Chapter 12: Cholinergic Drugs Affecting

Overview of the CNS: and PNS CNS → brain and spinal cord PNS → motor and sensory neurons → Motor neurons → somatic and autonomic nervous system Autonomic nervous system → sympathetic and parasympathetic division Sympathetic → adrenergic receptors → alpha/beta Parasympathetic → cholinergic receptors → muscarinic Sympathetic is FIGHT OR FLIGHT Parasympathetic is REST AND DIGEST Sympathetic and parasympathetic do not always produce opposite effects. EX: constriction of arterioles is controlled by sympathetic branch. Sympathetic stimulation causes constriction of arterioles and lack causes vasodilation. Sweat glands and controlled by sympathetic nerves. For info to be transmitted thru the NS , neurons have to communicate w each other, muscles and glands. In ANS communication involves 2 neurons – pre synaptic and post synaptic Synapse- separates a neuron from another neuron- its OUTSIDE THE CNS hence its name ganglionic synapse Preganglionic neurons- nerves carrying impulses exiting the spinal cord Postganglionic neurons- nerves on the other side of the ganglionic synapse, waiting to receive impulses Second synapse- comes after the second neuron and terminates AT THE TARGET ORGANS Autonomic drugs are not given to CORRECT physiologic defects,they are given to either STIMULATE or INHIBIT TARGET ORGANS (heart, lungs, glands, digestive tract) *** Ach (Acetylcholine) & norepinephrine (NE) → 2MAIN NEUROTRANSMITTERS OF ANS Ach→ parasympathetic NE→ sympathetic CHOLINERGIC NERVES- are nerves that release ACH 2 types of CHOLINERGIC RECEPTORS → NICOTINIC & MUSCARINIC Nicotinic→ located at the ganglionic synapse (the 1st one) in both parasympathetic and sympathetic Muscarinic→ located on target tissues affected by postganglionic neurons (2 nd synapse) in the parasympathetic side ONLY! Remember for parasympathetic - ACH is released at both synapses Drugs that affect nicotinic receptors cause effects in both autonomic and somatic NS ACTIVATION OF CHOLINERGIC RECEPTORS CAUSES → tachy, HTN, increase tone and mobility of digestive tract Nicotinic receptor blockers (ganglionic blockers) - produce controlled hypotension during sx or HTN emergencies ACH receptors affected by the 2nd synapse= classic s/s of parasympathetic stimulation (pupil constrict, salivation increase, low bp, low hr, gallbladder stimulation, GI stimulation, bronchiole constricts, stimulates erection in med, lubrication in female) Little more on ACH→ synthesized by Acetyl coA and choline→ stored in vesicles in presynaptic neuron waiting for an action potential→ once action potential gets there it fuses w the axon terminal membrane→ ACH is released into the synaptic cleft→ diffuses across to find nicotinic/muscarinic receptors→ ACH in the synaptic clef that is not bound to receptor is destroyed by ACHE (acetylcholinesterase) → choline in ACH is reused , taken up by presynaptic neuron to make more ACH→ CYCLE REPEATS. Drugs affecting parasympathetic NS: parasympathomimetics and anticholinergics Parasympathomimetics- aka CHOLINERGIC DRUGS → produce s/s of rest-digest response – STIMULATE PARASYMPATHETIC NS Anticholinergics- aka cholinergic blocking drugs → produce actions opposite those of the cholinergic drugs – INHIBIT THE PARASYMPATHETIC NS Remember autonomic system drugs don’t correct, they will only INHIBIT action or STIMULATE IT Parasympathomimetics divided into 2 classes→ 1) DIRECT ACTING (muscarinic receptor agonists) 2) INDIRECT ACTING (cholinesterase inhibitors/indirect inhibitors of ACHE enzyme) Direct acting parasympathomimetic/cholinergics: BIND DIRECTLY TO MUSCARINIC RECEPTORS- hence their name muscarinic receptor agonists. EX Bethanechol – BIND to cholinergic receptors to produce rest and digest response and s/s; BC they are resistant to AChE , they have a LONGER DURATION OF ACTION Cholinergic drugs – poorly absorbed in GI and DO NOT cross BBB Have little effect on ACH receptors in ganglia- moderately selective to muscarinic receptors ONLY , which is why AKA as MUSCARINIC RECEPTOR AGONISTS. Indirect acting parasympathomimetics/cholinesterase inhibitors : Note: almost all drugs in this class have “stigma/stigmine” in the name. + donepezil(Aricept) and galantamine (razadyne) Ex: neostigmine (Prostigmin) INHIBIT ACTIONS OF AChE which = < destruction of Ach → = longer duration of Ach That’s why these drugs AKA as cholinesterase inhibitors They are non-selective- AFFECT ALL Ach SITES: ganglia, muscarinic receptors, skeletal muscle, ach sites in CNS. (other) EX: Physostigma (Antilirium) ______________________________ Parasympathomimetics Have HIGH potential for serious A/E → so not widely used Some used for ophthalmology → to reduce intraocular pressure in pts w glaucoma ( PILOCARPINE [isopto carpine/Salagen] ) Others used for stimulation on smooth muscle of B/B AChE inhibitors also have other functions b/c on their nonspecificity – they have actions on skeletal and CNS Galantamine (Reminyl), donepezil (Aricept) , rivastigmine (Exelon) → GDR meds tx ALZHEIMERS – used to tx Alzheimer’s by increasing amt of Ach in cholinergic synapses of the brain which = IMPROVED MEMORY AND COGNITIVE FUNCTION Myasthenic Gravis- characterized by destroyed nicotinic receptors in skeletal muscles. Tx with pyridostigmine (mestinon/ Regonol) or neostigmtine (Prostigmin) STIMULATES MUSCLE CONTRACTION AND HELPS REVERSE SEVERE MUSCLE WEAKENESS TOO MUCH cholinergic meds→ NOT GOOD Can lead to CHOLINEERGIC CRISIS → s/s include hypersalivation, small pupils, muscle twitching, unusual paleness, sweating, muscle weakness, diff breathing. TX includes→ ATROPINE ADMIN BETHANECHOL (Urecholine) Direct acting parasympathomemtic – interacts w muscarinic receptors to stimulate PARASYMPATHETIC Most effects evident in GI and GU Stimulates smooth muscle contraction Stimulates smooth muscle tone and GI after anesthesia Txts urinary retention in NONOBSTRUCTIVE cases- only in cases d/t lack of muscle tone PO admin Can also be given SQ- 5mg 3-4x/day Monitor BP,HR,RR BEFORE admit ** Pregnancy cat C Use w caution in pts w disorders that cant handle increased contractions of digestive tract → ex: suspected obstruction. Active ulcer, inflammatory disease , urinary obstruction, or COPD s/e – salivation, sweating, abd cramping, hypotension, that could → fainting (PARASYMPATHETIC effects) contraindicated: pts w asthma , epilepsy, seizures, parkinsons, PUD, and hyperthyroidism – can worsen or exacerbate these conditions * effects increased if taken w cholinesterase inhibitors decreased effects if taken w procainamide(heart med), quinidine (heart med), atropine, epi MONITOR LIVER FUNCTION LABS : ALT/AST/ALP & Bilirubin Effects can be increased by angels trumpet, jimson weed and scopolia (herbs/food) TX overdose: ATROPINE SQ or IV (for emergencies) PHYSOSTIGMINE (Antilirium) Antidote for anticholinergic toxicity/ acetylcholinesterase inhibitor An indirect acting parasympathomimetic – inhibitis destruction of Ach by AChE (remember meds in indirect acting parasympathomimetic class have “stigma/stigmine” in the name” ) → physoSTIGMINE Works in neuromuscular junction (At target organ) + at central and peripheral locations where Ach is the neurotransmitter REVERSES toxic life threatening delirium caused by atropine, diphenhydramine, dimenhydramine, atropa belladonna ( Deadly nightshade) or Jimson Weed. Admin – IM OR IV – SLOWLY over 5 mins to avoid SEIZURES and RESP DISTRESS No continuous infusions !!* Monitor BP, HR, RR, for hypersalivation Pregnancy CAT C S/E: bradycardia, asystole, restlessness, nervousness, seizures, salivation, urinary freq, muscle twitching, resp paralysis use w caution in pts w asthma(b/c of r/o resp paralysis), epilepsy (b/c of r/o seizures), cardiovascular disease( b/c of r/o brady and heart block) , brady DC med for excess sweating, diarrhea, freq urination Increased effects if given w cholinergics, beta blockers Meds levels increased by systemic corticosteroids May decrease effects of neuromuscular blocking agents MONITOR LIVER FUNCTION TESTS: ALT/ASL/AST and BILIRUBIN Gingko balboa- increases toxic effects TX OVERDOSE: ATROPINE Pharmacotherapy w cholinergic meds : Continue assessment for therapeutic effects → tol adls, musculoskeletal strength , improvement in droopy eyelid, or double vision, improved chewing and swallowing Monitor B/b if drugs are given post op- will be present if drug is effective (onset 60mins, urination first → peristalsis.) THESE DRUGS NOT GIVEN FOR DECREASED URINE OUPUT DUE TO O B S T R U C T I O N (EX:BPH) Make sure pts have RSTRMS available near, reg toileting schedule Home safety assessment for r/o falls r/t HYPOTENSION Rest periods - > fatigue can lead to cholinergic or a myasthenic crisis in patients Monitor for s/s of excessive ANS, notify md for HR <60 , < BP, tremors, palpitations, urinary retention, dizziness, abd pain, changes in loc, confusion, depression, drowsiness. Orthostatic hypotension precautions Monitor muscle weakness. IF w/in 1 hr→ could indicate OVERDOSE IF w/in 3 hrs→ could indicate UNDERDOSAGE/DRUG RESISTANCE or MYASTHENIC CRISIS Check for subtle changes in muscle strength- voice quality, slurred speech . Monitor LIVER FUNCTION TESTS, ALT, AST, ASL, Bilirubin Provide EYE COMFORT d/t MIOSIS ( eye constriction—think MI-osis→ MINI- eyes ) + nightlight , advise not to drive at night for safety ANTICHOLINERGIC DRUGS – CHOLINERGIC BLOCKING DRUGS Block action of Ach , aka anticholinergics, cholinergic blockers, muscarinic antagonists, parasympatholytics,. At therapeutic doses, drugs are selective for muscarinic receptors and have little effect on Ach Nicotinic receptors. Anticholinergics act by COMPETING w Ach for BINDING SITES on MUSCARINIC RECEPTORS → blocking cholinergic responses at effector organs which → > sympathetic NS actions Therapeutic uses: mydriasis (dilation of pupil) , >HR, dry glandular secretions, relax bronchi (Asthma tX) Other main therapeutic uses for anticholinergics are GI disorders – PUD , slow GI mobility , < cramping and diarrhea r/t IBS Ophthalmic procedures- cause mydriasis (Dialtion) or cyclopegia (paralysis of ciliary muscle of eye) during eye procedures Cardiac rhythm abnormalities- to > HR in pts w brady Anesthesia adjuncts- to reverse anesthesia s/e , HR , bronchodilation, < GI motility, mydriasis, < secretions from glands HAS NO EFFECT ON NICOTINIC RECEPTORS IN GANGLIA OR ON SKELETAL MUSCLE Use has declined d/t newer and safer alternative meds May be used to tx hypermotility diseases of GI → IBS To suppress secretions during sx To > HR in someone w brady Dilate pupils during eye exams For the tx of reflexive brady in infants and infantile hypertrophiv pyloric stenosis Oral and SQ injections not interchangeable Monitor bp, hr, rr before admit and 1 hr after s/e: dry mouth, constipation, urinary retention, > HR (sympathetic effects) CNS excitement can progress to delirium or COMA PTS W GLAUCOMA CANNOT TAKE THIS MED- will increase intraocular pressure Don’t give to pts w GI obstruction, BPH, myasthenia gravis, cardiac insufficiency or acute hemorrhage Interacts w antihistamines, TCAS, quinidine, procainamide - > effects < effects of levodopa TX OVERDOSE : poisoning occurs when kids eat colorful purple berries of the deadly shade and mistake them for cherries. S/S of poisoning: intense PARASYMPATHETIC STIMULATION Can cause CNS stimulation or depression Admin short acting barbiturate or diazepam to control convulsions. PHYSOSTIGMINE is ANTIDOTE , QUICKLY REVERSES COMA caused by large doses of atropine Pharmacotherapy w anticholinergic drugs: Assess for therapeutic effects: HR, BP, RR WNL GI motility and cramping < Proper positioning for dyspnea – raise HOB Sips of water, ice chips, hard candies can help w mouth dryness. + alcohol free rinses (ones w alcohol in them will further dry the mouth) Monitor for s/s of excess ANS stimulation→ drowsiness, blurred vision, tachy, dry mouth , urinary hesitancy, < sweating ANTICHOLINERGICS ARE CONTRAINDICATED IN PTS W ACUTE OR NARROW ANGLE GLAUCOMA- Can > INTRAOCULAR PRESSURE Cardiac monitoring for HR and BP . if HR too > can = dysrhythmias Monitor for abd distention, and listen for bowel sounds Palpate bladder and monitor output Increase fluids and fiber * to prevent constipation d/t decreased GI mobility and bowel movements Minimal exposure to heat and strenuous exercise d/t inhibition of sweat glands , can lead to heat stroke bc body unable to rid heat. → Atropine fever.. + also avoid hot showers S/S of heatstroke→ dizziness, change in loc, pale skin, muscle cramping, nausea. Provide eye comfort d/t mydriasis (eye dilation) → dark room, soft cloth over eyes, sunglasses.