clinical pharmacology - endocrinology Flashcards
mx for hypothyroidism
Levothyroxine 50-100micrograms once daily
Check TFT after 6wk – if high then increase dose to 100 or reduce to 75 etc
Once you’ve got the dose right its stable
Thyroxine absorption affected by breakfast etc
mx for hyperthyroidism
carbimazole or proipylthyuracil
If really hyperthyroid start high
40mg of carbimazole once daily
Carbimazole has 1st pass metabolism. In hyperthyroidism highly overactive liver – so B blocker and carbimazole is cleared faster
B blocker will stop the palpitations but wont stop the thyroid problem
Propranolol 20mg 3 times daily (40mg if v sx)
Don’t gtive B blocker if they have asthma – cause acute asthmatic crisis and death
PTU – 200-400mg daily
mx of pituitary failure
Hydrocortisone or pred (pred better because once daily) – hydrocortisone 10mg morning 5mg noon, 5mg at 4pm
Pred – 4mg once daily
Testosterone – injection every 3mo nebido 1g by IM injection. Or less long acting like sustanon monthly. or gel everyday
Levothyroxine 50-100mg
In females – oestrogen ie OCP or HRT. HRT better because lower dose as possible
summarise cortisol’s diurnal rhythm
Rise starts at 5am before you wake up
Peak is at 8.32
Circadian rhythm – rise in cortisol
Conserved in all species
Mx of addison’s with cortisol and problem with this
cleared rapidly - so give a second dose
So get 3 peaks rather than smooth curves
bad because cells should be kept in synch by cortisol smooth curve
All cells have clock genes. Receptors for glucocorticoids change sensitivity depending on clock – kept in synch by ACTH release when light in early hours.
When under stress – desynch the clock
More sensitive to cortisone in afternoon than morning - because acetylation of GR receptors get less towards night
night shift mean stress at night when more sensitive
why cant we give cortisol once daily
half life is too short
what is plenadren
slow release cortisol
got 2 coats
means you have to keep absorobing it for several hours - if GI infection you might not absorb it all
Area under curve – ie total dose exposure = dose a lot less than with 3x a day hydrocortisone = less SE
Plenadren = lost weight because area under curve less, and miss the harmful peaks
hydrocortisone suppresses the immune system, plenadren improves it when people switch to that
SE - vertigo, headache, diarrhoea (has osmotic effect), fatigue
expensive
why is there mortality in Addison’s
don’t have crisis but generally over replaced.
So die of heart attack and stroke.
Either because too much steroid, or uncoupled from normal profile
what is fludrocortisone
fluorine added to aldosterone
not a normal steroid – longer to biodegrade – longer half life of 3.5 hrs – once daily admin
Fludrocortisone 50-100mcg once daily – adjust dose against the BP. Also check K – if too high fludrocortisone = low K
prednisolone for the mx of addison’s
longer half life nad more potent than cortisol - once daily dose
rapid absorption - so no problem if GI disease
profile similar to circaidian levels of cortisol so good for the immune system
replacement dose is 3-4mg once daily
if give higher doses - die earlier and have SE
pred more potent than people think 20mg of hydrocortisone = 3mg of pred
mx for congenital adrenal hyperplasia
have low cortisol and high testosterone that is surppresed with steroid
3x hydrocortisol doesn’t reproduce curve.
Single morning dose of pred = growth of children better
SE caused by excessive pred ie 5mg
weight gain
osteoporosis
adrenal suppression
what are the types of insulin
rapid acting analgue
short acting (human)
intermediate acting (human)
long acting analogue
biphasic mixtures (human, analogue)
what is the problem with giving natural insulin
when soluble natural insulin is given SC - forms hexamer under the skin because A and B chain have sticky ends
= delayed release
have to inject 30mins before meals
short acting insulin analgues
rapid acting
inject and eat straight away - dont contain C peptide
lispro - switch of B28 (pro)/B29 (Lys) = humalog
aspart = novorapid - (pro 28) to asp (28)
profile mimics normal insulin following a meal
twice the cost of soluble insulin - worth it to prevent hypos
long acting insulin analogues
different alterations in molecule to get a platau over time
need background release of insulin to prevent ketoproduction
improves QOL - less chance of hypo
insulatard
old drug - not now
normal insulin mixed with zinc
problem is after the peak it wears off
insulin glargine (Lantus)
long acting insulin, give least variation in plasma insulin levels for 24hr after injection, take once daily - modification of A chain
Things that make it longer – arginine in B31 and B32. A21 (Asn to Gly)
insulin determir (levemir)
Long chain fatty acid to B29 – made it stick to other things for ages so last for ages
delayed onset of 7hr
can be used as part of basal bolus
rapid acting and sort acting insulin profiles
Rapid acting – have meal and insulin at the same time – risk of hypo lower because wears of quick
Short acting with no modification – plain insulin quick acting – but not as quick as analgues because sticky at end – need to take 30min before
In short acting – peak late – so insulin keeps working so might have hypo unless eat more than you should
In rapid – good control and less risk of hypo
So it is worth paying rapid
insulin profiles of intermediate (isophane) and long-acting analogues
Old ones – Humulin I etc – the Zn ones – provide background insulin – can use in T2 if not good at oral control
Zn insulin wears off
Glargine and detemir – have basal insulin - ones you want
biphasic insulins
M3 – mixed insulin with 30% act rapid and long acting
One injection of M3 – short acting works with breakfast. Long acting insulatard works for lunch
Evening have another dose of the same – background to stop ketone production overnight
Analogue – mixed and novo – same principle as biphasic
normal insulin and glucose profile
Normal glucose only 6 for a very short time – also have huge rise of insulin – all cells respond to insulin
Glucose falls really quickly
Normal insulin – low but not 0 – breakfast stimulates pancreas to release insulin
basal-bolus regimens
One dose at night of basal background – detemir better later eg 10 at night
Can have whatever dose you want
But have to have 4 injections a day - boluses and long acting (long acting analogue must be given at the same time everyday)
adjust dose according to capillary blood glucose, exercise and quantity expected to be eaten
twice daily regimen for insulin
most common regimen in UK
biphasic insulin
if have regular meal times and diet
short acting component - controls wise in glycaemic level after breakfast and evening meal
longer acting - maintain glycaemic control from lunch until evening, and from late evening until morning
snacks needed between meals and before bed to prevent hypoglycaemia
once daily insulin regimen
only used in T2dm
use intermediate or long atcing insulin:
- insulinatard, humulin 1
- lantus or levemir (NICE criteria)
given same time each day
used in combination with oral anti-dm med - SFU, gliptins
adjusted depending in pre breakfast blood glucose level
potential errors in insulin prescription
omission
insulin name/type
admin tim e
insulin dose
transfer of info - transcription, discharge
use of u or iu instead of units
wrong syringe
how do you avoid insulin omission
know who is on insulin
prescribe on main chart as ‘insulin - see diabetic chart’, endorse supplementary chart section
plan ahead - ensure breakfast dose for next day is prescribed, if stable prescribe weekend dose in advance
ensure sufficient insulin in pen/vial for next 2 doses
if insulin due after hypo - treat the hypo, then give insulin after dose review with meal - otherwise become ketotic
insulin names on prescription
always write the names in full
use brand names
Humalog Mix 25
Humulin 1
NovoMix 30
how do you write units on prescriptions
never abbreviate
leave a space beyween dose and units ie 22 units
insulin syringe
must be made to measure and administer insulin, unless use pen
if staff adminster the insulin - must use safety insulin syringe
insulin pen and cartridge
one pen for one patient
store in pt’s POD locker - stable at room temp for 4wks, discard all insulin 4wks after opening
dont withdraw insulin form a pen or cartridge with a syringe
insulin strength
most insulin 100 units in 1ml
there are higher doses - in type 2 because so obese – otherwise whole vial goes with one dose:
- tresiba 200 units in 1ml - Flextouch pen
- Humalog 200 units in 1ml - Kiwipen
- Toujeo 300 units in 1ml - Solostar pen
biosimilar insulin
- abasaglar (insulin glargine 100 units in 1ml)
- toujeo (insulin glargine 300 units in 1ml)
not directly interchangable with Lantus insulin - dose reduction needed if switch to Lantus
what are the disadvantages of insulin
if drive HGV, cant work = Needs 3mo of data that prove that you never have a hypo- really difficult to get liscence
exenatide exempt
If good control – you have a lot of hypos
The more hypo = less chance of renal failure because good control
Weight gain because appetite improves = increased insulin = huge doses needed
why do you gain weight with insulin
if glycosuria stops - keep calories
increased appetite
imporved well being
poor control enables weight loss
what is hypoglycaemia
sympathetic activation begins at 2.5-3.5mM - warning
neuroglycopenia <2mM - confused
Definition of hypoglycaemia <4.0mM in pt with dm. if no dm it is less than 2.2
Don’t want normal glucose of 3.5 because will keep falling because on insulin
If inject insulin into healthy person and don’t let them eat – when 3.2 towards 2.5 = sympathetic activation (adrenaline) – palpitations and sweating – but still conscious and alert - just hungry and will make less insulin
In dm – already injected insulin so glucose will continue to fall
what is normal glucose
3.5-5.5mM
