Topic 41 - Corticosteroids Flashcards
What are the two types of endogenous steroid?
- Mineralocorticoid
2. Glucocorticoid aka. corticosteroids aka. glucocorticosteroids
What are other names for corticosteroids?
Glucocorticoid, glucocorticosteroid
What type of hormone is steroid?
Sex hormone
Describe mineralocorticoids, who they may be prescribed for, possible side effects, and examples.
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.
What are the good features of corticosteroids?
Anti-inflammation
Immunosuppressive
Anti-proliferation
Vasoconstricting
How can corticosteroids be taken by a patient?
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)
Is it preferred to have a topical steroid on the skin or mucosa?
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.
Is steroid a potent drug?
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.
Give some examples of corticosteroids
Hydrocortisone (cortisol), prednisolone, betamethasone
What effect do corticosteroids have on metabolism?
Decrease carb uptake and utilisation so can lead to hyperglycaemia
Increase protein breakdown
How do steroids work on the immune system?
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).
What effect does diabetes, liver or kidney impairment, thyroid disease and obesity have on free steroid?
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.
How much cortisol does our adrenal cortex produce daily?
20mg - the equiv of 5mg of prednisolone
What is adrenal suppression?
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).
What happens during times of trauma, infection and surgery for patients on long term steroids?
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.
When can an Addisonian crisis occur?
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
What monitoring occurs for those on long term steroids?
Cataracts - ophthalmoscopy Diabetes - HbA1c, urinalysis Osteoporosis - DEXA scan Hypertension - BP Developmental milestones achieved in children
What is Cushing’s syndrome? Describe the effects.
- 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.
What has a wider range of activity - immunomodulators or steroids?
Immunomodulators - can affect the immune system at various levels
Why were immunosuppressants/immunomodulators developed?
What problem is there?
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.
Uses of immunomodulators?
- 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
What are four examples of immunomodulators?
Azathioprine, ciclosporin, mycophenolate mofetil, tacrolimus
How does azathioprine work and what do you need to know before prescribing it? Side effect?
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.
How does mycophenolate mofetil work?
Are there any contraindications? Side effect?
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.
