Chaper 6- Endocrine System Flashcards
What’s another name for anti-dietetic hormone and wheres it produced and stored
Vasopressin
Produced: Hypothalamus
Stored: pituitary gland
What is diabetes insipidus
Increased amount of dilute urine and extreme thirst Due to the body has a lower than normal amount of anti diuretic hormone (controls urine output) caused by complications to the hypothalamus or pituitary
What’s the difference between cranial and nephrogenic DI and what’s the treatments
Cranial is when the hypothalamus doesn’t make enough insulin
Treatment is vasopressin or desmopressin
Nephrogenic is when the kidney doesn’t respond to ADH
Treatment include thiazide diuretics
How is vasopressin and desmopressin different
Desmopressin is more potent and has a longer duration of action
Desmopressin has no vasoconstriction effect, unlike vasopressin
How else is desmopressin used in other than diabetes insipidus treatment
Used in the differential diagnosis of diabetes insipidus
Used to boost factor 8 concentration in haemophilia
Test fibrinolytic response
Has a role in nocturnal enuresis
What other uses beside diabetes insipidus does vasopressin have
Initial Control of oesophageal variceal bleeding in portal hypertension
What can be used in the treatment of hyponatraemia resulting from inappropriate secretion of anti diuretic hormone
Blocking the effect of anti diuretic hormone (demeclocycline)
Vasopressin receptor antagonist (tolvaptan)
What does syndrome of inappropriate anti diuretic hormone cause?
Hyponatraemia
Name a few mineralcorticoid side effects
S/E: Hypertension Sodium retention Water retention Potassium loss Calcium loss
Common side effects of glucocorticoids
Diabetes (increase blood sugars) Osteoporosis (mobilise calcium) Avascular necrosis of the femoral head (death of bone tissue) Muscle wasting Peptic ulcers (anti inflammatory effect) Psychiatric reactions
How are side effects of steroids managed
Using the lowest effective dose for the shortest period possible
Take doses in the morning so they don’t suppress the natural adrenal activity which is most active at night
Alternate days prescribing (not in asthma)
Local treatment wherever possible
What’s the MHRA alert regarding corticosteroids
Report any blurred vision as chorioretinopathy risk have presented
And
Injections contain lactose
What steroid hormones does the adrenal cortex secrete?
(cortisol) -glucocorticoid
Aldosterone - mineralocorticoid
In replacement therapy what replaces cortisol and aldosterone
Cortisol is replaced by hydrocortisone
Aldosterone is replaced by fludrocortisone
In glucocorticoid therapy of other disease, why is hydrocortisone rarely used
As it also has mineralcorticoid activity which can lead to fluid retention
Why does prednisolone remain the drug of choice for most oral corticosteroid treatment
It has the largest margin of safety
What can abrupt withdrawal of a steroid cause
Adrenal deficiency Hypotension Death Withdrawal symptoms Cold and flu like symptoms Itching Weight loss
When is gradual withdrawal or titration needed for steroids
If they’ve been taking >40mg of prednisolone (or equivalent) for more than a week
Been taking evening doses
Received more than 3 week treatment at any dose
Recently repeated courses
Taking short course within a year of stopping long term
Other causes of adrenal suppression
Why should high dose steroids be used with caution in patients with a history of psychiatric problems
It can cause psychiatric reactions like Euphoria Nightmares Insomnia Behavioural changes
Who should people on steroids (immunosuppressive) stay away from
People with chicken pox, shingles, measles
Avoid live vaccines when receiving immunosuppressant
Why should steroids be used with caution in children
Possible growth restrictions
How does corticosteroids interact with warfarin
It enhances the anticoagulation effect at high doses
Reduced anticoagulation effect at low doses
How are potencies of corticosteroids in terms of their anti inflammatory effects compared
High glucocorticoid activity whilst also accompanied by relatively low mineralcorticoid activity (that’s when they’re most useful)
Whys dexamethasone and betamethasone the most suitable for high dose therapy conditions that require suppression
They have very high glucocorticoid activity and insignificant mineralcorticoid activity avoiding fluid retention
Name corticosteroids with predominately glucocorticoid effects and insignificant mineralcorticoid activity
Dexamethasone
Betamethasone
Deflazacort
Name corticosteroids with predominately mineralcorticoid effects and insignificant glucocorticoid activity
Fludrocortisone
Name corticosteroids with predominately glucocorticoid effects and minimal mineralcorticoid activity
Prednisolone
Methylprednisolone
Triamcinolone
Name corticosteroids with equal glucocorticoid effects and mineralcorticoid activity
Hydrocortisone
What’s Cushing syndrome
Abnormally high levels of cortisol
What’s used for Cushing syndrome and how does it work
Ketoconazole and metyrapone
Potent inhibitor of cortisol and aldosterone synthesis by inhibiting an enzyme
What’s the MHRA alert for ketoconazole
The use of it to treat fungal infection should be stopped due to the risk of hepatotoxicity
What is diabetes mellitus
Persistent hyperglycaemia caused by deficient insulin secretion or by resistance to action of insulin
Leading to abnormalities of carbohydrate, fat and protein
What’s the advice from dvla regarding driving with diabetes
Inform them if you’re on insulin
If you have a hypo episode
If on insulin take reading 2 hours before journey and every 2 hours while driving
Blood sugars should always be above 5mmol
Keep a snack with you
If blood sugar less than 4mmol stop the vehicle
What does hb1ac measure and what does it tell you
Glycated haemoglobin so red blood cells that are exposed to glucose
Monitors glycaemic control
Reliable predictor of microvascular and macrovascular complications and mortality
What is type 1 diabetes
Absolute insulin deficiency in which there is little or no endogenous insulin secretory capacity due to destruction of insulin producing beta cells in the pancreatic islet of langerhans
What’s the target hb1ac concentration for patients with type 1 diabetes
48mmol/mol (6.5%) or lower
What’s the target blood-glucose concentrations for fasting on waking, before meals, 90 minutes after eating and when driving
Fasting on waking : 5-7mmol/L
Before meals: 4-7mmol/L
90 minutes after meals: 5-9mmol/L
Driving: 5mmol/L
What therapy do all patients with type 1 diabetes require
Insulin therapy
What’s the basal-bolus insulin regime
One or more daily injections of intermediate acting or long acting insulin as the basal insulin
Alongside multiple bolus injections of short acting insulin before meals
What’s the mixed (biphasic) insulin regime
1, 2 or 3 insulin injections per day of short acting insulin mixed with intermediate acting insulin
(Can be mixed by the patient at the time of injection or premixed)
What’s the continuous subcutaneous insulin infusion (insulin pump)
A regular amount of insulin in the form of rapid acting insulin analogue or soluble insulin delivered via a subcutaneous needle or cannula
What’s the first line insulin regime offered to patients
Multiple daily injection basal-Bolus regime
Long acting detemir BD (OD glargine if not tolerated)
And a rapid acting insulin analogue as the volume or mealtime insulin
When should continuous subcutaneous insulin therapy be initiated
Patients who suffer disabling hypoglycaemia or have a high hb1ac concentration (69mmol/mol) or above while on the multiple daily injection regime
How should a patients knowledge of hypoglycaemia be assessed
Annually using a gold score of the Clarke score
How does insulin work?
It increases glucose uptake by adipose tissue and muscles and suppresses the hepatic glucose release
The role of Insulin is to lower blood glucose concentrations in order to prevent hyperglycaemia and its associated complications
Why are human insulin or human insulin analogues more preferred than animal insulin
Less immunogenic
Why’s insulin given IV
It is inactivated by GI enzymes
What can occur from injecting the same site with insulin and what’s the outcome
Lipohypertrophy
Erratic absorption of insulin, poor glycaemic control, lump under the skin
The three types of insulin preparations and how they act
Short acting: onset of action is 30-60min, duration of upto 9 hour
Intermediate: onset of 1-2HOURS, duration of 11-24 hours
Long acting: last upto 36 hours and take 2-4 days to produce a steady state
What is type 2 diabetes
A chronic metabolic condition characterised by insulin resistance. Insufficient insulin production also occurs overtime (more often diagnosed in adults)
Why does metformin not cause hypoglycaemia
It doesn’t stimulate insulin secretion
Why’s MR metformin sometimes indicated
Reduce GI side effects
Why may DPP-4 inhibitors (gliptins) be preferred over sulfonylureas?
No association to weight gain and less hypoglycaemic events
What negative side effect have sodium glucose co-transporter 2 inhibitors been associated with
Diabetic ketoacidosis
What hb1ac level should a patient being treated with a hypoglycaemic agent or 2 or more anti diabetic drugs aim for
53 mol/mol
What’s the first line for type 2 diabetes and why
Metformin
Weight loss
No hypo episodes
Long term CV benefits
What do you at if metformin is not sufficient alone
A second anti diabetic drug
Sulfonylurea (eg: gliclazide)
Pioglitazone
Dpp4 inhibitor (eg: linagliptin)
Sodium glucose cotransporter 2 inhibitor (eg: dapagliflozin)- if sulfonylurea not tolerated
If dual anti diabetic treatment not sufficient what do you do
Use 3 anti diabetic meds
Consider insulin based treatment
What’s given in diabetic nephrology to reduce incidence and why?
What’s the risk
ACEi or ARB
To reduce proteinurea and microalbunuria
ACEi potentials hypoglycaemic effects of anti diabetic drugs and insulin especially in renal impairment
How is diabetic neuropathy managed
Monotherapy with TCA, SNR for painful peripheral neuropathy (pregabalin or gabapentin can be considered)
Addition of opioid if not adequately controlled
Diabetic diahrrrhoea can be controlled by TCA or codeine
In neuropathic postural hypotension the mineralcorticoid fludrocortisone can be used
Antimuscarinic can be given for sweating
What are the symptoms of DKA- increased level of ketones (develop from high sugar in the blood due to a lack of insulin) (type 1) and HONK- high osmolarity without significant ketoacidosis (type 2) and How are they managed
Dehydration, acute hunger, thirst, abdominal pain, fruity breath and urine smell (DKA)
NG tube IV assess LMWH Urinary catheter Sliding scale insulin Replacement of fluid and electrolytes Consider abx
What are women with pre existing diabetes advised to take when becoming pregnant
Folic acid 5mg
What antidiabetics are suitable for pregnant or breastfeeding women
Metformin and insulin’s
Globenclamide (2nd and 3rd trimester)
How long should statins be discontinued for in a planned pregnancy
3 months
How is diabetic nephropathy measured?
Urinary microalbumuria (earliest sign of nephropathy)
Urinary protein
Serum creatinine
What’s considered hypoglycaemic and what are the symptoms and treatment both conscious and unconscious
Bsl< 4mmol/L
Symptoms: Pale skin, sweaty, tremor, rapid heart rate, confusion, affirmation, impaired consciousness
Treatment:
Conscious =10-20g oral glucose
Unconscious = IV dextrose
No IV access= glucagon IM injection
Which medications enhance blood glucose lowering activity
Antidiabetics ACEi MAOIs Salicylate Sulphonamide antibiotics
What medications may reduce blood glucose lowering activity
Corticosteroids Dietetics Sympathomimetics Thyroid hormones Contraceptives Beta blocker Alcohol
What drug class is metformin, how does it work and what’s a common side effect
Biguanides
Decreases glucogenesis and increases peripheral utilisation of glucose- acts only in the presence of endogenous insulin(taken 3times a day with food)
S/e: GI disturbances, metallic taste, lactic acidosis in renal impairment
Name a few sulphonyureas, how they work and side effects
Gliclazide, glipizide, glimepiride, tolburamide
It increases insulin secretion from the pancreas so requires at least some beta cell activity to be effective
(Should be taken once a day with food)
May cause hypoglycaemia and weight gain
Hypersensitivity is common
What drug class is pioglitazone, how does it work and what are side effects?
Thiazolidinedione
It reduces peripheral insulin resistance
S/e:
GI upset, weight gain, oedema, hypoglycaemia, anaemia, headache, liver toxicity, haematuria, visual disturbances
STOP OF LIVER TOXICITY PERSISTS
What are the MHRA alert for pioglitazone
Risk of heart failure when pioglitazone is combined with insulin
Risk of bladder cancer
Name drugs in the meglitinides drug class, how they work and side effects
Nareglinide, repaglinide
They stimulate insulin secretion, should be taken 30 minutes before food
May cause hypoglycaemia, hypersensitivity and GI upset
DPP4 inhibitors (gliptins) how they work and common side effects
Alogliptin, linagliptin, saxglipton, sitaglipton, vidagliptin
Inhibits DPP4 enzymes that break down incretins (incretins are produced in the gut in response to food and trigger insulin secretion and lower glucagon secretion)
Side effects:
Hypoglycaemia URTI, GI upset, peripheral oedema, pancreatitis
STOP IF PANCREATITIS OR LIVER TOXICITY OCCUR
SGLT2 inhibitors (gliflozin), how they work and side effects
Canagliflozin, empagliflozin, dapagliflozin
They inhibit SGLT2 in the renal tubules to reduce glucose reabsorption and increase glucose excretions
S/e: hypovalaemia, GI illness and complicated UTI
MHRA Alert for SGLT2 inhibitors
Risk of DKA
Increased risk of lower limb amputation
Glucagon like peptide-1 (GLP-1) receptor agonist, how they work and side effects
Exenatide, albiglutide, dulaglutide, liraglutide and lixisenatide
Mimic incretins by binding to the GLP-1 receptor and increasing insulin secretion
S/e: GI upset, headaches, weight loss, pancreatitis
STOP IF PANCREATITIS OCCURS
What other medications would you usually see diabetics on excluding antidiabetics and why
ACEi/ ARB
Statin
Aspirin
As diabetes is a risk factor for CVD so these reduce the risk
What do you do when a diabetic patient that takes their medication orally is going for surgery
Omit their medication and give insulin
Which sulphonyurea can you give in renal failure
Tolbutamide as it’s short acting
When do nice recommend treatment is continued for pioglitazones
If Hb1ac conc is reduced by atleast 0.5% within 6 months of use
What is osteoporosis
A progressive bone disease characterised by low bone mass measures by bone mineral density and deterioration of bone tissue
What’s the most common thing osteoporosis leads to
Increases risk of fragility fracture
What group of people does osteoporosis commonly occur in
Post menopausal women
Men over 50
Patients taking long term corticosteroids (glucocorticoid)
Other conditions like diabetes and rheumatoid arthritis
What’s the first class drug treatment is post menopausal osteoporosis
Oral bisphosphonates:
Alendronic acid and risedronate sodium
What can you give for post menopausal osteoporosis in patients that can’t take oral bisphosphonates
Iv bisphosphonates (Ibandronic acid or zolendronic acid)
Denosumab
Raloxifene
HRT- Teriparatide (for younger postmenopausal women <50ish)
Which HRT is reserved for postmenopausal women with severe osteoporosis at very high risk of vertebral fracture
How long is the treatment limited to
Teriparatide
24 months
What should be given with steroids for prophylaxis of glucocorticoid induced osteoporosis
Oral bisphosphonates
IV if oral not appropriate
What can be given for osteoporosis in men?
Oral bisphosphonates
Iv bisphosphonates if oral not indicated
denosumab if bisphosphonates not indicated
What group of men are at most risk of fracture
Men having long term androgen deprivation therapy for prostate cancer
When should bisphosphonates treatment be reviewed
5 years for oral, 3 years for IV
How do bisphosphonates work
Theure absorbed onto hydroxyapatite crystals in bone, slowing down both their rate of growth and dissolution- reducing the rate of bone turnover
What are MHRA alerts for bisphosphonates
Atypical femoral fractures
Osteonecrosis of the jaw
Osteonecrosis of the external auditory canal (ear)
How does denosumab work
It inhibits osteoclasts formation, function and survival so decreasing bone resorption
What are MHRA alerts for denosumab
Atypical femoral fractures
Osteonecrosis of the jaw
Osteonecrosis of the external auditory canal (ear)
Risk of hypercalcaemia following discontinuation
What OTC items can a patient buy to reduce risk of osteoporosis
Vitamin D
Calcium
Administration advise for alendronic acid
take with a full glass of water while sitting or standing
Taken 30 minutes before breakfast
Remain upright for a further 30 minutes after taking
What should be monitored with bisphosphonates and side effects that are alarming
Regular dental check up
Any thigh, groin pain
Oesaphageal reactions, ulcers, heartburn, abdo pain regurgitation
What’s are the anterior pituitary hormones
Corticotrophins (adrenocorticotropic hormones)
Gonadotrophins (follicle stimulating hormone and leutanising hormone)
Growth hormone
How does calcitonin work
It decreases blood calcium concentrations and is involved with PTH in the regulation of bone turnover and maintenance of calcium balance
What’s the most potent bisphosphonates
Zolendronic acid
What’s given to women to help with menopausal symptoms
Oestrogen together with progestogen- in women with a uterus
Colonidine for women who can’t take oestrogens
What does HRT increase the risk of
Thromboembolism Stroke Endometrial cancer Breast cancer Ovarian cancer
How does HRT affect chances of breast cancer
Increased risk 1-2 years of starting treatment
Risk related to duration of use but disappears within 5 years of stopping
How does HRT affect endometrial cancer risk?
Depends on dose and duration of oestrogen only HRT, risk is eliminated if progestogen is given continuously
How does HRT affect the risk of ovarian cancer
Long term use affected with increased risk, risk disappears within a few years of stopping
How does HRT affect risk of VTE
Increased risk mainly in the first year of use
How does HRT affect stroke risk
Risk increased with age
How does HRT affect risk of CHD
Increased risk in women who start 10 years after menopause
Reasons to stop HRT
Sudden severe chest pain Sudden breathlessness Unexplained swelling or pain in their leg Severe stomach pain Neurological effects Hepatitis, jaundice High BP
What needs to be added to oestrogen in women with a uterus
Progestogen to avoid cystic hyperplasia
What is endometriosis
Growth of endometrial like tissue outside the uterus
What’s the drug treatment for endometriosis
Pain management and contraceptives to suppress ovarian function
What’s heavy menorrhagia
Heavy menstrual bleeding (80mL or more) for longer than 7 days
What can be given for heavy menstrual bleeds
NSAIDs for pain
Tranexamic acid
Combined hormonal contraceptives
Cyclical oral progestogen
What do androgens (testosterone) cause
Masculinisation
What is clomifene used for and what’s the caution for it
Anti- oestrogen: stimulates ovulation so used in the treatment of infertility
It should not be used for longer than 6 chocked due to an increased risk of ovarian cancer
What’s cyproterone and what’s it used for
Anti androgen to inhibit the effect of testosterone
Used in the treatment of Aw set hyper-sexuality and sexual deviation in men
What’s treatment options for hyperthyroidism
Carbimazole for drug treatment (most common)
Propyl thiouracil
Or
Surgery
What’s often used to treat thyrotoxic crisis (thyroid storm) before surgery
IV fluids, Propanolol, iodine, carbimazole and hydrocortisone
What major adverse affect does carbimazole have and what synptom is the patient told to report immediately
Bone marrow suppression, neutropenia and agranulocytosis
Report any signs of a sore throat or infection
What’s the MHRA alert of carbimazole
Increased risk of congenital malformation
Risk of acute pancreatitis
What’s the treatment of choice for hypothyroidism
Levothyroxine sodium
What’s used in hypothyroid coma and why
Liothyronine as it is more rapidly metabolised so it’s effects are seen faster
What’s the side effects of levothyoxine
Diarrhoea Arrhythmia Palpitations Tachycardia Tremor Restlessness Sweating Fever Weight loss
What’s an interaction of thyroid hormones
They enhance the anticoagulation effect of warfarin
Apart from anti thyroid drugs, what else are good thyroid suppressing drugs
Iodine and propanolol
Why should bisphosphonates be taken before food
They bind calcium and iron salts so absorption will be reduced
Diabetes symptoms
Polydipsia Polyuria Tiredness / lethargic Vaginal itching Weight loss Frequent infections Boils
Symptoms of hypoglycaemia
Sweating
Confusion
Coma
Blunted by BB
Which SGLT-2 inhibitor is not recommended in combination with pioglitazone
Dapagliflozin
All possible corticosteroids side effects (clue: aching bosom)
Adrenal suppression Cushing syndrome, cataracts Hyperglycaemia Infection, insomnia Nervous system (psychiatric) Glaucoma, GI ulcers
Blood pressure increase Osteoporosis Skin thinning Obesity Muscle wasting
Symptoms of diabetes
Polyphagia Polydipsia Polyuria Weight loss Fatigue Blurred vision Poor wound healing
What’s the first line long acting insulin in pregnancy
Isolhane insulin
How does insulin requirement change during and after pregnancy
You will need more insulin in the 2nd and 3rd trimester and it will need to be immediately reduced after birth
What is diabetes gestational and how is it managed
Diabetes that develops during pregnancy
Fasting glucose < 7mmol = dietary and exercise then metformin
Fasting glucose >7mmol = insulin (with or without metformin)
When do you need to notify dvla in diabetes
Treatment with insulin (an anti diabetic for bigger vehicles)
Visual or renal or limb complications that affect driving
Two episodes of hypoglycaemia in the past 12 months
Hypoglycaemia while driving
When are insulin requirements increase or decrease
They are increased in an infection stress puberty and pregnancy
They are decreased in Endo crying disorders for example Addison’s disease and hypopituitarism
What blood and urine Ketone levels require immediate action
Urine 2+
Blood > 3mmol/L
When should you stop taking Metformin and why
If you’re dehydrated fever vomiting diarrhoea due to increased risk of lactic acidosis
What does thyroid hormones regulate
Metabolic rate Heart rate Digestive function Muscle control Brain development
Symptoms of hyperthyroid disorder
Heat intolerance Weight loss Diarrhoea Tachycardia Excitability Angina pain Tremors Sweating Arrhythmia
Symptoms of hypothyroidism
Cold intolerance Weight gain Constipation Bradycardia Lethargic Muscle cramps Slow movement Slow thoughts Depression Hair thinning
What would you give in a thyroidectomy
Iodine for 10 to 14 days before the partial thyroidectomy and then antithyroid drugs but not long-term
What would you give for hyperthyroidism in pregnancy
First trimester= propylthiouracil
2nd and 3rd= carbimazole
What’s the rapid acting insulin’s
Aspart (novorapid)
Glulisine (apidra)
Lispro (humalog)
Intermediate acting insulin
Isophane
Long lasting Insulin’s
Deglubec (tresiba)
Detemir (levemir)
Glargine (absaglar Lantus)
When would you give glucose in a patient being treated with DKA
When below 14mmol/L
When is a continuous subcutaneous insulin pump indicated
Suffer recurrent unpredictable hypoglycaemia
Glycaemic control >8.5%
Children under 12 where MIR is impractical (must undergo MIR training when 12-18)
How should insulin be stored
Fridge between 2-8
Once opened store at room temp for 28 days
If frozen discard
If left outside for 48hours discard
What’s the most common cause of hyperthyroidism
Graves’ disease
When are the most potent glucocorticoids used
When fluid retention is disadvantages (eg heart failure)
What can be a side effect of taking corticosteroids with anaesthesia
Dangerous fall in blood pressure
What’s given for type 2 diabetes post birth for breastfeeding
Metformin or glibenclamide
What type of induced hypoglycaemia should be treated in hospital and why
Sulphonylurea
as it can persist for hours
What doses of levothyroxine should you question
Doses above 200mcg
What drug enhances the effect of sulphonylurea
Chloramphenicol
What diabetic medication can you give to elderly of people woth poor kidney function
DDP4 inhibitor - eg: linagliptin
What should you monitor if linagliptin (dpp4 inhibitor) is given with other diabetic meds
Hypos
Which anti diabetic medication can reduce vitamin b12 absorption
Metformin
What should you counsel with acarbose and why
Take immediately before food as can cause bloating
Which DPP4 inhibitor is linked to Steven Johnson syndrome
Sitagliptin
What’s the first line anti hypertensive for a 70 year old patient also diabetic
ACEi
Which diabetic oral medication can lower vitamin b12
Met for in
What patients should be given a steroid card
Patients on long term corticosteroids (> 3 weeks)
Risk factors for DKA
Low beta cell function Alcohol Surgery Sudden reduction in insulin Acute illness
Symptoms of thyrotoxicosis
Increased HR >140 bpm Tachycardia, arrhythmia Heat intolerance >41 degrees Diarrhoea, nausea, vomitting, dehydration Seizures
MHRA alert regarding glp1 and insulin use
Increased risk of DKA
Especially when on both and insulin dose rapidly reduced or discontinued
3 MHRA alerts for SGLT2
DKA
Monitor ketone during treatment interruption for surgery
Reports of Fournier gangrene
Crcl cut off point for alendronic acid
35 ml/min
