ANTICHOLINERGIC DRUGS: CHOLINORECEPTOR BLOCKERS & CHOLINESTERASE REGENERATOR

1) ANTIMUSCARINIC ( M-receptor antagonists)

a) selective:

*DARIFENACIN: like atropine but modest selectivity for M3 receptors, tertiary amine, used in urinary urgency and incontinence, may cause exagerated parasympatholytic effect

*FESOTERODINE as darifenacin

*SOLIFENACIN as darifenacin

*TOLTERODINE as darifenacin

*PIRENZEPINE: significant M1 selectivity, used for peptic disease; may cause excessive parasympatholytic effect

*TELENZEPINE: as pirenzepine

b)nonselective: other than natural are synthetic

*ATROPINE natural!: does not distinguish between M1, M2, M3; lipid soluble; duration 2-4 h (excluding eye: more than 72hrs!!) used as mydriatic, cycloplegic, antidote for cholinesterase inhibitor toxicity ( stops exagerated muscarinic activity),used in retinal examination, may cause all parasympatholytic effects plus sedation, delirium, hyperthermia and flushing, icreased IOP in glaucoma, may interact with other antimuscarinics

action on:

#heart: small dose=>decrease in HR ca.4,5 BPM: M1 recreptors// higher dose=>inrease in HR ca.30,40 BPM: M2 receptors

#BP: small dose=> none// higher dose: can decrease BP ( property used during heart attack)

#skin vasodilation: skin is red in colour after atropine

#secretions: small dose=> decrease in secretion of bronchial secretions, sweat, saliva// higher dose: decrease in GI secretions

#eye: mydriasis & cycloplegia

#CNS: small dose=> none// higher dose=>CNS excitation, anxiety, halucinations, psychosomatic symptoms ( more evident in oldies)

*BENZOTROPINE: used in Parkinson's disease

*DICYCLOMINE: competitive antagonism at M3 receptors , reduces smooth mm and secretori activity of gut, acts up to 6 hrs, ,for gastrointestinal applications ( irritable bowel syndrome, minor diarhea), may cause tachycardia, confusion, urinary retention

=> similar to dicyclomine is GLYCOPYRROLATE & HYOSCYAMINE ( acts longer)

*HOMATROPINE (acts 12-24h), CYCLOPENTOLATE(acts 3-6h) , TROPICAMIDE( acts 15-60 min): used in producing mydriasis and cycloplegia

*TROPICAMIDE: M4 receptors: used in Alzheimer's

*IPRATROPIUM: competitive nonselective antagonist of all M receptors; reduces/prevents bronchospasm, used in COPD and as prevention in acute episodes of bronchospasms (asthma), may cause xerostomia, cough, interacts with other antimuscarinics

*OXYBUTYNIN: slightly M3 selective, reduces detrusor muscle tone and spasms, used in urge incontinence and postoperative spasms, may cause tachycardia, constipation, increased IOP, xerostomia. May interact with other antimuscarinics.

*SCOPOLAMINE natural! unknown mechanism in CNS; reduces vertigo and postoperative nausea, used in prevention of motion sickness, postop. nausea and vomiting; can cause tachycardia, blurred vision, xerostomia, delirium

*TROSPIUM: quetrnary amine, less CNS effect, used in urinary urgency

*TRIHEXYPHENIDYL: used in Parkinson's diesease ( ALSO TRIDIHEXYPHENIDYL)

2)ANTINICOTINIC (N-receptor antagonists)

---->nondepolarizing!!!

a) NN receptors

*HEXAMETHONIUM

*TRIMETHAPAN

*MECAMYLAMINE

b) NM receptors

#iso-quinone derrivatives

*TUBOCURARINE: antagonist at skeletal muscle nACh receptors, especially at neuromuscular junctions, causes ANS ganglion block CAN BE REVERSED BY AChE INHIBITORS LIKE NEOSTIGMINE; prevents depolarization by ACh, causes flaccid paralysis. Can cause histamine release with hypotension. Duration of action ca. 40-60min

*ATRACURIUM: antagonist at skeletal muscle nACH receptors, slight ability to release of histamine, metabolized by LAUDANOZINE (active metabolite, penetrates BBB, can lead to convulsions).Used in gas for, used as muscle relaxant, undergoes hepatic metabolism ans spontaneus breakdown ( Hofmann elimination), metabolic derrivatives readily cross BBB, may cause seizures in high concetrations, recently replaces by cistakurium (stereoisomer)

*CISATRACURIUM: spontaneous inactivation, quite safe for patients with cardiac problems, antagonizes effects of histamine, safer than atracurium

-> the most sensitive for this drug ale facial muscles: firstly undergo paralysis--> than limbs, trunk, diaphragm.

*MIVACURIUM: plasma ChE

#steroids

*PANCURORIUM: moderately blocks cardiac muscarinic receptors, undergoes renal elimination

*ROCURORIUM: undergoes hepatic metabolism

*VECURONIUM

--> DEPOLARIZING!

*SUCCINYLCHOLINE: agonist of ACh-N receptors causing initial twitch when persistent depolarizing; stimlates ANS ganglia and M receptors; short action( 5-10 min), inactivated by plasma esterases (butyrylcholinesterase&pseudocholinesterase: in liver and plasma), used in anaesthetic procedure when placing endotracheal tube, control of muscle contractions in status elipticus, may cause muscle pain, hyperkalemia, increased intragastric and IOP pressure

Cholinolytic side effects ( in general): PHYSOSTIGMINE AS AN ANTIDOTE! ( WHILE ATROPINE IS AN ANTIDOTE FOR CHOLINOMIMETIC POSIONING!!)

RED AS A BEET->FLUSHES

BLIND AS A BAT->CYCLOPLEGIA

DRY AS ABONE->DECREASED SWEATING

AGRESSIVE AS TIGER-> EXCITATION OF CNS