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Stimulation of nerve fibers liberate a substance at the nerve ending which activate a receptor in the organ supplied or another nerve cell This substance known as neurotransmitter
Nervous system
Includes neurons and ganglia outside of the brain and spinal cord
Peripheral Nervous System
Autonomic Nervous System (ANS) Its function involuntarily to regulate the everyday needs & requirements of the body without the conscious participation of the mind
Preganglionic neurons with cell bodies in CNS Postganglionic neurons with cell bodies in autonomic ganglia transmission from autonomic postganglionic neurons to effector organs in:
Parasympathetic system involve release of Ach Sympathetic system involve release of E & NE
Cholinergic Receptors
Two types, determined by:
Location Action once stimulated
1. Nicotinic Receptors
Located in the ganglia of both the PSNS and SNS Affects the skeletal muscle Named nicotinic because can be stimulated by nicotine
2.Muscarinic Receptors
Located mainly postsynaptically:
Smooth muscle Cardiac muscle Glands of parasympathetic fibers Effector organs of cholinergic sympathetic fibers
Adrenergic receptors
A receptor that binds, and activated by one of the catecholamine transmitters norepinephrine, epinephrine, dopamine. Adrenoceptors are classified as or receptors.
The differences between sympathetic & parasympathetic nervous system Sympathetic parasympathetic
Anatomy
The preganglionic The preganglionic neurons arises neurons come from cranial from thoracic & nerves (III. VII, lumbar regions of IX, X)& sacral spinal cord regions Adjusting response to stressful situations Maintain essential body functions
Function
Neurotransmitter
Acetylcholine (Ach)
Receptors
Action on the effector organ
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Parasympathetic Response Constricts pupils Constricts bronchioles and increase secretions Decreases heart rate Dilates Increases peristalsis
Increases heart rate Constricts(skin) Dilates(skeletal muscles) Relaxes smooth muscles of GIT Relaxes bladder muscle Relaxes uterine muscles Decreases salivation
Constricts bladder
Increases salivation
Most visceral organs are innervated by both sympathetic and parasympathetic fibers This results in dynamic antagonisms that precisely control visceral activity
Dual Innervation
Antagonistic effects oppose each other Example:
Sympathetic fibers increase heart and respiratory rates, and inhibit digestion and elimination Parasympathetic fibers decrease heart and respiratory rates, and allow for digestion and the discarding of wastes
Parasympathetic system Acetylcholine (Ach) is rapidly broken down by cholinesterase so not used therapeutically
Ach
acetylcholinesterase
choline + acetate
Giving Ach-like drugs (cholinergic agonists) Using drug that inhibit the action of acetylcholinesterase
2. Pilocarpine Used only as eye drops & causes miosis Uses: The drug of choice in the emergency lowering of intraocular pressure of glaucoma
MOA: prevents the break down of Ach by cholinesterase The actions of Ach are thus intensified at 2 sites of action: The parasympathetic nerve endings The nerve ending in voluntary muscles
Reversible Anticholinesterases Examples: 1. Neostigmine Its effect on NMJ of voluntary muscles & less to the eye & CVS Can be given orally, I.M., S.C. Uses: Treatment of disorders in NMJ of voluntary muscles (myasthenia gravis) Paralytic ileus Bladder atony
2. Physotigmine Has a wide range of action because it stimulates not only muscarinic & nicotinic receptors of ANS but also nicotinic receptors at NMJ Therapeutic uses: As eye drops to produce miosis & accommodation for near vision Atony bladder Antidote of anticholinergic drugs toxicity as Atropine
3.Rivastigmine Used in patients with Alzheimer's disease for the loss of cognitive function.
E.g. Insecticides, War gas, Isoflurophate, Parathion Actions: Generalized cholinergic stimulation (sweating, HR, miosis, salivation, diarrhea, urination, colic, , paralysis of motor function (causing breathing difficulties))
Atropine in doses can reverse many actions of Insecticides Pralidoxime (PAM) can reactivate the inhibited cholinesterase.
Cholinergic Antagonists
1. 2. 3. 4. 5. 1. Muscarinic antagonists: Atropine Given orally, I.M., S.C. Actions: HR Relaxation of bronchial muscles bronchial secretions Dilatation of the pupil (Mydriasis) with an inability to see near object clearly GIT motility & secretion
Therapeutic uses
1. Relief intestinal, biliary or renal colic (given I.V. or S.C.) 2. Locally to the eye to dilate the pupil but homatropine is often used 3. Preoperative medication 4. relief bronchial spasm (ipratropium is given by inhalation to treat asthma)
S/Es: Dry mouth Constipation Urinary retention With doses: Restlessness, Hallucination
2. Hyoscine (Scopolamine)
Similar to atropine but in smaller doses it causes CNS depression
Uses:
Preoperative medication Antiemetic & prevention of motion sickness
2. Neuromuscular Blockers
Agents that block cholinergic transmission between nicotinic receptors & motor nerve endings on the NMJ
2 types: Non-Depolarizing (Competitive) Blockers E.g. Tubocurarine MOA: They block nicotinic receptors & prevent Ach from binding Uses: Therapeutically in anesthesia during surgery as adjuvant drugs to relax skeletal muscles
Depolarizing Agents E.g. Succinylcholine (Suxamethonium) Suxamethonium has a rapid onset & short duration of action & mainly used for rapid endotrachial intubation at the beginning of anesthesia
MOA; The drug attach to the nicotinic receptor & act like Ach to depolarize the junction, but it is not destroyed by cholinesterase, so the continued binding of depolarizing agent renders the receptor incapable of transmitting further impulses, with time membrane repolarizes but receptor is desensitized to effect of Ach