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4th yr- CMS- Pharmacology and drugs > Corticosteroids and immune modulatory agents > Flashcards

Corticosteroids and immune modulatory agents Flashcards

1
Q

What happens in the brain when the body is under stress

A
  1. Hypothalamus releases corticotrophin releasing factor
  2. This stimulated the anterior pituitary gland to release adrenocorticotrophin hormone
  3. This stimulates the adrenal cortex to release mineralocorticoids and glucocorticoids
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2
Q

What is the release of mineralocorticoids and glucocorticoids controlled by

A

RAS

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3
Q

What is another name for glucocorticoids

A

corticosteroids

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4
Q

Name the 2 main types of endogenous steroids

A
  1. mineralocorticoids
  2. glucocorticoids
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5
Q

What do mineralocorticoids include

A

Aldosterone

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6
Q

What are mineralocorticoids involved in

A

Water and electrolyte balance

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7
Q

What do glucocorticoids include

A

Hydrocortisone

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8
Q

What are glucocorticoids involved in

A

Carbohydrate and protein metabolism

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9
Q

Why are glucocorticoids used for clinically

A

Used for their anti-inflammatory, immunosuppressive and steroid- replacement abilities

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10
Q

List soem synthetic corticosteroids

A
  1. Glucocorticoids,
  2. glucocorticosteroids,
  3. steroids
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11
Q

What are synthetic corticosteroids

A

They are analogues of endogenous adrenal steroid hormones

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12
Q

Describe the qualities of synthetic corticosteroids

A
  1. Anti-inflammatory
  2. Immunosuppressive
  3. Proliferate
  4. Vasoconstricting
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13
Q

Talk through the mode of action of synthetic corticosteroids

A

Bind to intracellular steroid receptors which then bind to specific DNA sequences to modify gene transcription
OR
They interact in various ways with cellular membranes and their receptors

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14
Q

What effect do corticosteroids have on the body

A

They stop transcribing genes and the subsequent pro inflammatory protein that drive so many choleric inflammatory disease

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15
Q

Which protein transport corticosteroids once they are absorbed

A

Transcortin and albumin

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16
Q

Which has better anti inflammatory and immunosuppressive qualities mineralocorticoids or corticosteroids

A

Corticosteroids

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17
Q

Name some clinically useful steroids

A
  1. Hydrocortisone
  2. Prednisolone
  3. Betamethasone
  4. Fludrocortisone
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18
Q

How can steroids be given

A

Most active orally but can be given through:
1. IV
2. Intra muscular
3. Eye drops
4. Ointment
5. Inhaled

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19
Q

Talk through the mode of action of glucocorticoids

A

Bind to intracellular receptors and results in reduced production of factors involved in immune and inflammatory responses

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20
Q

What do glucocorticoids do

A

They induce phospholipase release and suppress COX2

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21
Q

What does the inducing of phospholipase release and suppress COX2 lead to

A
  1. less IL-1,-2,-3,-6, TNF alpha and interferon gamma
  2. Less COX-2
  3. Endothelial leukocyte adhesion molecule 1
  4. Less release of histamine and leucotrienes from mast cells and basophils
  5. Less fibroblast production
  6. less induction, proliferation and effector phase of lymphocytes
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22
Q

List some diseases corticosteroids can be used as therapeutics for

A
  1. Asthma and other allergies
  2. Eczema/ dermatitis, lichen planus, vasculitis
  3. Erythema multiform
  4. Steven Johnsons syndrome
  5. Oral ulcerations
  6. Behçet’s disease
  7. Some blood disorders
  8. inflammatory bowel disease
  9. immunosuppression after organ failure
  10. Addisons disease
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23
Q

Where is cortisol secreted fro

A

The adrenal cortex

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24
Q

How much cortisol is secreted daily

A

The adrenal cortex secretes 20mg of cortisol daily

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25
Q

How much is 20mg of cortisol in prednisolone

A

5mg

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26
Q

What is an adrenal crisis

A

It is a medical emergency caused by lack of cortisol

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27
Q

When does an adrenal crisis occur

A

A sudden cessation of steroids therapies or not increasing dose sufficiently during period of physiological stress

28
Q

What might patents suffering from an adrenal crisis experience

A
  1. Lightheadness
  2. Dizziness
  3. Weakness
  4. Sweating
  5. Abdominal pain
  6. Nausea
  7. Vomitting
29
Q

How do we manage an adrenal crisis

A

Immediate replacement of IV or IM hydrocortisone and blood pressure support

30
Q

What can an unmanaged adrenal crisis lead to

A

Death through overwhelming hypovolaemic or septic shock

31
Q

What term is used to group the adverse effect of corticosteroids steroids

A

Cushings syndrome

32
Q

What is cushings syndrome

A

Term given to commonly encountered adverse sequelae effects with long term or very high dose potent steroids

33
Q

List some effects cushings syndrome has on the brain

A
  1. Euphoria
  2. Depression
  3. Psychosis
  4. Benign intracranial HTN
  5. Emotional liability
  6. Sleep disturbances
34
Q

List some effects cushings syndrome has on the face

A
  1. Cataracts in eyes
  2. Moon face
35
Q

List some effects cushings syndrome has on the neck and back

A

Fat deposition on back of base of neck

36
Q

List some effects cushings syndrome has on the Blood pressure

A

Hypertension

37
Q

List some effects cushings syndrome has on the abdomen

A

Increased fat deposition on the abdomen

38
Q

List some effects cushings syndrome has on muscles

A

Proximal muscle starts wasting
Easy brushing and poor wound healing

39
Q

List some effects cushings syndrome has on bone

A

Avascular necrosis
Osteoporosis

40
Q

When are immunosuppressants used

A
  1. Organ transpant
  2. Bone marrow transplan t
  3. Autoimmune condition s
  4. Inflammatory bowel disease
  5. Oral medicine
41
Q

Name soem common immunosuppressants

A
  1. azathioprine,
  2. mycophenolate mofetil,
  3. ciclosporin
  4. tacrolimus
    but many others exist
42
Q

List some problems with immunosuppressants

A
  1. Increased risk of infection 2. Diminished wound healing
  2. Increased risk of tumours especially lymphomas
43
Q

What is azathioprine

A

A synthetic purine along used as an immunosuppressants
It is a prodrug of mercaptopurine

44
Q

azathioprine is C________

45
Q

As azathioprine is cytotoxic what does it do

A

It inhibits both cell mediated and antibody mediated immune reposted and inhibits clonal proliferation of both t and B cells

46
Q

What does azathioprine do

A
  1. Inhibits both cell mediated and antibody mediated immune reposted and inhibits clonal proliferation of both t and B cells
  2. Inhibits purine synthesis and DNA synthesis
  3. Incorporates into your DNA to modify gene expression and has anti proliferation effects
47
Q

How is azathioprine broken down

A

Broken down by the enzyme TPMT

48
Q

What must we check before prescribing a patient azathioprine

A

Their TPMT levels

49
Q

What is there an increased risk of in patients taking azathioprine

A

Increased risk of malignancy including that of the skin gastrointestinal tract and haematogenous malignancies such as lymphoma

50
Q

What must you advice a patient taking azathioprine

A
  1. To avoid the sun due to increased skin cancer risk
  2. To have Annual flu and pneumococcal vaccines
51
Q

What is mycophenolate mofetil

A

It is an cytotoxic steroid used as an immunosuppressants
Is a prodrug of myphenolic acid

52
Q

State a key difference between mycophenolate mofetil and azathioprine

A

mycophenolate mofetils is more lymphocyte selective than azathioprine so has a narrower spectrum of activity

53
Q

What do we mean by prodrug of myphenolic acid

A

It is a reversible inhibitor of inosine monophosphate dehydrogenase

54
Q

What does mycophenolate mofetil do

A
  1. selectively inhibits synthesis of guanosine which inhibits proliferation of B and T cells
  2. inhibit leucotriene recruitment to sites of inflammation
55
Q

When is mycophenolate mofetil contraindicated

A

In pregnancy or breast feeding women

56
Q

Why is mycophenolate mofetil contraindicated in breast feeding and pregnant women

A

as it is toxic to foetuses as it selectively inhibits synthesis of guanosine which inhibits proliferation of B and T cells

57
Q

When is mycophenolate mofetils used

A
  1. Organ transpant rejection
  2. SLE
  3. Haemolytic anaemia
  4. Mucous membrane pemphigoid,
  5. pemphigus,
  6. scleroderma,
  7. GVHD,
    8.Crohn’s disease
58
Q

What are the adverse effects of mycophenolate mofetil

A
  1. Bone marrow suppression
  2. Gastrointestinal disturbances
  3. risk on non melanoma skin cancers
  4. Gastrointestinal cancer and lymphoma
59
Q

What is cyclosporin

A

A cyclic 11 amino acid polupeptide

60
Q

What do calcineurin inhibitors do

A

They prevent activation of T cells and binds to proteins which then inhibit calcineurin to bring its clinical effects

61
Q

What are the clinical effects of calcineurin inhibitors

A
  1. Inhibition of calcineurin activates transcription factors that stimulate IL-2
    2, reduces IL-2 production of cytotoxic (Tc) and cytokine-producing Th1 cells
  2. Also inhibits Th2-dependent B-cell response
62
Q

What does calcineurin do

A

Activated T cells to produce il-2 AND other pro inflammatory cytokines
Inhibits mast cell degranulation and histamine release

63
Q

What are calcineurin inhibitors metabolised by

A

P450 cytochrome chain of enzymes

64
Q

What is Tacrolimus

A

macrolide antibiotic used systemically as an anti-rejection agent or topically in oral disease to treat severe or refractory inflammatory mucosal disease

65
Q

What are red adverse effects of ciclosporin

A
  1. Nephrotoxicity (a high risk of this)
  2. Hypertension (a marked problem)
  3. Hepatotoxicity
  4. Gingival hyperplasia
  5. Increased risk of malignancies eg non melons skin cancers
66
Q

What are red adverse effects of tacrolimus

A
  1. Nephrotoxicity (a high risk of this)
  2. Hypertension (a marked problem)
  3. Hepatotoxicity
  4. Increased risk of malignancies eg non melons skin cancers

4th yr- CMS- Pharmacology and drugs (7 decks)

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