Chapter 6: Endocrine Flashcards
(213 cards)
1
Q
What is diabetes insipidus?
A
Where large amounts of dilute urine are produced which causes extreme thirst
2
Q
2 types of diabetes insipidus?
A
- cranial = vasopressin or desmopressin: the hypothalamus does not make enough ADH
- nephrogenic = thiazide diuretics; paradoxical effect: the kidneys do not respond to ADH
3
Q
What is desmopressin?
A
Desmopressin is a more potent analogue of vasopressin with a longer duration of action and no vasoconstrictor effects
4
Q
How does desmopressin work?
A
Desmopressin works by reducing the amount of urine produced in the body at night by the kidneys. This means that the bladder then fills with less urine during the night. Desmopressin is usually taken at bedtime
5
Q
What is vasopressin?
A
vasopressin, also called antidiuretic hormone, hormone that plays a key role in maintaining osmolality (the concentration of dissolved particles, such as salts and glucose, in the serum) and therefore in maintaining the volume of water in the extracellular fluid (the fluid space that surrounds cells).
6
Q
What is desmopressin used for ?
A
- diabetes insipidus
- nocturnal enuresis
7
Q
Desmopressin side effects?
A
- hyponatrarmic convulsions
8
Q
What does sydrome of inappropriate antidiuretic hormone secretion cause?
A
Causes hyponatraemia caused by inappropriate secretion of ADH
9
Q
What should be done if fluid restriction does not correct hyponatraemia?
A
- demeclocycline: blocks renal tubular effect of ADH
- tolvaptan: vasopressin antagonist
*Avoid rapid correction of hyponatraemia: causes osmotic demyelination of neurones; serious CNS effects
10
Q
What are corticosteroids uses?
A
- inlfammatory long-term diseases
- immunosuppressant
11
Q
Corticosteroids ?
A
- betamethasone
- deflazcort
- dexamethasone (palliative care; anorexia/raised intracranial pressure)
- fludrocortisone (postural hypotension)
- hydrocortisone (surgery and emergencies e.g. anaphylaxis)
- methylprednisolone
- prednisolone (asthma, copd, ibd, severe eczema)
- triamcinolone
12
Q
What does high mineralcorticoid activity lead to?
A
fluid retention
13
Q
Fludrocortisone uses?
A
Potent mineralcorticoid
- if fluid retention is useful - e.g. in low blood pressure
- e.g. neuropathic postural hypotension (diabetes) or adrenal insuficciency due to septic shock
- anti-inflammatory effect of no clinical relevance
14
Q
Hydrocortisone use?
A
Significant mineralcorticoid
- not for long term disease suppression - fluid retention
- useful glucocorticoid on short term basis via IV in surgeries or emergency e.g life threatning asthma or thyrotoxicosis
15
Q
What is the most potent mineralcorticoid?
A
Fludrocortisone
16
Q
What is hydrocortisone not used for?
A
Long-term disease suppression (fluid retention)
17
Q
Mineralcorticoid side effects?
A
Na+ and water retention = hypertension
K+ and Ca2+ loss
- Most marked with fludrocortisone
- Significant with hydrocortisone, corticotrophin, tetracosactide
- Negligible with betamethasone and dexamethasone
18
Q
What does high glucocorticoid activity equal?
A
ANTI-INFLAMMATORY
19
Q
What does high glucocorticoid activity equal?
A
ANTI-INFLAMMATORY
20
Q
Most potent glucocorticoid ?
A
Dexamethasone/betamethasone
21
Q
Dexamethasone/betamethasone uses?
A
(HIGH GLUCOCORTICOID ACTIVITY)
- used if fluid retention is a disadvantage e.g. heart failure
- very little mineralcorticoid activity
22
Q
Prednisolone/prednisone use ?
A
(Significant glucocorticoid activity)
- prednisolone most common steroid used by mouth
- e.g. acute or severe chronic asthma, COPD, IBD
23
Q
Another significant glucocorticoid?
A
Deflazcort
24
Q
What do high corticosteroid doses cause?
A
Avascular necrosis of femoral head
25
Glucocorticoid side effects?
- Endocrine
- Musculoskeletal:
- Gastro-intestinal
- Psychiatric reactions
- Infections (immunosuppression)
- Adrenal suppression
- Opthalmic
- Skin
- Central nervous system
- Growth restriction
- Cushings syndrome (high doses)
26
Glucocorticoid endocrine side effects?
diabetes (hyperglycaemia)
27
Glucocorticoid muscoskeletal side effects?
- osteoporosis (>3 months use: prophylaxis with biphosphonate) High corticoidsteroid doses cause avascular necrosis of femoral head)
- muscle wasting, proximal myopathy (caution with statins)
28
Glucocorticoid GI side effects?
Peptic ulcers, gastro-intestinal, dyspepsia
| Counselling: take with or after food
29
Glucocorticoid psychiatric side effects?
- A serious paranoid state or depression with suicide risk while taking systemic corticoidsteroids or on withdrawal
- Mood and behaviour changes; euphoria, irritable, mood lability, insomnia, nightmares, psychotic reactions, suicidal thoughts and behavioural disturbances
- Counselling: report immediately
30
Glucocorticoid infections (immunosuppression) side effect?
Increased susceptibility and severitym atypical clinical presentation. Serious infections not detected until advanced stage
- Avoid close contact with chickenpox or shingles, Exposed non-immune patients need passive immunisation with varicella-zoster immunoglobulin (applies to patients currently taking or stopped < 3 months. If chickenpox develops - need urgent specialist treatment)
- Avoid exposure to measles, Seek urgent medical advice if exposed. Prophylaxis with normal immunoglobunlin may be needed
31
Glucocorticoid adrenal suppression side effect?
- Adrenal suppression approx 1 year after stopping
- Fatigue, anorexia, n+v, hyponatraemia, hypotension, hyperkalaemia and hypoglycaemia
- Avoid abrupt withdrawal if use > 3 weeks (acute adrenal insufficiency. hypotension, death)
- Higher doses in significant intercurrent illness/stress. Patient must mention they are taking steroids or if they have stopped in less than a year during any treatment for illness or injury
- Anaesthesia = dangerous fall in blood pressure, need adrenal replacement with IV hydrocortisone
32
Glucocorticoid opthalmic side effects?
- Glaucoma, Cataracts
- MHRA advice: corticosteroids: rare risk of central serous chorioretinopathy with local sytemic use. Counselling: report blurred vision and visual disturbances, Consider referral to opthalmologist
33
Glucocorticoid skin side effects?
- Skin thinning
- Purple-red striae
- Bruising
34
Glucocorticoid CNS side effects?
- aggravated epilepsy
| - schizophrenia
35
Glucocortioid growth suppression side effect?
In children
36
MHRA advice for methylprednisoloe injectable medicine containing lactulose?
Do not use in patients with cows milk allergy. Serious reactions including bronchospasm and anaphylaxis reported in patients with cows milk allergy. If symptoms worsen or new allergic symptoms occur, stop and treat
37
How to manage steroid side effects?
- lowest effective dose for minimum period
- local treatment rather than systemic route
- single dose in the morning: suppressive action on cortisol secretion is least in the morning
- alternate day administration by taking 2 days worth as single dose to further reduce suppression
- intermittently with short courses
38
When to avoid abrupt withrawal of steroids ?
- long term use > 3 weeks
- >40mg prednisolone daily or equivalent for more than 1 week
- Repeat doses are taken in the evening
- Recent repeated courses
- Short course within 1 year of stopping long-term steroids
- Have other causes of adrenal suppression
39
What should be issued to every patient taking long-term corticoidsteroids for more than 3 weeks?
Steroid card
- consider issuing to patients using greater than maximum licensed doses of ICS
40
Corticosteroids and pregnant/breastfeeding?
- generally safe
| - monitor fluid retetntion in pregnant women
41
What is Adrenal replacement therapy?
Treatment usually involves corticosteroid (steroid) replacement therapy for life. Corticosteroid medicine is used to replace the hormones cortisol and aldosterone that your body no longer produces. It's usually taken in tablet form 2 or 3 times a day.
42
Adrenalectomy, addisons disease features and treatment ?
- low cortisol (natural glucocorticoid)
- low aldosterone (natural mineralcorticoid)
- replacement: hydrocortisone + fludrocortisone
43
Hypopituitarism features and treatment ?
- pituitary gland does not stimulate hormone secretion by target glands
- replacement: hydrocortisone but NOT fludrocortisone; (renin-angiotensin sytem will regulate aldosterone)
- replace other hormones e.g sex. thyroid hormones
44
What is cushings syndrome charactirised by?
Hypercortisolism (high cortisol)
45
Cushings syndrome symtpoms?
Skin thinning, easy bruising, reddish-purple stretch marks; striae, fat deposits in the face, moon face, acne, hirsutism and amenorrhoea
46
Cushings syndrome causes?
- Corticosteroids = reduce dose or withdraw
| - Tumour = surgery or cortisol-inhibiting drugs; (metyrapone (competitive) or ketoconazole (potent))
47
Cushings sydrome treatment?
- ketoconazole: life threatning hepatotoxicity, pt counselling: report signs or liver toxicity: anorexia, abdominal pain, dark urine, jaundice, itching, pale stools, n+v etc
- cortisol-inhibiting drugs; adrenal insufficiency. pt counselling: report fatigue, anorexia, n+v, hypotension. Adrenal suppression causes hyponatraemia, hyperkalaemia and hypoglycaemia
48
What is diabetes mellitus characterised by?
Hyperglycaemia
49
Type 1 diabetes ?
"insulin deficiency"
- pancreatic beta islet cells are destroyed causing insufficient insulin
- treatment with insulin
50
Type 2 diabetes?
"insulin resistance"
- reduced insulin secretion/peripheral resistance to insulin
- treatment with diet, oral antidiabetic drugs or insulin
51
Diabetes symptoms?
- polyphagia (excessive hunger)
- polydipsia (excessive thirst)
- polyuria (excessive urination)
- weight loss
- fatigue
- blurred vision
- poor wound healing
52
Diabetes long term macrovascular complications?
- diabetes is a strong risk factor for cardiovascular disease: coronary heart disease, cardiomyopathy, arrhythmias and sudden death, cerebrovascular disease and peripheral artery disease. Cardiovascular disease is the primary cause of death in diabetic patients.
53
What is given during primary prevention in diabetes?
Statin in type 1 and type 2 diabetes with a Qrisk >10%
| *low dose aspirin is not recommended for primary prevention. Ace inhibitors may have a role in preventing CVD
54
Microvascular complications for diabetes?
- eyes: retinopathy, treat hypertenison; protects visual activity
- kidneys: nephropathy (proteinuria/microalbuminuria)
- sensory painful neuropathy (diabetic foot)
- autonomic neuropathy
- gustatory neuropathy
- neuropathic postural hypotension
55
How to treat retinopathy?
Treat hypertension, protects visual acuity
56
How to treat nephropathy?
Treat with ACE inhibitor/ARB
NB: ACE inhibitors potentiates hypoglycaemic effects of hypoglycaemic effects of antidiabetic drug and insulin, especially in renal impairment
57
How to treat diabetic foot?
- analgesics: strong opioid = oxycodone/morphine; specialist use
- duloxetine, TCAs: amitriptyline, nortriptyline
- anti-epileptics: gabapentin, pregabalin, carbamazepine
58
How to treat autonomic neuropathy?
- diabetic diarrhoea: codeine or tetracycline
- gastroparesis: erythromycin
- erectile dysfunction: sildenafil
59
How to treat gustatory neuropathy?
(sweating face, scalp, head and neck)
| - treat wih antimuscarinic/antiperspirant
60
How to treat neuropathic postural hypotension?
Fludrocortisone and increased salt intake
61
When do insulin requirements increase in pregnancy?
- increase in 2nd and 3rd trimester
62
What is the aim HbA1c for pre-existing diabetes and pregnancy and what else should be taken to reduce the risk of congenital malformations?
Aim HbA1c level below 48mmol/mol (6.5%)
*5mg folic acid daily (diabetes is a high risk group for neural tube defects)
63
What is the first choice insulin treatment in pre-existing diabetes in pregnancy?
ISOPHANE INSULINE (humulin) (longer acting): may be appropriate to continue using long-acting analogues: glargine or determir, if good glycemic control before pregnancy
64
Other insulin treatment choices for pre-existing diabetes in pregnancy for women with difficulty achieveing glycaemic control?
CONTINUOUS SUBCUTANEOUS INFUSION PUMP: for women with difficulty achieving glycaemic control with multiple daily injections without significant disabling hypoglycaemia
65
What to do if there is an increased risk of hypoglycaemia postnatal period:
reduce insulin immediately after birth; monitor blood glucose to establish dose
66
Counselling for hypos in pregnancy in pre-existing diabetes?
Hypoglycaemic risks in all pregnant women treated with insulin (especially in first trimester)
- carry a fast acting form of glucose e.g. dextrose/glucose drink
- for type 1 - prescribe glucagon if needed
67
Pre-existing type 2 diabetes and pregnancy?
- stop all oral antidiabetic drugs except metformin, substitute with insulin
- metformin alone or with insulin
68
Breastfeeding and type 2 diabetes?
Continue metformin or resume glibenclamide post birth
69
For gestational diabetes when should treatment be stopped?
After birth
70
What is first and second line for fasting blood glucose < 7mmol/L at diagnosis of gestational diabetes ?
FIRST LINE: dietary and exercise measures
SECOND LINE: metformin if blood glucose target not met in 1-2 weeks
Alternative: Insulin (also added to metformin if alone not effective)
71
What is first line if fasting blood glucose >7mmol/L at diagnosis for gestational diabetes ?
FIRST LINE: insulin with or without metformin + dietary and exercise measures
72
What is first line for fasting blood glucose 6-6.9mmol/L with hydramnios (too much amniotic fluid) or macrosomia (newborn larger than average)?
FIRST LINE: insulin with or without metformin
73
What can be used in gestational diabetes for women intolerant of metformin and do not want insulin?
Glibenclamide (from 11 weeks gestation; after organogenesis)
74
When is DKA more common?
more common in type 1
75
DKA symptoms?
- severe hyperglycaemia
- high blood ketones
- ketonuria (ketones in urine)
- pear drop breath
- dehydration/excessive thirst
- polyuria
- nausea, vomiting
- anorexia
- abdominal pain
- difficulty breathing
- electrolyte imbalance
- mental confusion
- drowsiness
- diabetic coma
- convulsions
76
DKA treatment?
IV INFUSION
1. soluble insulin
2. fluids (saline)
3. potassium (do not give if anuria - no urine)
- Continue established long-acting insulin e.g. determir, glargine
- Add glucose to infusion when below 14mmol/L
- continue until patient able to eat and drink and blood pH above 7.3
- give SC fast acting insulin and meal, stop infusion one hour later
77
Diabetes and driving?
- Notify the DVLA when on insulin or any medication for group 2 drivers (do not need to notify in diet controlled diabetes)
* group 1 = cars and motorbikes
* group 2 = lorry, bus, coach
Hypoglycaemia:
- 2 episodes of sevre hypoglycaemia in past 12 months (one episode if group 2)
- impaired awareness
- disabling hypoglycaemia while driving
78
What monitoring should be done whilst driving to avoid hypoglycaemia?
- check blood glucose no more than 2 hours before driving and every 2 hours for long journey
- for those on insulin
- group 2 drivers on sulphonylurea, glinides.
- record readings at least twice a day even when not driving!
- drivers on insulin must always carry fast-acting sugar supply e.g. glucose tablet and avoid driving if meal is delayed
79
Blood glucose levels and driving?
5mmol/L = take a carbohydrate before driving
| < 4mmol/L = do not drive
80
What to do if hypoglycaemia occurs whilst driving?
1. stop vehicle in safe place and switch engine off
2. eat or drink a fast acting sugar and then long acting carbohydrate e.g. sandwich to maintain levels
3. wait 45 mins after blood glucose levels return to normal, before continuing journey
81
What is insulin?
Polypeptide hormone responsible for the metabolism of carbohydrates, fat and protein
82
3 types of insulin?
1. Human insulin (soluble insulin)
2. Human insulin analogues (rapid and long-acting)
3. Beef/pork insulin (short acting soluble animal)
83
Short acting soluble insulin?
- Human soluble
- Beef/pork
- Via SC/IM/IV diabetic emergencies and surgery
- Animal insulin may not be acceptable in moral/religious beief
- BOLUS INSULIN (short period of time)
- Take 15-30 mins before a meal
- Consume meal within 30 mins to avoid hypoglycaemia
84
Rapid- acting insulin analogue?
- LISPRO (humalog)
- ASPART (novorapid)
- GLULISINE (apridra)
- lower risk of hypo before lunch + late dinner, than soluble
- alternative to soluble in emergency
- BOLUS INSULIN
- take immediately before or after a meal
85
Intermediate acting insulin?
ISOPHANE (NPH) - Novolin N, Humulin N, Insulatard
- never give IV = thrombosis
- protamine causes allergic reactions
- BASAL INSULIN (set amounts of insulin at intervals)
- take BD in conjunction with soluble insulin
86
Long-acting insulin analogue?
- GLARGINE (lantus)
- DETEMIR OD/BD (levemir)
- DEGLUDEC (tresiba)
- PROTAMINE ZINC
- never give IV = thrombosis
- don't mix with soluble = binds in syringe
- BASAL INSULIN
- take OD at same time each day to cover 24 hour period
87
Insulin uses?
- type 1 diabetes, type 2 if antidiabetic medication fails
| - surgery, when hospitalised for an illness or DKA
88
When do insulin requirements increase?
- infections or intercurrent illness
- stress or accidental or surgical trauma
- puberty
- pregnancy (2nd/3rd trimester)
89
When do insulin requirements decrease?
- endocrine disorders (e.g. addisons disease, hypopituitarism)
- coeliac disease (gluten intolerance)
90
Insulin administration ?
- subcutaneous injection to buttocks, upper arm, abdomen or thigh
* IV injection reserved for urgent treatment e.g. DKA, during surgery or in serious illness for fine control
91
Types of insulin regimens ?
1. Mulitple injection regimen (MIR)
2. Biphasic mixtures regimen
3, Long/intermediate-acting regimen
4. Continuous subcutaneous infusion
92
Explain the multiple injection insulin regimen?
- short/rapid acting insulin before meals PLUS intermediate/long acting insulin given once or twice daily
93
Explain biphasic mixtures insulin regimen?
- short/rapid-acting insulin PRE-MIXED with intermediate/long acting insulin OD/BD before meal
- for patients who have difficulty with or prefer not to use MIR
- not for acutely ill patients as insulin requirements change
94
Explain long/intermediate acting insulin regimen?
- OD/BD with or without short/rapid acting insulin before meals
- long-acting insulin not for type 2 unless in certain criteria
95
Continuous subcutaneous infusion ?
- delivers basal insulin and patient-activated bolus doses at meal times
- must be highly motivated to monitor blood glucose regularly
- NOT recommended in type 2 diabetes
96
Type 1 diabetes starting insulin regimen?
Start treatment with multiple injection regimen
97
Type 2 diabetes starting insulin regimen?
- start treatment with isophane insulin once or twice daily + short acting (soluble) insulin as a biphasic or mulitple injection regimen
98
When is the continuous subcutaneous infusion pump recommended in type 1 diabetes?
- in patients who suffer recurrent unpredicatble hypoglycaemia in attempt to achieve target glycaemic control with multiple injection regimen OR
- glycaemic control >8.5% despite optimised MIR
- children under 12 where MIR is impractical; must go under MIR trial when 12-18 yrs old
99
Insulin side effects?
HYPOGLYCAEMIA
- do not miss meals
- right insulin, right dose, right time, right route
- do not do strenuous exercise shortly before administration; absorption increased from limb used
LIPODYSTROPHY
- rotate injection site; can be administered to buttocks upper arm, abdomen and thigh
LOCAL INJECTION SITE REACTIONS
- check injection technique
100
Insulin counselling in relation to food ?
- multiple injection regimen: must match (adjust) insulin dose according to carbohydrate intake
- biphasic regimen (fixed dose): must regulate and distribute carbohydrate intake throughout the day to match regimen
101
Insulin passports?
always supply PIL to patients recieving insulin
102
Insulin interactions: which drugs enhance the hypoglycaemic effect of insulin?
- ACE inhibitors (hyperkalaemia + hypoglycaemia linked )
- Beta-blockers (masks symptoms of hypoglycaemia)
- alcohol
103
Insulin interactions: which drugs antagonise hypoglycaemic effect of insulin?
(reduce action of insulin - resulting in hypERglycaemia)
- corticosteroids
- oral contraceptives
- loop/thiazide diuretics
104
When should you STOP metformin?
If dehydrated (fever, vomiting, diarrhoea) due to increased risk of lactic acidosis
105
When should you stop GLIFLOZINS?
Consider stopping gliflozins if dehydrated as they cause volume depletion
106
Which insuin has lower risk of hypos before lunch + late dinner?
Rapid acting insulin analogue:
lispo (humalog)
apart (novorapid)
glulisine (apridra)
107
Which insulin should you never give IV?
```
Isophane (NPA intermediate acting)
Long acting:
- glargine (lantus)
- detemir OD/BD (levemir)
- degludec (tresiba)
- protamine zinc
```
(thrombosis when given IV)
108
Errors administering insulin: NPSA alerts?
- dose should always be prescribed in "UNIT" not U or IU e.g. 10U can easily be misinterpreted as 100!
- never give IV syringe for SC injection; IV are in ml not units = overdose
- check injection techniquw SC not IV
- always check insulin container, pen and needle size
109
How should insulin be stored?
- store in fridge between 2-8 degrees when unopened
- once opened store at room temp and use by 28 days
- if left outside the fridge at 15-30c > 48hrs - discard
- if frozen must discard
110
Conversion from animal to human insulin?
Beef to human = reduce dose by 10%
| Pork to human = no dose change
111
Type 1 and insulin in surgery?
- night before = usual insulin
- day of surgery:
- IV glucose with potassium if not hyperkalaemic, according to patients fluid requirements. (lower in elderly, volume depleted patients, CVD)
- IV soluble insulin with NaCl piggy-backed onto infusion
- once patients start eating and drinking: sc before breakfast and stop IV 30 mins later
112
Metformin MOA?
(Biguanide)
- decreases liver gluconeogenesis and increases peripheral use
- FIRST LINE IN ALL PATIENTS WITH TYPE 2 DIABETES
113
Metformin side effects?
- lactic acidosis, avoid in: renal impairment (severe infection, dehydration, eGFR (<30ml/min) OR tissue hypoxia (MI, acute HF, liver impairment and resp failure)
- GI disturbance - take with or after meal and increase dose gradually OR switch to MR
- weight loss
- hypoglycaemia (rarely)
- taste disturbance
- reduced vitamin b12 absorption
114
Metformin c/i?
(renal impairment risk)
| - general anaesthesia, iodine containing contrast media
115
Sulphonylurea MOA?
Augments insulin secretion (makes bigger)
116
Sulphonylurea forms and features?
- SHORT ACTING = lower risk of hypos
- gliclazide, tolbutamide
- use in elderly and renal impairment
- LONG ACTING
- glibenclamide, glimepiride
- PREGNANCY
- glibenclamide in 2nd and 3rd trimester
117
Sulphonylurea side effects?
- hyponatraemia = glipizide, glimepiride
- sulphonylura-induced hypoglycaemia (must treat in hospital as may persist for hours)
- weight gain
- jaundice
- hypersensitivity reactions in first 6-8 weeks e.g skin rashes
*counselling = recognise symptoms of hypo especially when driving, always carry a sugary snack, never miss meals
118
Sulphonylureas interactions?
- warfarin and ACE inhibitors = increased hyPO
| - NSAIDs = reduced renal excretion
119
Pioglitazone MOA?
(thiazolinedione)
| - reduces peripheral resistance
120
NICE when should pioglitazone be continued ?
- continue if HbA1c reduced by 0.5% in 6 months
121
Pioglitazone side effects?
- heart failure; increased incidence when combined with insulin (c/i in history of HF)
- bladder cancer: c/i in history of bladder cancer or uninvestigated macroscopic haematuria (blood in urine) - report this, urgency and dysuria (painful urine)
- hepatotoxicity: report signs of liver toxicity: nausea, vomiting, abdominal pain, fatigue, dark urine, itching - STOP if jaundice occurs
122
SGLT-2 inhibitors MOA and examples?
(GLIFOZINS)
- inhibits sodium-glucose co-transporter 2 in renal proximal tubule to reduce glucose reabsorption and increase urinary excretion
- canaglifozin
- dapaglifozin
- empaglifozin
123
SGLT-2 inhibitor side effects?
- life threatning atypical DKA with only moderately raised blood glucose level, stop and test ketones if DKA suspected.
- report DKA symptoms
- volume depletion: report postural hypotension, dizziness
- constipation
- thirst
- polyuria
- UTIs
- genital infection
124
Canaglifozin MHRA advice/warning?
Increased risk of lower limb amputation (mainly toes)
| - report skin ulceration, discolouration, new pain, stay hydrated, preventative foot care, treat foot problems early
125
Wound healing and blood sugar levels?
Your blood sugar level is the main factor in how quickly your wound will heal. When your blood sugar level is higher than normal, it: prevents nutrients and oxygen from energizing cells. prevents your immune system from functioning efficiently.
126
DPP-4 inhibitors MOA and examples?
(GLIPTINS)
is to increase incretin levels, which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.
- alogliptin
- linagliptin
- saxagliptin
- sitagliptin
- vildagliptin
127
What is glucagon?
Glucagon is a peptide hormone secreted from the alpha cells of the pancreatic islets of Langerhans. Hypoglycemia is physiologically the most potent secretory stimulus and the best known action of glucagon is to promote the breakdown of glycogen to glucose in the liver. and thereby to maintain adequate plasma glucose concentrations.
128
DPP-4 inhibitors side effects?
- pancreatitis: report persistent severe abdominal pain
- vildagliptin - liver toxicity, STOP and report nausea and vomiting, abdominal pain, dark urine, fatigue, pruritis, jaundice
129
Meglitinides MOA and examples?
(GLINIDES)
- Stimulates insulin secretion
- nateglinide
- repaglinide
130
Meglitinides side effects?
- hypersensitivity reactions
- rashes
- urticaria (hives)
- pruritus
- nateglinide: abdominal pain; constipation, diarrhoea, nausea, vomiting (common)
- repaglinide: visual disturbance
- driving: particular care to avoid hypos and warn patients of problems
131
Meglitinides counselling?
- take 30 mins before main meal
| - rapid onset and short duration of action
132
Acarbose MOA?
- inhibits intestinal alpha-glucosidase enzymes and delays digestion/absorption of starch and sucrose
- reserved for use: when other oral hypogycaemics cannot be taken
133
Acarbose side effects?
- flatulence: improves with time, antacids do not help
- diarrhoea: withdraw or reduce dose
Counselling
- chew with first mouthful of food or swallow whole with little liquid immediately before food
- carry glucose (not sucrose) to counteract hypo cause by insulin or sulphonylureas
134
GLP-1 AGONIST MOA and examples?
(GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS)
- Binds to and activates GLP-1 receptors to increase insulin secretion, suppress glucagon secretion and slows gastric emptying
- prevents weight gain, SC injection
- exenatide
- abiglutide
- dulaglutide
- liraglutide
- lixisenatide
135
GLP-1 agonist side effects?
- pancreatitis: STOP if severe persistent abdominal pain
MIXED DOSES: do not administer AFTER a meal
- inject within 1 hour of next meal (lixisenatide)
- continue with next schedule dose (exenatide)
- inject within 3 days of next weekly dose (dulaglutide, albiglutide)
- pregnancy and contraception: use contraception MR exenatide (12 weeks after stopping), lixisenatide, albiglutide)
136
Which oral antidiabetic is c/i in renal impairment?
metformin
137
Which antidiabetics can cause weight loss?
- metformin
- GLP-1 inhibitors
- SGLT2 inhibitor (maybe)
138
Which antidiabetics cause weight gain?
- sulphonylureas
| - meglitinides
139
What antidiabetic drug can cause lactic acidosis?
Metformin
140
Which antidiabetic drug causes taste disturbance and reduced vitamin b12 absorption?
metformin
141
Which sulphonylureas are safe to use in elderly and renal impairment?
short acting
| - gliclazide and tolbutamide
142
Which antidiabetic drug is safe to use in the 2nd and 3rd trimester of pregnancy?
Glibenclamide
143
Which antidiabetic drug interacts with warfarin and ACE inhibitors to increase HYPO?
Sulphonylureas
144
What tests are done to diagnose diabetes?
HbA1c blood test
- recommended by WHO
- 6.5% (48mmol/mol) or above to diagnose type 2 diabetes
Oral Glucose Tolerance Test
- diagnosis of impaired glucose tolerance
- not recommended and not needed for patients with severe hyperglycaemic symptoms
145
What monitoring is done for diabetes?
- urinanalysis = ketones, protein (albumin)
- glucose blood monitoring = ketones and glucose)
(more routine in type 1 diabetes or in type 2 diabetics on insulin or oral hypoglycaemic e.g. sulfonylurea)
146
Fasting blood glucose target for diabetes?
4-7mmol/L
147
After food blood glucose targets?
<9mmol/L
148
HbA1c target for diabetic patients glycaemic control over the past 2-3 months? (measured every 3-6 months)
(OPTIMAL GLYCAEMIC CONTROL TARGET)
Diabetic patients = 6.5-7.5% (48-59mmol/L) or less
Diabetic patient at high risk of arterial disease =
149
Hypertension target for a diabetic patient? (with and without complications)
- without complications = 140/80mmHg
| - with complications = 130/80mmHg
150
What should diabetic patients with diabetes be offered first line?
- ACE inhibitor
| - African or caribbean patients should recieve both an Ace inhibitor and a diuretic or CCB first line
151
Total cholesterol target for normal vs diabetic patient?
- normal = <5mmol/L
| - high risk patient e.g. diabetes = <4mmol/L
152
Do diabetic patients come under risk groups for primary prevention?
- type 1 diabetes
| - type 2 and 10 year CVD risk >10%
153
What is hypoglycaemia defined as? (number)
- <4mmol/L
154
Hypoglycaemia signs and symptoms?
- hunger
- pale skin
- tingling lips
- sweating, chills, clammy
- dizziness
- shakiness
- palpitations
- blurred vision
- confusion
- irritability
- irrational behaviour
- slurred speech
- difficultuy concentrating
- drowsiness and coma
155
What is blunted hypoglycaemia?
- loss of warning signs is a particular hazard in insulin-treated patients
- too tight glycaemic control lowers level needed to trigger hypoglycaemic symptoms
- avoid frequent hypo episodes to restore warning signs
- beta blockers mask symptoms of hypoglycaemia and delay recovery
156
What needs to be administered in cases of hypoglycamia? (emergency in the community)
- 10-20g glucose/sucrose, if necessary repeat after 10-15 mins
- coca-cola 100-200ml
- lucozade energy original 55-100ml
- sugar lumps 3-6
- sugar 2-4 tsp
- ribena 19ml to be diluted
- provide long acting carb or next meal if due to sustain bg levels
- avoid chocolate/biscuits; fat delays glucose absorption
157
How is sulphonylurea-induced hypoglycaemia treated?
- always in hospital as it can persist for hours
158
What to administer if hypoglycaemia unresponsive or unconscious?
- sc/im glucagon
159
What to administer if unresponsive to glucagon after 10 mins or hypolycaemia prolonged ?
- IV glucose
160
What are the risk factors for osteoporosis ?
- low body weight
- elderly (65+yrs)
- cigarette smoking
- lack of exercise
- excess alcohol intake
- family history of osteoporosis
- menopause, especially if early
- long-term oral corticosteroids
161
What supplements/diet should high risk osteoporosis patients be on?
- patients at risk should maintain adequate calcium and vitamin D intake and correct any deficiency with supplements or diet
162
Treatment + prophylaxis of corticosteroid-induced osteoporosis?
For patients on oral corticosteroid for >/= 3 months low trauma fracture :
BIPHOSPHONATES
Alternatives:
- calcitriol (vitD3) - unlicensed
- HRT in women
- testosterone in men - unlicensed
163
what is given for PROPHYLAXIS for osteoporosis for post menopausal women?
1. BIPHOSPHONATES: alendronic acid is choice drug
Alternative: risedronate
- strontium ranelate if biphosphonate cannot be given
- HRT if other therapies cannot be given
- CSM: not first line in over 50s
- Raloxifene not recommended
164
What is given for the TREATMENT of osteoporosis in post-menopausal women?
1. BIPHONSPHONATES: alendronic acid
- Alternative: risedronate
- Strontium ranelate/raloxifene if biphosphonates cannot be given
- teriparatide (parathyroid hormone) if both biphonsophates and strontium ranelate cannot be given
165
What is not recommended for osteoporosis prophylaxis but is for the treatment ?
- raloxifene
166
How do biphosphonates work?
- slows the rate of bone growth and dissolution by adsorbing onto the hydroxyapatite crystals in bone
167
Biphosphonates examples?
- alendronic acid (used in prevention and treatment)
- risedronate sodium (used in prevention and treatment)
- ibandronic acid
- sodium clodronate
- pamidronate (IV)*
- zolendronic acid* (IV and most potent; highest risk of osteonecrosis of jaw)
* bone metastases in breast cancer/ severe hypercalaemia of malignancy
168
Which biphosphonate has the highest risk of osteonecrosis of jaw?
- zolendronic acid (most potent)
169
Which 2 biphosphonates can lead to bone metastases in breast cancer/ severe hypercalaemia of malignancy?
- pamidronate (IV)
| - zolendronic acid
170
Patient counselling for biphonsphate (alendronic acid)?
- alendronic acid 70mg weekly OR 10mg daily
- swallow whole with plenty of water
- while standing or sitting upright
- on an empty stomach 30 mins before breakfast or another oral medicine
- remain upright 30 mins after
171
Risedronate biphosphate counselling?
- risedronate 35mg weekly or 5mg daily
- can be taken like alendronic OR at any time of day
- leave 2 hour gap between risedronate and food, drink, antacids, calcium-containing products e.g milk, iron or mineral supplement
- stand or sit upright for 30 mins; avoid at bedtime/before rising
172
Biphosphonate side effects?
- oesophageal reactions: oesophagitis, strictures, ulcers and erosions --> stop and report dysphagia (difficulty swallowing), new or worsening heartburn or retrosternal pain
- atypical femoral features, reportt hip, thigh or groin pain (greater risk with long-term therapy; review after 5 or more years use)
- osteonecrosis of jaw: report any oral symptoms to a doctor and dentist: dental mobility, pain, swelling, non-healing sores or discharge. dental check up before starting, good hygeine and regular checkups. higher risk with zolendronic acid (potent and IV) - provide patient reminder card and inform of risk, ensures dentures fit properly etc
- osteonecrosis of external auditory canal: report ear pain, ear discharge (cholesteatoma) or ear infection during treatment, mainly in patietns with long term therapy of 2 years or longer (risk factors: ear op, chemo, steroid use, cotton-bud use)
173
How does strontium ranelate work (MOA)?
- bone formation stimulant and reduce bone resorption
- initiated by specialise for use in severe postmenopausal osteoporosis or in men at high risk of fracture where other therapies are unsuitable
174
Strontium ranelate side effects?
- serious cardiovascular diseases: including myocardial infarction and VTE. A cardiovascular risk assessment before initiating + every 6-12 months
- severe allergic reaction: dress. drug rash with eosinophilia and systemic symptoms
DRESS starts with a rash, fever, swollen glands, and a high WBC count. It can then affect kidneys, liver and lungs = can be FATAL, if skin rash occurs stop and report
175
Which HRT is used in osteoporosis?
- tibolone post menopause
| - oestrogen peri and post menopause
176
What is raloxifene and when is it used in osteoporosis?
- HRT; selective oestrogen receptor modulator
| - used for secondary prevention and treatment of vertebral fractures in post-menopausal osteoporosis
177
When is parathyroid hormone (teriparatide) used in osteoporosis?
- used in the treatment of postmenopauseal osteoporosis
| - increases serum calcium and reduces phosphate levels by negative feedback
178
When is cacitrol (vitd3) used in osteoporosis ?
- used for treatment of postmenopausal osteo
179
When is calcitonin (salmon) used for osteoporosis?
- not recommended; risk of malignancy with long term use
180
Other misc drug used for osteo not previously mentioned?
- denosumab (human monoclonal antibiody
181
How does HRT work ?
Replaces oestrogen with or without progestogen to relieve symptoms of menopause associated with low hormone levels
182
Types of HRT used?
NATURAL OESTROGENS
- estrone
- estradiol
- estriol
SYNTHETIC OESTROGENS
- ethinylestradiol
- mestranol
TIBOLONE ("combined" HRT taken continuoisly)
- oestrogenic, progestogenic and weak androgenic
183
What is vaginal atrophy and how is it treated ?
Vaginal dryness
| - topical oestrogens; vaginal creams, tablets and rings
184
What are vasomotors and how are they treated?
- hot flushes, night sweats
- systemic oestrogens; tablets or patches
- apply patch below waistline away from waist band or breast
- if contraindicated give clonidine: vasodilator antihypertensive but has unacceptable side effects
185
What choice of HRT shoudl women WITHOUT a uterus have?
- Oestrogen ALONE continuously
186
Which HRT should women with a uterus have?
- Combined: oestrogen and progestogen cyclically OR continuously (avoids withdrawal bleeding)
187
When is continuous combined HRT unsuitable?
- Unsuitable in peri-menopause or <12 months after last periods = irregular bleeding
- Rule out endometrial cancer if irregular bleeding continues after stopping continous combined HRT
188
HRT and surgery?
- stop 4-6 weeks before elective surgery: risk of venous thromboembolism; restart HRT when fully mobile
- non-elective surgery = parenteral anticoagulant, heparins and graduated compression stockings
189
HRT and contraception?
- HRT does not provide contraception
- under 50yrs = fertile 2 years after last period (use low oestrogen combined contraceptive; if free from venous/arterial disease risk factors)
- over 50yrs = fertile for 1 year after last period (use barrier protection)
190
HRT side effects?
- cancer (ovarian, breast, cervical, endometrial) *for endometrial add progesterone: reduces additional risk, at least 10/28 day cycle or given continuously
- CHD; if combined HRT started 10 years after menopause
191
Reasons to stop HRT?
- VTE: sudden severe chest pain, sudden breathlessness or cough with blood stained sputum (pulmonary embolism?) Unexplaines swelling or severe pain in calf of one leg (DVT?)
- Stroke: serious neurological effects: *see stroke symtpoms*
- liver dysfunction: jaundice, hepatitis, liver enlargment, severe stomach pain
- blood pressure: above systolic 160mmHg or diastolic 95mmHg
192
What risk factors contra-indicate HRT?
- prolonged immobility after surgery or leg injury (risk of VTE)
- thrombophlebitis (inflammation of blood vessel walls)
- angina, MI
- VTE
- recurrent VTE (unless anticoagulated)
- thrombophilic disorder (tendency to cause blood clots)
- liver disease
- untreated endometrial hyperplasia (endometrial cancer risk)
- undiagnosed vaginal bleeding (endometrial cancer?)
- oestrogen-dependent cancer
- history of breast cancer
193
What is clomifene?
- anti-ostreogen
- stimulates ovulation
USE;
- infertility in women due to oligomenorrhoea
- secondary amenorrhoea e.g. PCOS
- use for 6 cycles only; increased risk of ovarian cancer
194
Clomifene side effects?
- multiple pregnancies
195
What is testosterone used for?
- male sex hormone responsive condition
| - replacement therapy in androgen deficiency
196
Testosterone side effects?
- masculinisation: virilisation in women (exaggerated male characteristics), acne, anxiety, male pattern baldness, sexual development in pre-pubescent males
- do not apply testosterone gels to genital area
197
What is cyproterone used for?
Cyproterone acetate is an anti-androgen used in the treatment of severe hypersexuality and sexual deviation in the male. It inhibits spermatogenesis and produces reversible infertility (but is not a male contraceptive); abnormal sperm forms are produced. Fully informed consent is recommended and an initial spermatogram. As hepatic tumours have been produced in animal studies, careful consideration should be given to the risk/benefit ratio before treatment. Cyproterone acetate is also licensed for use alone in patients with metastatic prostate cancer refractory to gonadorelin analogue therapy, and has been used as an adjunct in prostatic cancer and in the treatment of acne and hirsutism in women.
*HEPATOTOXIC
198
Hyperthyroidism signs and symptoms?
- heat intolerance
- weight loss
- diarrhoea
- tachycardia
- excitability
- tremors
- angina pain
- sweating
- arrtythmias
199
What would lab results show if you have hyperthyroidism?
- High T4 (thyroxine) and high T3 (triiodothyronine)
| - Low TSH (thyroid stimulating hormone)
200
What do thyroid hormones regulate?
- metabolic rate
- heart rate
- digestive function
- muscle control
- brain development
201
What are carbimazole and propylthiouracil used for?
Anti-thyroid drugs interefere with synthesis of thyroid hormones. (used for overactive thyroid)
*carbimazole is drug of choice)
202
Carbimazole side effects?
- bone marrow suppression: (agranulocytosis and neutropenia), report signs of infection, fevere, malaise, mouth ulcers, sore throat
- rashes/itching
203
Propylthiouracil side effects?
- hepatotoxicity: report signs of liver failure; jaundice, nausea and vomiting, abdominal pain, pale stools, malaise, pruritis, dark urine, raised liver enzymes
204
What are the symptoms of thyrotoxicosis ?
(Too much thyroid hormone)
- increased heart rate >140Bpm, increased pulse rate
- tachycardia, arrythmias
- heat intolerance, >41c temperature
- diarrhoea, nausea and vomiting, dehydration
- seizures, delirium, confusion, psychosis
205
What can be used to treat thyrotoxicosis?
- anti-thyroid drugs
- fluids
- hydrocortisone
- radioactive sodium iodide solution
- propranolol for rapid symptom relief
206
Preparations for thyroidectomy?
- iodine 10-14 days before partial thyroidectomy
| - adjunct to anti-thyroid drugs but not long term
207
Hyperthyroidism in pregnancy?
- blocking replacement regimen and radioactive iodine is contra-indicated in pregnancy
- 1st trimester = propylthiouracil
- 2nd trimerster = carbimazole
208
Hypothyroidism symptoms?
- cold intolerance
- weight gain
- constipation
- bradycardia
- lethargy
- muscle cramps
- slow movements
- slow thoughts
- slow thoughts
- depression
- hair thinning
209
What would lab results show with hypothyroidism?
- Low T4 and T3
| - High TSH
210
Levothyroxine/liothyronine MOA?
Synthetic thyroid hormones as replacement therapy
211
Levothyroxine dose and how to take?
- drug of choice for maintenance
- doses: question doses above 200mcg
- how to take: take in the morning at least 30 mins before breakfast, caffeine-containing liquids or other medication
212
Liothyronine use?
- more rapid effect and more potent
- use: ideal in severe hypothyroid emergencies
- switching brands without a UK license may not be bioequivalent
213
Note for levothyroxine and liothyronine initial dose being too high?
- if metabolism increases too rapidly (excessive dosage) it causes hyperthyroidism symptoms
- reduce dose OR withold for 1-2 days and start again at lower dose
