Title 11. CHOLINERGIC AND ANTICHOLINERGIC DRUGS AND NEUROMUSCULAR BOCKERS.pdf ✅

PHARMD GURU Page 1 CHOLONERGIC SYSTEM CHOLINERGIC TRANSMISSION: Acetylcholine (ACh) is the neurotransmitter in the cholinergic system. The neurons that synthesize, store and release ACh are called cholinergic neurons. SYNTHESIS OF ACETYLCHOLINE: Choline enters the cholinergic neuron by carrier-mediated transport, where it reacts with acetyl-CoA with the help of choline acetyltransferase (ChAT) to form ACh. The ACh is then stored in storage vesicles. It is released into the synaptic deft when an action potential reaches the nerve terminals. The released ACh interacts with cholinergic receptors on effector cell and activates them. In the synaptic deft, the ACh is rapidly hydrolysed by acetylcholinesterase (AChE) enzyme. CHOLINERGIC AND ANTICHOLINERGIC DRUGS NEUROMUSCULAR BLOCKERS Fig: Synthesis, storage and fate of released Ach at the cholinergic nerve endings, ChAT, Choline acetyltransferase, AChe, acetylcholineserase.
PHARMD GURU Page 2 CHOLINESTERASES: Acetylcholine is rapidly hydrolysed to choline and acetic acid by enzymes cholin- esterases. There are two types of cholinesterases: 1. True cholinesterase or AChE: It is found in cholinergic neurons, ganglia, RBCs and neuromuscular junction (NM)). It rapidly hydrolyses ACh and methacholine. 2. Pseudocholinesterase or butyrylcholinesterase: It is found in Plasm, liver and glial cells. Pseudocholinesterase can act on a wide variety of esters including ACh (hydrolysis is slow) but does not hydrolyse methacholine. CHOLINERGIC RECEPTORS: They are divided broadly into two types—muscarinic and nicotinic. Muscarinic receptors are further divided into five different subtypes: M1-M5. Only M1, M2 and M3 are functionally recognized. M4 and M5 subtypes are found in the CNS. All muscarinic receptors are G-protein-coupled receptors and regulate the production of intracellular second messengers. Nicotinic receptors are divided into two subtypes—NN and NM . Activation of these receptors directly open the ion channels and causes depolarization of the membrane. The characteristics of muscarinic and nicotinic receptors are shown in Table 2.2.
PHARMD GURU Page 3 TABLE 2.2 CHARACTERISTICS OF MUSCARINIC AND NICOTINIC RECEPTOR SUBTYPES: RECEPTOR TYPE(S) CELLULAR RESPONSE FUNCTIONAL RESPONSE M1 & M3 ↑Inositol triphosphate(IP3) and ↑Diacylglycerol (DAG)  Increases learning and memory.  Promotes glandular secretion and smooth muscle contraction. M2 ↓Cyclic adenosine monophosphate(Camp), opening of K+ channels HYPERPOLARIZATION  Depresses SA node  Depresses AV node  Decreases atrial and ventricular contraction NN Opening of Ion channels (Na+, K+) DEPOLARIZATION  Release of adrenaline and noradrenaline from adrenal medulla NM Opening of ion channels (Na+, K+)  Depolarization  Skeletal muscle contraction
PHARMD GURU Page 4 CHOLINERGIC AGENTS (CHOLINOMIMETICS, PARASYMPATHOMIMETICS): Acetylcholine is a quaternary ammonium compound and is rapidly hydrolyzed by cholinesterases. Hence, it has no therapeutic application. It has to be given intravenously to study its pharmacological actions. Even when given intravenously, a large amount of the drug is destroyed by pseudocholinesterases in blood. CLASSIFICATION: