP-4 inhibitors - As the action of incretins are glucose dependent they do not stimulate the secretion of insulin at normal blood glucose levels or suppress glucagon release in response to hypoglycaemia. This means DPP-4 inhibitors are less likely to cause hypoglycaemia than sulphonylureas which stimulate insulin secretion irrespective of blood glucose.
Name the DDP-4 inhibitors
Alogliptin, Sitagliptin, Linagliptin and Saxagliptin
What are the potential adverse effects associated with the use of DPP-4 inhibitors?
- HYPOglycaemia where DPP-4 inhibitors are being used in combination with sulphonylureas and/or insulin
- All DPP-4 inhibitors are associated with acute pancreatitis which typically presents as persistent abdominal pain resolved upon stopping of the drug
- GI upset
- Headache
- Nasopharyngitis
- Peripheral oedema
Can DPP-4 inhibitors be used to treat Type 1 diabetes?
No
Can DPP-4 inhibitors be used to treat ketoacidosis?
No
Can DPP-4 inhibitors be used during pregnancy or breastfeeding?
No
How are DPP-4 inhibitors excreted?
Renally
When should DPP-4s be dose adjusted?
During moderate to severe renal impairment
When are DPP-4 inhibitors contraindicated?
DPP-4 inhibitors are contraindicated in patients with hypersensitivity to the drug class
When should DPP-4 inhibitors be used with caution?
- Elderly (>80 years)
- History of pancreatitis
Use of which other drug classes increases the risk of HYPOglycaemia in concurrent use with DPP-4 inhibitors?
- Sulphonylureas
- Insulin
- Alcohol
Which drug class may mask the symptoms of HYPOglycaemia?
Beta-blockers
What is the typical dosing of DPP-4 inhibitors?
Once daily
What quantity of the the daily dose of a DPP-4 inhibitor dose a combined formulation with metformin contain?
Half the daily dose
What is the key counselling point when advising a patient on the use of a DPP-4 inhibitor?
Acute Pancreatitis - seek medical attention if you develop severe or acute stomach pain radiating to the back
Which indicator is used to assess glycaemic control when using a DPP-4 inhibitor?
HbA1c
What are the target HbA1c levels for monotherapy and combined therapy with a DPP-4 inhibitor?
Monotherapy - <48mmol/mol
Combination therapy - <53mmol/mol
What HBA1c is generally a trigger to intensify treatment with an additional agent when using a formulation of a DPP-4 inhibitor?
> 58mmol/mol
What advantage do metformin and SGLT2 inhibitors have over use of DPP-4 inhibitors?
They reduce the risk of vascular complications
The efficacy of DPP-4 inhibitors is reduced by which medications that elevate levels of blood glucose?
- Prednisolone
- Thiazide
- Loop diuretics
What is the indication for metformin?
Type 2 diabetes as a a monotherapy or in combination with DPP-4 inhibitors, Sulphonylureas, or insulin
What is the mechanism of action for metformin?
Metformin (a biguanide) lowers blood glucose by reducing hepatic glucose output (glycogenolysis and gluconeogenesis)) and to a lesser extend increasing the uptake and utilisation of glucose by skeletal muscle. Metformin achieves its mechanism of action through activation of AMP (adenosine monophosphate- activated) kinase which acts as a metabolic sensor.
What are some key adverse effects of metformin use?
GI upset
- Nausea
- Vomiting
- Taste disturbance
- Diarrhoea
- Lactic acidosis
When should metformin be used with caution?
Renal impairment
Hepatic impairment
Chronic alcohol abuse
At what eGFR does metformin require dose adjusting, and what level dose it require stopping metformin?
Dose reduction - <45ml/min per 1.73m2
Stopped - <30ml/min per 1.73m2
When should metformin be held?
AKI
Severe tissue hypoxia (e.g. in sepsis, cardiac or respiratory failure, or myocardial infarction)
Acute alcohol intoxication
Which three medications reduce the efficacy of metformin?
Prednisolone
Thiazide
Loop diuretics
When and for how long should metformin be withheld regarding IV CONTRAST MEDIA?
Metformin must be withheld before and for 48 hours after the injection of IV contrast media when there is an increased risk of renal impairment, metformin accumulation, and lactic acidosis.
Which other drugs that have the potential to impair renal function should be used in caution with metformin?
ACE inhibitors
NSAIDs
Diuretics
What formulation of metformin should patients be started on initially, and why?
Standard release to minimise GI side effects
What is a common starting regimen for metformin?
500mg OD with breakfast, increasing by 500mg weekly to 500-850mg TDS with meals
What are the key points when counselling a patient who has been newly started on metformin?
- Inform their Dr they are taking metformin before having an X-ray or operation
- Seek urgent medical advice if they develop significant illness such as breathlessness, fever, or chest pain, as, in addition to treating the illness, metformin may need to be stopped or withheld due to the risk of a side effect called lactic acidosis
Ideally when should renal function be measured in patients taking metformin?
Before starting treatment and then at least annually during treatment. Renal function should be measured more frequenty (at least twice per yer) in patients with deteriorating renal function or at increased risk of renal impairment.
How should glycaemic control be measured in patients taking metformin and what is the target level when metformin is being used as a single agent?
HbA1c - <48mmol/mol
Does metformin stimulate insulin scretion?
No
When and how should treatment of type 2 diabetes be intensified when using metformin as a single agent?
A second agent should be added if HbA1c >58mmol/mol and a new target of <53 mmol/mol is set (balancing the risk of hyperglycaemia against the risk of treatment, in particular hypoglycaemia)
At what point and for long should increased physical activity be recommended before meformin is initiated?
HbA1c >48 mmol/mol
At least three months before metformin initiation
What primarily increases insulin resistance?
Increased body weight
What kind of hormone is insulin?
Anabolic
Does metformin cause weight gain?
No. Unlike the sulphonylureas, metformin does not stimulate the secretion of insulin, which as an anabolic hormone causes weight gain and can worsen diabetes mellitus over the long term.
What are the sulphonylureas indicated for?
Type 2 diabetes in combination with metformin (and/or other hyperglycaemic agents) or as a single agent to control blood glucose levels where metformin is contraindicated
What drug class is gliclazide
Sulphonylurea
What is the mechanism of action of sulphonylureas?
They stimulate pancreatic insulin secretion by blocking ATP dependen K+ channels in pancreatic beta-membranes causing depolarisation of the cell membranes and the opening of Ca2+ channels. This increases intracellular Ca2+ concentrations, stimulating the secretion of insulin. Sulphonylureas are only effective in patients with residual pancreas function.
What are the potential adverse effects associated with the use of sulphonylureas?
- GI upset
- HYPOglycaemia
- Rare sensitivity reactions (hepatic toxicity, drug hypersensitivity syndrome, and haematological abnormalities)
Where are the sulphonylureas metabolised?
The liver
How are the sulphonylureas excreted?
Unchanged drug and metabolites are excreted renally
Can sulphonylureas be used in renal impairment?
Yes, they should be used with caution in those with mild-moderate renal impairment due to the risk of hypoglycaemia. The lowest possible dose should be used and blood glucose should be carefully monitored
Gliclazide can be used in renal impairment but careful monitoring of blood glucose is essential
When should sulphonylreas be used with caution?
In those with increased risk of HYPOglycaemia:
- Hepatic impairment (reduced gluconeogenesis)
- Malnutrition
- Adrenal or pituitary insufficiency (lack of counter-regulatory hormones)
- Elderly
When is a dose adjustment required for the use of sulphonylureas?
In patients with hepatic impairment
The risk of HYPOglycaemia is increased by the co-prescription of which other drugs with the sulphonylureas?
Alchohol
Antidiabetic drugs:
- Metformin
- DPP-4 inhibitors
- Thiazolidinediones (*glitazones)
- Insulin
The efficacy of sulphonylureas are effected by which other drugs that elevate blood glucose?
- Prednisolone
- Thiazide
- Loop diuretics
What dose of standard release gliclazide has the same glucose lowerin effect as 30mg MR gliclazide?
80mg
What is a standard starting regimen for gliclazide?
40-80mg OD, then increased of 160-320mg if necessary (in 2x divided doses when exceeding 160mg)
When/how should sulphonyolureas be taken?
With meals (OD with breakfast or BD with breakfast and dinner for higher doses)
What are the key points when counselling a patient about the use of sulphonylureas such as gliclazide?
- Should be used in addition to healhy lifestyle measures
- Watch out for the symptoms of HYPOglycamia (dizziness, sweating, nausea, and confusion)
How is glycaemic control measured when using sulphonylureas?
HbA1c
What is the target HbA1c of a patient using gliclazide as a single agent to treat type-2 diabetes
<48 mmol/mol
When and how is treatment intensified for a patient using gliclazide as a single agent to treat type-2 diabtes
Treatment is itensified with the addiion of a second agent when HbA1c exceeds >58 mmol/mol and a new target of <53 mmol/mol is set
Which are more expensive; sulphonylureas or DPP-4 inhibitors
DPP-4 inhibitors are newer and more expensive
When are sulphonylureas contraindicated?
In the presence of ketoacidosis
Can sulphonylureas be used in pregnancy or breastfeeding?
No, due to the possible risk of neonatal or infant hypoglycaemia
During acute illness what should happen to treatment with sulphonylureas?
During acute illness, insulin resistance increases and renal and hepatic function may be impaired. As such oral hypoglycaemics become less effective at controlling blood glucose and side effects are more likely. Insulin treatment may be required temporarily as the dosage can be adjusted more easily than that of oral medications.
What drug class is prednisolone?
Corticosteroid
(Glucocorticoids)
What drug class is hydrocortisone?
Corticosteroid
(Glucocorticoids)
What drug class is dexamethasone?
Corticosteroid
(Glucocorticoids)
What are he indications for corticosteroids (glucocorticoids)
- To treat allergic and inflammatory disorders
- Supression of autoimmune disease
- In the treatment fof some cancers as part of chemotherapy or to reduce tumour-associated swelling
- Hormone replacement in adrenal insufficiency hypopituitarism
What are the mechanismsof action of corticosteroids (glucocorticoids)?
These corticosteroids mainly exert glucocorticoid effects.They bind to the cytosolic glucocorticoid receptors, which then translocate to the nucleus and bind to the glucocorticoid-response elements, which regulate gene expression. They upregulate antiinflammatory genes and downregulate pro-inflammatory genes (e.g. cytokines, tumour necrosis factor-alpha etc). 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 catabolism of muscle and fat.
These drugs also have mineralocorticoid effects, stimulating sodium and water retention and potassium excretion in the renal tubule.
What are the main adverse effects of cortcosteroid use (glucocorticoids)?
- Immunosuppression
- Diabetes mellitus
- Osteoporosis
- Cushing’s syndrome
- Skin thinning
- Gastritis and peptic ulcers
- Proximal muscle weakness
- Bruising
- Insomnia
- Confusion
- Psychosis
- Suicidal ideation
- HYPERtension
- HYPOkalaemia
- Oedema
- Adrenal supression
- Glaucoma
What immune side effects can corticosteroid use cause?
Immunosuppression
What metabolic side effects can corticosteroid use cause?
Diabetes mellitus
Osteoporosis
What side effects can result from increased catabolism associated with corticosteroid use?
Skin thinning
Gastritis
Easy bruising
Proximal muscle weaknes
What behavioural side effects can result from corticosteroid use?
Insomnia
Confusion
Psychosis
Suicidal ideation
What side effects can be caused by the mineralcorticoid effects of corticosteroid use?
Hypertension
Hypokalaemia
Oedema
Why is slow withdrawal of corticoid sterioids required?
To prevent Addisonian crisis and to allow for the recovery of endogenous adrenal function, and to prevent chronic glucocorticoid deficiency which presents as fatigue, weight loss and arthralgia (joint stiffness)
What is the MHRA warning for the use of systemic cortcosteroids
Rare risk of central serous chorioretinopathy wih local as well as systemic administration (Augut 207)
When should corticosteroids be prescribed with caution?
People with infection
Children - in whom it may suppress growh
How do corticosteroids interact with NSAIDs?
They both increase the rik of peptic ulceration and GI bleeding
Which drug classes increases the risk of HYPOkalaemia when taken with corticosteroids such as prednisolone?
Beta2-agonists
Theophylline
Loop diuretics
Thiazide diuretics
Which medications reduce the efficacy of corticosteroids such as prednisolone?
Cytochrome P450 inducers e.g
- phenytoin
- rifampicin
- carbamazepine
List the medications that interact wih corticosteroids
NSAIDs
Loop diuretics
Thiazide diuretcs
Beta2-agonists
Phenytoin
Carbamazepine
Rifampicin
When in the day should OD corticostroids be given and why?
In the morning to mimic the body’s natural circadian rythm and avoid insomnia
Between prednisolone, hydrocortisone, and dexamethasone, which is more potent and what are the equivalent dosages?
Dexamethasone is the more potent of the three
750micrograms dex = 5mg pred = 20mg hydrocort
What dose of dexamethasone is typically prescribed in emergencies (e.g. treatment of vasogenic oedema that may surround brain tumours)?
8mg BD IV or orally - then weaned down slowly as symptoms improve
What should happen to corticosteroid therapy during acute illness?
The dose is typically doubled as patients on long term steroids are usualy unable to increase endogenous secretion of cortisol in times of stress, therefore additional exogenous corticosteroid may be required.
When should courses of prednisolone be tapered down in adults?
- When the patient has received 40mg or more OD for 1 week or more
- Been given repeat doses in the evening
- Received more than 3 weeks of treatment
- Recently received repeat courses (particulalry in the last 3 weeks)
- Taken a short course within 1 year of stopping long term therapy
- Other possible causes of adrenal suppression
What is the typical dose of prednisolone used in an adult with an acute exacerbation of COPD?
30mg OD PO for 7-14 days
What is the typical dose of prednisolone used in an adult with an acute exacerbation of asthma?
40mg OD PO for at least 5 days
When should courses of prednisolone be tapered down in children?
- When the patient has received 40mg or more OD for 1 week or more / 2mg/kg OD for 1 week or more / 1mg/kg OD for 1 month or more
- Been given repeat doses in the evening
- Received more than 3 weeks of treatment
- Recently received repeat courses (particulalry in the last 3 weeks)
- Taken a short course within 1 year of stopping long term therapy
- Other possible causes of adrenal suppression
What drugs can be given to limit adverse effects of corticosteroid use in patients with relevant risk factors?
Bisphosphonates
PPIs
Which corticosteroid is typically used and how when oral aministration is not appropriate (e.g. inflammatory bowel disease flares, anaphylaxis, etc)?
IV hydrocortisone
When may the co-prescription of steroid sparing agents be necessary to limit adverse effects with corticosteroids? Which agents are typically co-prescribed?
In long term treatment of consitions such as inflammatory arthritis where the lowest dose of oral prednisolone is used to treat the disease and limit adverse effects.
Commonly co-prescribed drugs in these consitions are methotrexate and azathioprine.
What are the key points when counselling a patient newly started on corticosteroids such as oral prednisolone?
- Do not stop treatment suddnly
- Carry a steroid card incase they need treatment
- Discus the risks of long term steroid use such as osteoporosis, bone fracture, and diabetes so the patient can make an informed decision about their therapy
How should the efficacy of prednisolone treatment be monitored?
This depends on the condition being treated and the anticipated adverse effects
- Peak expiratory flow in excerbations of asthma and COPD
- Blood inflammatory markers for inflammaory arthritis
- HbA1c and blood gluose to monitor for potential diabetic levels
- DEXA scans to measure bone densiy for potntil osteoporosis
How do corticosteroids affect ACTH (pituitary adrenocorticotropic hormone) secretion and what are the consequences of this?
ACTH secretion is suppressed
- stimulus of normal adrenal cortisol production switched off
- Prolonged treatment causes adrenal atrophy which prevents endogenous cortisol secretion
- Sudden withdrawal can cause Addisonian crisis with cardiovascular collapse
- Chronic glucorticoid deficiency during withdrawal may present as fatigue, weight loss, and arthralgia
Concurrent therapy with drug class increases insulin requirements?
Systemic corticosteroids
What are the indications for insulin?
- Insulin replacement in people with type 1 diabetes and control of blood glucose in type 2 diabetes where oral hypoglycaemic treatment is inadequate or poorly tolerated
- Given intravenously, in the treatment of diabetic emergencies such as diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome
- Given alongside glucose to treat hyperglycaemia while other measures are being initiated
What are the main adverse effects of insulin use?
- Hypoglycaemia
- Fat overgrowth in repeated SC use at the site of injection
What are the 5 types of insulin?
- Rapid acting
- Short acting
- Intermediate acting
- Long acting
- Biphasic
What type of insulin is insulin glargine
Long acting
What type of insulin is insulin degludec?
Long acting
What type of insulin is insulin detemir?
Long acting
What type of insulin is insulin aspart?
Rapid acting
What type of insulin is insulin isophane?
Intermediate acting
What type of insulin is insulin lispro?
Rapid acting
What type of insulin is insulin glulisine?
Rapid acting
What type of insulin is soluble insulin?
Short acting
What types of insulin are usually in a biphasic insulin preparation?
Rapid and intermediate
What type of insulin is in Lantus preparations?
Glargine
What type of insulin is in Humalog preparations?
Lispro
What type of insulin is in Toujeo preparations?
Glargine
What type of insulin is in Levemir preparations?
Detemir
What kind of insulin is in Tresiba preparations?
Degludec
What kind of insulin is in Actrapid preparations?
Soluble insulin
What kind of insulin is in Fiasp prepaprations?
Aspart
What kind of insulin is in Humalog S preparations?
Soluble insulin
What kind of insulin is in Humalin I preparations?
Isophane
What kind of insulin is in Semglee preparations?
Glargine(-yfgn)
What is the mechanism of action of insulin in the treatment of HYPERkalaemia?
Insulin drives potassium ions into the cells, reducing serum K+ levels. However, when insulin treatment is stopped K+ leakback out of cells, so this is only a short-term measure while other treatments are initiated.
What is the general mechanism of action of insulin in the treatment of type 1 and 2 diabetes?
Insulin stimulates th uptake of glucose from circulaion into tissues, including skeletal muscle and fat, and increasess the use of glucose as an energy source. It also stimulates glycogen, lipid and protein synthesis and inhibits gluconeogenesis and ketogenesis.
Which yp of insulin is used whn IV insulin is required?
Soluble inulin (Actrapid)
Which types of insulin (inc. brand names) are typically used in a basal-bolus regimen?
Inulin glargine (Lantus) and insulin aspart (NovoRapid)
What is soluble insulin administered with in the treatment of HYPERkalaemia and why?
Glucose (20%), to avoid hypoglycaemia
What are the key points when counselling a patient on insulin use?
- Treatment does not replace the need to maintain helthy lifestyle such as exercise and diet
- Risk of hypoglycaemia and symptoms (i.e. dizziness, agitation, nausea, sweating and confusion)
- If they should develop hypoglycaemia they should take a sugary snack followed something starchy (i.e. sandwich etc)
If a correction dose of insulin is necessary what kind of insulin should be used and why?
Rapid acting insulin such as insulin aspart. Short acting insulins (Actrapid) should be avoided due to the 2-3 hour delay to their peak effect)
Where insulin is being given as a continuous IV infusion what should be monitored in addiion to serum glucose and how often?
Serum potassium ion (K+) levels should be monitored every 4 hours ideally to assess whether replacement is required
What should be considered in patients with renal impairment during insulin therapy?
The clearance of insulin will be reduced and there will therefore be an increased risk of hypoglycaemia
What are the 3 main types of long acting insulin?
Detemir, Glargine and Degludec
What are the 2 main types of rapid acting insulin
Aspart and Lispro
What is the main type of intermediate acting insulin?
Isophane
What is the main type of short acting insulin?
Soluble insulin
Which type of insulin preparations are used in a “twice daily” regimen?
Biphasic (rapid acting in combination with a intermediate acting insulin)
What are the indications for thyroid hormones?
- The treatment of primary hypothyroidism
- The treatment of hypothyroidism secondary to hypopituitarism
Levothyroxine is a synthetic version of which thyroid hormone?
Thyroxine (T4)
Liothyronine is a synthetic version of which thyroid homone?
Triiodothyronine (T3)
What is the mechanism of action of thyroid replacement hormones?
The thyroid gland produces thyroxine (T4) which is converted into the more active triiodothyronine (T3) in target tissues. These hormones regulate metabolism and growth and deficiency of these hormones causes hypothyroidism which presents as lethargy, weight gain, constipation and the slowing of mental processes.
Which thyroid hormone replacement is usually reserved for the treatment of severe or acute hypothyroidism?
Liothyronine as it has a shorter half-life and quicker onset (a few hours) and offset than levothyroxine.
What are the potential adverse effects associated with the use of thyroid replacement hormones?
Usually du to excessive dosing these symptoms are typically similar to those of hyperthyroidism:
Gastrointestinal
- diarrhoea
- weight loss
- vomiting
Cardiac
- palpittions
- arrythmias
- angina
Neurological
- tremor
- restlessness
- insomnia
Do thyroid replacement hormones increase heart rate?
Yes
What are the warnings associated wih thyroid hormone replacement therapies such as levothyroxine and liothyronine?
- As thyroid hormones increase heart rate and metabolism they can precipitate cardiac ischaemia in people with coronary artery disease, in whom therapy should be started at a low dose and with careful monitoring
- In hypopituitarism, corticosteroid therapy must be started before thyroid hormone replacement to avoid the precipitation of Addisonian crisis
How should treatment with thyroid hormone replacement be initiated in patients with coronary artery disease and why?
Thyroid replacement should be initiated carefully at a low dose and monitored closely to prevent the preciptation of cardiac ischaemia
How should thyroid hormone replacement therapy be started in patients with hypopituitarism and why?
Before thyroid hormone replacement is initiated the patient should be started on coticosteroid therapy to prevent the precipitation of Addisonian crisis
Which medications interact with thyroid hormones?
- Antacids
- Iron an calcium salts
- Cytochrome P450 inducers (carbemazepine and phenytoin)
- Insulin
- Warfarin
How do thyroid hormones interact with antacids and calcium and iron salts, and what precautions need to be taken?
The GI absorption of levothyroxine is reduced by antacids, calcium and iron salts, and as such adminitration of these drugs needs to be separated by at least 4 hours
When does a dose adjustment of levothyroxine need to be considered?
In patients taking cytochrome P450 inducers such as carbemazepine or phenytoin
How do thyroid hormones intract with warfarin?
Levothyroxine-induced chnges in metabolism can enhance the effects of warfarin
How does levothyroxine interact with insulin?
Levothyroxine-induced changes in metabolism can increase insulin and oral hypoglycaemic requirements
What is a typical starting dose of levothyroxine?
50-100 micrograms OD
What is a typical starting dose of levothyroxine in elderly patients with cardiac disease?
25 micrograms OD
How is liothyronine typically administred?
Intravenously
What is a typical maintenance dose of levothyroxine?
50-200 micrograms OD
What are the key points when counselling a patient on the use of levothyroxine?
- Treatment is for life
- It may take some time for them to feel back to “normal”
- Calcium or iron replacement and antacids should be taken at least 4 hours between these treatments and levothyroxine
- The signs of too much treatment include shakiness, anxiety, sleeplessness and diarrhoea
How often should thyroid function tests be performed for a patient taking levothyroxine?
3 months after initiation and then annually afterwrds
How is dosing guided in the initial weeks and months of treatment with levothyroxine?
Dosing is adjusted an guided according to symptoms
What measurement is used as the main guide to dosing with levothyroxine after the first 3 months of treatment?
TSH
What symptoms might patients experience shortly after initiating levothyroxine? How should this be dealt with and why?
Patients may begin to experience hyperthyroid symptoms shortly after starting levothyroxine. If this happens therapy should be continued at a lower dose while monitoring for reemergence of symptomsof hypothyroidism. Thyroid function tests will be unhelpful at this stage as TSH and T4 will likely be increased; TSH as this takes several weks for this to decrease following initiation of therapy and T4 because of the levothyroxine therapy.
What is a possible cause for a patient to develop symptoms of thyroid dysfunction during treatment with levothyroxine?
Switching to a different formulation of levothyroxine
What is the MHRA warning associated with levothyroxine?
New prescribing advice for patient who experience symptoms when switching between different levothyroxine products (May 2021)
What should be considered if a patient is switching to a different formulation of levothyroxine?
Thyroid function tests should be performed if the patient starts to experience symptoms of thyroid dysfunction. If symptoms are persistent, prescribing a formulation of levothyroxine that the patient is known to consistently tolerant of is recommended. If the patient remains symptomatic try switching the patient to an oral solution formulation.
Can levothyroxine be used in pregnancy and breastfeeding?
Yes, the amount excreted in breastmilk is too small to affect neonatal hypothyroidism tets
What are th clinical indications for the use of SGLT2 inhibitors?
- Type 2 diabetes in combination with other antidiabetic drugs or as a monotherapy if metformin is not tolerated
- Symptomatic chronic heart failure wih reduced ejection fraction, inadequately controlled with a bta-blocker, ACEi, and an aldosterone antagonist
- Chronic kidney disease with albuminuria, alongside an ACEi or ARB
Name the SGLT2 inhibitors
- Dapagliflozin
- Empagliflozin
- Canagliflozin
What is the mechanism of action of SGLT2 inhibitors with regards to the treatment of type 2 diabetes?
These drugs selectively and reversibly inhibit the sodium-glucose co-transporter 2 (SGLT2) in the proximal convuluted tubule of the nephron.
SGLT2 mediates active transport of glucose and sodium from filtrate into the blood, controlling the sodium content of the filtrate and recovering most of the filtered glucose.
SGLT2 inhibition impairs glucose resorption in the nephron increasing renal excretion of glucose an treating hyperglycaemia.
What is the mechanism of action of SGLT2 inhibitors with regards to the treatment of chronic heart failure?
These drugs selectively and reversibly inhibit the sodium-glucose co-transporter 2 (SGLT2) in the proximal convuluted tubule of the nephron.
SGLT2 mediates active transport of glucose and sodium from filtrate into the blood, controlling the sodium content of the filtrate and recovering most of the filtered glucose.
By increasing renal sodium excretion and water excretion, SGLT2 inhibitors reduce extracellular water volume, blood pressure an cardiac preload.
What is the mechanismof action of SGLT2 inhibitors with regards to the teatment ofchronic kidney disease wih albuminuria?
These drugs selectively and reversibly inhibit the sodium-glucose co-transporter 2 (SGLT2) in the proximal convuluted tubule of the nephron.
SGLT2 mediates active transport of glucose and sodium from filtrate into the blood, controlling the sodium content of the filtrate and recovering most of the filtered glucose.
Increased sodium delivery to the macula densa triggers tubuloglomerular feedback mechanisms that reduce intraglomerular pressure
What are the MHRA warnings asociated with the use of SGLT2 inhibitors?
- Risk of diabetic ketoacidosis (April 2016)
- Monitor ketone levels during treatment interuption for surgical procedures or acute serious medical illness (March 2020)
- Reports of Fournier’s gangrene (necrotising fasciitis of genitalia or perineum) (February 2019)
- Dapagliflozin specific -5mg should no longer be used inthetreatment of type 1 diabetes mellitus (November 2021)
When should SGLT2 inhibitors be withheld?
SGLT2 inhibitors should be withhld during acute illness (sick day rules) that causes or presnts a risk of volume depletion or hypotension
Which other drugs do SGLT2 inhibitors interact wih and to what effect?
- Glucose lowering medications such as insulin or sulphonylureas, etc - augments their effects - increases the risk of hypogycamia
- Blood pressure lowering medications - augments their effects - increased risk of hypotension
- Diuretics - augments their effects - increased risk of volume depletion
What are the most clinically significant potential adverse effects of the use of SGLT2 inhibitors?
- Hpoglycaemia (when use with other hypoglycaemic agents)
- Increased thirst (due to increased osmotic diuresis
- Increased risk of genital and urinary infections (due to glycosuria)
- Euglycaemic ketoacidosis (more common in the treatment of type 1 diabetes mellitus)
What general prescribing advice is given when starting an SGLT2 inhibitor for the treatmen of heart failure or CKD in a diabetic patient?
Other antihyperglycaemic medications may have to be ose adjusted to accomodate the glucose lowerin effect of theSGLT2 inhibitor
What is a typical dose of canagliflozin?
100mg OD
What is a typical dose of dapagliflozin?
10mg OD
What is the simplified mechanism of action of SGLT2 inhibitors?
Thy increase the amount of suger passed in the urine, which in turn increases the amount of water passed
How would you establish if a patient being treated with an SGLT2 inhibitor has euglycaemic dibetic ketoacidosis?
Check for urinary ketones - withhold the drug, check acid base status (e.g.by arterial blod or venous blood gas analysis) and seek expert advise
When should SGLT2 inhibitors be restarted after they have been withheld in acute illness?
When the patient feels better (i.e. is asymptomatic)
When should renal function be checked with regards to the use of SGLT2 inhibitors?
Before initiation and at least annually afterwards
When should SGLT2 inhibitors be stopped and what monitoring should be carried out?
In acute illness, especially if it requires hospital admission.
The patient should be monitored for signs of dehydration, hypovalaemia, and hypotension.
How long does treatment with an SGLT2 inhibitor typically last for?
Indefinitely
What are some conditions in which corticosteroids are typically used?
- Inflammatory conditions of the skin
- Ulceratice colitis
- Crohn’s disease
- Haemorrhoids
- Postural hypotension (fludrocortisone acetate)
- Septic shock resulting from adrenal insufficiency (hydrocortisone and fludrocortisone)
- Adrenal hyperplasia (dexamethasone and betamethasone)
- Raised intracranial pressure or cerebral oedema
- Asthma and COPD
- Rheumatoid arthritis
- Autoimmune hepatitis
In which conditions may high doses of corticosteroids need to be given?
- Exfoliative dermatitis
- Pemphigus
- Acute luekemia
- Transplant rejection
What is an unlicensed use for dexamethasone?
Bacterial meningitis
Which corticosteroids are licensed for adjunct treatment of Covid-19 requiring supplemental oxygen?
Dexamethasone
Hydrocortisone (when dex is unavailable)
What is the most common endogenous cause of Cushing’s syndrome?
Tumours secreting adrenocototrophic hormone or cortisol
Which medications are used to treat Cushing’s syndrome?
- Ketoconazole
- Metyrapone
- Osilodrostat
What is the basic mechanism of action of oral ketoconazole for the treatment of Cushing’s syndrome?
Ketoconazole is an imidazole derivative which acts as a potent inhibitor of cortisol and aldosterone synthesis
What is the aim of treatment when treating a patient with Cushing’s syndrome?
To lower cortisol to normal endogenous levels
What does HbA1c represent?
HbA1c reflects the average plasma glucose over the previous 2-3 months
What HbA1c level is considered diabetic?
> 48mmol/mol
What is a normal HbA1c in a non-diabetic person?
<36 mmol/mol
What are the clinical indications for the use of bisphosponates?
- Prevention of osteoporotic fragility fractures (alendronic acid is the first line)
- Severe hypercalcamia of malignany (pamidronate and zoledronic acid)
- Myeloma and breat cancer wih bone metatases (pamidronate and zoledronic acid)
- Paget’s disease of the bone
What is the mechanism of action of bisphosphonates?
They reduce bone turnover by inhibiting the action and promote apoptosis of oseoclasts, the cells responsible for bone resorption. Bisphosphonates have a similar structure tonaturally occurring pyrophosphate and hence they are readily incorporated into the bone.
What are the MHRA warnings associated with the use of bisphosphonates?
- Atypical femoral fractures
- Osteonecrosis of the jaw
- Osteonecrosis of the external auditory canal
What are the most prevalent side effects of biphosphonate use?
- Oesophagitis
- Hypophosphataemia
- Osteonecrosis of the jaw
- Atypical femoral fractures
How are bisphosphonates excreted?
Renally
Can bisphosphonates be used in renal impairment?
They should be avoided in severe renal impairment
In the presence of which conditions is the use of bisphosphonates contraindicated?
Hypocalcaemia
Upper GI disorders
Which substances reduce the absorption of bisphosphonates?
- Calcium salts
- Iron salts
- Antacids
How are zoledroic acid an pamidronate typically administered?
Intravenously
After what duration of alendronic acid use should a “bisphosphonates holiday” be considered?
5 years
What are the key points when counselling a patient on the use of alendronic acid, particularly with regards to administration?
- Take 30 minutes before any food, drink or other medication
- Must remain upright for at least minutes after taking
- Maintain good oral hygeine
- Be vigilant for hip or lower limb pain
What are the clinical indications for the use of oestrogens and progestogens?
- Hormonal contraception in patients who required highly effective and reversible contraception, particularly if the may also benefit its other effects such as improved acne symptoms with oestrogens
- Hormone replacement therapy to delay early menopause in woen <50yo and to treat distressing menopausal symptoms at any age
What is the mechanism of action of oestrogens and progestogens as contraceptives and as hormone replacement therapy?
Luteinising homone (LH) and follicle-stimulating hormone (FSH) control ovulation and ovarian production of oestrogen an progesterone.
In turn oestrogen and progesterone exert negative feedback on LH and FSH release.
In contraception, oestrogen and and/or progestrogens are given to suppress LH and FSH release and therefore ovulation.
They also act outise of the ovary. Their action in the cervix and endometrium contribute to their contraceptive effect.
Where in menopause, ymptoms are predominantly caused by a drop in oestrogen and progestrogen levels, replacement of these hormones can alleviate the symptoms.
What are some important adverse effects associated with the use of oestrogens and progestrogens?
- Irregular bleeding
- Mood changes
- 2x the risk of venous thromboembolism (Oestrogens in CHC)
- Increased risk of cardiovascular disease and stroke (Oestrogens in CHC)
- Increased risk of breast and cervical cancer
Do oestrogens and progestrogens cause weight gain?
No
Which kind of oral contraceptive does not increase the risk of VTE or cardiovascular disease?
Progesterone-only pills
In what condition is the use of all oestrogens and progestrogens contraindicated in?
Breast cancer
In which conditions should the use of CHCs be avoided?
- VTE
- Cardiovascular disease
Which group of medications may reduce the efficacy of contraceptives, particularly progestrogen-only formulations?
Cytochrome P450 inducers:
- Rifampicin
- Carbemazepine
The efficacy of which anti-epileptic medication is lowered in concurrent use with oral contraception?
Lamotrigine
What dose of ethinylestradiol is appropriate for most women?
30-35 micrograms
What is an appropriate alternative oral contraceptive where CHC is contraindicated?
Progesterone-only pill
What is the preferred formulation/therpy type of HRT for most women?
Combined oestrogen-progestrogen therapy
What type of formulation is best for treating women with just vaginal symptoms during menopause?
Vaginal oestrogen preparations
How many days of missed oral contraception necessitates use of additional contraeptive precautions, and for how longshoul these precautions be taken?
2 doses
7 days
If started when during a women’s cycle, does no additional contraceptive method need to be used when initiating oral contraceptive pills?
In the first 6 days - if started from day 7 onwards a barrier contraceptive should be used in addition to the pill
How are most combined formulations of hormonal contracetion meant to be taken?
Take for 21 days followed by a 7 day pill-free interval
Is continuous use (without pill-free intervals) of COC pills licensed?
No, but it is safe and effctive
What is one benefit (subjective) of the continued use of COC pills without pill-free period?
It eliminates or reduces withdrawal bleeding which some women may find desirable
What are the monitoring requirements when initiating COC pills?
Baseline BMI and BP
Repeated after 3 months and then annually thereon
What is the risk of starting combined HRT more than 10 years after menopause?
Increased risk of coronary heart disease
Which preparation type of HRT has an associated increased risk of breast cancer?
Combined oestrogen-progestrogen prepartions
