Endocrine pharmacology

Corticosteroids

Indications

1. Local or systemic use for inflammatory conditions.

Inhibit acute effects of inflammation e.g. capillary dilation oedema formation, white cell migration, fibrin deposition, phagocytosis.

Inhibit longer term effects such as capillary migration and deposition of collagen.

How would steroids alter the clinical features of a spreading soft tissue infection?

2. Suppression of immune response.

When would you want to suppress the body’s natural immune responses?

3. Replacement therapy in Addison’s disease.

Physiology

Produced from cholesterol by adrenal cortex.

There are 2 types of corticosteroids, glucocorticoids affect carbohydrate and protein metabolism. Mineralcorticoids affect sodium and other mineral homeostasis e.g. aldosterone.

Corticosteroids migrate into a target cell and bind to a cytoplasmic receptor. This steroid-receptor complex migrates into the nucleus. Here it regulates transcription of specific gene sequences. mRNA travels to ribosomes to cause production of specific proteins or enzymes.

Pharmacology

Glucocorticoids induce the production of lipocortins by inflammatory cells. These inhibit the production of phospholipase A2 and hence reduce production of arachidonic acid and cyclo-oxygenase products.

Reduction of immunological response. Lymphocyte mass and immunoglobulin production are reduced. Reduced monocytes and macrophage function.

Increased gluconeogenesis and glucose output by the liver, therefore increasing insulin levels.

Reduce glucose utilization by peripheral tissues.

Increase protein metabolism with mobilization of amino acids from peripheral tissues.

Adverse effects of steroid therapy

Rounded moon face, buffalo hump, obesity of trunk with thin limbs, purple striae, tendency to bruising, hyperglycaemia, Glucosuria, possible diabetes.

Loss of protein from skeletal muscles, muscular weakness

Fluid retention, hypokalaemia, hypertension

Infections

Osteoporosis, compression fractures of the vertebral bodies, avascular necrosis of head of femur

Psychosis, feeling of well being or euphoria, increased appetite, weight gain

Cataracts are rare

Dyspepsia

Impaired response to stress, e.g. illness, surgery, injury

Caution in pre-existing peptic ulceration, hypertension, congestive heart failure and osteoporosis.

Adrenal suppression

Therapy leads to inhibition of tropic hormones.

Over time there is atrophy of the adrenal cortex which may take 6 – 12 months to recover after long term therapy.

Short term therapy of 4-6 weeks can be stopped quickly

Long term therapy needs to be withdrawn under supervision over 6 months. May need more steroids during periods of stress such as illness or surgery.

Should report vomiting or diarrhoea

Medalert cards

Diabetes mellitus

Insulin 100 iu/ml

Duration of actions for different preparations is short, intermediate, long or mixed

Oral hypoglycaemics

Sulphonylureas

Stimulate beta cells to produce more insulin, inhibit gluconeogenesis and insulin degradation. May increase insulin receptor density.

Most common side effect is symptomatic hypoglycaemia

May be combined with other hypoglycaemic agents including insulin

Metformin (biguanides)

Decreased glucose absorption from gut

Increased glucose entry into cells

Anorectic effects

May cause nausea, vomiting, diarrhoea and rarely lactic acidosis

Thyroid disorders

Hyperthyroidism

Most common cause is Grave’s disease which may enter remission after a course of treatment. Autoimmune antibodies stimulate TSH receptor sites.

Thiourylene antithyroid drugs are all chemically similar. They inhibit thyroid hormone synthesis;

Inhibit iodine oxidation

Inhibit iodination of tyrosine

Inhibit coupling of iodotyrosines

Propylthiouracil also inhibits the conversion of T4 to T3

All may cause hypothyroidism and goitre when given long term.

Most common side effect is urticarial rash

Most dangerous side effect is granulocytopenia progressing to agranulocytosis

Other treatments include radioactive iodine or surgery.

Hypothyroidism

Thyroxine may be given orally to replace or supplement endogenous thyroid hormone. Dose may be titrated with TSH blood levels.