CBL 2 notes Flashcards

1
Q

What is the mechanism of action of sulfonylureas?

A

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.

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2
Q

What are the indications for sulfonyureas?

A

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

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3
Q

What are the commonly used different types of sulfonylureas?

A

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

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4
Q

What are the common side effects of sulfonylureas?

A

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

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5
Q

What are the common contraindications for sulfonylureas?

A

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

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6
Q

What is the important therapeutic information about sulfonylureas?

A

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

Severe interaction: metreleptin, chloramphenicol​

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

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7
Q

What are the common signs and symptoms of hypoglycemia?

A

Weakness
Sweating
Sleepiness
Pale skin
Dizziness
Irritability
Hunger
Headache
Blurred vision

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8
Q

What patient education is needed with sulfonylureas?

A

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

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9
Q

What monitoring is needed for sulfonylureas?

A

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.

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10
Q

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

A

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

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11
Q

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

A

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

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12
Q

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

A

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

Constipation​
Fluid imbalance ​
Hypotension

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13
Q

What are the possible interactions for SGLT2 inhibitors?

A

Blood pressure medication - risk of hypotension​

Other diabetic drugs – risk hypoglycemia ​

Alcohol ​

Levodopa – risk hypotension

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14
Q

What monitoring and patient education is required with SGLT2 inhibitors?

A

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

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15
Q

What is the therapeutic evaluation of SGLT2 inhibitors?

A

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

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16
Q

What is Conns syndrome?

A

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

17
Q

What are the risk factors for Conns syndrome?

A

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

18
Q

What is the management for conns syndrome?

A

Surgical removal of the adrenal adenoma

19
Q

What are the typical signs and symptoms of conns syndrome?

A

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

20
Q

What investigations should be done for conns syndrome?

A

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.

21
Q

What is the gold standard investigations for acromegaly?

A

Oral glucose tolerance test

22
Q

What is a pheochromocytoma?

A

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

23
Q

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

A

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

24
Q

What are the main aetiologies in pheochromocytoma?

A

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

25
What is the typical treatment for a pheochromocytoma?
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.
25
What are the main signs and symptoms of pheochromocytoma?
Palpitations - tachycardia Headaches - due to HTN Excessive sweating (Diaphoresis) Other - anxiety and tremor
26
What are the key investigations for a pheochromocytoma?
Golden standard - plasma free metanephrines (breakdown product of adrenaline = longer half life) 24hr urinary catecholamines Scans = CT/MRI, PET/MIBG
27
What are the key moa and indications for metformin?
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.
28
What monitoring is required for metforming?
Renal funcation - before and annually, if deterioates then twice a year If eFR <60 reduce dose, <30 stop med Monitor VitB12.
29
What are the common causes of prolonged elevated levels of glucocorticoids?
Cushings disease Adrenal adenoma Paraneoplastic syndrome Exogenous steroids.
30
What are GLP-1 agonists?
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.
31
How does GLP-1 agonists work?
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.
32
What are the side effects of GLP-1 receptor antagonists?
Should not be used in pancreatitis Risk of pancreatitis and dehydration GI problems - D&V Fatigue
33
What are the interactions with GLP-1 receptor angonists?
Any other GLP-1 agonist - risk of hypoglycaemia Acenocoumarol - can decrease anti-coagulant effect.