Endocrine Pharmacology

Endocrine pharmacology encompasses drugs affecting insulin and glucose metabolism, thyroid function, and adrenocortical hormones — all critical to managing common chronic diseases.

Insulin is a peptide hormone that cannot be given orally. Modern insulin formulations are designed to mimic physiological insulin secretion. Rapid-acting insulins (lispro, aspart, glulisine) have onset within 15 minutes and duration 3–5 hours, mimicking meal-related spikes. Regular insulin has onset 30–60 min. Intermediate-acting NPH (isophane) provides basal cover for 12–18 hours. Long-acting analogues (glargine, detemir, degludec) have onset 1–4 hours and flat, peakless profiles lasting 20–24 hours (degludec up to 42 hours), providing stable basal insulin with lower hypoglycaemia risk than NPH. Hypoglycaemia is the main adverse effect of all insulins; risk is increased by missed meals, exercise, alcohol, and renal impairment (reduced insulin clearance).

Oral hypoglycaemics target different aspects of type 2 diabetes pathophysiology. Metformin (biguanide) is first-line: it activates AMPK, reducing hepatic gluconeogenesis and improving peripheral insulin sensitivity. It does not cause hypoglycaemia and may modestly reduce cardiovascular events. It is contraindicated in eGFR <30 mL/min due to lactic acidosis risk. Sulfonylureas (glipizide, glibenclamide, gliclazide) close ATP-sensitive K+ channels on pancreatic beta cells, triggering depolarisation and insulin release — independent of glucose concentration, hence hypoglycaemia risk. They are less preferred in the elderly. SGLT2 inhibitors (empagliflozin, dapagliflozin) block sodium-glucose cotransporter 2 in the proximal tubule, reducing glucose reabsorption and causing glycosuria. Beyond glucose control, they reduce cardiovascular mortality and hospitalisation for heart failure, and slow CKD progression — major benefits confirmed in landmark trials (EMPA-REG, DAPA-HF, CREDENCE). GLP-1 receptor agonists (semaglutide, liraglutide) mimic incretin hormones, stimulating glucose-dependent insulin release, suppressing glucagon, slowing gastric emptying, and reducing appetite. They also reduce cardiovascular events and cause significant weight loss.

Thyroid pharmacology: hypothyroidism is treated with levothyroxine (thyroxine, T4), a synthetic thyroid hormone taken once daily on an empty stomach. Hyperthyroidism is treated with carbimazole (first-line in New Zealand), which inhibits thyroid peroxidase, blocking thyroid hormone synthesis. Propranolol provides rapid symptom relief (palpitations, tremor) by blocking beta-adrenergic effects of excess thyroid hormone before carbimazole achieves its full effect after 4–6 weeks.

Corticosteroids (prednisolone, dexamethasone, hydrocortisone) bind glucocorticoid receptors, translocating to the nucleus to modulate gene expression. Anti-inflammatory effects include reduced prostaglandin synthesis (via lipocortin inhibition of phospholipase A2) and suppression of cytokine production. Long-term adverse effects include: adrenal suppression (hypothalamic-pituitary-adrenal axis suppression — requires gradual withdrawal), osteoporosis, Cushing's syndrome (central obesity, striae, moon face), hyperglycaemia, cataracts, and infection susceptibility. In New Zealand, prednisolone is widely used in asthma, inflammatory bowel disease, and rheumatological conditions.