ENDO

Question 1

Diabetes insipidus treatment: cranial and nephrogenic

Hypo NA+ treatment not fixed by fluid restriction

Answer 1

Vasopressin, desmopressin
Desmo longer acting more potent no vasoconstrictor effect

Nephro - paradoxical effect of THIAZIDES

Demeclocycline

Tolvaptan - osmotic demyelination if rapid correction, LFTs, volume, fluid, sodium, electrolytes

Question 2

Dexamethasone and Betamethasone -

Answer 2

high glucocorticoid, long action, more suppression at night - suitable for conditions which require suppression of corticotropin secretion (congenital adrenal hyperplasia).
Overnight dexamethasone suppression test for diagnosing Cushing’s syndrome
Appropriate where water retention would be a disadvantage

Question 3

Which corticosteroid is used in anaphylaxis/hypersensitivty?

Answer 3

Hydrocortisone

Question 4

Corticosteroids MHRA side effects alert?

Answer 4

Central serous chorioretinopathy - report blurred vision, or other disturbances

Question 5

Mineralocorticoid Side effects?

Answer 5

Used if fluid retention beneficial - e.g. hypotension.

Hypertension, Water Retention, Sodium Retention.

Potassium Loss, Calcium Loss.

Most marked with fludrocortisone, but significant with hydrocortisone, corticotropin and tetracosactide

Question 6

Glucocorticoids?

Answer 6

Dexa, Beta - most potent
Prednisolone, and prednisone - predominantly gluco

Deflazacort - High glucocorticoid activity - derived from prednisolone.

Question 7

Glucocorticoid Side effects?

Answer 7

Diabetes (hyperglycaemia), Osteoporosis (>3m give prophylaxis with bisphosphonates), Avascular necrosis of femoral head, Muscle wasting (caution with statins), Peptic ulceration & perforation (take with or after food), Psychiatric reactions (paranoid state, depression with suicide).

Question 8

Corticosteroid side effects: ACHING BOSOM

Answer 8

Adrenal suppression, appetite larger, abrupt withdrawal reactions.
Cushing's syndrome, Cataracts
Hyperglycaemia, hyperlipidaemia
Infections, Insomnia
Nervous system, Psychiatric 
Glaucoma, GI Ulcers
Blood Pressure increase - hypertension
Osteoporosis 
Skin Thinning
Obesity
Muscle Wasting

Question 9

Avoid Abrupt Withdrawal?

Answer 9

Long term use > 3 weeks
>40mg prednisolone or equiv. for > 1 week
Repeat doses taken in the evening
Recent repeated courses
Short course within 1 year of stopping long term steroids
Other causes of adrenal suppression

Question 10

Chickenpox and Measles

Answer 10

Unless they have had chickenpox, patients receiving systemic corticosteroids or have used them in the past 3 months should have passive immunisation with varicella-zoster immunoglobulin.

Measles - avoid exposure to measles. Prophylaxis with IM normal immunoglobulin.

Specialist care, REFER.

Question 11

Special groups, pregnancy and children?

Answer 11

Pregnant - can use but monitor for fluid retention.

Children - Height and Weight measured yearly.

Question 12

Adrenal cortex secretes cortisol and aldosterone. In deficiency states give:

Answer 12

Hydrocortisone (cortisol) gluco and mineral Fludrocortisone.

Question 13

Addison’s disease or adrenalectomy treatment? Low cortisol low aldosterone

Answer 13

Hydroscortisone by mouth, 2 doses, larger in the morning and smaller in evening.
+ Fludrocortisone

Question 14

Hypopituitarism treatment? (pituitary gland does not stimulate hormone secretion by target glands)

Answer 14

Hydrocortisone, not with fludro as renin angiotensin system regulates aldosterone. Levothyroxine and sex hormones should also be given.

Question 15

MHRA Methylprenisolone?

Answer 15

Injection solu-medrone - not suitable in cows milk allergy - serious reactions, anaphylaxis.

Question 16

Cushing’s syndrome? High or Low cortisol? Treatment?

Answer 16

High. (causes: corticosteroids, Tumour)

Treatment: Surgery or Cortisol Inhibiting Drugs
Metyrapone (competitive), Ketoconazole (potent)

Question 17

Ketaconazole: Inhibits cortisol and aldosterone synthesis

Answer 17

MHRA - suspend oral licensing for fungal infections.
Risk of HEPATOTOXICITY (potentially life threatening)

Teratogenic - contraception.

Monitoring:
ECG before, and one week after.
Adrenal insufficiency monitor within one week then regularly. When levels normal every 3-6months. (fatigue, nausea, anorexia, hyponatraemia, hyperkalaemia, hypoglycaemia).
Hepatoxicity - LFTs before, then weekly for 1 month, then monthly for 6 months.
(pre-treatment LFTs should not exceed 2xULN
<3ULN - reduce dose
>3ULN discontinue.

Question 18

T1D - first line insulin?

Answer 18

multiple daily injection basal-bonus insulin regimen

Detemir first line line acting BD

THEN Glargine OD if detemir not tolerated or twice daily not acceptable

+ rapid acting insulin analogue before meals rather than soluble human insulin or animal insulin.

If multiple daily not possible. Twice daily mixed (biphasic) insulin regime considered.

If taking BD human insulin mixed suffering hypo give analogue mixed

Degludec also given OD

Question 19

Metformin?

Answer 19

No hypoglycaemia, positive effect on weight loss and long term CV benefits.
GI side effects - switch to MR
PCOS
Avoid in eGFR <30
Lactic acidosis avoid in Renal Impairment, or Tissue Hypoxia.

Question 20

Sulphonylureas?

Answer 20

Weight gain, hypoglycaemia.
Longer acting higher risk of hypo - glibenclamide, glimepiride.
Short acting better in elderly and renal impairment - gliclazide, tolbuatmide.

Hyponatraemia = glipizide, glimepiride.

Warfarin + ACE = increase risk of hypo
hypersensitivity, jaundice
NSAIDs - reduced renal excretion.

Question 21

Meglitinides?

Answer 21

Repaglinide, nateglinide. Hypersensitivity.
Rapid onset and short action - given around mealtimes.
Less preferred than SU.
Take 30 minutes before main meals.
Nateglinide - GI
Repaglinide - visual disturbance

Question 22

Thiazolidinedione?

Answer 22

Pioglitazone - long term risks, review ongoing benefit.

Heart Failure, Bladder Cancer, Hepatotoxicity.

Question 23

Dipeptiidylpeptidase-4 inhibitors?

Answer 23

Gliptins - no weight gain, less hypo than SU
Pancreatitis
Vidagliptin - Liver toxicity

Question 24

Sodium glucose co-transporter 2 inhibitors?

Answer 24

Gliflozins - Risk of DKA during periods of dehydration, stress, surgery, trauma, acute medical illness.
Canagliflozin and Empagliflozin can be beneficial in patients with T2D and CVD.

Only given as monotherapy in patients where metformin is CI only if DPP4 would be given and neither SU or pioglitazone are appropriate.

Life threatening DKA,
Volume Depletion,
Fournier’s Gangrene of genitalia or perineum
Canagliflozin - Lower limb amputation

Question 25

Glucagon-like Peptide-1 receptor agonists?

Answer 25

Given when triple therapy fails - Diraglutide, exenatide, liraglutide, lixisenatide. Liraglutide has proven cardiovascular benefit and considered in those with T2D and CVD. Give in triple therapy with metformin and SU. Only given if BMI >35 AND have problems with obesity, OR if BMI <35 but insulin has occupational implications AND if weight loss would be benefical. Only continue after 6 months if HbA1c reduced by 11mmol /mol or 1% and weight loss by 3%. Pancreatitis DO NOT ADMINISTER AFTER A MEAL Inject within 1 hour of next meal - lixisenatide Continue with next scheduled dose - exenatide If missed inject only if at least 3 days until next dose - dulaglutide, abilglutide. Exenatide - women of childbearing age - contraception during and 12 weeks after MR exenatide.

Question 26

DKA

Answer 26

Sodium Chloride 0.9%, Potassium Chloride (unless anuria), IV soluble insulin mixed with sodium chloride 0.9%, SC long-acting insulin analogue. Once glucose falls below 14mmol/L glucose 10% given IV with sodium chloride 0.9%. Continue infusion until blood ketone below 0.3mmol/L and blood pH above 7.3 and patient able to eat and drink, give SC fast acting and meal and stop IV insulin infusion 1 hour later.

Question 27

Elective surgery, Minor procedure with good glycaemic control?

Answer 27

Hba1c <69 8.5%, Usual insulin regimen. On the day before surgery usual insulin given as normal but once daily long acting insulin should be given at a dose reduced by 20%.

Question 28

Elective surgery, major procedures or poor glycaemic control.

Answer 28

Day before surgery: once daily long acting given at 80% of normal dose, usual insulin as normal. Day of surgery and during: once daily given at 80% of usual dose and all other insulin stopped until eating and drinking again. Start IV susbtrate KCl, glucose and NaCl. Variable rate IV insulin infusion of soluble insulin in NaCl. 6-10mmol ideal range. otherwise give IV glucose. Convert back once eating and drinking. Basal-bolus restarted when first postop meal-time insulin due. BD mixed insulin - restarted before breakfast or dinner. Stop variable rate 30-60mins after food.

Question 29

Oral antidiabetic drugs and surgery?

Answer 29

When insulin is given, all drugs GLP1 should be stopped. No insulin? Pioglitazone, DPP4, GLP1 can be continued during this period. SGLT2 and SU omitted on day of surgery. Metformin continued if eGFR > 60 and low risk of AKI otherwise can lead to accumulation and lactic acidosis. If missing more than one meal then stop metformin.

Question 30

Pregnancy and diabetes?

Answer 30

Aim for Hba1c of 48 6.5% Folic acid 5mg daily. All except metformin discontinued before pregnancy and substituted with insulin. After birth, metformin continued or glibenclamide resumed. 1st Line - isophane insulin for long acting. If good control already with long acting analogue then continue. CSCI if difficulty achieving glyceamic control with multiple daily injections of insulin without significant disabling hypo. First trimester and insulin high risk of hypo carry fast acting glucose. INCREASED RISK OF HYPO DURING POSTNATAL PERIOD REDUCE INSULIN IMMEDIATELY AFTER BIRTH.

Question 31

Gestational diabetes?

Answer 31

Fasting glucose below 7 - diet and exercise, if no improvement after 1-2 weeks give metformin or insulin if met CI/not tolerated. Fasting above 7 or fasting 6-6.9 with macrosomia or hydramnios insulin immediately with or without metformin. Glibenclamide from 11 weeks gestation after organogenesis who cannot tolerate metformin/not effective or do not wish to have insulin. Discontinue immediately after birth.

Question 32

Hypoglycaemia

Answer 32

10-20g glucose by mouth. If necessary repeat after 10-15mins. After initial treatment, snack providing sustained availability of carbs (sandwich, fruit, milk, biscuits) or next meal if it is due can prevent glucose from falling again. IF UNRESPONSIVE OR UNCONSCIOUS: Glucagon Injection. If not effective in 10 mins give IV glucose. Chronic hypo - Diazoxide by mouth. SU INDUCED HYPO - ALWAYS TREATED IN HOSPITAL.