(3) CARBACHOL (Carbamylcholine )   • Carbachol is is an ester of carbamic acid and poor substrate for AChEsterase. It is biotransformed by other esters at very slow rate.    • Carbachol has both Muscarinic and Nicotinic actions. Functions   (i) Actions :    • Carbachol has profound effects on both Cardiovascular system and GI system.    • It has ganglion stimulating activity and it may first stimulate and then depress these systems.    • It can cause release of epinephrine from adrenal medulla by its nicotinic functions.   On Eye :     • It cause miosis    • It cause spasm of accomodatiom in which the ciliary muscle of the eye remains in a constant state of contraction.    • Carbachol is also used to stimulate micturation by contraction of detrusor muscle. (ii) Therapeutic uses :     • Carbachol has high potency, receptor non-selectivity and relatively long duration of action.     • Carbachol is rarely used.     • Carbachol administered ocularly to induce miosis to reduce the intr

Cholinergic Agonists (direct acting)  • Cholinergic agonists mimic the effect of acetylcholine by binding directly to cholinoceptors (muscarinic & nicotinic).   • These agents are classified into 2 groups;     (1) Choline esters : it includes endogenous ACh and synthetic esters of choline. Such as Carbachol & Bethanechol .     (2) Naturally occuring Alkaloids : Nicotine & Pilocarpine .    • All direct-actings Cholinergic drugs have longer duration of action than Acetylcholine.    (1) ACETYLCHOLINE   • ACh is the quaternary ammonium compound that cannot penetrates membranes.    • It is nuerotransmitter of parasympathetic, somatic nerves & autonomic ganglia.    • It lacks the therapeutics importance b/c of multiple actions and its rapid inactivation by the cholinesterases.    • ACh has both muscarinic and nicotinic activity.    Functions :     (a) Decrease in heart rate and cardiac output :      • ACh mimics the effects of vagal stimulation on the heart.      • If in

 •Drugs affecting the autonomic nervous system(ANS) are divided into two groups according to the type of neuron involved in mechanism of action.    •The cholinergic drugs, which act on receptors activated by acetylcholine(Ach), Where as adrenergic drugs act on receptors stimulated by epinephrine or norepinephrine.    •The cholinergic drugs act by either stimulating or blocking the receptors of the ANS.  The cholinergic neuron   • The preganglionic fibres terminating in adrenal medulla.    • The postganglionic fibres of parasympathetic division use ACh as a neurotransmitter.  The postganglionic sumpayhetic division of sweat glands also uses ACh.    • Ina ddition, cholinergicneurons innervate the muscles of somatic system and play an important role in CNS.  NEUROTRANSMISSION @ CHOLINERGIC NEURON :   • Neurotransmission at cholinergic neurons involves 6 sequential steps :   (1) Synthesis of ACh   (2) Storage of ACh    (3) Release of ACh   (4) Binding of ACh to the receptor   (5) Degradati