Glucocorticoids. Immunosuppresant drugs

Question 1

Hydrocortisone (endogenous cortisol hormone)

Answer 1

Used to treat Addison’s disease where there is adrenal failure to produce glucocorticoids and often also mineralocorticoids so this treatment is replacement therapy.
Side effects: only typically occur when higher doses are used as low dose therapy usually takes place with no problems. Large doses or prolonged treatment can lead to Cushing’s syndrome.

Question 2

Prednisolone (synthetic glucocorticoids)

Answer 2

Used to treat inflammatory and autoimmune conditions (e.g. asthma, rheumatoid arthritis, ulcerative colitis, Crohn’s disease, multiple sclerosis, and autoimmune hepatitis). It is also used as an immunosuppressant in organ transplants. Additionally, it is used to treat neoplastic diseases (acute lymphocytic leukaemia, Hodgkin’s lymphoma)
Side effects: Low dose therapy usually without problems, Cushing’s syndrome (when used in large doses or prolonged treatment)

Question 3

Dexamethasone (synthetic glucocorticoids)

Answer 3

It is used in the clinic as a suppression test of ACTH production as it will suppress the hypothalamus and the pituitary, reducing ACTH secretion and therefore reducing hydrocortisone output. Failure of the suppression suggests hypersecretion of: ACTH (from benign pituitary adenoma so pituitary Cushing’s) or hypersecretion of glucocorticoids (from adrenal gland tumor; i.e. adrenal Cushing’s).

This drug is used to reduce cerebral oedema in patients with metastatic or primary brain tumors. Dexamethasone has minimal sodium and water retaining properties. It is also used to treat many inflammatory and autoimmune conditions (eg. rheumatoid arthritis, bronchospasms). Finally, it was also used for Covid-19 to reduce inflammation and damage to the lungs.
Side effects: Low dose therapy usually without problems. Cushing’s syndrome (large doses or prolonged treatment)

Question 4

Beclometasone (synthetic glucocorticoids)

Answer 4

Actions and Use: Used to treat asthma, so it is inhaled in combination with bronchodilators (salbutamol) -> effective local dose in bronchi with minimal systemic effects. It is also used in rhinitis (hay fever).
Side effects: oral candidiasis (yeast infection of mouth) and hoarseness.
* Side effects may usually be prevented by rinsing the mouth with water after using the inhaler.

Question 5

Fludrocortisone (synthetic mineralocorticoids)

Answer 5

Actions and Use: Acts on intracellular mineralocorticoid receptors in kidney -> stimulate synthesis of Na+ / K+ pumps to the basolateral membrane and of sodium channels to the luminal membrane -> increased Na+ reabsorption in distal tubules and increased K+ and H+ efflux. It is a replacement therapy for Addison’s disease (adrenal failure to produce mineralocorticoid and glucocorticoid). Used together with a glucocorticoid.
Side effects: hypertension, hypokalemia, edema

Question 6

NSAIDs (anti-inflammatory drug

Answer 6

The anti-inflammatory action is related to Inhibition of the COX-2, while their unwanted effects (particular those affecting the GI tract) are largely a result of their inhibition of COX1. Prostaglandins from COX2 induce vasodilation and capillary permeability to immune cells and factors.

Side effects:
- A large proportion of NSAID users experience GI disturbance through inhibition of COX-1 in GI, which decreases PGE2 resulting in less inhibition of histamine release. Histamine will increase gastric secretion and thus reduce the protection of the mucosa.
- Chronic use can lead to chronic discomfort, dyspepsia, diarrhea, nausea/vomiting, gastric bleeding/ulceration/perforation.

Question 7

Acetylsalicylic acid (anti-inflammatory drug)

Answer 7

COX inhibitor.
It is an analgesic and also antipyretic and anti-inflammatory but have better options for these last two so aspirin is mainly just used as analgesic and it can only be used short term due to the side effects.

Side effects: GI effects (bleeding, nausea, vomiting), aspirin-sensitive asthma and dizziness, tinnitus.

Question 8

Paracetamol (anti-inflammatory drug)

Answer 8

COX inhibitor.
Analgesic and antipyretic (suppress fever) and it only has a weak anti-inflammatory activity compared to other NSAIDs.

Side effects: few and uncommon at therapeutic dose (no gastric or platelet side-effects) but at toxic doses it can lead to overdose and suicide, nausea, vomiting and hepatotoxic leading to fatal liver damage.