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Human Diseases > W1 5 Anti-inflammatory steroids > Flashcards

W1 5 Anti-inflammatory steroids Flashcards

1
Q

Where are corticosteroids synthesised?

A

Middle layer of adrenal cortex

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2
Q

What are corticosteroids split into?

A

Glucocorticoids and mineralocorticoids

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3
Q

What is the endogenous glucocorticoid?

A

Cortisol

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4
Q

What is cortisol synthesised from?

A

Cholesterol. Retains 4 ring chemical structure.

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5
Q

What compound is made chemically to mimic cortisol?

A

Hydrocortisone

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6
Q

What chemical properties of hydrocortisone make it differ from cortisol?

A

Position of side-groups increase selectivity to gluco and mineralocorticoids
Fluoridation increases half-life of drugs
Double bond in ring increases potency

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7
Q

What actions does cortisol have?

A

Anti-inflammatory actions

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8
Q

What axis is cortisol part of?

A

Hypothalamus-pituitary adrenal axis - HPA axis

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9
Q

Describe the negative feedback loop involving cortisol - PG46

A

Hypothalamus releases CRH stimulating the anterior pituitary gland to release ACTH, stimulating the adrenal gland to release cortisol.
Cortisol negatively feedbacks on the HPA to decrease its own production
It acts on many tissues to have metabolic effects
Pro-inflammatory mediators flow to HPA axis to generate cortisol and limit inflammation
Chronic stimulation of cortisol might shut down the HPA system, causing atrophy
Stress, inflammation, immune system all can cause the system to release cortisol

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10
Q

What is the implication of being a steroid for absorption?

A

Steroids are lipophilic and easily absorbed in the gut
Not in plasma freely, so are bound to a carrier protein

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11
Q

Which proteins are steroids bound too?

A

Transcortin is a specific carrier protein. It has a high affinity for steroids but low capacity.
Majority are bound to albumin. It has a high capacity but low affinity.

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12
Q

Once in the tissues, the steroid freely diffuses into the cell cytoplasm, where the glucocorticoid receptor is located. What are the different domains of a glucocorticoid receptor?

A

Ligand binding domain - where steroid will bind
DNA binding domain - related to an action
HSP binding domain - anchors it to the cytoplasm

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13
Q

What happens as the steroid binds to the receptor?

A

The binding to the HSP is broken and thus free the receptor to allow it to move into the nucleus.

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14
Q

What happens once the steroid is inside the nucleus?

A

Can turn a gene on = trans activation - upregulates anti-inflammatory mediators
Can bind to genes and turn them off = transrepression - down regulates the pro-inflammatory mediators

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15
Q

How long does the typical steroid anti-inflammatory effect take?

A

6-8hrs

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16
Q

Do anti-inflammatory drugs need an initiating stimulus to work?

A

No, anti-inflammatory drugs will work independent of initiating stimulus

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17
Q

What happens to the body in an inflammatory response? PG48

A

We would have PLA2 breaking down phospholipids to make arachidonic acid, and COX2 to make prostanoids, which would have an inflammatory effect.

18
Q

What would a glucocorticoid do (to genes) to have an anti-inflammatory effect? PG48

A

Stimulate annexin-1 production which would inhibit PLA2 and stop the formation of arachidonic acid. (trans activation)
Stop the formation of COX2 (trans repression)
Annexin-1 can also inhibit the inflammatory response and promote recovery

19
Q

What non-genomic response can steroids have?

A

Stabilise lysosomal membranes. Prevents the release of pro-inflammatory enzymes from damaged cells.

20
Q

What are some examples of short-acting (<12hrs) glucocorticoids?

A

Hydrocortisone, cortisone

21
Q

What are some examples of intermediate-acting (12-36hrs) glucocorticoids?

A

Prednisolone
Prednisone
Triamicinalone

22
Q

What are some examples of long-acting (>36hrs) glucocorticoids?

A

Dexamethasone
Betamethasone
Paramethasone

23
Q

What uses do glucocorticoids have outside of dentistry?

A

Allergies, asthma, cancer

24
Q

How are glucocorticoids delivered for allergies like allergic rhinitis or dermatitis/eczema?

A

Usually aerosol or cream = ability to give a high local dose

25
Q

How are glucocorticoids delivered in asthma?

A

Inhalation of direct local access

26
Q

Are allergies and asthma treated chronically with glucocorticoids?

A

Yes chronic treatment, but delivery means there will be small systemic effect

27
Q

Briefly describe the role of glucocorticoids in cancer

A

(Not really important card - skip)
Curative role for lymphoid cancers to stop lymphocyte proliferation and cause immune suppression
Non-curative role as anti-emetic

28
Q

Uses of glucocorticoids in dentistry

A

Oral ulcerations - eg denture induced trauma
Pulpal hypersensitivity
Post-operative sequelae - to reduce post-surgical oedema

29
Q

Advantages of glucocorticoids

A

Easily absorbed into the GI tract and locally into skin/mucous membranes

30
Q

Disadvantages of glucocorticoids

A

Lack of specificity - have multiple effects
Are an anti-inflammatory but also have metabolic effects

31
Q

What are the adverse effects of glucocorticoids?

A

Chronic use causes same symptoms as Cushing’s disease

32
Q

What will chronic GC use cause?

A

Chronic GC use will chronically suppress the HPA axis and chronically reduce ACTH, leading to adrenal atrophy. Consider adrenal insufficiency. Sudden withdrawal will lead to adrenal crisis - a medical emergency.

33
Q

Symptoms of Cushing’s disease

A

Hyperglycaemia
Moon face
Increased susceptibility to infection
Oedema
CNS irritability
Personality changes
Osteoporosis
Thin skin
Purple striae
Bruises
Thin extremities

34
Q

What has similar features to adrenal crisis?

A

Addisons disease

35
Q

What are the features of adrenal crisis/addisons?

A

Hypoglycaemia, renal shutdown (decreased sodium and increased potassium), profound fatigue, dehydration, vascular collapse (cause hypotension), GI disturbances, weakness, weight loss
Pg50

36
Q

What are the adverse immune effects of chronic GC use and their implications?

A

Immune suppression - increased risk of infection
Wound healing
Skin/mucosa thinning - wound repair impaired

37
Q

Why does chronic GC use cause hyperglycaemia?

A

Glucocorticoids increase blood glucose levels, stimulating gluconeogenesis

38
Q

Why does chronic GC use cause osteoporosis?

A

Reduced Ca absorption from the gut and increase calcium secretion from the kidneys

39
Q

List all the metabolic implications of chronic GC use

A

Hyperglycaemia, myopathy, osteoporosis, body fat distribution, fluid retention, electrolyte balance (high sodium low potassium)

40
Q

What are the dental implications of chronic GC treatment?

A

Increased risk of infection from dental procedures
Impaired wound healing
Adrenal insufficiency - book surgery in morning for diurnal variation
Invasive surgery - requiring complete replacement ‘steroid cover’ - GA normally produce cortisol. If suppressed then not making it and so need cover.

Human Diseases (75 decks)

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