GANGLIONIC BLOCKING AGENTS
The Ganglionic blocking agents are drugs which act by competiting with Acetyl choline (Ach) from the cholinergic receptors present in the autonomic post ganglionic neurons.
Since the ganglia of both the sympathetic and parasympathetic nervous systems are cholinergic, these drugs interrupt the outflow through both system.
They are used mostly for their interruption of the sympathetic outflow in hypertension, vasopastic disorders and peripheral vascular disease. Thus lowering the B.P and increasing the peripheral blood flow.
CLASSIFICATION
Based on the mechanism these are classified as follows.
1.By Interfering with Ach release - Triethyl choline, Hemicholinium
2. By interference with post synoptic action of Ach - Eg : Hexamethonium
3. By prolonged depolarization - Eg : Nicotine
NEURO MUSCULAR BLOCKING AGENTS
Agents which blocks the transmission of Ach at the motor end place are called neuromuscular blocking agents. They are used in surgical anesthesia as adjuvant to relax the skeletal muscle.
CLASSIFICATION
1.Natural Compounds – Eg : Tubocurarine chloride, Metocurarine iodide, Pancuronium bromide.
2. Synthetic Compounds - Eg : Gallamine triethiodide, Decamethonium bromide, Pipecuranium bromide, Vecuronium bromide.
Tubocurarine chloride Synthesis
SAR for Neuro muscular blockers
- The drugs have quarternary ammonium group for good activity.
- The type of alkyl group present in quarternary ammonium group determines the charge distribution and binding characters.
- Non depolarizing drugs are bulky and more rigid than depolarizing drugs.
- As the strerric hindrance to receptor increases, the potency decreases. L-tubocurarine is less potent than d-tubocurarine.
- The depolarizing agents (Eg-Decamethonium) have a more flexible structure that enable bond rotation.
- The distance between quarternary ammonium groups can vary up to the limit of maximal bond distance usually 1.0 ± 0.1 nm.
MECHANISM OF ACTION
Neuro muscular blocking agents can block the neuro muscular transmission by
- Inhibiting acetyl choline synthesis
- Inhibiting Ach release and inhibit calcium entry have neuromuscular block.
Interfering with the post synoptic action of Ach. - Non depolarizing blocking agents act by competitive antagonism at Ach receptos of the end plate and these largely accounts for their action.
