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154
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Pharmacology

Endocrine

Question 1 of 180

Dexamethasone would be most useful for which of the following conditions:

Answer:

Dexamethasone has a very high glucocorticoid activity in conjunction with insignificant mineralocorticoid activity. This makes it particularly suitable for high-dose therapy in conditions where fluid retention would be a disadvantage such as in the management of raised intracranial pressure or cerebral oedema secondary to malignancy. Dexamethasone also has a long duration of action and this, coupled with its lack of mineralocorticoid action makes it particularly suitable for suppression of corticotropin secretion in congenital adrenal hyperplasia. In most individuals a single dose of dexamethasone at night, is sufficient to inhibit corticotropin secretion for 24 hours. This is the basis of the ‘overnight dexamethasone suppression test’ for diagnosing Cushing’s syndrome.

Corticosteroids

In comparing the relative potencies of corticosteroids in terms of their anti-inflammatory effects, it is worth noting that high glucocorticoid activity in itself is of no advantage unless it is accompanied by relatively low mineralocorticoid activity.

Anti-Inflammatory Potency

Equivalent anti-inflammatory doses of corticosteroids:

Prednisolone 5 mg = Dexamethasone 750 micrograms = Hydrocortisone 20 mg

This does not take into account their mineralocorticoid effects, nor their duration of action.

Side Effects

Overdose or prolonged use can exaggerate some of the normal physiological actions of corticosteroids leading to mineralocorticoid and glucocorticoid side effects. Mineralocorticoid side effects are most marked with fludrocortisone, but are significant with hydrocortisone, negligible with the high potency glucocorticoids, betamethasone and dexamethasone, and occur only slightly with methylprednisolone and prednisolone.

Mineralocorticoid side effects include:

  • hypertension
  • sodium retention
  • water retention and oedema
  • potassium loss
  • calcium loss

Glucocorticoid side effects include:

  • weight gain
  • hyperglycaemia and diabetes
  • osteoporosis and osteoporotic fractures
  • muscle wasting (proximal myopathy)
  • peptic ulceration and perforation
  • psychiatric reactions

Side effects can be minimised by using the lowest effective dose for the minimum period possible. The suppressive action of a corticosteroid on cortisol secretion is least when it is given as a single dose in the morning. Whenever possible local treatment with creams, intra-articular injections, inhalations, eye drops, or enemas should be used in preference to systemic treatment.

Adrenal Suppression

During prolonged therapy with corticosteroids, particularly with systemic use, adrenal atrophy develops and can persist for years after stopping. Abrupt withdrawal after a prolonged period can lead to acute adrenal insufficiency, hypotension, or death. Patients removed from long-term glucocorticoid therapy must be weaned off the drug over several days, using progressively lower doses to allow recovery of adrenal responsiveness.

To compensate for a diminished adrenocortical response caused by prolonged corticosteroid treatment, any significant intercurrent illness, trauma, or surgical procedure requires a temporary increase in corticosteroid dose, or if already stopped, a temporary reintroduction of corticosteroid treatment.

Patients on long-term corticosteroid treatment should carry a steroid treatment card which gives guidance on minimising risk and provides details of prescriber, drug, dosage and duration of treatment.

Infections

Prolonged courses of corticosteroids increase susceptibility to infections and severity of infections; clinical presentation of infections may also be atypical.

Unless they have had chickenpox, patients receiving oral or parenteral corticosteroids for purposes other than replacement should be regarded as being at risk of severe chickenpox. Manifestations of fulminant illness include pneumonia, hepatitis and disseminated intravascular coagulation; rash is not necessarily a prominent feature. Passive immunisation with varicella–zoster immunoglobulin is needed for exposed non–immune patients receiving systemic corticosteroids or for those who have used them within the previous 3 months. Confirmed chickenpox warrants specialist care and urgent treatment. Corticosteroids should not be stopped and dosage may need to be increased.

Patients taking corticosteroids should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.

Hydrocortisone

The relatively high mineralocorticoid activity of hydrocortisone, and the resulting fluid retention, makes it unsuitable for disease suppression on a long-term basis. However, hydrocortisone can be used for adrenal replacement therapy (together with fludrocortisone). Hydrocortisone is primarily used on a short-term basis by intravenous injection for the emergency management of some conditions such as acute asthma and allergic/anaphylactic reactions as an adjunct to adrenaline. The relatively moderate anti-inflammatory potency of hydrocortisone also makes it a useful topical corticosteroid for the management of inflammatory skin conditions because side effects (both topical and systemic) are less marked. Hydrocortisone acetate or one of the synthetic analogues is also generally used for local injection.

Prednisolone

Prednisolone, an intermediate-acting agent, has predominantly glucocorticoid activity with only minimal mineralocorticoid activity. Prednisolone is the corticosteroid most commonly used by mouth for long-term disease suppression, for example in rheumatoid arthritis and temporal arteritis.

Dexamethasone

Dexamethasone has a very high glucocorticoid activity in conjunction with insignificant mineralocorticoid activity. This makes it particularly suitable for high-dose therapy in conditions where fluid retention would be a disadvantage such as in the management of raised intracranial pressure or cerebral oedema secondary to malignancy. Dexamethasone also has a long duration of action and this, coupled with its lack of mineralocorticoid action makes it particularly suitable for suppression of corticotropin secretion in congenital adrenal hyperplasia. In most individuals a single dose of dexamethasone at night, is sufficient to inhibit corticotropin secretion for 24 hours. This is the basis of the ‘overnight dexamethasone suppression test’ for diagnosing Cushing’s syndrome.

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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