Cholinergic Drugs - Pharm Exam 3

types of cholinomimetic drugs

1. muscarinic

2. nicotinic

effects of cholinomimetic drugs

parasympathetic effects - rest, relax, digest (think opposite of fight or flight); mimics actions of acetylcholine

nicotinic receptors

neuromuscular end plate and skeletal muscle , autonomic ganglion cells , CNS

muscarinic receptors

nerves , heart and smooth muscle , glands and endothelium

cholimomimetic effect on eyes

sphincter muscle of iris and ciliary muscle contract (miosis) ; narrowing of the pupils

cholimomimetic effect on heart

decrease - rate, contractile strength of atria and ventricles, refractory period in atria

increase - refractory period in AV node

cholimomimetic effect on blood vessels

dilation

cholimomimetic effect on lungs

bronchial muscle contraction and bronchial gland secretion (mucus secretion)

cholimomimetic effect on GI tract

motility increased , sphincters relaxed , secretion stimulated (digestion)

cholimomimetic effects on urinary bladder

detrusor muscle contraction , sphincter relaxation

cholimomimetic effect on glands

sweat , salivary , lacrimal , nasopharyngeal secretion

direct acting cholimomimetic

one that binds and activates cholinoceptors (muscarinic receptors) ; two kinds - alkaloids and choline esters ; mimic acetylcholine effects directly

indirect acting cholimomimetic

don’t act on receptors directly but by increasing acetylcholine availability ; increase availability by blocking acetylcholinesterase ; two kinds - reversible and irreversible

examples of direct acting cholimomimetics

choline esters - acetylcholine , methacholine , carbachol , bethanechol

alkaloids - muscarine , pilocarpine , cevimeline

examples of indirect acting cholimomimetics

reversible - physostigmine , neostigmine , pyridostigmine , rivastigmine , galantamine , donepezil

irreversible - echothiophate , sarin , malathion , parathion , soman , diazinon

cholimomimetic clinical uses - eyes

glaucoma (increased intraocular pressure) - pressure reduced by facilitating aqueous humor flow ; 3rd choice drugs (not often used)

iris adhesions - atrophine and pilocarpine together to break adhesions (causes iris muscles contract relax repeatedly to break adhesions)

miotics - used in surgery - carbachol

cholimomimetic drugs clinical uses - myasthenia gravis

first line tx - pyridostigmine , works by blocking ACh breakdown (indirect acting) , sometimes neostigmine used but not often

cholimomimetic drugs clinical uses - neurogenic bladder

bethanechol - helps complete bladder emptying in hypotonic bladder pts, act on M1 receptors to contract detrusor muscle (and relax sphincter)

cholimomimetic drugs clinical uses - urinary retention

post op - prevent and tx urinary distention and retention , usually neostigmine

acute post op and post partum nonobstructive - bethanechol (only nonobstructive - do not want muscle contraction w/ obstruction)

cholimomimetic drug clinical uses - xerostomia

common in sjogren syndrome or post radiation tx head and neck cancer , cevimeline or pilocarpine increase saliva

cholimomimetic drug clinical uses - post op ileus and congenital megacolon

bethanchol to increase tone (aid digestion)

cholimomimetic drug clinical uses - snake bite

neostigmine for neurotoxic (not all) if antivenom unavailable

cholimomimetic drug clinical use - reversal of nondepolarizing blockade after surgery (lingering muscle weakness/ paralysis)

neostigmine preceded by atropine to block muscarinic effects , rapidly reverse muscle paralysis induced by neuromuscular blockers

cholimomimetic drug clinical uses - dementia

mild improvement , cholinesterase inhibitors - rivastigmine , donepezil , galantamine ; increased ACh → increase communication btwn nerve cells in brain

anticholinergic overdose

physostigmine antidote for belladonna or other poisoning , only if life threatening/ severely toxic

toxicity of direct acting muscarinic stimulatns

n/v/d , urinary urgency , diaphoresis , salivation , cutaneous vasodilation , bronchial constriction

tx w/ atropine , 1-2mg parenterally

note - some mushrooms are muscarinic stimulants and pt may present w/ these sx

physiologic response to nicotine

stimulation of - CNS , sympathetic and parasympathetic ganglia , adrenal medulla ; does not relax you

PNS effects of nicotine

tremor , tachycardia , HTN , cutaneous vasoconstriction , increase stomach secretions , increase gut motility

nicotine poisoning

1. CNS - convulsions , coma , respiratory arrest

2. depolarization blockade and respiratory paralysis (every neuron in the body becomes to stimulated/ excited that it goes into a silent state)

3. HTN and arrhythmias

nicotine poisoning tx

1. muscarinic excess tx w/ atropine

2. diazepam used as anticonvulsant if seizures

   note - metabolized and excreted rapidly so pt usually recover if hypoxia not occur

green tobacco poisoning

occurs from handling green tobacco when wet , presents w/ n/v and dizziness

varenicline (chantix)

direct acting nicotinic agonist (partial agonist) used for smoking cessation , somewhat selective for Nn receptor , orally active , half life 14-20 hours , toxicity - ha , increased GI activity , n/v/d , HTN , sleep disturbance ; contraindications - do not use w/ other CNS stimulants

organophosphates

ester of phosphoric acid and an organic etoh that inhibits cholinesterase , readily absorbed through skin , used as insecticides (pesticides) and chemical warfare agents

organophosphate poisoning

miosis , salivation , diaphoresis , bronchial constriction , vomiting , diarrhea

tx - decontamination (clean pesticide residue off pt) , maintenance on vital signs , atropine , cholinesterase regenerator

organophosphate aging

process where after binding to cholinesterase, organophosphate chemically modified and become more firmly bound to enzyme

cholinesterase regenerator

tx organophosphate poisoning , chemical antagonist binds phosphorus of organophosphates → frees up ACh ; reactivates cholinesterase which has been phosphorylated by organophosphate pesticides , minimal penetration into CNS (which requires atropine to reverse CNS effects)

pralidoxime (also known as 2-PAM or protopam)

bethanechol

direct acting choline ester ; MOA muscarinic antagonist , uses - post op and neurogenic ileus and urinary retention ; toxicity - ha, bronchospasm ; interactions - do not use w/ other parasympathomimetics

direct acting alkaloids

pilocarpine and cevimeline (synthetic)

MOA muscarinic antagonist , uses - glaucoma , Sjogren syndrome (xerostomia) ; toxicity - parasympathomimetic effects ; interactions - do not use w/ other parasympathomimetics

cholinesterase inhibitors

neostigmine and pyridostigmine

MOA forms covalent bond w/ ACh esterase but then hydrolyzed and released ; uses - myasthenia gravis (drug of choice) , post op and neurogenic ileus and urinary retention ; toxicity - does not enter CNS ; interactions - does not have additive effects w/ other parasympathomimetics

malathion

orhanophosphate , MOA covalent bond w/ ACh esterase , uses - topically for head lice ; toxicity - ha, nausea , dizziness , cramps , blurred vision

miotic

drug that constricts pupil

mydriatic

drug that dilates pupil

parasympatholytic

antimuscarinic ; drug that blocks muscarinic receptors of autonomic effector tissues and reduces effects of parasympathetic nerve stimulation

types of cholinoreceptor antagonists

1. muscarinic

2. nicotinic

types of cholinoreceptor muscarinic antagonists

1. LAMA (long acting muscarinic antagonist)

2. SAMA (short acting muscarinic antagonist)

types of cholinoreceptor nicotinic antagonists

1. ganglion blockers

2. NMJ blockers (most widely used, work by blocking muscarinic ACh receptors)

atropine (hyoscyamine)

antimuscarinic; used to tx hypermotility , IBS sx (specifically IBS-D) , antidote for organophosphate poisoning , tx bradycardia , used pre op to decrease mucous membrane secretions , used SL to decreased saliva secretions (hospice pt drooling) , vagolytic (inhibit action of vagus nerve) ; contraindications - narrow angle glaucoma

belladonna alkaloids

antimuscarinics ; mixture of atropine and its naturally occurring congeners (chemical constituents) derived from deadly nightshade plant (atropa belladonna) , one of the ingredients in Donnatal and similar compounds

hyoscyamine (levsin)

antimuscarinic , used to tx IBS and biliary colic

scopolamine

antimuscarinic ; derived from henbane plant , used for motino sickness , more marked CNS effects (producing sedation and in large doses amnesia) , patch for travel sickness prevention

antimuscarinics for COPD

works to decrease secretions w/ in lungs to provide relief; pts benefit from effects of inhaled ipratropium, titropium , aclidinium , unmeclidinum ; inhalation route provides little systemic effects

antimuscarinics for overactive bladder

work on epithelium lining of urinary tract and nerves to detrusor muscle ; oxybutynin , trospium , solifenacin , tolterodine , fesoterodine

anticholinergic contraindications

use w/ caution in elderly men due to potential for acute urinary retention

scopolamine

muscarinic antagonist ; used for vertigo and post op nausea ; toxicity - tachycardia , blurred vision , xerostomia ; interactions - do not use w/ other antimuscarinics

benztropine (cogentin)

antimuscarinic; used for tx parkinsons and acute dystonic rxns , inhibits ACh muscarinic M1 and M3 receptors ; contraindications - narrow angle glaucoma

atropine

antimuscarinic ; blocks all muscarinic receptors ; uses - retinal exams , cholinesterase poisoning ; toxicity - tachycardia , confusion , urinary retention , increased intraocular pressure ; contraindications - do not use w/ other antimuscarinics

dicyclomine (bentyl)

antimuscarinic/ muscarinic antagonist ; used for tx biliary colic and IBS ; MOA blocks action of ACh at parasympathetic sites in smooth muscle , secretory glands , and CNS

ipratropium (atrovent)

antimuscarinic ; synthetic analog of atropine used in tx of asthma and COPD ; used in combo w/ albuterol (beta agonist) as nebulizer solution , used in aerosol metered dose inhaler , used in nasal spray

ipratropium

antimuscarinic ; MOA blocks action of ACh in bronchial smooth muscle resulting in bronchodilation and decreased mucus secretion ; minimal systemic absorption ; contraindications - sensitivity to drug

oxybutynin (ditropan)

antimuscarninc ; MOA inhibits action of ACh on smooth muscle ; used as urinary tract antispasmodic ; interactions. -ketoconazole (increase levels, should be admin hours apart)

trihexyphenidyl (artane)

antimuscarinic ; centrally acting anticholinergic used in tx parkinson’s (blocks smooth muscle spasm) ; usually tried first (first line) for v mild sx

nicotinic antagonist categories/ classes

nondepolarizing NMJ blockers

depolarizing NMJ blockers

ganglionic blockers

spasmolytics

succinylcholine

depolarizing NMJ blocker ; MOA agonist at nicotinic receptor , depolarizes motor end plate → continuous depolarization results in muscle relaxation and paralysis ; uses/indications - paralytic for surgery or on breathing machine ; contraindications - pt decreased activity of plasma pseudocholinesterase (would cause extreme sensitivity)

tubocurarine

nicotinic antagonist ; MOA blocks ACh from binding to receptors on motor end plate depolarizing NMJ blocking agent ; uses/indications - induce paralysis for anesthesia ; contraindications - hypersensitivity ; adverse effects - prolonged paralysis ; interactions - potentiated by aminoglycosides (common abx in hospital setting)