BASIC - ENDOCRINE

Question 1

Names of rapid acting insulin?

Answer 1

• Insulin Aspart (e.g. Novorapid)
• Insulin Lispro (Humalog)
• Insulin glulisine (Apidra)

Question 2

Names of short-acting insulin?

Answer 2

• Humulin & Novolin Regular

Question 3

Names of intermediate acting insulin?

Answer 3

• Humulin & Novolin N

Question 4

Names of long-acting insulin?

Answer 4

• Insulin glargine (Lantus)

- Insulin detemir (Levemir)

Question 5

Names of pre-mixed insulin?

Answer 5

• Humulin 70/30 & 50/50
• Novolin 70/30
• Humalog Mix 75/25
• Humalog Mix 50/50
• Novolog Mix 70/30

Question 6

Indications of insulin?

Answer 6

Type 1 & 2 diabetes
IV in DKA and hyperglycaemic hyperosmolar syndrome
Perioperative glycaemic control in selected diabetic patients
Hyperkalaemia

Question 7

Mechanism of insulin?

Answer 7

• Similar function to endogenous insulin
• Stimulates glucose uptake into skeletal muscle and fat
• Increases use of glucose as energy source
• Stimulates glycogen, lipid and protein synthesis
• Inhibits gluconeogenesis and ketogenesis
• Drives K+ into cells – short-term measure

Question 8

Side effects of insulin?

Answer 8

Hypoglycaemia

SC injection – fat hypertrophy

Question 9

Caution of insulin?

Answer 9

• Insulin clearance reduced in renal impairment (risk of hypoglycaemia)

Question 10

Interactions of insulin?

Answer 10

• Combining insulin and other OHAs increase risk of hypoglycaemia
• Corticosteroids increases insulin requirements

Question 11

How it insulin prescribed?

Answer 11

• Prescribed in units – normal daily requirements are 30-50 units

Question 12

Symptoms of hypoglycaemia and how to treat?

Answer 12

• Hypoglycaemia, symptoms to watch out for (e.g. dizziness, agitation, nausea, sweating and confusion)
  o Explain that, if hypoglycaemia develops, they should take something sugary (e.g. glucose tablets or a sugary drink) then something starchy

Question 13

What is Basal bolus regimens?

Answer 13

 Combination of 1/2 slow acting insulin before bedtime (glargine) with 3 injections of rapid acting insulin after/before meals (Humalog/Novorapid)
 Can adjust for meals and infections better
 Need to test sugars more, at school inject (psychological)

Question 14

What is 2/3x day pre-mixed regimen?

Answer 14

Not suitable for kids’ normal daily activity

Difficult to control/change insulin dosages

Question 15

What is continuous SC insulin pump?

Answer 15

 Gives basal infusion and bolus when eat
 Needle changed every 2-3 days
 Cannot use in sports, swimming, baths (if disconnected – DKA)

Question 16

Monitoring of insulin?

Answer 16

o Self-monitoring of blood glucose
 At least 4 times a day, before meals and before bed
 Targets – FPG 5-7 on waking, PG 4-7 before meals, PG 5-9 90 mins after eating
o HbA1c monitored regularly (at least annually)
 Aim for HbA1c of 48 mmol/mol or lower
o If IV then serum K+ measured every 4 hours

Question 17

Names of sulphonylureas?

Answer 17

Gliclazide

Question 18

Indications of sulphonylureas?

Answer 18

Type 2 DM (2nd line single agent or in combination)

Question 19

Mechanism of sulphonylureas?

Answer 19

• Stimulates pancreatic insulin secretion
• Block ATP-dependent K+ channels in pancreatic B-cell membranes and open voltage-gated Ca2+ channels
• Only effective in residual pancreatic function
• Weight gain

Question 20

Side Effect of sulphonylureas?

Answer 20

• GI upset (nausea, vomiting, diarrhoea, constipation)
• Hypoglycaemia
• Cholestatic jaundice
• Rashes
• Agranulocytosis

Question 21

Dose changes in renal and hepatic impairment of sulphonylureas?

Answer 21

o Dose reduction in liver and renal impairment

Question 22

Caution of sulphonylureas?

Answer 22

o Malnutrition, elderly and hepatic impairment

Question 23

Interactions of sulphonylureas?

Answer 23

• Risk of hypoglycaemia with other OHAs and insulin

- Efficacy reduced by prednisolone, thiazide and loop diuretics

Question 24

Dose of sulphonylureas?

Answer 24

• Oral, SR/MR (different doses)
• Usually dose 40-80mg OD
• Long-term treatment so should not be stopped or changed
• Take with meals

Question 25

Monitoring of sulphonylureas?

Answer 25

``` o HbA1c (target <53mmol/mol) o LFTs and U&Es before treatment ```

Question 26

Indications of metformin (biguanide)?

Answer 26

Type 2 DM (1st choice) or used in combination with other OHA

Question 27

Mechanism of metformin?

Answer 27

- Increases sensitivity to insulin - Suppresses hepatic glucose production (glycogenolysis and gluconeogenesis), intestinal glucose absorption and increases glucose uptake by skeletal muscles - Reduces weight gain (induce weight loss) - Excreted unchanged by kidney

Question 28

Side Effects of metformin?

Answer 28

- GI upset (nausea, vomiting, taste disturbance, diarrhoea) - Lactic acidosis o In illness, worsened renal impairment, increased lactate production and reduced lactate metabolism

Question 29

Contraindications of metformin?

Answer 29

o Severe renal impairment (dose reduction in moderate) | o Withheld in AKI, tissue hypoxia, acute alcohol intoxication

Question 30

Caution of metformin?

Answer 30

o Hepatic impairment o Chronic alcohol overuse o Other nephrotoxic drugs (NSAIDs, diuretics, ACEi)

Question 31

Interactions of metformin?

Answer 31

- Withheld before and 48 hours after IV contrast media | - Prednisolone, thiazide and loop diuretics elevate blood glucose so oppose actions of metformin

Question 32

Prescription of metformin?

Answer 32

- Oral tablet - GI upset started at low dose and increased gradually - Commonly 500mg OD with breakfast then increasing 500mg weekly to BDS - Swallow tablets whole with glass of water with or after food

Question 33

Monitoring of metformin? Missed dose rules? Aims according to HbA1c?

Answer 33

o HbA1c target 48mmol/mol o U&Es before starting treatment, then at least annually - If miss a dose, take ASAP unless near next dose If >58 - intensify treatment If on one OHA not associated with hypos - Aim 48mmol/L If on drug associated with hypos - Aim 53mmol/L

Question 34

Name of thiazolidinediones?

Answer 34

Pioglitazone

Question 35

Indications of thiazolidinediones? (pioglitazone)

Answer 35

Type 2 DM (single agent where metformin not tolerated, second or third agent)

Question 36

Mechanism of thiazolidinediones? (pioglitazone)

Answer 36

- Insulin sensitizers - Activate nuclear PPARgamma which induces genes to enhance insulin action in skeletal muscle, adipose tissue and liver - Increased peripheral glucose uptake and reduced hepatic gluconeogenesis - Weight gain

Question 37

Side effects of thiazolidinediones? (pioglitazone)

Answer 37

- GI upset, Anaemia, Dizziness, headache, disturbed vision - Oedema and cardiac failure - Bladder cancer - Bone fractures

Question 38

Contraindications of thiazolidinediones? (pioglitazone)

Answer 38

- Heart failure - CVD - Bladder cancer or macroscopic haematuria

Question 39

Caution of thiazolidinediones? (pioglitazone)

Answer 39

- Smoking, occupational exposure - Elderly - Hepatic impairment (metabolised in liver)

Question 40

Interactions of thiazolidinediones? (pioglitazone)

Answer 40

Other OHAs increase risk of hypoglycaemia

Question 41

Prescription of thiazolidinediones? (pioglitazone)

Answer 41

- Oral - 15-30mg OD with breakfast and can be increased - Long-term treatment should not be stopped or changed - Taken in morning with glass of water

Question 42

Monitoring of thiazolidinediones? (pioglitazone)

Answer 42

o HbA1c before and 3-6 months after commencing | o LFTs before and during treatments

Question 43

Names of thyroid hormones?

Answer 43

Levothyroxine, liothyronine

Question 44

Indications of levothyroxine?

Answer 44

Levothyroxine, liothyronine

Question 45

Mechanism of levothyroxine?

Answer 45

- Thyroid gland produces thyroxine (T4), which is converted into active triiodothyronine (T3) in target tissues - Regulate metabolism and growth - Levothyroxine (synthetic T4) is usual treatment. Liothyronine (synthetic T3) acts quick so used in emergency treatment of hypothyroidism

Question 46

Side Effects of levothyroxine?

Answer 46

- Diarrhoea, vomiting, weight loss - Palpitations, arrhythmias, angina, flushing - Tremor, restlessness, insomnia - Menstrual irregularities

Question 47

Contraindications of levothyroxine?

Answer 47

o Thyrotoxicosis | o Pregnancy – may require increased dose – specialist care

Question 48

Cautions of levothyroxine?

Answer 48

o Coronary artery disease (low dose starting), MI, HF o Diabetes mellitus (dose of antidiabetic drug may need increasing) o Hypopituitarism – need corticosteroid therapy before levothyroxine to avoid Addisonian crisis

Question 49

Interactions of levothyroxine?

Answer 49

- GI absorption affected by antacids, calcium or iron salts o Separate by at least 4 hours - Levothyroxine can change insulin or OHA requirements in diabetes

Question 50

Prescription of levothyroxine?

Answer 50

o Oral initially 50-100 micrograms OD, adjusted in 25-50 microgram steps every 3-4 weeks to response o Maintenance of 100-200 micrograms OD, taken >30 minutes before breakfast or coffee/tea o If elderly or cardiac disease – initial 25 micrograms daily and adjust dose to maintenance of 50-200 micrograms

Question 51

Monitoring of levothyroxine?

Answer 51

o Review patient monthly, dose changes guided by symptoms o TFTs at 3 months after starting or a dose change o Stable patients have annual review and TFTs

Question 52

Indications of carbimazole?

Answer 52

- Hyperthyroidism

Question 53

MEchanism of carbimazole?

Answer 53

- Thyroid gland produces thyroxine (T4), which is converted into active triiodothyronine (T3) in target tissues - Regulate metabolism and growth - Carbimazole reduces the amount of hormone released by thyroid - Does not affect thyroxine already made and stored so takes 4-8 weeks to work

Question 54

Side Effects of carbimazole?

Answer 54

- Nausea, vomiting, stomach upset - Headache, muscle and joint pain - Skin rash and itching - Taste disturbances - Bone marrow suppression o Neutropenia and agranulocytosis  Report infective symptoms (sore throat), perform WBC if clinical evidence of infection  Stop promptly if neutropenia

Question 55

Contraindications of carbimazole?

Answer 55

o Pregnancy – use contraception when on therapy (congenital malformations, especially first trimester) o Severe blood disorders o Severe liver disease o Acute pancreatitis

Question 56

Interactions of carbimazole?

Answer 56

- Risk of myelosuppression with other medication that causes this - Warfarin enhances anticoagulant effects – additional monitoring needed

Question 57

Prescription of carbimazole?

Answer 57

o 15-40mg OD continue until patient euthyroid, usually after 4-8 weeks o Reduce dose gradually, therapy usually given for 12-18 months

Question 58

Monitoring of carbimazole?

Answer 58

o Before treatment – FBC and LFT | o During treatment – TFTs every 4-6 weeks for first few months, then every 3 months

Question 59

Patient communication of carbimazole?

Answer 59

o Report any infective signs (sore throat, mouth ulcers, bruising, fever, malaise) o Advise against pregnancy on medication – use effective contraception

Question 60

Names of glucocorticoids?

Answer 60

Prednisolone, hydrocortisone, dexamethasone

Question 61

Indications of glucocorticoids?

Answer 61

Allergic or inflammatory disorders (anaphylaxis, eczema, asthma, COPD) Severe croup Autoimmune disease (IBD, ITP, inflammatory arthritis) Cancer treatment Myasthenia Gravis, Polymyalgia rheumatica, GCA, Lupus Proctitis Joint injections Adrenal insufficiency/Hypopituitarism

Question 62

MEchanism of glucocorticoids?

Answer 62

- Bind to cytosolic glucocorticoid receptors which upregulate anti-inflammatory genes and downregulate pro-inflammatory genes (cytokines, TNFa) - Suppression of circulating monocytes and eosinophils - Metabolic effects o Increased gluconeogenesis o Increased catabolism - Mineralocorticoid effects o Stimulate Na and water retention and K excretion

Question 63

Side Effects of glucocorticoids?

Answer 63

``` Immunosuppression Diabetes mellitus Insomnia, psychosis and suicidal ideas Osteoporosis Metabolic o Proximal muscle weakness, skin thinning with easy bruising and gastritis Mineralocorticoid o Hypertension, hypokalaemia and oedema Prolonged o Adrenal atrophy leading to Addisonian crisis if withdrawn suddenly ```

Question 64

Cautions of glucocorticoids?

Answer 64

- Infection - Children (suppress growth) - Hepatic or Renal impairment

Question 65

Interactions of glucocorticoids?

Answer 65

Risk of peptic ulceration – NSAIDs Hypokalaemia – B2-agonists, theophylline, loop and thiazide diuretics Affected by CYP450 enzymes

Question 66

Prescription of glucocorticoids?

Answer 66

o Can be given orally, IM, IV o OD, taken in the morning to mimic natural circadian rhythm o Consider use of bisphosphonates and PPIs if long-term and risk

Question 67

Monitoring of glucocorticoids?

Answer 67

o For children – height and weight monitored annually – refer to paediatrician if slow o Prolonged treatment – HbA1c or DEXA scan

Question 68

Cessation of glucocorticoids?

Answer 68

o Abrupt withdrawal can lead to adrenal insufficiency | o Gradual withdrawal used if treatment >3 weeks, received >40mg, repeated evening doses

Question 69

Patient communication in glucocorticoids?

Answer 69

o Should feel better in 1-2 days o Do not stop immediately o Steroid card to carry round at all times o If ill, double usual dose