Corticosteroids and Immune Modulatory Agents

Question 1

What system do corticosteroids and immunomodulatory agents have a significant effect on?

Answer 1

the immune system

Question 2

what are the main properties of corticosteroids?

Answer 2

anti-inflammatory and immunosuppression

Question 3

what can potent corticosteroids affect?

Answer 3

Hypothalamus, pituitary, adrenal or HPA axis

Question 4

Why were immunomodulators/immunosuppressants used?

Answer 4

minimise effects of long-term corticosteroid use

Question 5

what might corticosteroids be prescribed for?

Answer 5

• dermatology - topical steroids for inflammatory skin conditions eg: eczema, dermatitis, lichen planus
• respiratory - inhaled steroid for control of mild-moderate asthma
• gastroenterology - used in high dose for long period of time to treat acute flares of severe inflammatory bowel disease (eg: crohns and ulcerative colitis)
• blood disorders (autoimmune anaemias)
• immunosuppression after organ transplants
• rheumatoid arthritis

Question 6

what can happen in situations of stress when a patient is given exogenous steroids? what can this present as?

Answer 6

the adrenal glands are not able to produce enough cortisol to maintain blood pressure, fluid balance
- can present as an Addisonian crisis

Question 7

what might you consider doing if carrying out a potentially stressful procedure?

Answer 7

whether the pt needs an additional exogenous prescription to make up for any increased requirement due to physiological stress

Question 8

what is cortisol?

Answer 8

Cortisol is a steroid hormone, in the glucocorticoid class of hormone

Question 9

what happens to your bodys natural cortisol production when taking corticosteroids?

Answer 9

steroids provides your body with cortisol so your adrenal glands temporarily shut down and do not produce cortisol

Question 10

what are some of the risks with taking long term steroids?

Answer 10

increased susceptibility to infection (eg: oral candida)
or osteoporosis due to steroid effect on bone metabolism

Question 11

what are the 2 main types of endogenous steroids?

Answer 11

mineralocorticoids and glucocorticosteroids

Question 12

why might mineralocorticoids (aldosterone/fludrocortisone) be prescribed?

Answer 12

typically for postural hypotension or long term maintenance of Additions disease (mostly related to fluid balance and control of electrolytes in the body

Question 13

what is the mode of action of steroids? how do they do this?

Answer 13

prevent the immune system from over-reacting and their immune/inflammatory systems from being activated. they bind to receptors intracellularly that affect gene transcription to either suppress or promote the activation of certain genes OR reduce prod. of interleukins = less prod. of prostaglandins (in inflammatory), dampen prod. of histamine

Question 14

when does adrenal suppression occur?

Answer 14

after long term use of high dose corticosteroids OR v potent ones - causes adrenal glands to shut down (short courses can suppress the HPA axis BUT the body can recover)

Question 15

How can we ensure the body recovers after drug withdrawal of corticosteroids?

Answer 15

done so very gradually (over period of weeks) to allow the HPA axis to recover and produce its own endogenous cortisol again

Question 16

during periods of infection, trauma or surgery what will happen to the dose of patients on long term steroids?

Answer 16

at least continue the same dose/increase it so that there is sufficient exogenous steroid to make up for that which would normally be produced when body is under stress

Question 17

what is adrenal crisis?

Answer 17

occurs on sudden cessation of steroids of steroid therapies or not increasing the dose sufficiently during periods of physiological stress

Question 18

what is an acute adrenal crisis caused by? what might the patient experience?

Answer 18

lack of cortisol
- experience light-headedness, dizziness, weakness, sweating, abdominal pain, nausea and vomiting or even loss of consciousness

Question 19

what is cushings syndrome? what features are displayed?

Answer 19

commonly occurs after prescription of long-term corticosteroids - pt displays body habits of pt taking long term or potent steroids
- present with
→ fat deposition at base of neck
→ swelling and rounding of the face due to fluid retention
→ proximal muscle wasting with deposition of more fat around abdominal organs
→ hypertension and diabetes

Question 20

what are some adverse effects of steroid use?

Answer 20

osteoporosis
easy bruising
poor wound healing
long term: development of cataracts (if pt can’t see they will struggle to maintain oral hygiene)

Question 21

why do steroids need to be prescribed early on in the day?

Answer 21

natural circadian rhythm and production of steroids peaking early morning when produced naturally by the body

Question 21

why do steroids need to be prescribed early on in the day?

Answer 21

natural circadian rhythm and production of steroids peaking early morning when produced naturally by the body

Question 22

what are immunomodulators/immunosuppressants prescribed for?

Answer 22

crohns, ulcerative colitis
* Used in prevention of rejection following organ transplant (to prevent host versus graft reactions where the recipient’s body attempts to destroy the grafted tissue from the donor)
* Bone marrow transplants (graft versus host where the grafted donor cells attack the recipient’s own cells and cause significant morbidity if not mortality)
* Autoimmune conditions eg: glomerulonephritis, SLE, RA
* In oral medicine, can be prescribed for pemphigus vulgaris, major aphthous ulceration, erythema multiform and severe Lichen Planus

Question 23

what are some examples of biologics?

Answer 23

abatacept (Orencia)
adalimumab (Humira)
dupilumab (Dupixent)
etanercept (Enbrel)
infliximab (Remicade)
mepolizumab (Nucala)
omalizumab (Xolair)
rituximab

Question 24

what are some examples of immunosuppressants?

Answer 24

methotrexate
sulfasalazine
cyclosporine
azathioprine
leflunomide
hydroxychloroquine

Question 25

what do corticosteroids typically end in?

Answer 25

-one

Question 26

what are the risks of immunomodulators?

Answer 26

• infections (suppresses immune system)
• wound healing will take longer
• cancer (increased with Azathioprine and Mycophenolate)
• severe allergic response

Question 27

what should be monitored for a patinet on immunosuppressants?

Answer 27

• bloods
• pre-screening bloods that are agent specific eg: TPMT
• FBC, U&E’s, LFTs
• skin monitoring (non-melanoma skin cancer is risk)
• eye tests