CBL 2 notes

Question 1

What is the mechanism of action of sulfonylureas?

Answer 1

Insulinotropic drug -> increase secretion on insulin from beta cells -> increase glucose uptake -> prevent hyperglycemia
Targtes ATP-sensitive potassium channels on pancreastic beta cells - causing depolarisation.

Question 2

What are the indications for sulfonyureas?

Answer 2

T2DM - patients must still have some residual function of beta cells
Cannot be used in T1DM
Effective blood glucose control
Maintain HbA1c target range = 53mmol/mol

Question 3

What are the commonly used different types of sulfonylureas?

Answer 3

Gliclazide - standard release or slow release tables with breakfast
Glipizide - tablets 30mins before breakfast or lunch
Tolbutamide - table, once a day before first meal of the day

Question 4

What are the common side effects of sulfonylureas?

Answer 4

Hypoglycemia <4mmol/L - moderate risk
Common - tummy ache, sickness, diarrhoea, weight gain.

Question 5

What are the common contraindications for sulfonylureas?

Answer 5

Ketoacidosis (norm/hypo DKA)
Hypersensntivity to sulfonamides
Hepatic or renal impairement
For glicazide - avoid in acute porphyrias (heme defect)

Question 6

What is the important therapeutic information about sulfonylureas?

Answer 6

Interactions with other drugs that cause hypos – metformin, SGLT2 inhibitors​

Severe interaction: metreleptin, chloramphenicol​

Stop in pregnancy and breast feeding -> risk of neonatal hypos.

Question 7

What are the common signs and symptoms of hypoglycemia?

Answer 7

Weakness
Sweating
Sleepiness
Pale skin
Dizziness
Irritability
Hunger
Headache
Blurred vision

Question 8

What patient education is needed with sulfonylureas?

Answer 8

Risk when driving must be reported to DVLA - recommended BM machine to measure blood glucose before driving.
How to recognise a hypo.

Question 9

What monitoring is needed for sulfonylureas?

Answer 9

Before starting - QRISK2 - high CVD risk - SGLT2 might be more appropriate alternative
General T2DM - every 3 months when newly diagnosed then every 6 months once your stable.

Question 10

What is the mechanism of actions of SGLT2 inhibitors? (dapagliflozin)

Answer 10

Reversibly inhibits SGLT2 in PCT of nephron
Reduces glucose reabsorption
Increases urinary glucose excretion

Question 11

What are the indications for SGLT-2 inhibitors such as dapaglifolzin?

Answer 11

10mg once daily orally with or without food ​

T2DM as monotherapy if metformin is inappropriate ​

T2DM in combination with insulin or other anti diabetic drugs ​

Symptomatic chronic heart failure ​

Chronic kidney disease

Question 12

What are some common sides effects of SGLT2 inhibitors (dapagliflozin)?

Answer 12

Back pain ​
Dizziness ​
Hypoglycemia (combination with insulin or sulfonylurea)​
Prostatitis ​
Increased Urinary tract infection risk ​

Constipation​
Fluid imbalance ​
Hypotension

Question 13

What are the possible interactions for SGLT2 inhibitors?

Answer 13

Blood pressure medication - risk of hypotension​

Other diabetic drugs – risk hypoglycemia ​

Alcohol ​

Levodopa – risk hypotension

Question 14

What monitoring and patient education is required with SGLT2 inhibitors?

Answer 14

Signs and symptoms of DKA
Renal funcation
Blood pressure
Notify DVLA is risk of hypoglycemia

Question 15

What is the therapeutic evaluation of SGLT2 inhibitors?

Answer 15

AVOID In pregnancy and breast feeding​
AVOID INITIATION eGFR <15mL/min/1.732​
CONTRAINDICATED IN T1DM, DKA​
CAUTION in hepatic impairment ​
CAUTION in elderly + those hypotension​
CAUTION in peripheral arterial disease, foot ulcers

Question 16

What is Conns syndrome?

Answer 16

An adrenal adenoma secreting alsoterone
Funcational tumour or benign cortical adenoma
Form of primary aldosteronism

Question 17

What are the risk factors for Conns syndrome?

Answer 17

Genetic mutations (MENIN type 1, ARMC5)
Smokers
Increasing age
Female sex

Question 18

What is the management for conns syndrome?

Answer 18

Surgical removal of the adrenal adenoma

Question 19

What are the typical signs and symptoms of conns syndrome?

Answer 19

Persistent HTN - light-headed, headaches, blurred vision
Hypokalemia - muscle weakness, fatigue, parasethesia
Metabolic alkalosis

Question 20

What investigations should be done for conns syndrome?

Answer 20

Bedside: BP (HTN), ECG
Bloods: U&Es ( hypoK+, hyper Na+), VBG (metabolic alkalosis), Aldosterone to renin ratio (high)
Imaging - CT/MRI adrenals to look for tumour
Adrenal vein sampling.

Question 21

What is the gold standard investigations for acromegaly?

Answer 21

Oral glucose tolerance test

Question 22

What is a pheochromocytoma?

Answer 22

Tumour that arises from chromaffin cells from the medulla of the adrenal gland
Autonomous secretion of catecholamines (intermittent and paroxsymal)

Question 23

What are some of the receptors targeted by catecholamines?
Consequences in pheochromocytoma

Answer 23

Alpha 1 adrenergic - vasoconstriction -> HTN
Beta 1 adrenergic - contractactility -> tachycardia
Beta 2 adrenergic - glycogenolysis -> hyperglycemia

Question 24

What are the main aetiologies in pheochromocytoma?

Answer 24

Up to 40% genetic
MEN2 - multiple endocrine neoplasia T2 (AD mutation)
NF1 (AD mutation)
Von Hippel-Lindau Disease

Question 25

What is the typical treatment for a pheochromocytoma?

Answer 25

Surgical removal of tumour
Prep for surgery - alpha blockers (phenoxybenzamine - 10mg), beta blocker (propanolol) if indicated
Re-measurement of catecholamines levels to confirm curative effect.

Question 25

What are the main signs and symptoms of pheochromocytoma?

Answer 25

Palpitations - tachycardia
Headaches - due to HTN
Excessive sweating (Diaphoresis)

Other - anxiety and tremor

Question 26

What are the key investigations for a pheochromocytoma?

Answer 26

Golden standard - plasma free metanephrines (breakdown product of adrenaline = longer half life)
24hr urinary catecholamines
Scans = CT/MRI, PET/MIBG

Question 27

What are the key moa and indications for metformin?

Answer 27

Decreases hepatic gluconeogenesis
Increases peripheral use of glucose

Used in type 2 diabetes and sometimes type 1
500mg with meals up to max 2g a day
May also be used in PCOS.

Question 28

What monitoring is required for metforming?

Answer 28

Renal funcation - before and annually, if deterioates then twice a year
If eFR <60 reduce dose, <30 stop med
Monitor VitB12.

Question 29

What are the common causes of prolonged elevated levels of glucocorticoids?

Answer 29

Cushings disease
Adrenal adenoma
Paraneoplastic syndrome
Exogenous steroids.

Question 30

What are GLP-1 agonists?

Answer 30

Glucagon-like peptide 1 receptor agonists - reduce weight and prevent heart disease, improve glycaemic control
Sub-cut injections once a week or table form.
All end in glutide. e,g dulaglutide.

Question 31

How does GLP-1 agonists work?

Answer 31

Increase insulin secretion
Slow gastric emptying
Reduce postprandial glucagon secretion
Reduce blood glucose and reduce atherosclerosis
Weight loss due to reduced appetite and food cravings.

Question 32

What are the side effects of GLP-1 receptor antagonists?

Answer 32

Should not be used in pancreatitis
Risk of pancreatitis and dehydration
GI problems - D&V
Fatigue

Question 33

What are the interactions with GLP-1 receptor angonists?

Answer 33

Any other GLP-1 agonist - risk of hypoglycaemia
Acenocoumarol - can decrease anti-coagulant effect.