Cholinergic agonists and antagonists

Question 1

4 primary direct effects on the CV system

Answer 1

Vasodilation (M3)
Decrease cardiac rate (M2)
Decrease rate of conduction in the SA and AVnodes (M2)
Decrease force of contration (M2)

Question 2

IV injection of small dose of ACh

Answer 2

fall in blood pressure- vasodilation, reflex tachycardia

Question 3

IV injection Large dose ACh

Answer 3

brady cardia, decrease through Vnode, vasodilation and hypotension.- CV system

Question 4

ACh effects on tissue

Answer 4

CV system- bradycardia, decrease in conduction velocity, AV block at high doses, decrease in contrctilty
Eye- contraction and miosis, accomodation of lens to near vision, watery lacrimal secretions
glands- secretions
bronchi- increase in secretions.
GI- increase in tone, peristaltic activity, increased in secretions and relaxation of sphincters.
Urinary- contraction of detrusor muscle, relaxation of sphincter.
sweat glands- diaphoresis
Male reproductive tract- erection
Uterus- varible.

Question 5

large doses of ACh after atropine administration causes

Answer 5

nicotinic effects, increase in blood pressure due to sympathetic ganglia stimulation and vasoconstriction.

Question 6

Choline esters-

Answer 6

ACh, carbachol, bethanechol, methacholine

poorly absorved and distributed into CNS
differ in susceptibility to be hydrolyzed by cholinesterase. ACh very rapid. others are more resistant.

quarternary ammonium compounds.

Question 7

naturally occuring alkaloids

Answer 7

arecholine, muscarine, pilocarpine, nicotine, lobeline.

Question 8

Acetylcholine uses.

Answer 8

no systemic use.

used to obtain rapid miosis after delivery of lens in cataract surgery, penetrating keratoplsty and iredectomy

Question 9

Bethanechol

Answer 9

NOT hydrolyzed by AChE, inactivated by other esterases. little or no nicotinic action but
STRONG muscarinc activity

used to treat postop or post partum non obstructive urinary retention and for neruogenic atony of the urinary bladder with retention.

ADVERSE: can cause generalized cholinergic stimulation- sweating salivation, flushing, low BP, nausea, abdominal pain, diarrhea, bronchospasm.

Question 10

Carbachol

Answer 10

both muscarinic and nicotinc agonist

poorly hydrolized by esterases

used for intraocular miosis during surgery, reduces intraocular pressure after cataract surgery.

Question 11

Methacholine

Answer 11

hydrolyzed by ACh but slowly, resistant to non specific cholineesterase or butyrylcholinesterase.
predominantly MUSCARINIC, slight nicotinc

used in diagnosis of bronchial airway hyper-reactivity in subjects who do not have clinically apparent asthma

Question 12

PIlocarpine

Answer 12

tertiary amine,

stable to hydrolysis by AChE
partial muscarinic agonist

used in Glaucoma- second line agent for open angle glaucoma. used to manage acute angle-closure,

you use several drugs to treat glaucoma- timolol, pilocarpine, apraclonidine, acetzolamide and an osmotic agent like glycerol and IV mannitol.

ADVERSE- can enter brain and cause CNS disturbances. stimulates seaeating and salivation.

Question 13

Nicotine

Answer 13

Tertiary amine. affect NMJ slighlty more. causes ganglionic stimulation which means both para and sympathetic actions.

CVS- mainly sympathomimetic- increased heart rate and blood pressure due to release of adrenergic release.

GI- largely parasympathomimetic- nausea, diarrhea, vomiting, voiding of the urine. causes stimulation of salivary and bronchial secertions.

high doses cause NM blockade.

acute poisoning.- nausea, alsivation, ab pain, vomiting diarrhea, cold sweat, mental confusion, ewakness. low BP, weak pulse, collapse may be followed by convulsions, death may occur from paralysis of respiratory muscles and Central respiratory failure

highly liposoluble, so absorption is fast via oral mucosa, lungs, GI mucosa and skin. corsses placental membrane and is secreted in milk.

Question 14

Indirect acting cholinergic agonists(anticholinesterases)

Answer 14

simple alcohols bearing a quaternary ammonium group- edropohonium
carbamates- neostigmine, physostigmine, pyridostigmine
Organophosphates- Ecothiophate, parathion, malathion

Question 15

endrophonium

Answer 15

Quarternary ammonium

binds reversibly to active site of enzyme. short lived- 2-10 minutes.

used to diagnose myasthenia gravis, reverse neuromuscular block produced by non-depolarizing muscular blockers.

Question 16

Carbamates-

Answer 16

form covalent bond with the enzyme. the carbamate-cholinesterase bond spontaneoulsy hydrolyzes in 30 min-6 hours. clinical recovery in several hours, rarely over 24

Question 17

organophoshpate-

Answer 17

phosphorylate the active site of the enzyme and the bond is extremely stable. ageing strengthens the bond

pralidoxime can split the bond if it hasn’t undergone ageing

Question 18

Organ system effects of anticholinesterases

Answer 18

CNS- diffuse activation of EEG, subjective alerting response. high concentration may cause convulsions, coma and respiratory arrest

CVS- increase activation on both sympathetic and parasympathetic ganglia supplying the heart and and at the ACh receptors on cardiac and vascular smooth muscles. in heart, -bradycardia, chronotropic, dromotropic, and inotropic effects are evoked and caridac output falls.due to bradycardia,- M2 receptors
-vasconstriction becasue there aren’t any M3 innervations. large doses cause hypotenstion.

NMJ-low concentrations- increased contraction strength. higher concentrations- fibrillation of muscle fibers.

Question 19

physostigmine

Answer 19

tertiary amine- can enter CNS- used to treat overdoses of anticholinergic drugs. Do NOT use for TCA overdose becsue of depression of cardiac conduction.

ADVERSE- convulsions with high doses
bradycardia, paralysis of skeletal muscle.

Question 20

Neostigmine

Answer 20

quarternary ammonium- can’t enter CNS

used to reverse non-depolarizing neuromuscular blockers after surgery.(most common used), used for symptomatic treatment of myasthenia gravis (pyridiostigmine most)
used for prevention and treatment of post op distention and urinary retention.

ADVERSE: salivation- flushing, low blood pressure, nausea, ab pain, diarhea, bronchospasm.

Question 21

Pyridostimine

Answer 21

quarternary ammonium- doesn’t cross CNS

used for myasthenia gravis

Question 22

Echothiophate

Answer 22

used for chornic open angle glaucoma, subacute or chronic angle closure galucoma after iridectomy or surgery is refused or contraindicated.

Question 23

Malathion/Parathion

Answer 23

activated in body by conversion to oxygen analogs
parathion not metabolized
malathion is considered safe for sale to general public

Question 24

tabun, sarin, soman

Answer 24

synthetic toxic agents. fully distributed to all parts of body.

Question 25

other inhibitors of AChE

Answer 25

tacrine, donepezil, rivastimne, galantamine- used for alzheimer’s disease.

Question 26

Pralidoxime

Answer 26

used to reactivate AChE used only for organophosphate unless there is significant carbamate toxicity.

Question 27

Bella donna alkaloids:

Answer 27

atropine and scopolamine

Question 28

atropine

Answer 28

binds competitively to muscarinic receptors, preventing acetylcholine from binding tertiary amine. both central and peripheral muscarinc blocker blocker

eye-mydriasis, unresponsivenss to light, cycloplegia. intraocular pressure may rise dangeroulsy

GI- can be used as antispasmodic. Gastric motility is reduced, but HCl production is affected, not effective in promoting healing of peptic ulcers

Urinary system: decreases hypermotlity of urinary bladder

CVS- blockade of atrial M2 receptors and tachycardia. (lower doses, bradycardia. ) at toxic doses, can cause cutaneous vasodilation (atropine flush)

Secertions- salivary, sweat, lacrymal glands blocked, high body temp may result. is an antisialoagogue prior to surgery decreases respiratory secretions

uses: when excessive muscarinc symptoms are severe
- antisiologge, prior to surgery to reduce secretions of respiratory tract
-to increase heart rate or decrease AV-block when bradycardia, or AVblock are hyemodynamically significant and thought to be due to excess vagal tone.
-as an antidote for cholinergic drugs
-as an atidote for amanita muscaria
to alleviate the muscarinic side effects of anticholinesterase.

ready absorbed, patially metabolized by liver, elimnated in urine. half life of 4 hours

adverse effects- dry mouth blurred vision, sandy eys, tachycardia, constipation. restlessness. confusion, halluciantions, delirium, depression. in older indifivdiuals, problems with glaucoma.

Question 29

Scopoloamine

Answer 29

Belladona alkaloid- tertiary amine
Cholinergic antagonist(muscarinic)
DOC for motion sickness. Blocks short term memory used for anesthtic procedures. 

has a greater and longer duration of action in CNS than atropine

same adverse effects/contraindications as atropine.

Question 30

Iprotropium/tiotropium

Answer 30

QAC-cholinergic antagonist(muscarinic)
Bronchodilation(M3 antagonist)
used to as inhaltion of treatment for CPD and adjuvant therapy in asthma- same contraindication/adverse effects as atropine.

Question 31

Homatropine/cyclopentolate/tropicamide

Answer 31

tertiary amine- cholinergic antagonist(muscarinic)
causes mydriasis and cyclopelgia/ preffered over atropine because of shorter duration of action

are able to ender CNS

Question 32

Benztropine/Trihexyphenidyl

Answer 32

tertiary amines cholinergic antagonist(muscarinic)
restores balance of input after loss of dopaminergic neruons in the nigrostriatal pathway.
used for parkinsonism, extrapyramidal effects(drug induced movement disorders of antypsychotic drugs ( D2)

same contraindications as atropine.

are able to enter CNS

Question 33

Glycopyrrolate

Answer 33

QAC cholinergic antagonist(muscarinic
-used orally for inhibition of GI motility
Parenteral used to prevent bradycardia during surgery

Question 34

Tolterodine

Answer 34

tertiary amine cholinergic antagonist(muscarinic
relaxes smooth muscle-
used for overactive bladder

can enter CNS

Question 35

Mecamylamine/Trimethaphan/Hexamethonium

Answer 35

Cholinergic antagonist- ganglion blocker

antagonize nicotinic receptors on both parasympathetic and sympathetic autonomic ganglia

effects- arterioles and veins are under predominant sympathetic control - so you will have dilation and hypotension (alpha 1

block parasympathetics at the heart and iris and ciliary muscle- will cause tachycardia, mydriasis and cycloplegia(far vision)

gI urinary bladder salivary galnds lose parasympathetics, reduced motility, secertions, urinary retention, zerostomai

sweat galnds lose sympathetics, anhydrosis.

Adverse effects- vasodilation, venodilation, hypotension, tachycardia, mydriasis, decrease in gi urinary motility, xerostoma, anhydrosis,

use to treat hypertension bbeen replaced.

Question 36

Tubocarpine

Answer 36

structural analog of ACh- non depolarizing neuromuscular blocker/cholinergic antagonist
indications- anesthesia leads to muscle weakness and flaccid paralysis.

actions can be overcome by AChE inhibitors such as neostimine or edrophonium.

minimal oral abosrptoin so it is given Iv. Poor membrane penetartion so no crossing B.

Adverse effects- may cause histamine release and may bind to Muscarinic receptors.

Question 37

Succinylcholine

Answer 37

structural analogs of ACh–depolarizing neuromuscular blocker/cholinergic antagonists.

activates NM causing depolarization which leads to transient disorganized contraction which leads to desensitization followed by flaccid paralysis.

useful for ET intubation/electroconvulsive therapy.

continuous Iv infusion, rapid hydrolysis by plasma cholinesterase. rapid onset and brief duration. not metabolized effectively at the synapse.

can cause malignant hyperthermia, an AD disorder with excess release of calcium from SR, usually combined with halogenated anesthetic. (Tx dantrolene.

Question 38

Hemicholinium

Answer 38

Cholinergic Antagonists: Drugs Acting Presynaptically

blocks choline transporter CHT1

still under research

Question 39

vesamicol

Answer 39

blocks the vesicular ACh H+ antiporter VAChT preventing storage of ACh,
still under research

Question 40

boulinum toxin

Answer 40

prevents synaptic vesicle fusion inhibiting ACh release (synaptobrevin)