clinical pharmacology - endocrinology

Question 1

mx for hypothyroidism

Answer 1

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

Question 2

mx for hyperthyroidism

Answer 2

carbimazole or proipylthyuracil

If really hyperthyroid start high

40mg of carbimazole once daily

Carbimazole has 1^st 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

Question 3

mx of pituitary failure

Answer 3

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

Question 4

summarise cortisol’s diurnal rhythm

Answer 4

Rise starts at 5am before you wake up

Peak is at 8.32

Circadian rhythm – rise in cortisol

Conserved in all species

Question 5

Mx of addison’s with cortisol and problem with this

Answer 5

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

Question 6

why cant we give cortisol once daily

Answer 6

half life is too short

Question 7

what is plenadren

Answer 7

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

Question 8

why is there mortality in Addison’s

Answer 8

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

Question 9

what is fludrocortisone

Answer 9

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

Question 10

prednisolone for the mx of addison’s

Answer 10

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

Question 11

mx for congenital adrenal hyperplasia

Answer 11

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

Question 12

SE caused by excessive pred ie 5mg

Answer 12

weight gain

osteoporosis

adrenal suppression

Question 13

what are the types of insulin

Answer 13

rapid acting analgue

short acting (human)

intermediate acting (human)

long acting analogue

biphasic mixtures (human, analogue)

Question 14

what is the problem with giving natural insulin

Answer 14

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

Question 15

short acting insulin analgues

Answer 15

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

Question 16

long acting insulin analogues

Answer 16

different alterations in molecule to get a platau over time

need background release of insulin to prevent ketoproduction

improves QOL - less chance of hypo

Question 17

insulatard

Answer 17

old drug - not now

normal insulin mixed with zinc

problem is after the peak it wears off

Question 18

insulin glargine (Lantus)

Answer 18

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)

Question 19

insulin determir (levemir)

Answer 19

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

Question 20

rapid acting and sort acting insulin profiles

Answer 20

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

Question 21

insulin profiles of intermediate (isophane) and long-acting analogues

Answer 21

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

Question 22

biphasic insulins

Answer 22

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

Question 23

normal insulin and glucose profile

Answer 23

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

Question 24

basal-bolus regimens

Answer 24

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

Question 25

twice daily regimen for insulin

Answer 25

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

Question 26

once daily insulin regimen

Answer 26

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

Question 27

potential errors in insulin prescription

Answer 27

omission

insulin name/type

admin tim e

insulin dose

transfer of info - transcription, discharge

use of u or iu instead of units

wrong syringe

Question 28

how do you avoid insulin omission

Answer 28

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

Question 29

insulin names on prescription

Answer 29

always write the names in full

use brand names

Humalog Mix 25

Humulin 1

NovoMix 30

Question 30

how do you write units on prescriptions

Answer 30

never abbreviate

leave a space beyween dose and units ie 22 units

Question 31

insulin syringe

Answer 31

must be made to measure and administer insulin, unless use pen

if staff adminster the insulin - must use safety insulin syringe

Question 32

insulin pen and cartridge

Answer 32

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

Question 33

insulin strength

Answer 33

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

Question 34

biosimilar insulin

Answer 34

• 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

Question 35

what are the disadvantages of insulin

Answer 35

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

Question 36

why do you gain weight with insulin

Answer 36

if glycosuria stops - keep calories

increased appetite

imporved well being

poor control enables weight loss

Question 37

what is hypoglycaemia

Answer 37

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

Question 38

what is normal glucose

Answer 38

3.5-5.5mM