Autonomic Nervous System (ANS)Cholinergic Drugs -2أ0م0د0وحدة بشير اليوزبكي
Objectives
At end of this lecture, the students should be able to: 1- Identify functions of the PSNS. 2- List the effects of stimulation of cholinoceptors. 3- State the classification of cholinergic drugs. 4- Discuss the direct acting cholinergic drugs. In a way, consistence with standards scientific curriculum for the College of Medicine/ University of Mosul. .Functions of the PSNS
- The parasympathetic system maintains essential body functions, such as digestive processes and elimination of wastes. - It is generally dominant over the sympathetic system in "rest and digest" situations. - The parasympathetic system is: 1- Not a functional entity as such. 2- Never discharges as a complete system 3- The system functions to affect specific organs, such as the stomach or eye.Effects of stimulation of cholinoceptors at the postganglionic nerve endings (Ach)
1- Eye: * Meiosis (decrease pupil size)& spasm of the cilliary m, so the eye is accommodated for near vision. * Decrease I.O.P (The iris is pulled away from the angle of anterior chamber & trabecular mesh work at base of cilliary muscle open so facilitate outflow of aqueous humor into canal of schlem which drain anterior chamber of eye).Effects of stimulation of cholinoceptors at the postganglionic nerve endings (Ach)
2- Exocrine glands: * Increase secretion especially of salivary, lachrymal, bronchial, and sweat gland. 3- Heart: * Bradycardia (decrease heart rates), with A-v block & eventually cardiac arrest. Notes: The action of Ach on heart mimic vagal stimulation. - Vagal activity regulates the heart by the release of Ach at SA node.Effects of stimulation of cholinoceptors at the postganglionic nerve endings (Ach)
4- Bronchi: a- Contraction of bronchial muscle lead to Bronchoconstriction b- Increase secretion (lead to symptoms in asthmatic). 5- Alimentary tract (GIT): a- Increase motor activity colicky abdominal pain b- Increase exocrine secretion. c- Sphincter tone is reduced & patient may defecate unconsciously d- Lower esophageal sphincter tone (LOS) is reduced , so create a risk of regurgitation & inhalation .Effects of stimulation of cholinoceptors at the postganglionic nerve endings (Ach)
6- Bladder and uterus: - The tone of detrusor muscle is increased so cause contraction & the drug promote micturation. Note: Human uterus is not notably sensitive to muscarinic agonists. 7- N-m junction: Muscle fasciculation.
Effects of stimulation of cholinoceptors at the postganglionic nerve endings (Ach)
8- CNS: - Stimulation followed by depression, mental excitement with confusion, restlessness, insomnia, tremors & even convulsions. 9- Bd vessels: - Ach cause vasodilatation & decrease Bdp. Note: Although no innervations of vasculature by PS exist, there are cholinergic receptor (non innervated cholinergic receptor (MR)) on blood vessels that respond causing vasodilatation.Cholinergic agents, Cholinomimetic drugs, parasympathomimetic drugs
Definition: Are drugs that directly and indirectly promote the function of the neurotransmitter Ach. Mechanism of cholinergic drugs: It has a mimic action of Ach, it binds with receptors on cell membrane of the target organ, changes the permeability of the cell membrane & permitting Ca and Na to flow into the ceIls, this depolarization in the cell membrane causing response.Classification of cholinergic drugs
1. Direct acting: Includes: a- Choline ester: Ach, Bethanechol, Carbachol. b- Alkaloid: Pilocarpine, Muscarine, Nicotine.2- Indirect acting cholinergic agents: a- Indirect acting reversible: 1- Short acting: edrophonium. 2- Intermediate & long acting: neostigmine, physostigmine, pyridostigmine, tacrine. b- Indirect acting irreversible (very long acting): The organophosphorous e.g. echothiophate. Isoflurophate.
1. Direct acting cholinergic drugs
They work by binding directly & activate to the muscarinic and or nicotinic receptors. a- Choline ester: 1- Acetylcholine (Ach): quaternary ammonium compound - Ach has both M & N activity. Note: - Ach as a drug is therapeutically of no importance because of: 1- Multiplicity of action. 2- Rapid inactivation by Ach esterase enzyme.1. Direct acting cholinergic drugs
a- Choline ester: 2- Bethanechol It is structurally related to acetylcholine; the acetate is replaced by carbamate and the choline is methylated. Because, it is not hydrolyzed by Achesterase, although it is inactivated through hydrolysis by other esterases, it has a longer duration of action of about 1 hour.1. Direct acting cholinergic drugs Bethanechol
Action: - It does have strong muscarinic activity mainly but it has little or no nicotinic actions. - Its major actions are on the smooth musculature of the bladder and GIT. Therapeutic applications of Bethanechol: - In urologic treatment, is used to stimulate the atonic bladder, particularly in postpartum or postoperative non obstructive urinary retention.