Endo Flashcards
(137 cards)
1
Q
Types of diabetes insipidus
A
Pituitary/Cranial: ADH deficiency.
Nephrogenic/partial: ADh resistance.
2
Q
What is diabetes insipidus?
A
Normally: ADH (vasopressin) produced in hypatholamus and stored in pituitary gland. Low water levels stimulate ADH release which reduces water loss through the kidneys leading to more concentrated urine.
Diabetes insipidus: reduced ADH production/response means kidneys don’t retain enough water = diluted urine and less water in the body leading to polyuria and thirst -> dehydration.
3
Q
Treatment of diabetes insipidus
A
Pituitary/cranial: replace ADH with vasopressin or desmopressin.
Nephrogenic/partial: thiazide-like diuretic (has a pardoxical effect and actually causes anti-diuretic effect rather than diuretic effect).
4
Q
Desmopressin considerations:
A
Causes fluid retention - drink only to satisfy 1-2h before sleeping, and avoid drinking 8h after dose.
Causes hyponatraemia (hypervolemic)- symptoms headache, nausea, convulsions. Avoid concurrent use with hyponatraemic drugs e.g., SSRis, carbamazepine, diuretics.
Contraindicated in >65 due to higher risk of renal impairment and hyponatraemia
5
Q
Difference between desmopressin and vasopressin
A
Desmopressin is a synthetic form of vasopressin which is more potent and has a longer duration of action, and does not have vasoconstrictor effect
6
Q
What is SIADH?
A
Syndrome of inappropriate ADH secretion.
Normally: ADH (vasopressin) produced in hypatholamus and stored in pituitary gland. Low water levels stimulate ADH release which reduces water loss through the kidneys leading to more concentrated urine.
SIADH: excessive ADH secretion causes body to retain water which can lead to fluid retention and hypervolemic hyponatraemia.
7
Q
Treatment of SIADH
A
Aim is to counteract hypervolemic hyponatraemia:
- Fluid restriction
- Demclocycline - tetracycline which reduces renal tubule cells responsiveness to ADH (kind of inducing nephrogenic diabetes insipidus)
- Tolvalptan - vasopressin V2 receptor antagonist. Can cause rapid hyponatraemia correction which can lead osmotic demyelination leading to serious neurological events.
8
Q
What is Addison’s Disease?
A
Primary adrenal insuffiency caused by destruction of the adrenal cortex, leading to reduced production of glucocorticoids and adrenal androgens.
9
Q
Symptoms of Addison’s disease
A
- Fatigue
- Hyperpigmentation
- GI disturbances: weight loss, nausea, abdominal pain, salt craving
- Musculoskeletal symptoms: muscle weakness/cramps, joint pain.
- Cardiovascular symptoms: postural hypotension
10
Q
Treatment of Addison’s disease
A
Replacement of glucocorticoids and mineralocorticoids:
* Glucocorticoid: 1st hydrocortisone, 2nd prednisolone
* Mineralocorticoid: fludrocortisone
* Androgen replacement (unlicensed): DHEA
11
Q
What is adrenal crisis?
A
A life-threatening emergency which can occur in Addison’s disease caused by a severe shortage of cortisol (and aldosterone) leading to:
* Hypotension - dizziness, fainting
* Hypoglycaemia - weakness, confusion, seizures
* N & V & D leading to dehydration
* Hyponatraemua and hyperkalaemia - confusion, muscle weakness, arrythmias
12
Q
Treatment of adrenal crisis
A
Call 999.
At A&E will receive IM/IV hydrocortisone + IV sodium chloride 0.9% (saline) infusion
13
Q
What can cause secondary adrenal insufficiency?
A
Rapid withdrawal of steroid treatment
14
Q
What are glucocorticoid steroids?
A
Dexamethasone and betamethasone (also prednisolone, prednisone, and deflazacort) have high glucocorticoid activity:
* High anti-inflammatory effect
* Low fluid retention
Preferred when fluid retention would be disadvantage.
15
Q
What are mineralocorticoid steroids?
A
Fludrocortisone (also hydrocortisone) have high mineralocorticoid activity:
* Low anti-inflammatory effect
* High fluid retention
Used for postural hypotension.
16
Q
Glucocrticoid side effects
A
- Diabetes
- Osteoporosis
- Avascular necrosis of the femoral head and muscle wasting
- Gastric ulceration and perforation
17
Q
Mineralocorticoid side effects
A
- Sodium + water retention - hypertension
- Potassium loss - hypokalaemia
- Calcium loss - hypocalcaemia
18
Q
Corticosteroids adverse effects
A
- MHRA warning: Psychiatric side effects e.g., maniam anxiety, depression, sleeping disorders - can occur early in treatment and requires urgent medical help.
- MHRA warning: Central serious chorioretinopathy - blurred and distorted vision in (usually) one eye. Mostly with local administration but can also happen with systemic.
- Adrenocortical insufficiency: prolonged use canc ause insufficiency and abrupt withdrawal can cause acute adrenal insufficiency which can be fatal. Can also occur with illness, trauma, or surgery, so pts may require a temporary increase in dose.
- Immunosuppression - increased susceptibility and severity of infections. Can also mask infections so may only be noticed at an advanced stage.
- Cushing’s disease - high cortisol (and androgens) leading to moon face, weight gain, stretch marks, acne, and hirsutism (facial hair).
- Raised intracranial pressure - usually occurs after withdrawal.
- Hypokalaemia
- Peptic ulcers
- Hyperglycaemia and diabetes
- Osteoporosis
- Insomnia (take in morning)
- Stunted growth
- SKin thinning if used topically
19
Q
What should immunosuppressed patients / on steroids avoid?
A
- Chickenpox - avoid contact with chickenpox or herpes zoster as can be fatal. Exposure requires urgent medical attention and a confirmed diagnosis requires urgent specialist treatment. Prophylactic passive immunisation with z-voster immunoglobulin may be given if exposure occurs.
- Measles - exposure requires immediate medical care and may require prophylaxis with IM normal immunoglobulin.
- Live vaccines - postpone until at least 3 months aftfer stopping.
20
Q
How can adverse effects of steroids be avoided?
A
- Use lowest effective dose for minimum possible time
- Take as a single dose in the morning to mimic circadian rhythm and avoid insomnia.
- PPI for gastroprotection
- Total dose for 2 days can be taken as a single dose on alternate days.
- Intermittent short courses rather than long-term therapy.
- Local treatment rather than systemic e.g., intra-articular injections, creams, inhalers, enemas, eyedrops
- Give patient steroid card so they are aware
21
Q
Can corticosteroids be used in pregnancy?
A
If benefits to mother outweigh risk to foetus.
Monitor mother for fluid retention.
22
Q
Can corticosteroids be used in breastfeeding?
A
Yes - unlikely to cause systemic side effects in infant.
However, avoid prolonged high-dose therapy to minimuse risk of adrenal suppression in the infant. Monitor for symptoms and try to wait 4h between dose and breastfeeding.
23
Q
What monitoring do corticosteroids require?
A
Before:
* BP
* BMI
* HbA1c / fasting glucose
* Triglycerides
* Potassium
* Optometrist assessment for glaucoma and cataracts
During:
* BP
* BMI
* HbA1c
* Triglycerides
* Osteoporosis and falls risk
* Adrenal suppression
* Eye disorders
24
Q
When do steroids need to be gradually withdrawn?
A
- > 40mg prednisolone or equivalent daily for > 1 week.
- Repeat evening doses
- > 3 weeks treatment
- Recent repeat courses
- Previous long-term therapy in last few months/years
- Other possible causes of adrenal suppression e.g., alcohol, stress.
25
What potency is topical hydrocortisone?
Mild
26
What potency is topical clobetasone?
Moderate
27
What potency is topical betamethasone?
High / strong
28
What potency is topical clobetasol?
Very high / strong
29
Which medicines can induce diabetes?
Antipsychotics
Beta-blockers
Glucocorticoids
Statins
30
Sypmtoms of diabetes
* Polyuria and nocturia
* Polydipsia
* Lethargy
* Unintentional weight loss (T1)
* Thrush and UTIs
* Blurred vision (uncommon in children)
* Longer healing time for cuts
31
Driving with diabetes rules
All drivers:
* Must notify DVLA if using insulin or sulfonylureas
* Should be assessed on awareness of hypoglycaemia and the capability of bringing their vehicle to a safe controlled stop.
* If using insulin should always carry meter and test strips.
* Should check glucose within 2h before a journey and every 2h when driving (or more if higher risk)
* CBG <5mmol/L have a snack
* CBG <4mmol/L cannot drive.
* Keep emergency supply of fast-acting carbs in vehicle.
* Eat regular meals and snacks
* Take rest periods on long journeys
Group 1 drivers (normal car or motorbike):
* adequate awareness of hypoglycaemia.
* Max 1 episode of severe hypoglycaemia while awake in preceding 12 months.
Group 2 drivers (lorries, trucks, buses):
* must report ALL episodes of severe hypoglycemia including during sleep.
* Full awareness of hypoglycaemia
* No episodes of severe hypoglycaemia in the preceding 12 months.
* Must use a blood glucose meter with sufficient memory to store 6 weeks of readings.
* If visual complications occur must stop driving and notify DVLA.
32
What should diabetics do if hypoglycaemia occurs when driving?
If CBG <4mmol/L:
* Safely stop vehicle ASAP
* Switch of engine, remove keys from ignition and move from driver's seat.
* Treat hypo with source of glucose
* Can restart driving 45 mins after glucose has returned to >5mmol/L
33
Typical features of T1DM
* Hyperglycaemia >11mol/L
* Ketosis
* Rapid weight loss
* BMI <25kg/m2
* Age <50
* Family history of autoimmune disease
34
How often should T1 diabetics measure CBG?
At least 4 times a day, including before each meal and before bed.
35
T1DM CBG targets.
* Waking (long fasting): 5-7mmol/L
* Pre-meal (fasting): 4-7mmol/L
* 90 mins post-meal: 5-9mmol/L
* Pre-bed time: indivualised to ensure waking reading of 5-7mmol/l.
36
How should insulin be injected?
Into SC fat (pinch skin) of:
* Abdomen (fastest absorption)
* Outer thighs (slow absorption)
* Buttocks (slowest absorption)
Arm not recommended due to difficulty.
Rotate injection site to prevent lipohypertropht (causes delayed absoprtion) and alternate between left and right side of body each week.
37
What are the 3 main insulin regimens?
* Basal/bolus: Long/intermediate insulin OD/BD + short/rapid acting before meals
* Biphasic: 1-3 injections/ day of short + intermediate acting insulin mixed together.
* Continuous subcutaneous insulin infusion (insulin pump) for adults who suffer disabling or uncontrolled hypoglycaemia.
38
First and second line basal insulins
1. Detemir BD
2. Detemir OD or Glargine OD
39
Which insulins are rapid-acting?
Lispro
Aspart
Glargine
| no LAGing
40
When are rapid-acting insulins administered?
Just before or with a meal
41
What is the onset and duration of rapid-acting insulin?
Onset: <15 mins
Duration: 2-5h
42
Which insulins or soluble insulins?
Human
Bovine
Porcine
43
When are soluble insulins administered?
15-30 mins before meals.
44
What is the onset and duration of soluble insulins?
Onset: 30-60 mins, peak action in 1-4h
Duration: upto 8h
45
Is soluble insulin short, intermediate, or long actong?
Short acting
46
Which insulins are intermediate acting?
Biphasic isophane (isophane + soluble)
Biphasic aspart (Isophane + aspart)
Biphasic lispro (isophane + lispro)
47
What is the onset and duration of intermediate acting insulins?
Onset: 1-2h, max effects 3-12h
Duration 11-24h
48
Which insulins are long-acting?
Detemir
Degludec
Glargine
49
What is the onset and duration of long-acting insulin?
Onset: 2-4 days to reach steady state
Duration: 24h (Degludec = 42h)
50
Insulin storage requirements
* Store at 2-8C (fridge) while not using.
* DO NOT FREEZE
* Take out 15-20 mins before injection to avoid pain.
* Stable at room temp for 28 days.
* Protect from sunlight and excessive heat.
51
When might insulin doses need to be adjusted?
Increase insulin:
* Infection
* Stress
* Trauma
* Using some meds e.g., levothyroxine
Decrease inuslin:
* Exercise
* Intercurrent illness
* Reduced food intake
* Impaired renal function
* Some endocrine disorders e.g., hypothyroidism, coeliac, Addisons
* Surgery
52
How should insulin be adjusted for elective surgery?
Minor procedure & good glycaemic control:
* Day before: reduce OD long-acting dose by 20%
* Other insulins use as usual.
Major procedure or poor glycaemic control:
* Day before: reduce OD long-acting dose by 20%. Other insulins use as usual.
On the day:
* Reduce OD long-acting dose by 20%
* Stop other insulins till eating.
* IV infusion of KCL + Glucose + NaCl
* Variable rate IV soluble human insulin in NaCl 0.9% via pump.
* Hourly blood glucose measurements for 12h.
* Give IV glucose 20% if CBG <6mmol/L.
After surgery convert back to SC insulin when normal eating/drinking:
- Basal/bolus: restart with first meal and continue infusions until 30-60 mins after meal.
- Long-acting regimen: continue 20% reduced dose until discharge.
- BD regimen: restart with breakfast or evening meal and continue infusions until 30-60 mins after meal.
53
What is considered pre-diabetic and diagnosis of T2DM?
Pre-diabetic HbA1c: 42-47mmol/mol
Diabetic HbA1c: 48mmol/mol
Diabetic fasting plasma glucose: 7mmol/L +
54
Treatment of diabetes in patients with low CVD risk
1. Metformin
2. Metformin + Pioglitazone or a sulfonylurea
3. Metformin + SGLT2i or DPP4i
4. Triple therapy
5. Triple therapy including insulin
55
Treatment of diabetes in patients with high CVD risk
If patient has CVD, HF, or is >40 with QRISK2 >10%:
1. Metformin
2. + SGLT2i when metformin tolerated. (or use alone if metformin not tolerated)
3. Add Pioglitazone or a sulfonylurea or a DPP4i for dual/triple therapy
4. Triple therapy including insulin
56
HbA1c targets in T2DM
* Diet/lifestyle only: 48mmol/mol (6.5%)
* Single drug not associated with hypoglycaemia: 48mmol/mol (6.5%)
* Single drug associated with hypoglycaemia: 53mmol/mol (7.0%)
* HbA1c not controlled by single drug (>58mmol/mol): 53mmol/mol (7.0%)
57
What drug class is metformin?
Biguanide
58
How do biguanides work?
Metformin decreases gluconeogenesis and increases peripheral utilisation of glucose.
59
Metformin considerations
* Risk of B12 anaemia
* Risk of lactic acidosis - increased if eGFR<30, dehydrated, or drinking alcohol.
* Avoid eGFR <30. Stop in AKI - risk of lactic acidosis.
* Commonly causes N & V &D - increase dose slowly and can switch to MR preparation to decrease,
60
Name 5 DPP-4 inhibitors
Alogliptin
Linagliptin
Saxagliptin
Sitagliptin
Vildagliptin
61
How do DPP4 inhibitors work?
Prevent dipeptidyl peptidase-4 breaking down incretins (e.g., GLP-1) which increases insulin secretion and decreases glucagon secretion.
62
DPP4 inhibitors considerations
* Contraindicated in ketoacidosis
* V & A contraindicated in HF, caution with saxagliptin.
* Avoid in severe hepatic impairment
* Can cause pancreatitis - discontinue of severe abdominal pain occurs.
63
What drug class is pioglitazone
Thiazolidinediones
64
How does piogliotazone work?
* Decreases gluconeogenesis
* Increases insulin sensitivity - binds to PPAR-gamma in adipose tissue, muscle, and liver to modulate expression of genes involved in glucose and lipid metaboluism.
65
Why is pioglitazone not used as often?
Contraindicated in HF and bladder cancer.
Increased risk of:
* Bladder cancer - report haematuria, dysuria, polyuria. Review after 3-6 months.
* Bone fractures
* Infection
* Hepatotoxicity - report N & V, dark urine, fatigue.
66
Name 4 sulfonylureas
Long-acting: Glibenclamide and Glumepiride
Short acting: Gliclazide and Tolbutamide
67
How do sulfonylureas work?
Binds to sulfonylurea receptor SUR1 to block ATP-sensitive K+ channels on pancreatic beta-cells to depolarise the membrane and trigger influx of Ca2+ via voltage-gated calcium channels, which promotes insulin secretion.
68
When should sulphonylureas be avoided?
* Acute porphyria
* Hepatic failure - higher risk of hypoglycaemia
* Renal failure - higher risk of hypoglycaemia
* Long-acting sulfonylureas in elderly - higher risk of prolonged hypoglycaemia
69
Name 4 SGLT2 inhibitors
Canagliflozin
Dapagliflozin
Empagliflozin
Ertugliflozin
70
How do SGLT2 inhibitors work?
Inhibit sodium-glucose co-transporter 2 in the renal proximal convoluted tubule to prevent the coupled reabsorption of sodium and glucose, increasing their excretion in the urine.
71
SGLT2 inhibtiors adverse effects
* UTIs
* Thrush
* Fournier's gangrene (necrotising fasciitis of the genitalia or perineum)
* Diabetic ketoacidosis (DKA) - stop in acute infection/illness
* Volume depletion/hypovolaemia - water follows Na and glucose in urine.
* Renal impairment
* Canagliflozin can increase risk of lower-limb amputation
72
Benefits of SGLT2 inhibitors
* Cardio-protective: treats HF and decreases BP
* Weight loss
* Reno-protective: used in treatment of CKD.
73
How do SGLT2 inhibitors impair renal function and have a reno-protective effect?
Initially: increases excretion of Na, glucose and water in urine which causes a haemodynamic drop in intraglomerular pressure which causes a drop in eGFR of 5-10%.
Long-term, slows CKD progression by:
* Reduced intraglomerular hypertension and subsequent hyperfiltration.
* Reduced urinary albumin excretion
* Reduced inflammation and fibrosis
74
Name 6 GLP-1 agonists
Dulaglutide
Exenatide
Liraglutide
Lixisenatide
Semaglutide
Tirzepatide
75
How do GLP-1 agonists work?
Activate GLP1 receptors in:
* Pancreas: increased insulin secretion and reduced glucagon secretion
* Brain: appetite suppression
* GIT: slowed gastric emptying.
76
GLP-1 agonist adverse effects
* Acute pancreatitis - report persistent severe abdo pain.
* GI effects - weight loss, nausea, vomiting
* Dehydration - avoid fluid depletion
* MHRA: Risk of DKA when concomitant insulin rapidly reduced
* MHRA: Risk of pulmonary aspirin during general anaesthesia
* MHRA: risk of misuse.
77
How does acarbose work?
Inhibits glucosidase and amylase to slow digestion of complex carbohydrates into simple sugars in the small intestine to decrease absorption in the blood.
78
What drug class is Repaglinide?
Meglitide
79
Common adverse effct of acarbose
High risk of GI side effects - may need to reduce dose.
80
How do meglitinides such as Repaglinide work?
Binds to sulfonylurea receptor SUR1 to block ATP-sensitive K+ channels on pancreatic beta-cells to depolarise the membrane and trigger influx of Ca2+ via voltage-gated calcium channels, which promotes insulin secretion.
81
What is the difference between meglitides and sulfonylureas?
Meglitinides have a faster onset and shorter duration of action (weaker binding affinity and faster dissociation to SUR1) so taken with meals.
82
Which antidiabetics cause weight gain?
Pioglitazone
Sulfonylureas
83
Which antidiabetics are weight neutral?
DPP4i
Metformin (although in practice appears to cause weight loss)
84
85
Which antidiabetics cause weight loss?
GLP-1 agonists
SGLT2 inihibitors
86
Which antidiabetics do not require any caution or dose reduction in renal impairement?
Pioglitazone
87
Which antidiabetics should be avoided in hepatic impairment?
Pioglitazone
88
Which antidiabetics require a dose reduction in hepatic function?
Dose reduction or avoid:
* SGLT2 inhibitors
* GLP-1 agonists
* sulfonylureas
Dose reduction or use with caution:
* DPP-4 inhibitors
Withdraw metformin if hypoxia likely
89
Which patients with T1DM require primary prevention with statin therapy?
* >40
* T1DM >10 years
* Established nephropathy
* Other CVD risk factors
Can be considered if aged 18-40.
90
Which patients with T2DM require primary prevention with statin therapy?
* Aged 25-84 and have QRISK3 score of 10+%
Can be given without these if benefits > risks.
91
Target BP in T1DM
* ACR (albumin:creatinine ratio) < 70mg/mmol : BP<140/90mmHg
* ACR>70mg/mmol: BP <130/80mmHg
* >80 (regardless of ACR):<150/90mmHg
92
How is kidney disease / nephropathy diagnosed?
Early morning urine sample to measure urinary albumin:creatinine ratio (ACR)
* >3mg/mmol = proteinuria. Repeat test within 3 months.
* >70mg/mmol = extensive proteinuria = nephropathy diagnosis.
93
How is diabetic nephropathy treated?
T1DM:
* ACR >3mg/mmol: ARB or ACE inhibitor.
T2DM:
* ACR >3mg/mmol: ARB or ACE inhibitor.
* ACR >30mg/mmol and eGFR 25-75: ARB/ACE inhibitor + SGLT2i (Dapagliflozin)
94
How does diabetic nephropathy occur?
Persistent hyperglycaemia damages capillaries and glomeruli which leads to hyperfiltration and leakage od albumin into the urine.
95
How does diabetic neuropathy occur?
* Excess glucose causes stress to neurons.
* Endothelial dysfunction reduces blood flow to veseels supplying nerves leading to hypoxia and damage.
* Inflammation damages nerve tissue
96
Symptoms of neuropathy
* Peripheral: numbness, tingling, and burning in hands, feet and legs.
* Autonomic: impaired function in nerves of GIT, CV, sexual, bladder leading to gastroparesis, orthostatic hypotension, erectile dysfunction etc.
* Proximal: pain and weakness in thighs and hips.
* Focal: sudden and localised weakness due to cranial and peripheral nerves
97
How is peripheral neuropathy treated?
Amitriptyline
Duloxetine
Gabapentin
Pregabalin
98
How is autonomic neuropathy treated?
Symptom specific:
* Erectile dysfunction: Sildenafil, vardenafil, tadalafil.
* Gastroparesis: domperidone, metoclopramide.
* Hyperhidrosis: antimuscarinics e.g., topical glycopyrrolate, po oxybutynin, po glycopyrronoum bromide.
99
Symptoms of DKA
* Polydipsia
* Polyuria
* Vomiting and diarrhoea
* Abdominal pain
* Visual distrubance
* Lethargy/confusion
* Fruity acetone breath
100
What should be done if DKA is suspected?
1. Measure blood sugar.
2. If CBG >11mol/L check ketone levels.
3. If 0.6-1.5mmol (small risk) retest in 2h. If 1.6-2.9 (moderate risk) contact GP. If 3mmol+, this is a medical emergency.
4. Measure venous pH.
DKA:
* CBG >11mmol/L
* Ketones >3mmol/L
* Venous pH <7.3
101
How is DKA treated?
* IV human soluble insulin
* IV 0.9% NaCl +/- KCl
IV glucose can be given if risk of hypoglycaemia.
102
When is DKA classed as resolved?
Ketones < 0.6mmol/L and venous pH >7.3
103
Symptoms of hypoglycaemia
Mild:
* hunger
* anxiety or irritability
* palpitations
* sweating
* tingling lips
Moderate
- weakness
- impaired vision
- confusion
- irrational behaviour
Severe
- convulsions
- loss of consciousness
- coma
104
Treatment of hypoglycaemia
Patient is conscious and able to swallow:
* Fasting-acting carbohydrate 10-20g oral: 3-6 glucose tabs, 2-4 spoonfuls sugar, 90-180ml sugary drink.
* Recheck CBG and repeat every 15 mins
Patient is unconsious or unable to swallow:
* IM glucagon or ring 999
* If alcohol-induced, get to hospital for IV glucose.
105
Diabetes sick day rules
SICK:
* Sugar: Check CBG every 1-2h, including overnight.
* Insulin: Continue with insulin and oral antdiabetic agents
* Carbs: Maintain hydration and carbohydrate intake
* Ketones: Check ketones every 3-5 hours, including overnight.
In T2DM, if there is a risk of dehydration, withhold:
* ACE inhibitors - impaired renal function
* Diuretics - impaired renal function
* NSAIDs- impaired renal function
* Metformin - lactic acidosis
* SGLT2is - DKA
* GLP-1 agonists
106
If a diabetic patient becomes pregnant, what are some things to consider?
* Higher risk of complications in pregnancy e.g., premature delivery, pre-eclampsia.
* HbA1c < 48mmol/mol
* First choice insulins: rapid-acting, long-acting isophane.
* Metformin can also be used in pregnancy. Other oral agents are not recommended.
* Folic acid 5mg before conception and until week 12
* Concurrent meds which may need to be stopped: statins, ACE inhibitors.
107
How is gestational diabetes treated?
Fasting BG <7mmol/L:
1. Diet and exercise
2. If after 2 weeks not managed, start metformin.
3. Insulin monotherapy if not tolerated or as an add on if uncontrolled on metformin monotherapy.
Fasting BG >7mmol/L: Diet and exercise + insulin +/- metformin
Fasting BG 6-6.9mmol/L + complications: Diet and exercise + insulin +/- metformin
108
What is osteoporosis?
Low bone mass and structural detioration of bone
109
How is osteoporosis diagnosed?
* Use QFracture (preferred) or FRAX to calculate risk of fragility fractures in suspected patients.
* If high risk, confirm with dual energy X-ray absorptiometry (DEXA) scan.
* Diagnosis: T-score of -2.5 or lower.
110
What are risk factors for osteoporosis?
* Female
* >50
* Menopause
* Extended glucocorticoid treatment (>3 months)
* Smoking
* Drinking (>14u / week)
* History of fractures
* Low BMI
* Calcium or vitamin D deficiency
* Physical inactivity.
111
Treatment of osteoporosis
1. Lifestyle changes:
* Balanced diet
* Increased vit D and calcium intake via diet or supplements.
* Exercise
* Smoking cessation
* Reduce alcohol intake
2. Oral bisphosphonates
3. Strontium, denosumab, teriparatide
In post-menopausal women other options include: HRT and tibolone. Raloxifene (oestrogen receptor modulator) in severe cases.
Glucocorticoid-induced: teriparatide or denosumab work better.
112
When would prophylaxis of glucocorticoid-induced osteoporosis be required?
Women with any of:
* 70+
* Previous fragility fracture
* Taking large doses of glucocorticoids
Men 70+ with either:
* High dose glucocorticoid - 7.5mg+/day of prednisolone or equivalent >3 months.
* FRAX proabability of major fracture exceeding the intervention threshold.
113
When should the need for osteoporosis treatment be reviewed?
After 5 years
(3 years for Zolendronic acid)
114
Missed bisphosphonate dose rule
Take on the day it is remembered, then continue taking weekly on usual day.
Do not take 2 on the same day.
115
Bisphosphonates adverse effects
* Oesophageal reactions - oesophagitis, oesophageal ulcers, oesophageal erosion. Avoid concurrent use of NSAIDs. Take with a whole glass of water and stay upright 30 mins.
* MHRA: atypical femoral fractures - report thigh, hip or groin pain.
* MHRA: osteonecrosis of the jaw - report any dental pain, swelling, non-healing sores or discharge. Complete ongoing dental treatment before starting bisphosphonate.
* MHRAL osteonecrosis of external auditory canal - reprt ear pain, discharge, or ear infection.
* Poor absorption - take on an empty stomach and wait 30 mins before food, other meds, or calcium supplements and antacids.
116
Symptoms of menopause
Mental: Anxiety, mood swings, brain fog
Vasomotor: Hot flushes, sweats
Musculoskeletal: Joint and muscle pain
Urogenital and sexual: vaginal atrophy, low libido.
117
When does menopause typically occur?
45-55
118
Difference between perimenopause and menopause
Perimenopause: symptoms of menopause but periods have not fully stopped.
Menopause: not had a period for 12 months (not drug-induced).
119
Which oestrogens are available in HRT?
Estradiol
Estrone
Estriol
Ethinylestradiol
Mestranol
120
Which progestogens are available in HRT?
Desogestrel
Medroxyprogesterone
Norethisterone
Levonorgestrel
121
General treatment of menopause symptoms
Oestrogen with progestogen as a monthly cyclical, 3-monthly cyclical, or continuous regimen.
Progestogen provides endometrial protection, so patients who have had a hysterectomy can just use oestrogen.
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Risks associated with HRT
* VTE (greatest with oral)
* CVD (in women >60)
* Stroke (in women >60)
* Breast cancer - increased risk with combined and long exposure - risk lasts 10+ years after.
* Endometrial cancer - increased risk with oestrogen only and tibolone.
* Ovarian cancer - small increase which disappears a few years after stopping.
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Combined HRT treatment regimens
Monthly cyclical:
* Oestrogen daily
* Progestogen for last 10-14 days of the month
3-monthly cyclical:
* Oestrogen daily
* Progestogen for 14 days every 13 weeks
Continuous (not for perimenopausal women):
* Oestrogen and progestogen daily.
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Rules for surgery in women taking HRT
Elective: stop HRT 4-6 weeks prioir and reinitiate when patient is fully mobile.
Non-elective syrgery: give prophylactic heparin and use graduated compression stockings.
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Reasons to stop HRT
Stop HRT pending investigation and treatment if:
* Signs of hepatic impairment / toxicity - jaundice, abdominal pain, red urine, itchy skin, N & V.
* New hypertension or increase in BP
* New onset migraine
* Pregnancy
* VTE - confirmed, suspected, or increased risk (prolonghed immobility, surgery etc).
* CNS effects e.g., severe prolonged headaches, fainting, new epileptic seizure, motor disturbances, numbness.
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Signs of hyperthyroidism
High T3 + T4
Low TSH
Symptoms of increased metabolism and activity:
* Anxiety + irritation
* Heat sensitivity
* Insomnia + fatigue
* Diarrhoea
* Polyuria
* Palpitations
* Hyperactivity
* Goitre
* Weight loss
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Hyperthyroidism treatment
1. Carbimazole
2. Propylthiouracil
Beta-blockers for symptomatic relief of palpitations, anxiety etc.
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Adverse effects of carbimazole
MHRA warnings:
* Congenital maloformations - ensure on contraception and switch to propylthiouracil 6 months prior to trying for a baby.
* Acute pancreatitis - stop immediately and permanently.
* Bone marrow suppression - stop and report signs of anaemia, SOB, pale, bruising/bleeding, sore throat, ulcers, infection.
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When is propylthiouracil contraindicated?
Liver disorder.
During treatment, warn patientes to report jaundice, dark urine, nausea.
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What is Graves' disease and how is it managed?
An autoimmune disease which produces antibodies which attack the thyroid and cause it to overproduce thyroid hormones.
1. Radioactive iodine: destroys thyroid cells to reduce hormone production.
2. Carbimazole + levothyroxine (block and replace regimen for 12-18 months)
3. Surgery to remove thyroid gland.
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How long after radioactive iodine treatment can patients start trying to become pregnant?
Men: 4 months
Women: 6 months
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Signs of hypothyroidism
Low T3 and T4
High TSH
Signs of decreased metabolism and activity:
- Tiredness
- Weight gain
- Depression
- Constipation
- Cold intolerance
- Dry skin
- Menstrual irregularities.
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Treatment of hypothyroidism
1. Levothyroxine
2. Liothyronine (rarely used, 4-5x stronger than levothyroxine)
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How should levothyroxine be taken?
In the morning, at least 30 mins before food or caffeine.
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MHRA warning for levothyroxine
Avoid switching brands or formulations as patients may experience symptoms. Consider TFT if patient reports symptoms. If symptoms persist despite returning to original brand/formulation, consider oral solution formulation.
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What monitoring does levothyroxine require?
TSH - 3 months until stable then yearly.
T4 - if symptoms of hypothyroisim persist after treatment initiation.
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Levothyroxine interactions
* Antacids, Ca, aluminium, Mg - reduces levothyroxine absorption. Leave 4h gap.
* Ferrous sulphate - reduced levothyroxine absorption. Leave 2h gap.
* Orlistat - reduced levothyroxine absorption.
* CYP 450 inhibitors and inducers
* Anti-diabetic agents - levothyroxine can cause hyperglycaemia.
