Pharmacology of Steroids Flashcards
(48 cards)
1
Q
What are the two types of steroids?
A
- Non-hormonal
- Hormonal steroids
2
Q
What are non-hormonal steroids?
A
- Cholesterol: important in atherogenesis (CV disease)
3
Q
What are corticosteroids?
A
- Steroid hormones from adrenal cortex
4
Q
What are the two types of corticosteroids?
A
- Glucocorticoids
- Mineralocorticoids
5
Q
What is the function of glucocorticoids?
A
- Metabolic and anti-inflammatory functions like asthma
- E.g. cortisol
6
Q
What is the function of mineralocorticoids?
A
- Renal regulation of electrolytes and ater
- E.g Aldosterone
7
Q
What are the endocrine glands?
A
- Pituitary glands
- Thyroid gland
- Thymus
- Adrenal glans
- Pancreas
- Ovary
- Testis
8
Q
What is the function of the pituitary gland?
A
- Regulation of vital body functions, e.g. temperature
9
Q
What is the function of thyroid gland?
A
- Produces thyroid hormones that regulate body’s metabolism
10
Q
What is the function of thymus?
A
- Development of T-lymphocytes
11
Q
What is the function of adrenal gland?
A
- On top of kidneys
- Produce adrenaline
12
Q
What is the function of pancreas?
A
- Insulin secretion
- Maintenance of blood sugar
13
Q
What are the 4 zones of hormone synthesis in the adrenal glands and what do they synthesise?
A
- Zona glomerulosa- mineralcoricoids
- Zona fasciculata- glucocorticoids
- Zona reticularis- androgens
- Adrenal medulla- catecholamines (Adrenaline not steroids)
14
Q
What is cholesterol?
A
- Precursor of all glucocorticoids, mineralocorticoids and sex hormones
15
Q
What is the function of cholesterol?
A
- Vital physiological role in regulating fluidity and function of phospholipid bilayer membranes in all cells
- Makes membrane less deformable and less water-permeable
- Means no cell wall is necessary in animals
16
Q
How is cholesterol derived?
A
- From diet
- Or synthesised in hepatocytes by hydroxy-methyl-glutaryl (HMG) CoA reductase
17
Q
How is cholesterol transported between liver and tissues?
A
- Lipoproteins
18
Q
What are lipoproteins?
A
- Not cells
- Inside- triglycerides (fatty inside)
- Single phospholipid as the inside is lipid-friendly
19
Q
What is the name for lipoproteins without lipids?
A
- Apolipoprotein
20
Q
What are LDLs?
A
- Low density lipoproteins
21
Q
What is the danger in excess LDL?
A
- Excess LDL deposits cholesterol in fatty plaques (Atheroma) leading to CAD
- Clogging underneath blood vessels
22
Q
How can you prevent the build up of plaques in vessels?
A
- Statins
- Drugs that inhibit enzyme making cholesterol
23
Q
What are the effects of corticosteroids?
A
- Survival hormones
- Prepares body for starvation/dehydration
24
Q
How do corticosteroids prepare the body for starvation?
A
- Mobilising energy storage (first glucose, then fat, then protein)
- Glycogen, fat stores, protein from bones/muscles
- Inflammatory response is also suppressed
25
How do corticosteroids conserve water?
- Reduce urine production
- Retain sodium = retain water
- Mineralocorticoid action
26
What are the main actions of glucocorticosteroids?
- Metabolic- mobilising nutrients (Catabolism)- although this is unwanted
- Anti-inflammatory
27
Give examples of synthetic GCS drugs
- Developed to supplement endogenous cortisol in combatting chronic inflammatory disease
- Prenisolone and dexamethasone for systemic GCS, like arthritis
- Betamethasone- topical GCS, e.g. eczema
- Fluticasone- inhaled GCS, e.g. asthma
28
What is the HPA axis?
Stress shock --> hypothalamus --> anterior pituitary --> ACTH (through blood) --> adrenal cortex -->
29
What is ACTH?
adrenocorticotrophic hormone
30
What are the catabolic effects of the HPA axis?
- Preparation for a period of stavation
- Hyperglycaemia
- Mobilisation of lipids
- Breakdown of proteins
31
What are the anti-inflammatory effects?
- Decreased leucocyte activity
| - Decreased inflammatory mediators
32
Describe negative feedback in the HPA axis
- Increased cortisol leads to ACTH --> hypothalamus to reduce
- Increased cortisol--> x pituitary gland --> x hypothalamus
33
Describe the use of synthetic drugs in the HPA axis
- Exogenous GCS- mimic cortisol
- Anti-inflammatory mediators
- Feedback pituitary/hypothalamus
- Atrophy of hypothalamus
- Drugs cannot be stopped abruptly if taken for a long period of time
- Long periods of dosage required
- Slow withdrawal required to allow HPA axis to recover
- Reduce systemic metabolic effect
34
Outline the mechanisms of action for GCS
- Binds to cytoplasmic receptors and modulates transcription of hundreds of inflammatory genes
- GCS blocks transcription of pro-inflammatory genes and induces anti-inflammatory genes
35
How does GCS block the transcription of pro-inflammatory genes?
- Cycloxygenase-2 (source of prostaglandin)
- Adhesion molecules (ICAM)
- Complement components, immunoglobulins (IgG, IgE)
- Cytokines (TNF-α, GM-CSF, interleukins)
36
How does GCS induce anti-inflammatory genes?
- Ribonucleases (break down inflammatory mRNAs)
| - Interleukin-10, annexin-1
37
What are the consequences of GCS mechanism of action?
- Effects are slow in onset
- ->Reducing oedema- 2-6 hours
- ->Suppressing cytokines 6-18 hours
- -> Inhibiting leukocytes
- Effects are slow in offset- might take days
- More broad spectrum
38
What are some clinical uses for glucocorticoid drugs?
- Anti-inflammatory/ immunosuppressant therapy
| - Asthma, allergy, rheumatoid arthritis, inflammatory bowel disease, after organ transplant, cerebral oedema
39
What are the consequences of overuse of synthetic glucocorticoid?
- Excessive production of cortisol
- Cushing's disease
- Inhibited by metrapone
40
What are the signs of Cushing's disease?
- Euphoria
- 'Buffalo' hump
- Hypertension
- Thinning of skin
- Thin arms and legs
Cataracts
- Moon face with red (plethoric) cheeks
- Increased abdominal fat
- Easy bruising
- Poor wound healing
41
How do exogenous GCS suppress HPA axis?
- CNS stress, shock and pain
- Hypothalamus
- Corticotrophin releasing factor
- Anterior pituitary
- ACTH to adrenal glands
- Release of cortisol to reduce hypothalamus function
42
What type of therapy reduces hypothalamus function?
- Prednisolone therapy
43
What is the main endogenous mineralocorticoid?
- Aldosterone
44
Where is aldosterone released from and what triggers it?
- Release from zone glomerulosa
| - Triggered by low plasma sodium and indirectly by renin-angiotensin system
45
Where do mineralocorticoids act?
- Mineralocorticoid receptor
- Present mainly in cytoplasm of kidney tubule epithelial cells
- Fluid can go to bladder or reabsorption
46
What does aldosterone detect and do?
- Detects low volume
- Increases gene transcription of epithelial Na+ channels (ENac)
- Increases Na+ an water reabsorption across luminal membrane into blood
- K+ and H+ secreted in urine
47
Give an example of an MR agonist and its use
- Fludrocortisone
| - Used as replacement therapy in adrenal insufficiency (Addison's disease)
48
Give an example of a competitive MR antagonist
- Spironolactone
- Diuretic and K+ sparing actions
- Used with other diuretics to reduce blood volume (e.g. in hypertension) while preventing hypokalaemia
- Used in hyperaldosternoism (Conn's syndrome)
