Pharmacology chapters
Antithyroid drugs and corticosteroids
Thyroxine replacement, the antithyroid drugs (carbimazole, propylthiouracil, iodine, radioactive iodine, beta blockers) and their dangers, and the corticosteroids: mechanism, relative potencies, uses, the long list of adverse effects, adrenal suppression and how to stop steroids safely.
- Levothyroxine (T4) replaces thyroid hormone in hypothyroidism; adjust the dose by TSH every 6–8 weeks; start low in the elderly and in heart disease (can provoke angina); overdose causes AF and osteoporosis.
- Carbimazole (converted to methimazole) and propylthiouracil block thyroid peroxidase; PTU also blocks peripheral T4 → T3 conversion and is used in the first trimester and in thyroid storm, but carries a risk of severe liver toxicity; both can cause agranulocytosis (stop and check a blood count if a sore throat or fever appears); iodine acutely blocks hormone release (Wolff-Chaikoff), and β blockers control symptoms.
- Corticosteroids act on intracellular receptors to change gene transcription (anti-inflammatory and immunosuppressive); long-term use causes Cushingoid features, osteoporosis, diabetes, infection, peptic ulceration (with NSAIDs), cataract, hypertension, mood change and adrenal suppression, so after more than about 3 weeks they must be tapered, and doses doubled during illness ("sick-day rules").
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Thyroid hormones
Synthesis: iodide is trapped by the thyroid (sodium-iodide symporter), oxidised and attached to tyrosine on thyroglobulin (organification), and iodotyrosines are coupled to form T3 and T4. Thyroid peroxidase drives oxidation, organification and coupling. Most circulating hormone is T4; it is converted to the more active T3 in tissues.
Levothyroxine (T4)
- Uses: hypothyroidism, after thyroidectomy, TSH suppression in thyroid cancer.
- Dose: usually about 1.6 micrograms/kg/day in healthy adults; start low (25–50 micrograms) in the elderly and people with ischaemic heart disease (can precipitate angina or MI).
- Monitoring: TSH about 6–8 weeks after each dose change (T4 has a long half-life of about 7 days).
- Take on an empty stomach; absorption is reduced by iron, calcium, antacids and PPIs.
- Over-replacement: AF, angina, osteoporosis, symptoms of hyperthyroidism.
- Pregnancy: dose requirement usually rises.
- Liothyronine (T3): faster and shorter-acting; used in myxoedema coma (with T4) in some protocols.
Antithyroid drugs
Thionamides
| Feature | Carbimazole (→ methimazole) | Propylthiouracil (PTU) |
|---|---|---|
| Main action | Inhibit thyroid peroxidase (organification and coupling) | Same, plus blocks peripheral T4 → T3 conversion |
| Dosing | Once daily | Two or three times a day |
| Pregnancy | Avoided in the first trimester (aplasia cutis, embryopathy); preferred later | Preferred in the first trimester; then usually switched |
| Liver | Cholestatic jaundice (rare) | Severe hepatotoxicity (can be fatal), so not first-line otherwise |
| Thyroid storm | Used | Preferred in some protocols (blocks T4 → T3) |
Shared adverse effects: rash and itch (commonest), agranulocytosis (rare, usually in the first months): warn patients to stop the drug and get an urgent blood count if they develop a sore throat, mouth ulcers or fever. Both cross the placenta (fetal hypothyroidism if over-treated).
Regimens: dose titration or block and replace (high dose + levothyroxine) for 12–18 months in Graves disease.
Other treatments for hyperthyroidism
- Iodine (potassium iodide, Lugol's iodine): large doses block hormone release and organification (Wolff-Chaikoff effect); rapid but temporary (escape after 10–14 days). Used before thyroid surgery (reduces gland vascularity) and in thyroid storm (given after a thionamide).
- Radioactive iodine (I-131): destroys thyroid tissue; definitive treatment for Graves and toxic nodules; contraindicated in pregnancy and breastfeeding; avoid pregnancy for at least 6 months afterwards; may worsen thyroid eye disease; most patients eventually become hypothyroid.
- β blockers (propranolol): quick relief of adrenergic symptoms (tremor, palpitations, anxiety); propranolol also slightly reduces T4 → T3 conversion.
- Surgery: thyroidectomy.
Thyroid storm
A life-threatening crisis (fever, tachycardia, AF, heart failure, agitation, vomiting), often after surgery, infection or stopping drugs. Treatment: propranolol, PTU (or carbimazole), iodine an hour later, hydrocortisone (also blocks T4 → T3), cooling (paracetamol, not aspirin), fluids and treating the trigger.
Drugs affecting the thyroid: amiodarone (hypo- or hyperthyroidism), lithium (hypothyroidism, goitre), interferon-α.
Corticosteroids
Mechanism
Glucocorticoids enter cells and bind cytoplasmic receptors; the complex moves to the nucleus and changes gene transcription:
- Switch off inflammatory genes: less cytokines (IL-1, TNF), less COX-2, less phospholipase A2 activity (via lipocortin/annexin-1) → fewer prostaglandins and leukotrienes.
- Fewer circulating lymphocytes and eosinophils, more neutrophils (demargination); reduced capillary permeability.
- Metabolic: gluconeogenesis, insulin resistance, protein breakdown, fat redistribution.
Relative potency
| Drug | Glucocorticoid (anti-inflammatory) potency | Mineralocorticoid (salt-retaining) potency | Notes |
|---|---|---|---|
| Hydrocortisone | 1 | 1 | Replacement in adrenal insufficiency; acute adrenal crisis, anaphylaxis and severe asthma (IV) |
| Prednisolone | 4 | 0.8 | Most used oral anti-inflammatory steroid |
| Methylprednisolone | 5 | Minimal | Pulse IV therapy |
| Dexamethasone, betamethasone | 25–30 | Nil | Cerebral oedema, fetal lung maturation (preterm labour), dexamethasone suppression test, nausea in chemotherapy, croup, bacterial meningitis (some) |
| Fludrocortisone | 10 | 125–150 | Mineralocorticoid replacement (Addison disease), postural hypotension |
Equivalent anti-inflammatory doses:
hydrocortisone 20 mg ≈ prednisolone 5 mg ≈ dexamethasone 0.75 mg
Patient on prednisolone 20 mg → dexamethasone?
20 ÷ 5 = 4 "units" × 0.75 = 3 mg dexamethasone
Prednisolone 40 mg → hydrocortisone?
40 ÷ 5 = 8 × 20 = 160 mg hydrocortisone
(hydrocortisone also adds strong salt retention at that dose)
Uses
- Replacement: Addison disease (hydrocortisone + fludrocortisone), congenital adrenal hyperplasia, hypopituitarism.
- Inflammatory and autoimmune disease: asthma (inhaled: beclometasone, budesonide), COPD exacerbations, rheumatoid arthritis, SLE, vasculitis, inflammatory bowel disease, nephrotic syndrome in children, autoimmune hepatitis, skin disorders (topical).
- Allergy: anaphylaxis (adjunct after adrenaline), angioedema.
- Immunosuppression: transplants, haematological cancers (lymphoma, ALL).
- Others: cerebral oedema (tumours), fetal lung maturation (dexamethasone or betamethasone in preterm labour), septic shock (refractory), TB meningitis and pericarditis, giant cell arteritis (prevents blindness), Bell's palsy, croup, hypercalcaemia (sarcoid, myeloma), nausea.
Adverse effects of long-term use
Remember "CUSHINGOID":
- Cataracts, glaucoma.
- Ulcers (peptic, especially with NSAIDs).
- Skin thinning, striae, bruising, acne, poor wound healing.
- Hypertension, hyperglycaemia (steroid-induced diabetes), hypokalaemia, fluid retention.
- Infections (masked signs; TB reactivation, oral thrush with inhaled steroids), immunosuppression.
- Necrosis of the femoral head (avascular necrosis).
- Growth suppression in children.
- Osteoporosis (fractures) – give bone protection in long courses; obesity (central, moon face, buffalo hump).
- Insomnia, mood change, psychosis, euphoria.
- Diabetes, proximal myopathy, and adrenal suppression.
Adrenal suppression and stopping steroids
Exogenous steroids suppress ACTH → the adrenal cortex atrophies.
- After use for more than about 3 weeks (or repeated courses, or high doses), stopping suddenly can cause adrenal insufficiency (hypotension, hypoglycaemia, hyponatraemia, collapse). Taper the dose.
- Sick-day rules: during significant illness, surgery or trauma, increase (often double) the steroid dose; give IM/IV hydrocortisone if vomiting.
- Carry a steroid card.
- Acute adrenal crisis: IV hydrocortisone (100 mg in adults), IV fluids (saline), glucose; treat the cause.
Expect: levothyroxine monitoring (TSH) and starting doses, carbimazole vs PTU (T4 → T3, pregnancy trimesters, liver toxicity), agranulocytosis warning, iodine (Wolff-Chaikoff, pre-operative), radioactive iodine contraindications, thyroid storm management, glucocorticoid mechanism (lipocortin, phospholipase A2), relative potency (dexamethasone, fludrocortisone), uses (cerebral oedema, fetal lung maturity), long-term adverse effects, adrenal suppression, tapering and sick-day rules.
Quick revision
- Levothyroxine: monitor TSH; start low in elderly and heart disease.
- Carbimazole and PTU: thyroid peroxidase; PTU also blocks T4 → T3; PTU in first trimester; PTU hepatotoxic.
- Sore throat on thionamide → stop and check neutrophils.
- Iodine: Wolff-Chaikoff; before surgery. Radioiodine: not in pregnancy.
- Prednisolone 4×, dexamethasone 25× hydrocortisone; fludrocortisone mainly mineralocorticoid.
- Long-term steroids: Cushingoid, osteoporosis, diabetes, infections, cataract, ulcers.
- Taper after more than 3 weeks; sick-day rules; adrenal crisis → IV hydrocortisone.
Written by The House Job from standard pharmacology references (Katzung's Basic and Clinical Pharmacology).
FAQ
How does propylthiouracil differ from carbimazole?
Both inhibit thyroid peroxidase, but propylthiouracil also blocks conversion of T4 to T3 in the tissues; it is preferred in the first trimester of pregnancy and in thyroid storm, but carries a higher risk of serious liver damage.
What should a patient on carbimazole do if they develop a sore throat?
Stop the drug and have an urgent full blood count to check for agranulocytosis.
Which steroid has no mineralocorticoid activity?
Dexamethasone (and betamethasone).
Why must long-term steroids be tapered?
They suppress ACTH and the adrenal glands; stopping suddenly can cause acute adrenal insufficiency.