Physiology and Mechanism of Action
Endogenous calcitonin is a 32-amino acid polypeptide secreted by C-cells (parafollicular cells) of the thyroid gland. The physiological stimulus for increased secretion is hypercalcemia (elevated plasma $Ca^{2+}$ level).
The pharmacodynamics of the drug are mediated through three main sites of action:
- Bone tissue: Calcitonin decreases osteoclast activity, leading to reduced bone resorption (breakdown) and inhibition of demineralization.
- Kidneys: It decreases the reabsorption of calcium and phosphates in the proximal tubules, promoting their excretion.
- Central nervous system (CNS): Calcitonin exerts a pronounced analgesic effect, acting as a co-analgesic.
Net effect: A rapid and sustained reduction in plasma calcium ion concentration.
Comparative Characteristics of Preparations
Both natural and synthetic calcitonin preparations are used in clinical practice:
- Calcitrin (Calcitrinum): A natural preparation extracted from porcine thyroid glands, administered parenterally (intramuscularly or subcutaneously).
- Miacalcic (Miacalcic): A synthetic analogue of salmon calcitonin.
Advantages of synthetic salmon calcitonin: Compared to mammalian calcitonin, it exhibits a higher affinity for human receptors, providing a longer and more pronounced therapeutic effect.
Indications for Use
Calcitonin preparations are prescribed for conditions associated with bone loss or pathological bone remodeling:
- Osteoporosis: Prevention of disease progression.
- Paget's disease (osteitis deformans).
- Traumatology: Delayed fracture healing.
- Bone pain: Associated with osteolysis (bone tissue destruction). In this context, calcitonin acts as an adjuvant analgesic, effectively managing specific pain syndromes that standard analgesics fail to relieve.
Adverse Effects and Contraindications
The safety profile is similar for both endogenous-derived and synthetic calcitonin preparations (such as Miacalcic).
Adverse effects:
- Vascular reactions: Flushing («hot flashes»), increased blood pressure.
- Neurological disorders: Dizziness.
Contraindications:
- Pre-existing hypocalcemia (since the drug further lowers calcium levels).
- Children under 6 years of age (due to insufficient clinical safety and efficacy data).
Dosage Forms and Administration
The drug is available in two main pharmaceutical forms:
- Solution for injection: 1 mL ampoules (concentration 100 IU/mL). Standard administration is 100 IU intramuscularly.
- Nasal spray: Metered-dose aerosol in bottles. One bottle typically contains 14 doses, with a concentration of 200 IU per dose. Administered as 200–400 IU into the nasal cavity (the total daily dose may be given at once).
Spray pharmacokinetics: Therapeutic effect begins 1 hour after nasal administration. The half-life ($t_{1/2}$) is short, ranging from 16 to 43 minutes.
Physiological Interactions
To fully understand the pharmacology of calcitonin, its interactions with other hormones must be considered:
- Thyroid hormones (thyroxine, triiodothyronine) enhance tissue sensitivity to calcitonin and parathyroid hormone, ensuring normal osteogenesis.
- Parathyroid hormone (PTH) is a functional antagonist of calcitonin. A drop in blood calcium (including that induced by calcitonin) is detected by calcium-sensing receptors on the membranes of the parathyroid glands, stimulating PTH secretion to mobilize calcium from bones.
- Interesting fact: Calcitonin gene-related peptide (CGRP) is released from sensory nerve endings during axon reflex stimulation (e.g., local irritants), participating in local vasodilation.