Steroids Flashcards
what are the main adrenal issues
• Destruction of adrenal tissue
○ Addison’s Disease
• Excess adrenal action
○ Cushing’s Disease
• Therapeutic corticosteroids
○ Suppression of adrenal action
○ Steroid adverse effects
what are the different areas of the adrenal gland and what do they produce
• Zona glomerulosa
○ Aldosterone
§ (renin / angiotensin)
• Zona fasicularis ○ Cortisol § Hypothalamus / pituitary § Controlled by negative feedback loop system § Released by pituitary production …
• Zona reticularis
○ Adrenal androgens
the zonas are found in the cortex of the adrenal gland histologically
the zona reticularis is the closest to the medulla
what are the 2 main parts to the adrenal gland
outer cortex
inner medulla
explain adrenal regulation
hypothalamus causes CRH to have positive affect on the pituitary gland (i think - picture isn’t clear lol) and this produces ACTH which has a positive effect on the adrenal cortex which then produces DHEA, aldosterone and cortisol which then triggers the negative feedback loop which acts on the hypothalamus and the pituitary gland
explain adrenal hormones
• Largely the same compound but tweaked differently - a small change can alter the shape
○ Synthetically very similar but quite different
○ They all tend to come broadly from cholesterol (same precursors)
• Some people are lacking certain metabolic enzymes
○ Eg no progesterone then cannot make cortisol but can make more of another
what is the function of aldosterone
Salt and water regulation
○ Enhances sodium (Na+) reabsorption and potassium (K+) loss
○ Renin-angiotensin system
○ Indirect effect on blood pressure
§ Part of blood pressure control system as Angiotensin 2 increases blood pressure
○ Released from adrenal gland
End product of renin-angiotensin system
how is the action of aldosterone inhibited
inhibited / reduced in effect by:
○ ACE inhibitors § Angiotensin converting enzyme inhibitors § Side effects □ Cough □ Angio-oedema □ Oral lichenoid drug reactions
○ AT2 blockers
§ Angiotensin 2 reduced availability to work
§ Block angiotensin receptor
□ Sits on receptor and then nothing can get in to make the blood vessel constrict
□ Tends to be very effective against blood pressure
what is angio-oedema
- Sudden onset tissue fluid
- Complement system firing off gives the features you expect with inflammation
○ This system can fire off for no reason
○ Caused by the complement cascade instead of being caused by bacteria or tissue damage - There is nothing harmful in the tissues but they react as if they are (inflammation)
- Causes fluid and blood changes
- Lasts an hour or so
what is a lichenoid reaction
- ACE inhibitor has caused a tissue reaction
- Yellow bits are lost epithelium
- Common for dentist to ask the patient’s GP to change the patient’s medication from a ACE inhibitor to AT2 blocker - This allows you to control blood pressure without this side effect
name a drug acting on angiotensin
Losart 50
= Losartan Potassium INN 50mg
what is cortisol
• natural Glucocorticoid
• “physiological” steroid effects
• Doesn’t work through the surface receptor
○ The receptor will take the steroid into the nucleus where it changes the protein transcription
○ Steroids work within the cell
• Works inside the cell nucleus
how is cortisol released in the body
• Circadian release - nocturnal peak
○ Release more at night time than during the day
§ This is why you grow more when you are asleep than when you are awake
○ If you want to measure a hormone that naturally has a variation then:
§ Know level at time of day
Or
§ Take samples all at the same time of day to have a way of measuring
□ Difficult
Cortisol is present in your blood at normal levels
what are the physiological steroid effects of cortisol
○ Antagonist to insulin
§ Glucogenesis, fat and protein breakdown
§ Makes it harder for insulin to do what insulin does □ Cortisol makes it difficult for glucose to move into cells
○ Lowers the immune reactivity
§ Makes system less excitable than it would otherwise be (duller than it should be)
○ Raises blood pressure
○ Inhibits bone synthesis
§ Makes bone less enthusiastically - Cortisol makes bone production gradually reduce
explain cortisol control
stressors act on the hypothalamus to release CRH
this has a positive impact on the pituitary gland and this releases ACTH
ACTH has a positive effect on the adrenal gland
which then produces cortisol which then inhibits CRH
name therapeutic steroids
- Hydrocortisone (cortisol equivalent = 1)
- Prednisolone (4)
- Triamcinolone (5)
- Dexamethasone (25)
- Betamethasone (30)
explain prednisolone in terms of hydrocortisone and the problems that arises with therapeutic steroids
- 5mg prednisolone = 20 mg hydrocortisone
○ 4 times more potent than cortisol
○ Switch off negative feedback to make any more
○ Problems:
§ Swap natural cortisol and its effect on hypothalamus
§ Switches off release of ACTH □ Appropriate if you have enough and you don’t want anymore
§ However, when you stop taking the tablets then the adrenal system needs to switch back on again
So if you take tablets for a while then the adrenal gland isn’t used to it for a while so it shrivels up a little and when you stop it takes a bit longer to get the system back into action again
explain adrenal suppression
dexamethasone suppression of ACTH release
DXM mimics effect of cortisol so reduce the CRH release which acts on the anterior pituitary gland
this means ACTH release is reduced acting on the adrenal cortex
as a result cortisol release is reduced as well
what are the positive effects of therapeutic steroids
• Enhanced glucocorticoid effect
○ Not just doing what cortisol will do but doing much more than you would expect
• Enhanced mineralocorticoid effect
○ Salt and water retention
○ Hypertension
○ Mimics aldosterone but is not the same shape
what are the adverse effects of therapeutic steroids
○ Hypertension
○ Type 2 diabetes
§ Antagonist effect of insulin □ Raise insulin secretion to keep blood glucose normal
§ More insulin needed for blood sugar to be constant the the quicker you get type 2
○ Osteoporosis
○ Increased infection risk
○ Peptic ulceration
§ Stop prostaglandin secretions and this changes mucous secretion layer in the stomach
§ Steroid tablet - risk for months / years, some changes in weeks but will go back to normal □ Amount given is important
○ Thinning of the skin
○ Easy bruising
○ Cataracts and glaucoma
○ Hyperlipidaemia (atherosclerosis)
○ Increased cancer risk
○ Psychiatric disturbance
explain adrenal dysfunction in terms of hyperfunction
Hyperfunction - too much
○ Glucocorticoids - Cushing’s Syndrome = High level of cortisol in blood
§ Adrenal tumour - primary
§ Pituitary tumour - secondary
□ Producing ACTH = makes lots of cortisol
○ Aldosterone - Conn’s Syndrome
§ Adrenal tumour - Lots of aldosterone
explain adrenal dysfunction in terms of hypofunction
Hypofunction - too little
○ Addison’s disease - primary
§ Not enough function
§ Gland itself is damage or destroyed and cannot produce cortisol
○ Pituitary failure - secondary
§ Cannot ask pituitary to make it
what is cushings syndrome
Cushings Syndrome [F 4:1 M]
○ Cushing’s disease
§ Pituitary tumour (ACTH)
□ Secondary to this is high levels of cortisol
§ 70% spontaneous Cushing’s patients
○ Adrenal adenoma or hyperplasia
○ Ectopic ACTH production
§ Some lung tumours
□ Produce as a by product of a hormone similar to ACTH
□ Causes a lot of cortisol to be produced
what is conn’s syndrome
- Adrenal tumour
* Adrenal hyperplasia
what are the signs of cushing’s syndrome
○ Centripetal obesity § Moon face § Buffalo hump ○ Hypertension ○ Thin skin and purpura ○ Muscle weakness ○ Osteoporotic changes and fractures
what are the symptoms of cushing’s syndrome
○ ‘diabetes mellitus’ features
§ Thirsty
§ Peeing a lot
§ Tired
○ Poor resistance to infections
§ Fungus infection □ Candida more likely (cannot fight as well)
○ Osteoporotic changes
§ Back pain
§ Bone fractures
§ Get this early in life
○ Psychiatric disorders § Depression § Emotional lability § Psychosis § Affects how the brain works □ Get agitated □ Can't sleep
○ Hirsutism
○ Skin and mucosal pigmentation
§ Happens due to ACTH
○ Amenorrhoea, impotence & infertility
§ Related to the fact that adrenal antigens are similar chemically to the glucocorticoids
§ Starts interfering with adrenal antigens
what is abdominal striae
thinning of the skin
skin stretches, leaves stretch marks
bruising and bleeding under the surface
what does a buffalo hump change (cushing’s disease)
how fat is distributed / stored
in the protein sequence containing ACTH, what other segment is found within the ACTH segment and what effect does it have on the body
melanocyte protein segment is found within the ACTH segment
so if the patient has high levels of ACTH then they will start to develop pigmentation of the skin and mucosa
