Topic 41 - Corticosteroids

Question 1

What are the two types of endogenous steroid?

Answer 1

1. Mineralocorticoid

2. Glucocorticoid aka. corticosteroids aka. glucocorticosteroids

Question 2

What are other names for corticosteroids?

Answer 2

Glucocorticoid, glucocorticosteroid

Question 3

What type of hormone is steroid?

Answer 3

Sex hormone

Question 4

Describe mineralocorticoids, who they may be prescribed for, possible side effects, and examples.

Answer 4

These are fluid balancing and control the level of water and electrolyte balance in our bodies. They can be prescribed in those with Addison’s disease and also for those with postural hypertension. The side effects include hypertension (which could be good in a person with low BP) and also fluid retention due to retention of either water or salt. Examples include aldosterone and fludrocortisone.

Question 5

What are the good features of corticosteroids?

Answer 5

Anti-inflammation
Immunosuppressive
Anti-proliferation
Vasoconstricting

Question 6

How can corticosteroids be taken by a patient?

Answer 6

Topically - for treatment of eczema or psoriasis
Ingested as an oral tablet - for acute flares of IBD
Intravenously - anaphylaxis
Intra-articular
Inhaled - for inhalers for COPD asthma bronchitis etc.
Intramuscular
Intralesional - in tx of oral facial granulomatosis or ulceration due to oral lichen planus etc.
Eye drops.
(can be used to replace steroids in Addison’s, in cancer and blood disorders, after a transplant or Steven-Johns syndrome)

Question 7

Is it preferred to have a topical steroid on the skin or mucosa?

Answer 7

On the skin, steroid can cause thinning, hyperpigmentation, poor wound healing etc. especially if used prolonged and in high amounts. But on mucosa, saliva can wash away some of the steroid and so mucosa seems to be much more resistant.

Question 8

Is steroid a potent drug?

Answer 8

Corticosteroids can differ in potencies. There are some very potent and some not much.
If intralesional steroid is used e.g. it can tip a patient from pre-DM to type 2 DM and they’ll need all the diabetic management now.

Question 9

Give some examples of corticosteroids

Answer 9

Hydrocortisone (cortisol), prednisolone, betamethasone

Question 10

What effect do corticosteroids have on metabolism?

Answer 10

Decrease carb uptake and utilisation so can lead to hyperglycaemia
Increase protein breakdown

Question 11

How do steroids work on the immune system?

Answer 11

They bind to intracellular receptors and bind to a specific DNA sequence to affect gene transcription. Because of this, they stop the genes being transcribed so that pro-inflammatory proteins like interferon-gamma, interleukins and TNF-alpha are not produced which can drive chronic inflammatory conditions. With less of these, there’s less production of arachidonic acid and its metabolites, which leads to less prostaglandin release. There’s also less release of histamine because of less mast cell degranulation. And therefore less induction, proliferation and effector phases of lymphocytes, so less antibodies.
(Or they could act on cell membranes and receptors).

Question 12

What effect does diabetes, liver or kidney impairment, thyroid disease and obesity have on free steroid?

Answer 12

Steroids are carried around the blood in the plasma proteins albumin or transcortin. When any of those conditions are present, there’s less number of transporters so more free steroid in the body.

Question 13

How much cortisol does our adrenal cortex produce daily?

Answer 13

20mg - the equiv of 5mg of prednisolone

Question 14

What is adrenal suppression?

Answer 14

Long courses of high dose steroid can result in HPA axis suppression and the body can not produce sufficient endogenous cortisol anymore.
(Short courses can too but the body can recover from it).

Question 15

What happens during times of trauma, infection and surgery for patients on long term steroids?

Answer 15

When patients are under psychological stress, they require more or the same dose of exogenous steroid to make up for the lack of endogenous steroid produced.

Question 16

When can an Addisonian crisis occur?

Answer 16

When pts are stopping steroid medication they should do it gradually over a period of time.

Sudden cessation of steroid medication or not supplementing at a time of physiological stress can result in an Addisonian crisis which is an actual medical emergency where patient experiences dizziness, weakness, sweating, abdominal pain, vomiting and even loss of consciousness.

Can refer to oral surgery dept so that they can double dosage in the morning and can be treated in hospital in case of Addisonian crisis

Question 17

What monitoring occurs for those on long term steroids?

Answer 17

Cataracts - ophthalmoscopy
Diabetes - HbA1c, urinalysis
Osteoporosis - DEXA scan
Hypertension - BP 
Developmental milestones achieved in children

Question 18

What is Cushing’s syndrome? Describe the effects.

Answer 18

• Increased body habitus because of increased deposition at base of neck and abdomen and swelling of the face (due to retained fluid and redisposition of fat)
• Proximal muscle wasting
• Easy bruising and poor healing
• Osteoporosis
• Diabetes - can be worse in a pt who already has and de novo
• Hypertension - can be worse in a pt who already has and de novo
• Benign cranial hypertension - can increase risk of thromboembolic events
• Cataracts - may then struggle with OH
• Emotional lability, heightened feelings in those with depression and euphoria (can make worse in those with depression or BPD), psychosis
• Because of circadian rhythms, prescribe in the morning as taken at night it can cause sleep disturbance and nightmares
• All conditions it causes (hypertension and osteoporosis) have their own side effects.

Question 19

What has a wider range of activity - immunomodulators or steroids?

Answer 19

Immunomodulators - can affect the immune system at various levels

Question 20

Why were immunosuppressants/immunomodulators developed?

What problem is there?

Answer 20

As steroid-sparing agents, to counteract the effects of steroids.
Have side effects themselves as they can’t target the specific part of the immune system that causes the patient’s clinical disease.

Question 21

Uses of immunomodulators?

Answer 21

• After organ transplant to prevent host versus graft reactions
• After bone marrow transplants - host versus graft reactions where donor cells attack recipient cells and can cause morbidity and mortality
• Autoimmune conditions like rheumatoid arthritis
• IBD - Chron’s, ulcerative colitis
• In oral med, used for oral lichen planus, pemphigus, pemphigoid, erythema multiforme, orofacial granulomatosis and major aphthous ulceration

Question 22

What are four examples of immunomodulators?

Answer 22

Azathioprine, ciclosporin, mycophenolate mofetil, tacrolimus

Question 23

How does azathioprine work and what do you need to know before prescribing it? Side effect?

Answer 23

Azathioprine is a cytotoxic drug and steroid sparing agent and so affects cell-mediated and antibody-mediated immune response. It inhibits clonal proliferation of T-cells and B-cells. It also inhibits purine synthesis and DNA synthesis. It incorporates into DNA and can affect gene expression and is anti-proliferative.
Used in pemphigus and SLE.
Need to know levels of TPMT as this is the enzyme that breaks it down. Know these levels before prescribing as if pt doesn’t have enough TPMT and are still prescribed azathioprine at normal dose (should prescribe less or none), then they can suffer liver failure and bone marrow suppression. If they have high levels of TPMT, more of the drug will need to be prescribed to achieve therapeutic window.

in the long term increase the risk of patients developing a non-melanoma skin cancer, lymphomas and GI tumours. Other side effects in separate flashcard.

Question 24

How does mycophenolate mofetil work?

Are there any contraindications? Side effect?

Answer 24

It’s a cytotoxic steroid-sparing agent but with a narrower spectrum activity than azathioprine (which is a positive as pts are less at risk from infection then). It’s a prodrug of mycophenolic acid, which is a reversible inhibitor of inosine monophosphate dehydrogenase. It inhibits guanine synthesis and so inhibits T-cell and B-cell proliferation. It also inhibits leukotriene recruitment at sites of inflammation.
Used in organ transplants, pemphigus, SLE, etc check.
It is contraindicated in pregnant women, women of childbearing age and men who have sex with women of childbearing age because it’s a teratogenic drug.

In the long term can increase the risk of patients developing a non-melanoma skin cancer, lymphomas and GI tumours. Other side effects in separate flashcard.

Question 25

How does ciclosporin work? And what are the side effects?

Answer 25

It’s a calcineurin inhibitor, which means it inhibits activation of transcription factors that stimulate interleukin production. Interleukins are inflammatory mediators that trigger production of cytotoxic t-lymphocytes. It also inhibits the b-cell response and suppresses antibody production.
Ciclosporin is prescribed after organ transplant to prevent failure.
- It is metabolised by P450 pathway so check BNF for drug interactions including with antibiotics.
- It can cause gingival hyperplasia made worse with poor plaque control.
- Can cause hypertension.
- Nephrotoxic so can affect the kidneys, with a high risk of morbidity.
- Can also affect liver.
- Other side effects in separate flashcard.

Question 26

How does tacrolimus work? What are its uses? Side effects?

Answer 26

It’s a calcineurin inhibitor, which means it inhibits activation of transcription factors that stimulate interleukin production. Interleukins are inflammatory mediators that trigger production of cytotoxic t-lymphocytes. It also inhibits the b-cell response and suppresses antibody production.

It can be used topically unlike the other immunomodulatory drugs we’ve covered, and doesn’t have to just be used systemically.
- It can be used for organ transplants.
- Is a macrolide antibiotic so can be used topically as a steroid sparing agent in those with eczema and psoriasis
- Can be used topically in the mouth as a steroid sparing agent for those with oral lichen planus, or intraoral lupus lesions etc.
There is a risk of malignant or dysplastic change so pt would need to be warned and it should only be prescribed by a specialist. And withdrawal should be done within 3-6 months.

Side effects: hepatoxicity, nephrotoxicity, hypertension. Other side effects in separate flashcard.

Question 27

What are the risks using immunomodulatory drugs?

Answer 27

• Poor wound healing (cutaneous and mucosal).
• Infection (immune response dampened so common colds can become life threatening and can get sepsis).
• Cancer
• Severe allergic response (like Steven-Johns in aza and myco)
• Hepatic failure - can affect your kidney/liver and lead to organ failure
• Pancreatitis - mainly a prob for pts using this drug who have IBD. Can either be mild symptoms or fatal if untreated.
• Haemolysis - haemolytic anaemia and bone marrow suppression would warrant stopping the drug immediately when identified.

Question 28

Is there a reason why you’d stop prescribing mycophenolate mofetil or azathioprine 1-2 days after prescribing?

Answer 28

These drugs can cause Steven-Johns syndrome so if a patient developed a blistering rash, you would stop the course.

Question 29

What pre-screening bloods would be required for immunomodulatory drugs?

Answer 29

• BBV as you don’t want to run the risk of reactivating a latent or undiagnosed HIV or hepatitis infection
• TB (take a blood test and chest x-ray for those at risk of having TB)
• Occasionally minor serology tests to ensure there’s no CMV, EBV or Varicella Zoster.
• TPMT for azathioprine

Question 30

How do you monitor those on immunomodulatory drugs, and how often for?

Answer 30

Patients will require lifelong monitoring or for as long as they’re on the medication, at least.

Blood tests:
- FBC
- U&E
- LFTs
This is to identify any hepatotoxicity, any lymphopenia and any anaemia. These are done weekly/fortnightly for first 6 weeks and gradually reduce to every 3-4 months.
- Drug level - e.g. ciclosporin has a narrow therapeutic index so have to ensure it’s not reaching toxic levels.

• Skin monitoring to identify any non-melanoma skin cancers early. Pt should be educated on how to check this themselves too.
• Regular eye tests for those on hydroxychloroquine (an anti-malarial drug that has an immunomodulatory effect, which can deposit drug on the retina and lead to retinopathy and blindness). If at increased risk, they don’t need to just be seen by optician but also the ophthalmologist.