Flashcards in CPTP 3.15 Drugs used in Inflammation Allergy and Pain 3 Deck (39)
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1
Describe briefly the mechanism of action of corticosteroids
• Binds to cytoplasm receptors
• Complex dimerises with another
• This dimer binds to steroid responsive elements in DNA
• Protein synthesis is either induced or inhibited
2
Why can cortisol not be given as a drug?
What is given instead?
It would be broken down too rapidly
Hydrocortisone is given (cortisol prodrug)
3
What are the effects or glucocorticoids on:
• Carbohydrate metabolism
• Protein metabolism
• Stress
• Endocrine hormones
Carbohydarates:
• Increased gluconeogenesis
• Decreased glucose uptake
Proteins:
• Decreased synthesis and increased catabolism
Stress:
• Raises glucose to provide energy needed to combat stress
Endocrine hormones:
• Feedback inhibition:
> Glucocorticoids
> TSH
4
What are the pharmacologically useful effects of endogenous glucocorticoids?
• Anti-inflammatory action; inhibits both early and late stage reactions
• Decrease immune cells in plasma
5
Describe the early and late stage inflammatory responses (bi-phasic)
Early stage
• Redness
• Pain
• Swelling
Late stage
• Proliferative reactions
• Wound repair
6
How do glucocorticoids bring about their anti-inflammatory effects?
• Upregulates anti-inflammatory proteins
• Downregulates pro-inflammatory proteins
• Inhibits the degranulation of mast cells (so histamine not released)
• Induces annexin lipocortin 1
• Inhibits COX EXPRESSION (thus inhibiting eicosanoids)
This ultimately acts to:
• Reduce vasodilation
• Decreased clonal expansion of T and B cells
ACUTELY:
• Decrease leukocytes in acute inflammation
CHRONICALLY:
• Decrease mononuclear cells
• Reduce fibrosis and blood vessel proliferation
7
Which anti-inflammatory proteins are upregulated by glucocorticoids?
• IκB
Cytokines:
• IL-4
• IL-10
• Transforming growth factor (TGF) Beta
8
What does IκB do?
Inhibits NFκB
9
Which pro-inflammatory proteins are downregulated by glucocorticoids?
• TNF𝛼
• IL-1
• IL-2
• IL-6
• Nitric oxide synthase
• COX-2
10
Which pro-inflammatory protein is the one which stimulates T-cell proliferation?
IL-2
11
What does annexin lipocortin 1 do?
• Inhibits various leukocyte functions (the inflammatory events)
• Inhibits phospholipase A2
12
What effect does glucocorticoids have on prostaglandins?
IMG 10
(By virtue of:
• Upregulates anti-inflammatory proteins
• Downregulates pro-inflammatory proteins
• Induces annexin lipocortin 1
• Inhibits COX EXPRESSION)
13
What is the most rapid effect of glucocorticoids?
The prevention of degranulation of mast cells
14
What is the main adverse effect of long-term glucocorticoids and what is the mechanism for this?
Osteoporosis
• Blocks the induction of the osteocalcin gene, which is a calcium homeostasis gene responsible for building up bones
• Modifies transcription of collagenase gene
15
What is the objective with corticosteroid drugs in terms of targets?
Affect the glucocorticoid system but not the mineralocorticoid system
16
Name the corticosteroid drugs, stating which are short acting, intermediate acting and long acting
SHORT-ACTING
• Hydrocortisone
• Fludrocortisone
INTERMEDIATE-ACTING
• Prednisolone
• Methylprednisolone
LONG-ACTING
• Betamethasone
17
How much more potent are fludrocortisone and betamethasone in comparison to hydrocortisone?
Fludracortisone: 10x
Betamethasone: 25x
18
Which of the corticosteroid drugs is completely glucocorticoid-specific?
Betamethasone
19
Which diseases may require corticosteroid replacement therapy?
Addison's disease
• A disease in which the adrenal glands do not produce enough corticosteroids
Autoimmune conditions of the adrenal gland
Tumours which suppress corticosteroid release
• Pituitary tumours
• Adrenal tumouts
20
Why are topically applied or inhaled corticosteroids preferable?
To minimise adverse effects
21
In which cases can corticosteroids be used for cancer treatment?
Can be used as chemotherapy for cancers involving over-activation of the immune system
• Leukaemia
• Hodgkin's lymphoma
22
How is the dose of hydrocortisone administered when given orally, and why?
• 2/3 dose given in morning
• 1/3 dose given in evening
This is done to mimic the endogenous biphasic release of cortisol
23
How is hydrocortisone administered? What is each route used for?
Orally
• Replacement therapy
Parenterally
• Severe acute inflammation
Topically
• Any externally visible inflammation (e.g. atopic dermatitis)
24
How is prednisolone administered? What is each route used for?
Orally
• Asthma
• Hypersensitivity
25
What is betamethosone used for?
• Used for autoimmune diseases such as as UC or rheumatoid arthritis
• Used as a last resort for severe asthma
26
Why are other drugs tried before betamethasone?
Lower potency corticosteroids (and doses) must be tried first, to minimise side effects, and then titrate up
27
How are glucocorticoids administered for asthema and COPD?
Inhalation
28
What are the ranks for topical potency of glucocorticoids?
1) Mild
2) Moderately potent
3) Potent
4) Very potent
29
How does the vehicle of delivery alter the potency of topical medication?
Ointments are more potent than creams
• Ointments = oil based
• Creams = water based
30
