CBL 2 notes Flashcards
What is the mechanism of action of sulfonylureas?
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.
What are the indications for sulfonyureas?
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
What are the commonly used different types of sulfonylureas?
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
What are the common side effects of sulfonylureas?
Hypoglycemia <4mmol/L - moderate risk
Common - tummy ache, sickness, diarrhoea, weight gain.
What are the common contraindications for sulfonylureas?
Ketoacidosis (norm/hypo DKA)
Hypersensntivity to sulfonamides
Hepatic or renal impairement
For glicazide - avoid in acute porphyrias (heme defect)
What is the important therapeutic information about sulfonylureas?
Interactions with other drugs that cause hypos – metformin, SGLT2 inhibitors
Severe interaction: metreleptin, chloramphenicol
Stop in pregnancy and breast feeding -> risk of neonatal hypos.
What are the common signs and symptoms of hypoglycemia?
Weakness
Sweating
Sleepiness
Pale skin
Dizziness
Irritability
Hunger
Headache
Blurred vision
What patient education is needed with sulfonylureas?
Risk when driving must be reported to DVLA - recommended BM machine to measure blood glucose before driving.
How to recognise a hypo.
What monitoring is needed for sulfonylureas?
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.
What is the mechanism of actions of SGLT2 inhibitors? (dapagliflozin)
Reversibly inhibits SGLT2 in PCT of nephron
Reduces glucose reabsorption
Increases urinary glucose excretion
What are the indications for SGLT-2 inhibitors such as dapaglifolzin?
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
What are some common sides effects of SGLT2 inhibitors (dapagliflozin)?
Back pain
Dizziness
Hypoglycemia (combination with insulin or sulfonylurea)
Prostatitis
Increased Urinary tract infection risk
Constipation
Fluid imbalance
Hypotension
What are the possible interactions for SGLT2 inhibitors?
Blood pressure medication - risk of hypotension
Other diabetic drugs – risk hypoglycemia
Alcohol
Levodopa – risk hypotension
What monitoring and patient education is required with SGLT2 inhibitors?
Signs and symptoms of DKA
Renal funcation
Blood pressure
Notify DVLA is risk of hypoglycemia
What is the therapeutic evaluation of SGLT2 inhibitors?
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
What is Conns syndrome?
An adrenal adenoma secreting alsoterone
Funcational tumour or benign cortical adenoma
Form of primary aldosteronism
What are the risk factors for Conns syndrome?
Genetic mutations (MENIN type 1, ARMC5)
Smokers
Increasing age
Female sex
What is the management for conns syndrome?
Surgical removal of the adrenal adenoma
What are the typical signs and symptoms of conns syndrome?
Persistent HTN - light-headed, headaches, blurred vision
Hypokalemia - muscle weakness, fatigue, parasethesia
Metabolic alkalosis
What investigations should be done for conns syndrome?
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.
What is the gold standard investigations for acromegaly?
Oral glucose tolerance test
What is a pheochromocytoma?
Tumour that arises from chromaffin cells from the medulla of the adrenal gland
Autonomous secretion of catecholamines (intermittent and paroxsymal)
What are some of the receptors targeted by catecholamines?
Consequences in pheochromocytoma
Alpha 1 adrenergic - vasoconstriction -> HTN
Beta 1 adrenergic - contractactility -> tachycardia
Beta 2 adrenergic - glycogenolysis -> hyperglycemia
What are the main aetiologies in pheochromocytoma?
Up to 40% genetic
MEN2 - multiple endocrine neoplasia T2 (AD mutation)
NF1 (AD mutation)
Von Hippel-Lindau Disease
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.
What are the main signs and symptoms of pheochromocytoma?
Palpitations - tachycardia
Headaches - due to HTN
Excessive sweating (Diaphoresis)
Other - anxiety and tremor
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
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.
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.
What are the common causes of prolonged elevated levels of glucocorticoids?
Cushings disease
Adrenal adenoma
Paraneoplastic syndrome
Exogenous steroids.
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.
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.
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
What are the interactions with GLP-1 receptor angonists?
Any other GLP-1 agonist - risk of hypoglycaemia
Acenocoumarol - can decrease anti-coagulant effect.
