Dr.Muhammad Ahmed

Contents Ans Sympathetic Parasypathetic Muscaranic receptors

Learning Objectives To understand the Ans ClassifyParasympathomimetics& Sympathomimetics drugs Explain Mechanism of action Describe the effects of cholinergic drugs. Demonstrate the effect of cholinergic and anti cholinergic drugs in mice.

ANS The Autonomic nervous system maintains maintains the internal enviornment of the body called HOMEOSTASIS. Role of ANS in homeostasis links to target organs CVS. Smooth muscle of GI and gland

Effect of drug on ANS Drugs affecting the ANS are divided into two groups. According to the type of neurons involved in their mechanism of action Cholinergics – Acts on the receptors stimulated by Ach Adrenergics - Acts on the receptors stimulated by Norepinephrine

Parasympathomimetics& Sympathomimetics Drugs that produce Parasympathetic like actions Parasympathomimetics Cholinergics Drugs that oppose Parasympathetic Parasympatholytic Anticholinergics Drugs that produce sympathetic like action Sympathomimetics Adrenergics Drugs that oppose sympathetic Sympatholytics Antiadrenergics

Parasympathomimetics Drugs Drugs that stimulate muscarinic receptors Direct Parasympathomimetics Indirect Parasympathomimetics (Anti-cholinesterases) Direct Parasympathomimetics: They stimulate the muscarinic receptors directly. Indirect Parasympathomimetics (Anti-cholinesterases): They inhibit cholinesterase enzyme leading to accumulation of endogenous acetylcholine at both muscarinic and nicotinic receptors Mechanism of action

Sites of Cholinergic Activity -Preganglionic synapses of both sympathetic and parasympathetic ganglia - Parasympathetic postganglionic neuroeffector junctions - All somatic motor end plates on skeletal muscles M2M4M5M3M1 Adenylyl cyclase cAMP Hyperpolarization (heart) Cardiac inhibition Antagonism of smooth muscle relaxation RECEPTOR INTRACELLULAR TRANSDUCER ELECTRICAL MECHANICAL PHYSIOLOGICAL RESPONSES Phospholipase C Diacyl-glycerol IP 3 Depolarization Smooth muscle contraction Glandular secretion

Muscarinic receptor types experiments that led to their discovery M1 - Neurotransmission in Cortex and Ganglia M2 - Agonist-mediated bradycardia, tremor, autoinhibition of release in several brain regions M3 - Smooth muscle contraction, gland secreation, pupil dilation, food intake and possibly weight gain M4 and M5 – Central Nervous System (CNS) roles.

Cholinergic agonists Cholinergic agonists mimic the effects of acetylcholine by binding to cholinoceptors. These agents are synthetic esters of choline such as carbachol and bethanechol and naturally occurring alkaloids such as Pilocarpine. All are direct acting cholinergic drugs. They have longer duration of action than acetyl choline.

Pilocarpine preferentially binds to muscarinic receptors and is sometimes referred to as muscarinic agents. Pilocarpine causes salivation and promote sweating.

The toxic potential of cholinergic stimulants varies markedly depending on the absorption of the drug. Pilocarpine causes predictable signs of muscarine excess when given overdoses. Their effect include, nausea, vomiting, diarrhea, salivation, urgency of micturation, sweating, Cutaneous vasodilatation, and bronchial constriction..

All these effects are blocked competitively by atropine