Endo Flashcards
(84 cards)
Metformin
MOA
Side effects
Contraindications
Mechanism of action = Impoves glucose tolerance
- Activates AMP-activated protein kinase (AMPK)
- Increases insulin sensitivity
- Decreases hepatic gluconeogenesis
- May also reduce gastrointestinal absorption of carbohydrates
Uses
- T2DM (doesn’t cause hypo or weight gain)
- PCOS
- Fatty liver
Adverse effects
Gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
Reduced vitamin B12 absorption - rarely a clinical problem
Lactic acidosis* with severe liver disease or renal failure
Contraindications
- !!CKD!!!: NICE recommend that the dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)
- May cause lactic acidosis if taken during a period where there is tissue hypoxia. Examples include a recent myocardial infarction, sepsis, acute kidney injury and severe dehydration (D&V)
- Iodine-containing x-ray contrast media: examples include peripheral arterial angiography, coronary angiography, intravenous pyelography (IVP); there is an increasing risk of provoking renal impairment due to contrast nephropathy; metformin should be discontinued on the day of the procedure and for 48 hours thereafter
alcohol abuse is a relative contraindication
Sitagliptin
MOA
Important points
Side effects
dipeptidyl peptidase 4 (DPP-4) inhibitor.
Don’t cause weight gain
Don’t cause hypoglycaemia
Side effects
Pancreatitis
Sulphonylurea
MOA
side effects
Examples
Stimulate pancreatic beta cells to secrete insulin
Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion - Low Na
Liver dysfunction (cholestatic)
e.g. Gliclazide
Glitazones side effects
Weight gain
Fluid retention
Liver dysfunction
Fractures
hypocalcaemia
Symptoms
Causes
Tingling Muscle cramps Hyperactive deep tendon reflexes Chovstek + Trousseau Prolonged QT Convulsions
Causes Hypoparathyroid Low calcium or vitamin D infections some medications, such as phenytoin (Dilantin), phenobarbital, and rifampin stress anxiety intense exercise irregular magnesium or phosphate levels kidney disease
What is Exanatide
USe
Adverse effects
Glucagon-like peptide-1 (GLP-1) mimetics
- increase insulin secretion and inhibit glucagon secretion (work as incretin mimetic)
- Given SC
Typically result in weight loss in T2Dm
Consider adding exenatide to metformin and a sulfonylurea if:
BMI >= 35 kg/m² in people of European descent and there are problems associated with high weight, or
BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities.
Adverse effects
- Main = N&V
- pancreatitis
Can only continue using if
11 mmol/mol (1%) reduction in HbA1c and 3% weight loss after 6 months to justify the ongoing prescription of GLP-1 mimetics.
What are SGLT2 inhibitors
Use
Examples
Side effects
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
Use - Diabetes
Examples include canagliflozin, dapagliflozin and empagliflozin.
Important adverse effects include
Urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus.
Diagnosis of DKA
Management
Key points
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick
Management
Fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially. Please see an example fluid regime below.
Insulin: an intravenous infusion should be started at 0.1 unit/kg/hour.
Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started
Correction of hypokalaemia
long-acting insulin should be continued, short-acting insulin should be stopped
What are thiazolinediones
Use
MOA
Example
Adverse effects
Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.
The PPAR-gamma receptor is an intracellular nuclear receptor. It’s natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function.
Example = Pioglitazone
Adverse effects
weight gain
liver impairment: monitor LFTs
fluid retention - therefore CI IN HF
The risk of fluid retention is increased if the patient also takes insulin
INCREASED FRACTURE RISK😒
BLADDER CANCER: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
Causes of gynaecomastia
Gynaecomastia describes an abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia
Causes of gynaecomastia physiological: normal in puberty syndromes with androgen deficiency: Kallman's, Klinefelter's testicular failure: e.g. mumps liver disease testicular cancer e.g. seminoma secreting hCG ectopic tumour secretion hyperthyroidism haemodialysis drugs: see below
Drug causes of gynaecomastia spironolactone (most common drug cause) cimetidine digoxin cannabis finasteride gonadorelin analogues e.g. Goserelin, buserelin oestrogens, anabolic steroids
Digoxin Isoniazid Cimetidine Ketoconazole Marijuana Ethanol + Oestrogen Azathioprine Thyroxine
Management = dopamine agonists e.g. bromocriptine
What is Nelson’s syndrome
Nelson’s syndrome occurs due to rapid enlargement of a pituitary corticotroph adenoma (ACTH producing adenoma) that occurs after the removal of both adrenal glands (bilateral adrenalectomy) which is an operation used for Cushing’s syndrome. Removal of both adrenal glands eliminates the production of cortisol, and the lack of cortisol’s negative feedback can allow any pre-existing pituitary adenoma to grow unchecked. Continued growth can cause mass effects due to physical compression of brain tissue. Increased production of adrenocorticotrophic hormone (ACTH) can result in increased melanocyte stimulating hormone (MSH) which can result in HYPERPIGMENTATION
Nelson’s syndrome is now rare because bilateral adrenalectomy is now only used in extreme circumstances. After bilateral adrenalectom follow-up should include awareness of Nelson’s syndrome. Monitoring of ACTH level and pituitary MRI are recommended 3-6 months after surgery and regularly thereafter
Diagnosis of IFG and IGT
Difference
IFG: A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
IGT: fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
IFG and IGT denote different denote different abnormalities of glucose regulation (fasting and post-prandial).
- Lower risk of progression to DM in IFG
Management
- Both: Lifestyle advice + annual review
What are gliptins
MOA
Side effects
Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Key points
oral preparation
trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia
do not cause weight gain
NICE guidelines on DPP-4 inhibitors
NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedion
Side effects
Pancreatitis
T1 diabetes blood glucose targets
Management
Illness advice
Other option to multiple daily insulin injections
In type 1 diabetics, blood glucose targets:
5-7 mmol/l on waking and
4-7 mmol/l before meals at other times of the day
Aim for 48% HbA1c
Type of insulin
- Offer multiple daily injection basal–bolus insulin regimens, rather than twice‑daily mixed insulin regimens, as the insulin injection regimen of choice for all adults
Twice‑daily insulin detemir is the regime of choice. Once-daily insulin glargine or insulin detemir is an alternative
offer rapid‑acting insulin analogues injected before meals, rather than rapid‑acting soluble human or animal insulins, for mealtime insulin replacement for adults with type 1 diabetes
NICE recommend considering adding metformin if the BMI >= 25 kg/m²
DO NOT STOP using insulin during acute illness
- Maintain calorie intake
- Check blood glucose 4 or more times a day and look for ketones; increase insulin dose if glucose rising; advice to get specialist diabetes nurse/gp help if concerned
- Admit if vomiting, dehydrated, ketotic, a child or pregnant
Insulin pumps (continuous SC insulin) can be considered when disabling hypos have been occurring or person unable to achieve target HbA1c despite careful management
What is pseudo Cushings
Pseudo-Cushing’s
mimics Cushing’s
often due to alcohol excess or severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
insulin stress test may be used to differentiate
Osmolaritiy
2 Na + 2 K + Glucose + Urea (all in mmol/L).
Orlistat criteria for use
NICE have defined criteria for the use of orlistat. It should only be prescribed as part of an overall plan for managing obesity in adults who have:
1) BMI of 28 kg/m^2 or more with associated risk factors, or
2) BMI of 30 kg/m^2 or more
3) continued weight loss e.g. 5% at 3 months
Orlistat is normally used for < 1 year
MOA
inhibit pancreatic lipases, which in turn will decrease the absorption of lipids from the intestine
What is Klinefelter’s syndrome
Features
Klinefelter’s syndrome is associated with karyotype 47, XXY.
Features often taller than average lack of secondary sexual characteristics small, firm testes infertile gynaecomastia - increased incidence of breast cancer elevated gonadotrophin levels but low testosterone - high LH and low testosterone
Diagnosis is by karyotype (chromosomal analysis).
What is hashimotos’ thyroiditis
Features
How to monitor progress
Hashimoto’s thyroiditis (chronic autoimmune thyroiditis) is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. It is 10 times more common in women
Features
features of hypothyroidism
goitre: firm, non-tender
anti-thyroid peroxidase and also anti-Tg antibodies
Hashimoto’s thyroiditis = hypothyroidism + goitre + anti-TPO
TSH to monitor progress
What is addisonian crisis
Presentation
Causes
Management
Causes
Sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
Presentation
- Shock
- Hypoglycaemia
Management
- Hydrocortisone 100 mg IM/IV - give 6hrly until stable
- Crystalloid 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
continue hydrocortisone 6 hourly until the patient is stable.
- Check blood glucose - may need
No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
Oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Causes of hypogylcaemia
Causes of hypoglycaemia can be remembered by the mnemonic EXPLAIN
Exogenous drugs (typically sulfonylureas or insulin) Pituitary insufficiency Liver failure Addison's disease Islet cell tumours (insulinomas) Non-pancreatic neoplasms
What is subclinical hypothyroidism
Management
Basics
TSH raised but T3, T4 normal
no obvious symptoms
Significance
risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)
risk increased by the presence of thyroid autoantibodies
Management
Not all patients require treatment. NICE Clinical Knowledge Summaries (CKS) have produced guidelines. Note that not all patients will fall within the age boundaries given and hence these are guidelines in the broader sense.
TSH is between 4 - 10mU/L and the free thyroxine level is within the normal range
if < 65 years with symptoms suggestive of hypothyroidism, give a trial of levothyroxine. If there is no improvement in symptoms, stop levothyroxine
‘in older people (especially those aged over 80 years) follow a ‘watch and wait’ strategy, generally avoiding hormonal treatment’
if asymptomatic people, observe and repeat thyroid function in 6 months
TSH is > 10mU/L and the free thyroxine level is within the normal range start treatment (even if asymptomatic) with levothyroxine if <= 70 years 'in older people (especially those aged over 80 years) follow a 'watch and wait' strategy, generally avoiding hormonal treatment'
What is sick euthyroid
Management
Sick euthyroid syndrome = low T3/T4 and normal TSH with acute illness
In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3).
Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
T1 DM
Cause
Management
Risk
Associated conditions
Genes - hla types
What is LADA
Cause
Insulin deficiency from autoimmune destruction of insulin secreting beta cells
Management
NEED INSULIN
Risk
- DKA
- Weight loss
Associated conditions
- Other autoimmune (HLA DR3 +/- DR4)
LADA = latent autoimmune diabetes of adults = t1dm with slower progression to insulin dependence in later life
