Endocrine System Flashcards
1
Q
What is the mechanism of action of metformin?
A
Decreases glucoseneogenesis and increases peripheral utilisation of glucose
(Acts only in the presence of insulin = only effective when there is some functioning of pancreases cells)
THEREFORE DOESNT CAUSE HYPOGLYCAEMIA as doesn’t stimulate insulin secretion
2
Q
Dose of metformin
A
Type II; MAX 2g per day
MR versions to prevent stomach issues
Polycystic ovary syndrome
First choice for all patients
3
Q
Metformin contraindication
A
Acute metabolic acidosis including lactic acidosis and ketoacidosis
EGFR <30 mL/min/1.73 m2 or <45 mL/min.1.73 m2 for MR versions
4
Q
Risk factors for lactic acidosis
A
HF or recent MI
Alcohol intoxication
Renal impairment
Respiratory failure
Dehydration
Fasting
Liver impairment
Ketosis
5
Q
Adverse effects of Metformin
A
GI disorders; abdominal pain, diarrhoea, decreased appetite, altered taste
Consider switch to MR Or slow dose increase
Lactic acidosis risk
Decrease B12 absorption
Weight loss
Taste disturbances
6
Q
Symptoms of lactic acidosis
A
Dyspnoea
Muscle cramps
Abdominal pain
Hypothermia
Asthenia
7
Q
Mechanism of action of sulphonylurea?
A
Stimulates the release of insulin from pancreatic beta cells therefore decreasing the concentration of glucose
RISK OF HYPOGLYCAEMIA
8
Q
Adverse effects of Sulphonylurea?
A
Weight gain
GI disturbances
Hypoglycaemia (greater risk with long acting)
Hepatic impairment (jaundice, hepatitis, hepatic failure)
Allergic skin reaction in first 6-8 wks
9
Q
Long acting Sulphonylurea
A
Glibenclamide
Glimepiride
10
Q
Short acting sulphonylurea
A
Gliclazide
Tolbutamide
Glipizide
11
Q
Gliclazide advantage
A
Metabolised by liver therefore can be used in renal impairment patients
Short acting = lower risk of hypos
12
Q
Caution and CI in sulphonylureas
A
Elderly patients - best to give short acting
Patients with G6PD deficiency
Acute porphyria
Ketoacidosis
Avoid/reduce dose in renal impairment
Given if metformin is CI as first line and pt is not overweight
13
Q
How do you take sulphonylureas?
A
With or immediately after breaskfast
14
Q
sulphonylurea interactions?
A
Warfarin and ACEi increase the risk of hypos
NSAIDs decrease renal excretion
15
Q
Alpha glucosidase inhibitors mechanism of action and example?
A
Acarbose
Inhibits alpha glucosidase. Delays digestion and absorption stage of sucrose
Poorer anti diabetic medication
16
Q
What do you give is pt is in acarbose and is having a hypo?
A
Give glucose
Interferes with sucrose absorption therefore give glucose
17
Q
Side effects of alpha glucosidase inhibitor?
A
Flatulence
Diarrhoea
18
Q
Pioglitazone mechanism of action?
A
Is a thiazolidinedione
Reduces insulin resistance leading to reduction in blood glucose concentration
(Enhances action as it increases insulin sensitivity in tissues = reduces blood glucose)
19
Q
Pioglitazone side effects?
A
Bone fracture
Weight gain
Visual impairmentt
Increase infection risk
Nausea
Thirst
Urinary disorders
20
Q
MHRA alerts for Pioglitazone
A
CV safety; HF (symptoms; fluid retention, weight gain)
Risk of bladder cancer (symptoms; haematuria, dysuria, urinary urgency)
21
Q
Patient and carer advise for pioglitazone
A
Report signs of liver toxicity
Unexplained N&V
Abdominal pain
Fatigue
Anorexia
Dark urine
22
Q
Contraindications for pioglitazone?
A
bladder cancer history
Liver impairment
HF
Haematuria
23
Q
Pioglitazone interactions
A
Clopidogrel can increase pioglitazone exposure = severe interaction
24
Q
Pioglitazone monitoring
A
Signs and symptoms of fluid retention (weight gain or oedema)
Liver functions (hepatotoxic / toxicity)
25
DPP4-I (Gliptins) mechanism of actions?
Inhibition of DPP-4 increases insulin secretion and lowers glucagon secretion
(Helps increase insulin as it prevents incretin breakdown by DPP-4 which produced insulin)
26
Examples of DD4-I (gliptins)?
Alogliptin, linagliptin, sitagliptin, saxagliptin and vindagliptin
27
Adverse effects of gliptins?
Increased risk of upper respiratory tract infections
Discontinue if severe abdominal pain = sign of pancreatitis
GI disturbances
Skin reactions
28
Contraindication with gliptins?
Ketoacidosis
29
Renal and hepatic impairment when using gliptins?
Dose adjustment is necessary for all gliptins EXCEPT LINAGLIPTIN
30
Gliptins interaction?
With combination of sulfonylureas use lower dose to decrease risk of hypos
31
SGLT-2 I mechanism of action?
Reduce glucose re absorption and increase glucose excretion via urine
32
Examples of SGLT2-I?
Canagliflozin, dapagliflozin and empafiglozin
33
MRHA alerts with SGLT2-I?
Fournier gangrene
Canafliglozin specific ; lower limb amputation
Risk life threatening DKA
Monitor blood ketone levels during treatment interruption for surgical procedures or acute medical treatment
34
Fournier gangrene
Report; severe pain, tenderness, erythema, or swelling in the genital or perineal area
Accompanied by fever or malaise urogenital infection or perineal abscess may precede necrotising fasciitis
35
Risk of lower limb amputation with canagliflozin
Mainly toes
Consider stopping if pt develops lower limb complications
Start treatment of lower limb complications ASAP
Advise patients to stay well hydrated
36
DKA risk
Symptoms; dry skin/mouth, flushed face, headache, confusion, tried, sleepiness blurred vision
Test for ketones
Discontinue if suspected cause is SGLT2-I - not to continue
Discontinue during acute illness / surgery
37
Side effects of SGLT-2I?
Genital infections ; UTI risk
Polyuria
Thirst
38
GLP1 mimetic mechanism of action?
Increase insulin secretion and suppresses glycogen secretion whilst also delaying gastric emptying
39
When is GLP1 mimetics used?
For combination therapy when other treatment options have failed
Review 3 months; 3% weight reduction
Can be if triple therapy has has failed
40
When should you continue pioglitazone?
If HBA1c has decreased by 0.5% within 6 months of starting treatment
41
Adverse effects of GLP1 mimetics?
GI discomfort
Pancreatitis then discontinue permanently
42
MHRA alert GLP1 mimemtics
Serious life threatening DKA risk concomitant insulin therapy was rapidly reduced
43
Contraindications GLP1 mimetics
Ketoacidosis
Renal impairment
Severe GI disease
EGFR < 30
Liraglutide avoid IBD, diabetic gastroparesis, hepatic impairment and mod-severe HF
44
Contraception and GLP1 mimetics?
Contraception must be used during treatment with exenatide or lixisenatide and for 12 weeks after stopping MR exenatide
45
How to take GLP1 mimetics?
Take oral medication 1 hour before OR 4 hours after dose
Administer before a meal
IR should be injected daily or MR at weekly intervals
46
Rapid acting analogue insulin
Insulin aspart (fiasp and novo rapid)
Insulin glutisine (apidra)
Insulin lispro (Humalog)
Faster onset of action within 15 mins lasts for 2 to 5 hours
Given S/C before meals
Shorter duration of action than soluble insulin (better than soluble for glycaemic control, reduction in Hba1c and hypo incidence)
47
Soluble (short acting) insulin
Actrapid (Human Actrapid)
Humulin S
Hypurin bovine/porcine
Insuman
Acts within 30 to 60 mins lasting up to 9 hours
Preffered in emergencies (IV instant onset)
Animal insulin
48
Intermediate acting insulin
Isophane insulin (Humilin I)
Intermediate duration of action
Mimics the effect of basal insulin
1-2 hours onset with action go 11-24 hours
Can be mixed with other insulin
Isophane + (insulin + protamine) = e.g Novo mix, M3
Premixed or biphasic
Protamine is fish so can cause allergic reaction
49
Biphasic
Intermediate acting insulin + short acting insulin
Novomix 30
Humalog Mix 25 and 50
Humulin M3
50
Long acting insulin
Determir (Levemir) - given OD or BD
Glargine (lantus, toujeo) OD
Degludec (Tresiba) OD
May last up to 36 hours
Mainly adjuvant to type II diabetic treatment
51
Management of diabeties
Weight, BP, smoking status, HBA1c, urinary albumin, creatinine, cholesterol, eyes, foot, thyroid disease
52
What is basal bolus insulin regimen?
Multiple daily injections
Preferred especially if patient is newly diagnosed (1st choice)
Must match carbohydrate intake
Offered flexibility to tailor insulin therapy with carbohydrate load of each meal
- ONE or more separate daily injection of long acting or intermediate as basal
AND
- multiple bolus injections of short acting insulin before meals
53
What is a mixed (Biphasic) regiment?
One, two or three insulin injections per day as short acting and intermediate
Can be mixed by patient or pre-mixed
Pre mixed analogue insulins (rapid acting + intermediate) e.g Humalog Mix 25, 50 and novo mix
Premixed human insulin (soluble insulin + intermediate) e.g humulin M2, M3 M5 insuman comb 15/20/50
Not recommended in newly diagnosed type I; as insulin is fixed not change dose (can’t adjust) new diagnosed = no flexibility not soluble.
54
What is a continuous S/C insulin infusion (insulin pump)?
Regular or continuous amount of insulin
Usually rapid acting analogue or soluble insulin
Delivered by programmable pump and insulin reservoir via cannula or subcut needle
Only for adults who suffer from disabling hypoglycaemia or high HBA1c (69 mol/mol +)
Initiated by specialists
55
What can cause poor glucose control?
Adherence, injection technique, injection site problem
Blood glucose monitoring skills, lifestyle issues (diet, alcohol, exercise)
Psychological issues, renal disease, thyroid disorders
56
What can decrease insulin requirements?
Physical activity, inter current illness (diarrhoea, vomiting = increases glucose excretion), reduce food intake, impaired renal function, certain endocrine disorders (Addison disease, coeliac)
LOWER DOSE REQUIRED OR CAN CAUSE HYPO
57
What can increase insulin requirements?
Infection, stress, accidental or surgical trauma
Pregnancy (2nd and 3rd) and puberty
HIGHER DOSE REQUIRED OR HYPER
58
How to administer insulin?
Inject with area with most S/C fat (e.g abdomen is fastest absorption route) or outer thigh/buttock
Rotate site of injection or lipohypertrophy risk
Check injection sites for signs of injection, swelling, bruising and lipohypertrophy
59
Type II diabeties
Insulin deficiency or resistance
Associated with obesity, physical inactivity, raised BP, dylipidaemia and tendency to develop thrombosis it increases CV risk
Associated with long term micro vascular and macro vascular complications
Typically develop later in life but is increasingly being diagnosed in children
60
What is the target HBA1c with single drug (not with sulphonylurea)?
48 mmol
61
What is target HBA1c with 2+ drugs or sulphonylurea?
53 mmol
62
What is first step monotherapy?
Lifestyle and dietary fail
HBA1c is 48 mmol
Give metformin (gold standard)
IR or MR and increase in intervals
If metformin is CI give DDP4I, sulphonylurea or pioglitazone
63
What is the first intensification of treatment (DUAL THERAPY)?
If metformin with lifestyle changes is not effective the ADD;
Sulphonylurea, pioglitazone, DPP4I or SGLT2
64
What is the second intensification treatment (TRIPLE THERAPY)?
If dual therapy is unsuccessful ADD a third drug;
Metformin + DPP4I + sulphonylurea
Metformin + pioglitazone + sulphonylurea
Metformin + sulphonylurea + SGLT2
Metformin + pioglitazone + SGLT2 ( NOT DAPAGLIFAZONE)
May start insulin programme at this stage
65
What shouldn’t dapagliflozin be used with?
SGLT2I dapagliflozin shouldn’t be used with pioglitazone as it increased hypo risk
Dapagliflozin is also licensed with HF with reduced ejection fraction
66
Symptoms of hypoglycaemia?
Shaking trembling
Sweating
Pins and needles in lips and tongue
Hunger
Palpitations
Headahe
Double vision
Difficulty concentration, confusion, change in behaviour, slurred speech, convulsions = EMERGENCY
67
What class of drugs masks hypoglycaemia signs?
Beta blockers
68
What is disadvantage of tight glycaemic control and hypoglycaemia?
Lowers the level needed to trigger hypo signs/symptoms
Avoid frequent hypo episodes to restore warning signs
69
What is the management of hypoglycaemia?
Initially 10-20 g sugar (liquid is absorbed faster)
Lucazade, cocoa cola (100 mL), Ribera, glycogen dextrogel
If patient is unconscious glucagon 1 mg (IM or SC) - transfer urgent to hospital
Admit to hospital if hypo is caused by oral anti diabetic especially SGLT2I as it can persist for hours
70
What foods should you avoid if your diabetic?
Fat sugary food
Fat will delay absorption of glucose and lengthen the time of glucose release = longer period of time of glucose release
71
Diabetics and CVD risk?
Increase risk factor
Address other factors e.g smoking, hypertension, obesity and hyperlipidemia (QRISK >10% give statin)
Reduce risk ACEi , lipid regulating drugs and low dose aspirin (if required for secondary prevention)
72
What is diabetic nephropathy?
Kidney damage
Test for urinary protein and serum creatinine
Urine microalbuminuria; earliest signs problems with filtrations
ALL patients should be given ACEi (or ARB if CI) even if Afro-Caribbean
ACEi can potential hypo effects of drugs + insulin esp renal impairment
73
Painkillers used for neuropathy?
Paracetamol or NSAIDs
Duloxetine (amitriptyline or notriptyline off licence)
Gabapentin tried if above is ineffective
Opioid analgesics (tramadol, morphine, oxycodone)
Capsaicin cream (licensed for painful diabetic neuropathy but produces intense burning sensation during initial treatment period)
74
Complications of diabeties
CVD
Nephropathy
Neuropathy
Diarrhoea (codeine or tetracyclines)
Erectile dysfunction (sildenafil)
Gastroenteritis (Erythromycin)
75
What is diabetic ketoacidosis?
Medical emergency
Occurs as a consequence of absolute relative insulin deficency
76
Signs and symptoms of DKA?
Rapid weight loss
N&V
Abdominal pain
Fast and deep breathing
Sleepiness
Sweet smell to breath or metallic taste in mouth
High ketones in urine (breakdown of fat)
77
Management of DKA?
Fluid
Electrolytes
Insulin
Sodium/ potassium chloride 0.9% infusion
Mix with a soluble insulin
78
Diabetes effect during pregnancy
Insulin requirement increases in second and third trimester
Can affect foetal development ; high risk neural tube defects
Keep <48 mmol HBA1C
79
What folic acid is given to pregnant diabetic patients?
5 mg for first 12 weeks
High risk neural tube defects
80
What diabetic drugs are used during pregnancy?
Glibenclamide used during breastfeeding and 2nd and 3rd trimester
Metformin can be used
All anti diabetic drugs except metformin should be discontinued before pregnancy and put on insulin
Rapid acting insulin is best
Higher risk of hypo in first trimester with insulin; prescribe glucagon
81
Gestational diabeties
Once given birth goes away; so stop treatment
Fasting blood glucose <7 mmol at diagnosis
1) diet and exercise alone
2) metformin (if blood target not met in 1-2 weeks)
3) add insulin if metformin ineffective
Glibenclamide can be given as a alternative if metformin not tolerated (2/3rd trimester)
82
What is sick day rule?
Continue taking your diabetic drugs and insulin as normal
Test blood glucose every 4 hours
Drink extra (calorie free) liquids and try eat as normal
Weight check every day
Check temp for signs of infection; plenty of water and sugar if cant eat
Ketone check 2+ in urine or 3+ in blood = GP
83
Diabetic target and hypertension
Without complications; 140/90 mmHg
With complications; 130/80 mmHg
ACEi is first line regardless of Afro-Caribbean
84
Diabetic and cholesterol target
Normal patients <5 mmol/L
Diabetics <4 mmol/L
85
What is the target range HBA1c for type I diabetics?
Less or equal to 46mmol/mol
86
What should plasma glucose level be before meals at other times of the day?
4-7 mmol/L
87
What should a random plasma glucose concentration be?
<11 mmol/L
88
What is Type I diabetes?
Absolute deficiency due to little or no insulin secretion
Destruction of insulin producing beta cells in the pancreatic islets of Langerhans
Autoimmune
89
Signs and symptoms of diabetes?
Increased thirst (polydipsya)
Frequent urination especially at night (polyuria)
Hyperglycaemia (random levels >11)
Extreme hunger
Unintended weight loss
Irritability and other mood changed
Fatigue and weakness
Blurred vision
90
How often should you monitor type I or II blood glucose?
Type I; every 3-6 months (more frequently if blood glucose changing rapidly)
Type II; every 3-6 month until medication and HBA1c are stable then monitor every 6 months
91
What is HBA1c?
Reflects average plasma glucose over previous 2-3 months
Provides a good indication of glycemic control
92
What is Oral glucose tolerance Test?
Diagnosis impaired glucose tolerance
NOT recommended for pts with severe hyperglycaemic symptoms
Measuring blood glucose after fasting for 8 hours and then 2 hours after drinking a standard anhydrous glucose drink
93
Diabetes and alcohol
Masks signs of hypo
Drink in moderation and with food
94
DVLA advise for diabetics?
Report treatment with insulin, license type and if they have diabetic complications (eps of hypo 2/+ in past 12 months, impaired driving or disabling)
Carry glucose monitor and test strips
Check 2 hours before driving and every 2 hours while driving
95
What blood glucose level is needed to drive?
>5 and drive ; take snack if levels fall below
Ensure fast acting carbohydrate in car
NOT to drive if below 4 or warning signs of hyp
96
What happens if hypo occurs while driving?
Stop vehicle, park, switch of engine, in safe space, eat/drink suitable source of sugar wait until 45 mins after blood glucose is normal before continuing journey
97
What is a diabetes insipidus?
When there is a lack of ADH
98
What are Macrovascular complications
Large blood vessels;
Coronary artery disease
Peripheral arterial disease
Cerebrovascular disease
99
What are microvascular complications?
Small blood vessels;
Neuropathy
Nephropathy
Retinopathy
100
What are steroids used for?
Dexamethasone; crushing syndrome diagnosis, croup, N&V, palliative care, cerebral oedema
Hydrocortisone; thyroid storm, anaphylaxis, IBD, acute asthma
Prednisolone; exacerbation of asthma/COPD, IBD myasthenia gravies
Fludrocortisone postural hypotension
101
What is the MHRA advice for all corticosteroids?
Chorioretinopathy
Retinal disorder with local and systemic use
Recently been reported through use of local admin routes (inhalation, intranasal, topical)
ADVICE; report blurred vision, disturbances
Refer to ophthalmologist
102
Contraindications for corticosteroids?
Avoid in systemic infection (unless being treated)
Avoid corticosteroid in strokes or head injury
103
Monitoring in corticosteroids in children?
Height and weight in children
104
Mineralcorticosteroids
Fludrocortisone
Affects minerals and therefore causes water retention
Cause; hypertension, Na retention, water retention, potassiumm loss
Stronger the glucocorticoid the less mineral corticoid activity it has
105
What is hydrocortisone?
Equal parts mineralcorticoid activity and glucocorticoid activity
106
Glucocorticoid activity
Works on inflammation and immune response
Beclamethasone, dexamethasone, prednisolone etc.
Causes; diabeties, osteoporosis, muscle wasting, peptic ulcerations, perforation psychotic reactions
107
Adrenal suppression
Symptoms; fatigue, weight loss, N/V, salt craving (serious)
Adrenal glands dont produce adequate amounts of corticosteroids primarily cortisol but also aldosterone which regulate Na, K and water retention
80% is due to addisons disease
108
Addisons disease
Add steroids as they dont have enough
Low cortisol and low aldosterone
Replacement with mimics such as hydrocortisone (in morning to mimic cortisol) and fludrocortisone
109
How to minimise corticosteroid side effects
Use at lowest effective doses for shortest period
Use PPI if at risk of ulceration (i.e taking NSAID, history of peptic ulcer)
Prolonged therapy greater than 3 weeks can cause adrenal suppression
Local treatment VS systemic
Single dose in the morning; suppressive action on cortisol secretion is least in the morning
Give short Course
Large volume spacer devices if high dose required to increase airway deposition and reduce oropharyngeal deposition
110
When should steroid dose be increased
During severe illness, trauma or surgery requires a temp increase in corticosteroid dose
111
Methylprednisolone MHRA alert
Injectables contain lactose
Not to use in cow milk allergy
112
What drugs have high glucocorticoid activity?
Betamethasone and dexamethaosne (high glucocorticoid very little mineralcorticoid activity)
Therefore suitable in conditions where fluid retention is not required e.g HF
113
Adverse effects on electrolytes of corticosteroids
Increase sodium
Increase water
Decrease potassium
Decrease calcium
114
Systemic s/e of corticosteroids
Psychiatric reactions; suicidal thoughts + depression (seek medical attention), irritability, insomnia, mood, irritability
Infections; increase susceptibility and severity, (can be exacerbated), atypical or found at advanced stages
Chickenpox; if not already had at high risk of severe chickenpox
Skin thinning , purple/red, bruising
Growth restriction in children
115
Treatment cessation of corticosteroid?
Gradual withdrawal considered for patients whose disease is unlikely to relapse and have;
Received >40 mg prednisolone (or equiv.) daily for >1 week
Repeat doses in the evening
Received 3/4 weeks treatment
Recently received repeated courses (esp if taken >3 weeks)
Taken short course within 1 year of stopping long term therapy
Other causes of adrenal suppression
116
Corticosteroids and interactions?
Risk of GI perforation with nicorandil, NSAIDs and SSRIs
Risk of torsade’s de pointe;s due to decrease potassium with; digoxin, amiodarone, quinine, anti-psychotics, clarithromycin
Live vaccines are a severe interaciton
117
Hypopituitarism
Pituitary gland doesn’t stimulate hormone secretion by target glands
Replace with hydrocortisone NOT fludrocortisone (as that will be done by renin-angiotensin system)
Replace other hormones e.g sex, thyroid
118
What is Crushing syndrome
Characterised by high cortisol
Symptoms; skin thinning, easy bruising, red/purple marks, moon face, hiritusim
Caused by; corticosteroids, tumour
Treat with ketoconazole or cortisol inhibiting drugs
119
What do thyroid hormones do?
HR, digestive function, muscle control. Brain development
120
Symptoms of hyperthyroidism?
Heat intolerance
Weight loss
Diarrhoea
Tachycardia
Tremors
Angina
Sweating
HIGH T4 and T3 but LOW TSH
121
How is hyperthyroidism treated?
Thyroidectomy or carbimazole or popythiouracil (not commonly used)
122
What is blocking replacement regimen?
Stops patient going from one extreme to the other
Over treatment can cause hypothyroidism under can cause hyperthyroidism
Combination of carbimazole and levothyroxine used
Avoid in pregnant women
123
What is thyrotoxic crisis (thyroid storm) and the symptoms?
Too much thyroid hormone
Poorly controlled overactive thyroid which is life threatening
Medical emergency
Symptoms; rapid heart beat, high temperature, diarrhoea, vomiting, jaundice, loss of consciousness,
124
What is the treatment of thyrotoxic crisis?
IV fluids
Propranolol (rapid symptom relief)
Hydrocortisone
Oral iodine solution, carbimazole
125
Thyroidectomy
Iodine 10-14 days before partial Thyroidectomy
Adjunct to anti-thyroid drugs but not long term
126
Hyperthyroidism in pregnancy
Radioactive iodine therapy is CI
Carbimazole and propylthiouracil cross the placenta = foetal goitre and hypothyroidism
Propylithiouracil is drug of choice in 1st trimester (carbimazole = congenital effects) BUT is stopped and switched to carbimazole in 2nd trimester due to help toxicity risk
127
Carbimazole
Prodrug which once metabolised prevents the synthesis of thyroid hormones
CI in severe blood disorders
Indicated for hyperthyroidism
128
Carbimazole signs to report?
Symptoms and signs of infection (mouth ulcers, bruising fever, malaise) , especially sore throat
Neutropenia and agranulocytosis - bone marrow suppression, WBC at signs of infection
129
MHRA warnings with carbimazole
Congenital defects during pregnancy esp in 1st trimester
Acute pancreatitis (N/V, abdominal pain, fever, rapid pulse)
(Also causes neutropenia and agranulocytosis)
130
Propylthiouracil
Alternative to carbimazole
Monitor hepatoxicity; liver, jaundice, malaise n/v
Discontinue if severe liver enzyme abnormalities develop
Recognise signs of liver disorder
131
Hypothyroidism symptoms
Cold intolerance
Weight gain
Constipation
Bradycardia
Lethargy
Muscle cramps
LOW T4 LOW T3 but HIGH TSH
132
What max dose levothyroxine?
Question doses above 200 mg +
133
Levothyroxine label
Take dose 30 - 60 mins before breakfast caffeine containing liquids or other medications
134
Monitoring requirement for levothyroxine?
TSH levels 3 monthly until stable within range reading produced
135
Liothyronine
Has a rapid onset of action - used in severe states
Shorter duration of action
Can potential hyperthyroidism symptoms
IV used best choice in hypothyroidism coma
136
Levothyroxine contraindications
Thyrotoxicosis
137
Levothyroxine and pregnancy
Can be used
Need to keep thyroid function checked as thyroid hormone requirement increases in pregnancy
138
What drugs do you need to monitor TFT?
Lithium
Amiodarone
139
What is Graves’ disease?
Autoimmune disease
Main reasons for hyperthyroidism
140
What is the second like treatment if you have diabetes and CVD risk?
Give metformin and SGLT2-I
141
What is osteoporosis?
Progressive bone disease characterised by low bone mineral density (BMD) and deterioration of microarchitecture
Due to miss match of bone formation and bone breakdown
No symptoms usually diagnosed after a fall known as a fragility fracture
Typically seen in wrist, hip and spinal vertebrae
142
Risk factors that reduce bone mineral density?
Age (65+)
Immobility BMI <18
Cigarette smoking
Excess alcohol
Diabetes, COPD
Hyperparathyroidism, hyperthyroidism
Chronic kidney and liver disease
Early menopause
143
Risk factors that reduce bone strength?
Smoking or drinking alcohol
Age
Corticosteroids, SSRI, PPI, anti epileptics, pioglitazone
RA
Previous history of fragility fractures
Parental history of hip fracture
144
Lifestyle treatment for osteoarthritis.
Increase physical activity
Stop smoking
Maintain BMI (20-25 kg/m2)
Reduce alcohol intake
Increase dietary intake of vitamin D and calcium (or supplements)
Elderly patients have increase risk of fall; appropriate getting up/ walking techniques
145
Reversible causes osteoarthritis?
Hyperparathyroidism
Hyperthyroidism
Hypogonadism
Osteomalacia
146
Post menopausal osteoporosis
Oral biphosphonates are 1st line ; reduce rate bone turnover
If 1st line CI give ibrandronic acid, denosumab or raloxifene
HRT restricted to younger post menopausal women to to adverse effects of CVD and cancer in older post menopausal women on long term HRT (HRT considered premature menopause consider 5 years)
147
Glucocorticoid- induced osteoporosis
Cause bone loss and increase risk of fractures
Greater rate of bone loss occurs early after initiation of glucocorticoid and increase with dose and duration
Prophylaxis and treatment; same use oral biphosphonates ; alendronic acid or risidronate
148
Osteoporosis in men
1st line oral biphosophonates;
Alendronic acid 10 mg OD (70 is unlicensed) or risedronate 35 mg weekly
Alternative is zolendronic acid or denosumab if 1st line not good
Alternative to alternative teriparatide or strontium ranelate
149
MHRA alerts with biphosphonates
Atypical femoral fractures; report any thoughts, hip/groin pain during treatment
Osteonecrosis of the jaw; maintain good oral hygiene, routine dental checks (greater risk in IV than oral)
Osteonecrosis of external auditory canal; report ear pain, ear infection during treatment
150
Alendronic Acid safety facts
S/e oesophageal reactions; dysphasia, new/wording, heartburn, swelling
10 mg OD for men
70 mg or 10 mg women
Swallow whole and oral solution swallowed as single 100 mL dose
Plenty water
30 mins before breakfast (empty stomach) and stay up right after for 30 mins
151
What are the IV biphosphonates?
Zolendronic acid
Pramidronate
More potent is IV high risk of Osteonecrosis of the jaw
Bone metastasis in breast cancer / severe hypercalcaemia of malignancy
152
Strontium ranelate
Started / initiated by specialist for severe post menopausal osteoporosis or in men at high-risk of fracture where other therapies are not suitable
CAUSE; severe CVD (MI, VTE), severe allergic reaction, rash, fever, swollen glands,
153
Treatment duration of osteoporosis
No evidence of 10 years treatment; specialist treatment input
Review after 5 years treatment with alendronic/risedronate/ ibrandronic
Review after 3 years with zolendronic
Continue treatment if; 75+, fracture history, fragility fracture during treatment, long term glucosteroids
154
Contraindications for biphosphonates
Hypocalcaemia
Abnormalities of the oesophagus
155
What is DEXA scan
Measure bone mineral density and bone loss in patients taking systemic corticosteroids or over 65 OR 40+ taking an equivalent dose of prednisolone 7.5 mg daily for 3-4 months BMD should be assessed
156
When is early menopause?
<45 years
Premature is before 40 years
157
Natural menopause age?
> or greater than 50 years
158
When does menopause occur?
Ages 45-55
Diagnosed clinically after 12 months of no period (amenorrhoea)
159
Symptoms of menopause?
Vasomotor symptoms; Hot flushes, night sweats
Vaginal atrophy
Accelerated skin aging
Decreased muscle mass
Sexual dysfunction
Bone loss
Mood changes
Sleep disturbances
160
Tibolone
Oestrogenic, progetogenic and has weak androgenic activity
Give continuously without cyclic progestogen
161
Who should be given progestogen?
Combined HRT; oestrogen + progestogen
Women WITH A UTERUS
Given to reduce risk of endometrial cancer and cystic hyperplasia
162
Risks from HRT
Breast cancer
Endometrial cancer
Ovarian cancer
Venous thromboembolism
Stroke
Coronary heart disease (only women who start combined HRT more than 10 years after menopause)
163
How to minimise HRT risk?
Minimum effective dose at shortest duration
Review treatment at least annually and consider alternative treatment for osteoporosis
Benefits Vs risks
164
Risk of Breast cancer and HRT
All HRT increase risk of breast cancer within 1-2 years of initiating treatment
Increase risk is related to duration of HRT and not age
Risk disappears 5 years from stopping
165
Breast cancer symptoms
New lump or area of thickened tissue that was not there before
Changes in size/shape of breasts
Bloodstained discharge
166
Risk of endometrial cancer and HRT
Depends on dose and duration of oestrogen only HRT
Progestogen is given cyclically to reduce risk of endometrial cancer BUT it increases breast cancer risk
ONLY given to women WITH A uterus or if they have no uterus but have endometriosis
167
HRT and contraception
HRT doesn’t provide contraception
Under 50 years; still fertile after last period use low oestrogen combined contraception
Over 50 years; fertile one year after last period; use condoms
168
Risk of ovarian cancer
Long term use of combined HRT for oestrogen only HRT is associated with small increase risk of ovarian cancer
Risk disappears within a few years of stopping
169
Risk of Venous thromboembolism and HRT?
Women using combined or oestrogen only HRT are at risk of DVT and PE esp in first year of use
Further risk increase; personal history, predisposing factors, varicose veins, obese with BMI >30, immobile etc
Using patches reduces risk
170
Risk of Stroke and VTE?
Increases with age
Older women at greatest risk
Combined HRT or oestrogen only HRT increase risk of stroke slightly
Tibolone increase risk by 2.2 times from 1st year of treatment
Use patches decrease risk
171
Risk of coronary heart disease and HRT?
HRT doesn’t prevent CHD and should not be prescribed for this purpose
Increase risk CHD who start combined HRT after 10 years menopause - starting closer to menopause is better
172
Benefits of HRT
Controls menopausal symptoms
Decrease risk of developing T2DM, osteoporosis
Limited evidence suggests improved muscle mass and strength
173
HRT and surgery
Major surgery and HRT = risk VTE
To stop HRT 4-6 weeks before surgery and restart after patient is fully mobile
If HRT cant be stopped (urgent or unselective surgery) give LMWH and graduated compression hosiery
174
When to stop HRT
Sudden severe chest pain
Sudden breathlessness
Unexplained swelling to calf pain
Severe stomach pain
Serious neurological effects (headaches, hearing, disturbances, dysphasia)
Jaundice, liver enlargement, hepatitis
Prolonged immobility after surgery or leg injury
175
Ulipristal acetate
Ella one
Progestogen receptor modulator with partial progestogen antagonist effect
Treatment of fibroids and hormonal emergency contraception
176
Androgens
Male sex hormones
Cause masculinisation
Used replacement therapy in castrated adults and those who hypogonadal (low hormone)
E.g testosterone (testogel, testin, tostran)
177
Cyproterone acetate
Male sex hormone antagonism - anti androgens
Treatment if severe hyper-sexuality and sexual deviation in men
Inhibits spermatogenisis and also used prostate cancer
Can cause acne and hiritusm in women
MHRA alert; minimise risk of meningemia (dose dependent risk)
178
Finasteride
Metabolises testosterone into the more potent androgen
For benign prostatic hyperplasia 5 mg
For alopecia in men 1 mg
MHRA advice; suicidal thoughts and depression, male breast cancer reported
Avoid women crushing and handling tablets or capsules
S/e decrease libido, impotence, breast tenderness and enlargement
179
Clomifene
Anti-oestrogen
Ovulation stimulant
Use infertility due to oligomenorrhoea or secondary (e.g PCOS)
Use for 6 cycles only due to risk in ovarian cancer
S/e multiple pregnancies
180
What is endometriosis?
The tissue lining the womb grows elsewhere
181
What corticosteroid is used to diagnose crushing syndrome?
Dexamethasone
182
What is example of mineralcorticoid adverse effects?
Hypocalcaemia
