Endocrine

Question 1

Name 3 examples of systemic cortiosteroids and 3 indications for their use:

Answer 1

• prednisolone, hydrocortisone, dexamethasone
• to treat allergic or inflamm disorders (anaphylaxis, asthma)
• supress autoimmune disease e.g. IBD, arthritis
• to treat some cancers (as part of chemo/to reduces tumour swelling)
• hormone replacement in Adrenal insufficiency or hypopituitarism

Question 2

Corticosteroids MOA..bind to ____ receptors which ___ to the ___ and bind to _____-response elements that regulate ____ expression. They upregulate ___-_____ ___ and down-regulate ___-_____ ___.
They also suppress circulating ___ and __.
Metabolic effects include increased ____ from increased circulating amino and fatty acids released by catabolism of __ and fat.
Also have ______ effects, stimulating Na+ and water ___ and K+ ___ in the renal tubule

Answer 2

• glucocorticoid receptors –> translocate to nucleus, bind to glucocorticoid-REs
• regulate gene expression, upreg anti-inflamm genes, downreg. pro-inflamm genes
• supress circulating monocytes and eosinophils
• increased gluconeogenesis (from catabolism of muscle and fat)
• mineralocorticoid effect, Na+/water retention and K+ excretion

Question 3

Name 8 important adverse effects that may arise from systemic corticosteroid therapy
(think about MOA to remember these)

Answer 3

• immunosuppression
• metabolic effects: DM, osteoporosis
• increased catabolism: proximal muscle weakness, skin thinning, easy bruising, gastritis
• mood/behaviour: insomnia, confusion, psychosis, suicidal ideation
• mineralocorticoid effects: HT, hypokalaemia, oedema
• adrenal atrophy in prolonged rx (–> addisonian crisis on sudden withdrawal..fatigue, weight loss, arthralgia)

Question 4

What 2 medication classes should be considered alongside long-term systemic corticosteroid therapy to reduce adverse effects?

Answer 4

• bisphosphonates

- PPIs

Question 5

When should you exercise caution in prescribing systemic corticosteroids?

Answer 5

• people with an infection

- children (can supress growth)

Question 6

corticosteroids increase the risk of peptic ulcers/GI bleeding when used with ____
and enhance hypokalaemia when used in pts also taking __-agonists, th____, ___ or ___ diuretics.
Efficacy can be reduced by cytochrome P450 inducers such as….

Answer 6

• NSAIDS
• B2 agonists, theophylline, loop or thiazide
• rifampicin, phenytoin, carbamazepine

Question 7

In a pt undergoing long-term systemic corticosteroid therapy who becomes acutely ill, what should you do with their dose while unwell and then once recovered?

Answer 7

(atrophic adrenal glands won’t be able to increase cortisol in response to stress - do this artificially)

• double the dose during acute illness
• reduce back to maintenance dose on recovery

Question 8

Dipeptidyl peptidase 4 inhibitors are used in combo w Metformin for T2DM. What is the suffix for this class and by what mechanism to they exert their effects?

Answer 8

__gliptin e.g. sitagliptin, linagliptin

• incretins (GLP1 and GIP) are rapidly inactivated/hydrolysed by DDP-4
• inhibitors of this enzyme increase plasma conc of active incretins
• incretins promote insulin secretion and suppress glucagon release so lower BM

Question 9

DPP-4 inhibitors e.g. sitagliptin, main SEs include:

-and <1 % develop acute _____ (suspect if persistent ___ pain)

Answer 9

SEs: GI upset, headache, nasopharyngitis, peripheral oedema

-<1%: acute pancreatitis, persistent abdo pain

Question 10

Give 3 CIs for the use of DPP-4 inhibitors e.g. sitagliptin

NB: caution in elderly, those w pancreatitis hx or renal impairment

Answer 10

• CI: HISTORY OF HYPERSENSITIVITY TO CLASS
• CI: TYPE 1 DIABETES TREATMENT
• CI: KETOACIDOSIS
• CI: PREGNANCY
• CI: BREAST FEEDING

Question 11

DPP-4 inhibitors e.g. sitagliptin efficacy and use is done via HbA1 results:
-if used as monotherapy target HbA1c is

Answer 11

• aim <48 mmol if monotherapy
• <53 mmol if with metformin
• if remains >58 mmol add on

Question 12

Name 3 effects insulin has on processes:

Answer 12

• stimulates glucose uptake
• stimulates glycogen, lipid and protein synthesis
• inhibits gluconeogenesis and ketogenesis
• drives K+ into cells

Question 13

Suggest one serious SE of insulin rx and one more cosmetic SE

Answer 13

• HYPOGLYCAEMIA (can -> coma/death), higher risk in renal impairment (less clearance)
• lipohypertrophy at site of repeated injection

Question 14

Concurrent insulin use with other hypoglycaemic agents increases risk of hypoglycaemia. Concurrent use with what common drug class requires insulin doses to be increased?

Answer 14

-concurrent corticosteroid use

Question 15

Metformin is a biguanide that lowers blood glucose mainly by reducing what? as well as what effect on muscle?

Answer 15

• reduces hepatic glucose output (glycogenolysis and gluconeogenesis)
• increased glucose uptake and use by skeletal muscle

Question 16

Can monotherapy with metformin cause hypoglycaemia ?

NB: metformin can cause weight loss

Answer 16

-Nope

Question 17

Suggest a common SEs of metformin use?

Answer 17

• GI upset: nausea, vomiting, taste disturbance, anorexia, diarrhoea
• rarely lactic acidosis

Question 18

What organ excretes metformin

Answer 18

-kidney

Question 19

if eGFR is

Answer 19

• <30mL/min
• stop in AKI
• stop if severe tissue hypoxia (e.g. sepsis, cardio/resp failure, MI)

Question 20

Due to risk of hypoglycaemia, metformin should be withheld in acute ____ _____ and used caution in patients with chronic ____ ____

Answer 20

• acute alcohol intoxication

- chronic alcohol abuse

Question 21

Metformin must be withheld before and for 48hrs after injection of what and why?

Answer 21

• IV contrast media

- as increased risk of renal impairment, metformin accumulation and lactic acidosis

Question 22

Metformin and GI SEs when starting, how is best to manage?

Answer 22

• start on a low dose, increase gradually e.g. 500mg once daily
• swallow tablets whole with a glass of water, with or after food to minimise SEs

Question 23

Metformin efficacy is assessed via HbA1 results:

• if used as monotherapy target HbA1c is < ____
• if used in combo with other drugs, target is ____ triggers an add on therapy

Answer 23

• aim <48 mmol if monotherapy
• <53 mmol if used in combo
• if remains >58 mmol add on

Question 24

What blood test should be measured before starting Metformin? And repeated at least annuallly?

Answer 24

-U&Es to check renal function

if RF or deteriorating kidney function, repeat more regularly

Question 25

Gliclazide is an example of what type of drug used to treat T2DM either with Metformin, or alone (if CI to metformin)

Answer 25

-Sulphonylurea

Question 26

Sulphonylureas e.g. g_____ lower blood glucose by stimulating what? They block which channels where leading to cell membrane depolarisation and opening of which channels, leading to increased intracellular ___ conc, so stimulates _____ _____

Answer 26

- gliclazide - stimulates pancreatic insulin release - block ATP-dependent K+ channels in beta-islet cell membranes - so voltage gated Ca2+ channels open, increased Ca2+ conc - stimulates insulin secretion

Question 27

Sulphonylureas are only effective in pts with _____ ____ function. And as insulin is an anabolic hormone and this drug class stimulates it's secretion what is an adverse effect of this drug class use?

Answer 27

- residual pancreatic function | - weight gain

Question 28

Give 2 SEs of Sulphonylureas (gliclazide)

Answer 28

- GI upset: N&V, diarrhoea, constipation - Hypoglycaemia - Rare hypersensitivity reactions: hepatic toxicity, agranulocytosis

Question 29

Sulphonylureas (gliclazide) cautions: suggest 1

Answer 29

- hepatic impairment - renal impairment - those at increased risk of hypoglycaemia

Question 30

What medication class can mask symptoms of hypoglycaemia in patients on Sulphonylureas (gliclazide):

Answer 30

-Beta-blockers

Question 31

What communication points are important to get across when commencing a pt on any anti-diabetic drug?

Answer 31

- x has been prescribed as a long-term therapy to control BM and reduce the risk of diabetic complications e.g. micro/macro eye, kidney, heart - tablets aren't replacement for lifestyle, keep exercise and good diet - warn of hypo sx (dizzy, nausea, sweating, confusion), take sugar then starchy snack if happens and seek medical advice if recurs

Question 32

Give 4 actions of insulin

Answer 32

- stimulates glucose uptake from circulation-> tissues - increases use of glucose for energy - stimulates glycogen, lipid and protein synthesis - inhibits gluconeogenesis - inhibits ketogenesis - drives K+ into cells

Question 33

Where IV insulin is required what type is chosen (e.g. rapid acting=immediate action, short duration, short acting = early onset, short duration, intermediate acting = intermediate action and duration or long acting - flat profile w regular administration)

Answer 33

-short acting e.g. Actrapid, it is a soluble insulin

Question 34

Typical daily insulin requirements are roughly how many units? (varies on weight, diet, activity and insulin resistance)

Answer 34

-30 to 50 units

Question 35

In diabetic emergencies/peri-op glycaemic control, a 1 unit/m: IV solution is made by diluting Actrapid __ units in __% ____ ____ __mL (vs. in hyperkalaemia rx is roughly Actrapid 10units is given in 20% dextrose 100mL over 15mins)

Answer 35

-50 units in 0.9% sodium chloride 50 mL

Question 36

If insulin is given as a continuous IV infusion, what should be measured every 4hrs to guide need for replacement?

Answer 36

measure serum K+