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Block 15 > Cortcoid Therapy > Flashcards

Cortcoid Therapy Flashcards

1
Q

Describe the structure of Corticoids?

A

Cyclopentanoperhydrophenanthrene (3 cyclohexane rings and a singe cyclopentane ring)
There are different side groups leading to different functions- cortisol (metabolic effect), aldosterone (Na+ reabsorption), testosterone (development)

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2
Q

What is a hormone?

A

Chemical substance produced in the body that controls and regulates the activity of certain cels or organs-amino acids/protein based

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3
Q

What are steroids?

A

Any large group of fat soluble organic compounds such as sterols, bile acids, sex hormones which have specific physiological action-fat based

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4
Q

What are mineralocorticoids?

A

Corticosteroids involved with maintaining salt balance in the body such as aldosterone

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5
Q

What are glucocorticoids?

A

Any large group of corticosteroids (hydrocortisone) which are involved in the metabolism of carbohydrates, proteins ad fats and have anti-inflammatory activity

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6
Q

What are catecholamines?

A

Any of a class of aromatic amines which includes a number f neurotransmitters such as adrenaline and dopamine

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7
Q

What is the function of mineralocorticoids

A

Control of Na+/Cl- and K+
Adrenoortical hormones essential for maintenance of adequate fluid volume in extracellular and intravascular fluid compartments, Normal CO, BP
Target action at kidneys
Insufficiency can cause fatal shock due to low CO

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8
Q

What are the functions of cortisol

A

Increase catabolism of protein in bone, skin, muscle and connective tissue
Decrease cellular utilisation of glucose
Increase output of glucose from liver

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9
Q

What are androgens

A

Hormones
Influence growth and development of males
Predominant androgen is testosterone
Also present in women but if levels are too high can cause male characteristics

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10
Q
  1. Describe Corticoid production

2. Give an example of issue with an enzyme involved in this process?

A
  1. Produced from cholesterol. Driven by enzymes
  2. Defect with cholesterol desmolase affects aldosterone, cortisol and testosterone production, whereas 18-oxidase defect only affects aldosterone production
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11
Q

Describe deficiency in 17 alpha hydroxyase that causes congenital adrenal hyperplasia

A

Substrates=pregnenolone, progesterone which produce 17-OH pregnenolone or 17-OH
Decreased androgen, increased mineralocorticoid
Rare

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12
Q

Describe deficiency of 21-hydroxylase and 11 beta hydroxyase

A

Substrate=progesterone, 17-hydroxyase progesteone
Products=deoxycorticosterone, 11 deoxycortisol
Androgens increase
Mineralocorticoids decrease
>90% CAH

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13
Q

Describe 11 beta insufficiency?

A

Substrate=doxycorticosterone
Product=cortisterone
Increased androgen and mineralocorticoid
5% CAH

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14
Q

How is glucocorticoid production controlled?

A

Hypothalamus detects low blood concentration of glucocorticoids -> synthesis/secretion of CRH -> anterior pituitary synthesise and secretes ACTH -> adrenal gland synthesise and secrete cortisol -> negative feedback on hypothalamus

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15
Q

Describe transactivation of glucocorticoids

A

Translocation into nucleus -> binds to +ve GRE -> transcription -> express IL-10, annexin Al, tyrosine aminotransferase, serine dehydrogenase

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16
Q

Describe transrepression of glucocorticids in cells

A

Translocation into nucleus -> competition for nuclear coactivators/ direct or indirect interaction with TF ->transcription ->suppressed synthesis of proinflammatory proteins (IL-1,2,6,8, VEGF, COX 2, prostagalndins, TNF, IFN-y

17
Q

What are the clinical uses of glucocorticoids?

A

Adrenal failure (Addison’s)
Localised application -eczema, asthma, arthritis
Rheumatoid arthritis= dexamethasone
Immune suppression for organ transplant=prednisolone
Cancer treatment

18
Q

What are the adverse effects of synthetic steroids?

A

Synthetic glucocorticoids cause -ve feedback on hypothalamus -> CRF and ACTH production -> reduce glucocorticoid production by adrenal cortex -> dependent -> suppression of endogenous glucocorticoids cause shrinkage of adrenal gland

19
Q

Side effects of inhaled glucocorticoids ?

A

Local immunosuppressant can evoke opportunistic Candida albicans (oral thrush)
Local effects on vocal cords result in dysphonia (hoarseness)
More localised effects

20
Q

What are the side effects of oral glucocorticoids?

A

Growth stunting (Cushing’s syndrome)

21
Q

How can Cushing’s syndrome induce osteoporosis

A

Increase osteoclast activity and decreased osteoblasts leading to bone breakdown

22
Q

How can Cushing’s syndrome cause muscle wasting

A

Protein catabolism induced by steroids

23
Q

How can Cushing’s syndrome reduce wound healing

A

Reduced capability of fibroblast to lay collagen

24
Q

What cardiac remodelling can be caused by Cushing’s syndrome?

A

LV hypertrophy

Cardiac arrhythmias due to changes in K+levels

25
Q

What are the symptoms of Cushing’s syndrome ?

A 
CNS irritability
Emotional disturbances 
Hyper tension
Cardiac hypertrophy 
Hyperplasia, tumour
Purple striae 
Skin ulcers
Amenorrhea 
Erectile disfunction
Muscle wasting 
Osteoporosis 
Obesity 
Red and round face
26
Q

How can adrenal insufficiency by prevented?

A

Don’t suddenly discontinue glucocorticoid therapy as can’t produce own steroids due to adrenal gland atrophy
Remove over period of time

27
Q

How is modulation of the glucocorticoid pathway medically beneficial?

A

Block cortisol production using metyrapone triggering ACTH production. Then detect 17 alpha hydroxypregnenolone metabolite in blood and measure effective release of ACTH (determine if patient has inability to produce ACTH)

28
Q

What is the mechanism of mineralocorticoid action

A

Aldosterone accesses mineralocorticoid receptor within cell
Accesses nucleus driving gene transcription
New Na+ channels formed
More Na+ reabsorbed
Amiloride-blocks Na+ channel
Spironolactone- blocks activity of mineralocorticoid receptor and hence blocks aldosterone activity

29
Q

What are the issues with mineralocorticoid excess?

A 
Primary hyperaldosteronism (Conns) 
Leads to hypertension ad low blood potassium due to adenoma or adrenal cancer or hyperplasia
30
Q

What needs to be taken into consideration when treating patients?

A

Steroids can have glucocorticoid and mineralocorticoid activity such as hydrocortisone that affects both where as prednisolone has a preference to glucocorticoid activity
Activity does not link to potency

Block 15 (11 decks)

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