Parathyroid Hormone and Its Physiological Role
Parathyroid hormone (PTH) is an 84-amino-acid polypeptide. Its secretion is tightly regulated by the calcium-sensing receptor (CaSR) located on the membranes of parathyroid gland cells. When extracellular calcium ion concentrations drop, the receptor is triggered, increasing hormone secretion.
The primary function of PTH is to raise serum calcium levels. This is achieved through three main mechanisms:
- Bone: PTH stimulates osteoclast activity, leading to the mobilization of calcium from bone stores directly into the bloodstream.
- Kidneys: Increases renal tubular calcium reabsorption (reducing urinary calcium excretion) while increasing phosphate excretion (phosphaturic effect, acting as an antagonist to calcium).
- Intestines: Indirectly enhances intestinal calcium absorption.
- Additionally, PTH acts synergistically with vitamin D by increasing the renal synthesis of calcitriol, which further promotes calcium retention.
Parathyroid Preparations
In clinical practice, Parathyreoidinum is used to manage parathyroid hypofunction (e.g., in spasmophilia or tetany). This is a natural biological extract derived from bovine parathyroid glands, administered parenterally (subcutaneously or intramuscularly).
A critical pharmacokinetic feature of this preparation is its long latent period. The clinical effect develops only 4 hours after injection and lasts for about 24 hours. Consequently, acute tetany management requires administering calcium salts first for immediate symptom relief, followed by parathyroid extract.
Long-term therapy can lead to tachyphylaxis (tolerance). Once hypocalcemia is resolved, the drug is discontinued immediately. Subsequent maintenance therapy relies on vitamin D supplements and a high-calcium, low-phosphorus diet.
Calcitonin: Mechanism of Calcium Reduction
Calcitonin is a 32-amino-acid polypeptide synthesized by the parafollicular C-cells of the thyroid gland. Unlike PTH, its secretion is stimulated by hypercalcemia (elevated plasma calcium).
The mechanism of action of calcitonin aims to lower blood calcium levels:
- Bone: It inhibits osteoclast activity, reducing bone resorption (breakdown) and halting decalcification.
- Kidneys: It decreases the reabsorption of both calcium and phosphates in the proximal tubules.
- Central Nervous System: The hormone exerts a pronounced analgesic effect.
Clinical Application of Calcitonin
Pharmacology utilizes both natural calcitonin extracts and synthetic analogs. A classic example is calcitrin (Calcitrinum), extracted from porcine thyroid glands and administered intramuscularly or subcutaneously.
Key indications include:
- Prevention of osteoporosis progression.
- Paget's disease of bone (osteitis deformans).
- Delayed fracture healing.
- Bone pain caused by osteolysis.
Use may be accompanied by adverse effects, such as vascular reactions (increased blood pressure, flushing) and dizziness. Calcitonin preparations are strictly contraindicated in hypocalcemia and in children under 6 years of age due to insufficient clinical data.
Synthetic Salmon Calcitonin
Special mention should be made of Miacalcic, a synthetic analog of salmon calcitonin. Its primary advantage over mammalian calcitonin is a significantly higher affinity for human receptors, providing a more potent and prolonged therapeutic effect.
- The drug is available as a convenient metered nasal spray (typically containing 14 doses of 200 IU each). A daily dose of 200–400 IU can be administered at once. The onset of action occurs within an hour after instillation, and the elimination half-life ranges from 16 to 43 minutes. Its safety profile, indications, and contraindications are identical to those of native calcitonin.