Mechanism of Action and Targets
Ganglionic blockers disrupt nerve impulse propagation from preganglionic to postganglionic fibers of the autonomic nervous system.
Key drug targets include:
- N-cholinergic receptors of autonomic ganglionic neurons (both sympathetic and parasympathetic).
- Chromaffin cells of the adrenal medulla — receptor blockade here decreases the release of endogenous catecholamines (epinephrine and norepinephrine), further enhancing the vasodilator effect.
- Carotid bodies — suppression of reflex excitation of the respiratory and vasomotor centers.
Cardiovascular Effects
The key pathogenetic mechanism in cardiology is the elimination of sympathetic nervous system stimulation on the heart and vasculature.
Due to sympathetic ganglion blockade, the following hemodynamic changes occur:
- Decreased arterial tone and a general drop in blood pressure (BP).
- Venodilation, leading to blood pooling and decreased venous return.
- Decreased central venous pressure and cardiac stroke volume.
Note: The sharp drop in blood pressure often triggers reflex tachycardia and carries a high risk of orthostatic collapse.
Effects of Parasympathetic Ganglion Blockade
Because these drugs are non-selective, they also shut down the parasympathetic system, causing numerous unwanted effects:
- Vision: Cycloplegia (loss of accommodation for near vision). Mydriasis (pupillary dilation) is less pronounced than with muscarinic antagonists.
- Heart: Increased heart rate (tachycardia).
- Smooth muscle: Marked decrease in tone of the gastrointestinal tract (GIT) and urinary bladder.
- Secretions: Inhibition of salivary glands (dry mouth — xerostomia), bronchial, gastric, and intestinal glands.
Unlike muscarinic antagonists (M-blockers), ganglionic blockers do not significantly affect bronchial tone.
Indications and Classification
Due to extensive adverse effects, ganglionic blockers are no longer used for chronic hypertension management. Today, they are reserved for acute situations.
1. Management of Emergencies: Medium-duration agents (acting 2.5–3 hours) are used — azamethonium bromide and hexamethonium. Indications:
- Hypertensive crises.
- Pulmonary edema associated with severe hypertension.
- Peripheral arterial spasms.
2. Surgical Practice ("Controlled Hypotension"): Short-acting ganglionic blockers (duration 10–20 minutes) administered via continuous IV infusion — trimethaphan camsylate and trepirium iodide. Objectives:
- Minimizing surgical field bleeding.
- Preventing cerebral edema during neurosurgery.
- Blocking undesirable reflex cardiovascular responses during anesthesia.
Adverse Effects and Contraindications
Long-term use is impossible due to severe complications.
The main hazard is orthostatic hypotension leading to syncope, caused by blood pooling in dilated veins. For prevention, patients must remain strictly on bed rest for 1.5–2 hours post-injection.
Gastrointestinal and urinary complications include constipation, paralytic ileus (intestinal obstruction), and acute urinary retention.
Absolute Contraindications:
- Marked hypotension, hypovolemia, and shock.
- Acute myocardial infarction.
- Severe hepatic and renal impairment.
- Closed-angle glaucoma (mydriasis blocks the anterior chamber angle, impairing aqueous humor outflow and causing a sharp spike in intraocular pressure).
- Benign prostatic hyperplasia (risk of urinary retention).
- Thrombosis predisposition (decreased blood pressure causes stasis and triggers thrombus formation).
Management of Complications and Overdose
Treatment depends on the predominant symptoms:
- Intestinal or bladder atony: Administration of direct-acting M-cholinomimetics (aceclidine) or anticholinesterase agents (neostigmine bromide).
- Severe hypotension: $\alpha$-adrenergic agonists are used to restore vascular tone and raise blood pressure.
- Respiratory depression: Analeptic agents are indicated in case of ganglionic blocker overdose.