Cholinergic Agonists and Antagonists

Question 1

Direct-acting cholinomimetic Drug list

Answer 1

a) Acetylcholine
b) Bethanechol
c) Carbachol
d) Cevimeline
e) Methacholine
f) Pilocarpine
g) Varenicline (Chantix)

Question 2

Cholinesterase Inhibitor Drug list

Answer 2

a) Ambenonium
b) Donepezil
c) Echothiophate
d) Edrophonium
e) Galantamine
f) Neostigmine
g) Physostigmine
h) Pyridostigmine
i) Rivastigmine
j) Tacrine

Question 3

Cholinesterase regenerator drug list

Answer 3

a) Pralidoxime

Question 4

Antimuscarinic drugs used for motion sickness

Answer 4

i) Scopolamine

Question 5

antimuscarinic drugs used for gi disorders

Answer 5

i) Atropine
ii) Dicyclomine
iii) Glycopyrrolate
iv) Hyoscyamine

Question 6

antimuscarinic drugs used in ophthalmology

Answer 6

i) Atropine
ii) Cyclopentolate
iii) Homatropine
iv) Scopolamine
v) Tropicamide

Question 7

antimuscarinic drugs used for resp disorders

Answer 7

i) Ipratropium

ii) Tiotropium

Question 8

antimuscarinic drugs used for urinary disorders

Answer 8

i) Darifenacin
ii) Fesoterodine
iii) Oxybutynin
iv) Solifenacin
v) Tolterodine
vi) Trospium

Question 9

antimuscarinic drugs used for cholinergic poisoning

Answer 9

i) Atropine (+ pralidoxime)

Question 10

antimuscarinic drugs used for movment disorders

Answer 10

i) Benztropine
ii) Biperiden
iii) Orphenadrine
iv) Procyclidine
v) Trihexyphenidyl

Question 11

Acetylcholine as a drug

Answer 11

i) Approved for intraocular use during surgery and causes miosis (reduction in pupil size)
ii) Rarely given systemically due to rapid hydrolysis by cholinesterase

Question 12

methacholine

Answer 12

i) Administered by inhalation for the diagnosis of bronchial airway hyperreactivity in patients who do not have clinically apparent asthma
ii) Rarely used due to need for emergency resuscitation equipment, oxygen, and medications to treat severe bronchospasm (e.g., β2 adrenergic receptor agonists)

Question 13

bethanechol

Answer 13

i) Can be used to treat patients with urinary retention and heartburn
ii) Selective mAChR agonist
iii) Little cardiovascular stimulation
iv) May produce urinary tract infection if sphincter fails to relax

Question 14

carbachol

Answer 14

i) Nonspecific cholinergic agonist that is used for the treatment of glaucoma or to produce miosis during surgery or ophthalmic examination

Question 15

cevimeline

Answer 15

i) Oral tablet used to treat dry mouth (xerostomia) in patients with Sjögren’s syndrome
ii) Metabolized via P450 pathways and eliminated in urine

Question 16

pilocarpine

Answer 16

i) Approved for xerostomia treatment in patients with Sjögren’s syndrome or head and neck cancer treatment related xerostomia (PO), miosis during ophthalmic procedures (topical), and for glaucoma (topical)
ii) Pure mAChR agonist

Question 17

Varenicline

Answer 17

i) FDA approved for smoking cessation
ii) Partial agonist that binds with high affinity and selectivity to α4β2 nicotinic ACh receptors located in the brain; stimulates receptor-mediated activity, but at a substantially lower level than nicotine
iii) Stimulation and subsequent moderate, sustained release of mesolimbic dopamine are thought to reduce craving and withdrawal symptoms associated with smoking cessation (reward pathway)
iv) Greater than 90% eliminated in urine as unchanged drug
v) Nausea is most common adverse effect; serious adverse effects include neuropsychiatric symptoms, including changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide
vi) Treatment comes with the following warning: If patients, their families, or caregivers notice agitation, depressed mood, or changes in behavior that are not typical for the patient or if the patient has suicidal thoughts or actions, the patient should stop taking varenicline and contact their healthcare professional

Question 18

ambenonium

Answer 18

quaternary and charged ache inhibitor

Question 19

donepezil

Answer 19

tertiary uncharged ache inhibitor, dementia

Question 20

echothiophate

Answer 20

organophosphate - ache inhibitor, this one is charged and not highly lipid soluble (exception), so it doesn’t go cns

Question 21

edrophonium

Answer 21

alcohol, ache inhibitor, quaternary and charged, reverses paralysis after anesthesia

Question 22

galantamine

Answer 22

tertiary ucharged ache inhibitor, used for dementia

Question 23

neostigmine

Answer 23

carbamic ester ache inhibitor, quaternary and charged, effects seen at nmj, reverse paralysis after anesthesia and to block parasympathetic effects during reversal os skeletal muscle relaxation

Question 24

physostigmine

Answer 24

carbamic ester ache inhibitor, tertiary and uncharged, reverses Intoxication due to anticholinergic agents that can produce cutaneous vasodilation, anhidrosis, anhydrotic hyperthermia, nonreactive mydriasis, delirium, hallucinations, and a reduction or elimination of the desire to urinate, which are generally the result of reduced or blocked mAChR stimulation
iii) Physostigmine can reverse the above mentioned anticholinergic effects and is preferred because it crosses the blood-brain barrier
Also treats overdoeses or Machr antagonists

Question 25

pyridostigmine

Answer 25

carbamic ester ache inhibitor, quaternary and charged, prophylaxis for ache inhibitor poisoning (nerve gas)

Question 26

rivastigmine

Answer 26

tertiary unchaged ache inhibitor, used for dementia

Question 27

tacrine

Answer 27

tertiary uncharged ache inhibitor, used for dementia but not the best one

Question 28

pralidoxime

Answer 28

cholinesterase regenerator, charged and only at nmj, given with atropine for cholinergic poisoning

Question 29

scopolamine

Answer 29

has more marked CNS effects producing drowsiness and amnesia (toxic doses of scopolamine can cause excitement, agitation, hallucinations, and coma)

Vestibular disturbances (motion sickness)

oldest agents for seasickness and can be administered by injection, PO, and transdermal patch

useful in preoperative settings to limit increased airway secretions caused by irritant anesthetics

mostion sickness and ophthalmology

Question 30

atropine

Answer 30

for excess muscarinic stimulation from parasympathetic ganglia and parenteral anticonvulsants (diazepam) for CNS stimulation

antidote recommended for cholinergic poisoning

ineffective against the peripheral neuromuscular stimulation (nAChRs)

therapy for organophosphate exposure

The prototype antimuscarinic compound

tertiary amine that can get into the cns

half life of 2 hours and 60% is unchanged in urine

40% is changed by type 1 and type II and is excreted in urine

Atropine is a reversible antagonist of mAChRs; blockade from a small dose can be overcome by a
larger dose of ACh or equivalent muscarinic agonist
ii) Tissues most sensitive to atropine are salivary,
bronchial, and sweat glands while acid secretion by the
gastric parietal cells is the least sensitive
iii) Antimuscarinic effects generally follow the graph at the
right as doses of atropine increase, but can vary for
other antimuscarinic agents
iv) Atropine antagonizes the actions of all 5 mAChRs and
does not distinguish between receptor types while
other antimuscarinic compounds can be selective for
one or another of these subgroups

minimal stimulant effects on the CNS (particularly the parasympathetic medullary centers) and a slower, longer-lasting sedative effect on the brain

The net CV effects of atropine in patients with normal
hemodynamics are not dramatic: tachycardia may
occur, but there is little effect on blood pressure

Low doses of atropine result in initial bradycardia
before the effects of peripheral vagal block manifest
(see blue line in figure at right between atropine doses
of 0.1 – 1 μg/kg; attributed to the block of presynaptic
M1 receptors on parasympathetic postganglionic nerve
terminals in the SA node, which normally inhibit ACh release)
(4) Moderate to high doses of atropine cause tachycardia by blockade of vagal slowing

Gastric secretion is blocked less effectively than salivary secretion: the volume and amount of acid, pepsin, and mucin are all reduced but large doses of atropine may be required

Atropine suppresses thermoregulatory sweating by inhibiting sympathetic cholinergic nerve fibers (there is no parasympathetic innervation of sweat glands)

In children, ordinary doses of antimuscarinic agents may cause “atropine fever” (body temperature is elevated only if large doses are administered in adults)

Atropine blocks vagal reflexes induced by surgical manipulation of visceral organs
(2) Atropine or glycopyrrolate is paired with neostigmine to block parasympathetic effects during reversal of skeletal muscle relaxation

useful in preoperative settings to limit increased airway secretions caused by irritant anesthetics (e.g., ether)

the first drug of choice for symptomatic bradycardia in an advanced cardiac life support (ACLS) setting

mAChR antagonists may be used in the treatment of common traveler’s diarrhea and other mild or self-limited conditions of hypermotility
ii) Often combined with an opioid antidiarrheal drug to discourage abuse of the opioid agent (classic example is the combination of atropine and diphenoxylate with the trade name Lomotil)

provide symptomatic relief in the treatment of urinary urgency caused by minor inflammatory bladder disorders

Tertiary antimuscarinic agents (preferably atropine) are utilized to treat both CNS and peripheral effects of excessive stimulation of mAChRs due to cholinergic poisoning

In life-threatening situations, as much as 1 gram of atropine per day may be required for as long as 1 month for full control of muscarinic excess

Rapid-onset cholinergic poisoning caused by mushrooms is characterized entirely by signs of muscarinic excess within 15-30 minutes [e.g., nausea, vomiting, diarrhea, urinary urgency, vasodilation, reflex tachycardia (occasionally bradycardia), sweating, salivation, and sometimes bronchoconstriction] and is adequately treated with atropine

Atropine is of no use in delayed-onset mushroom poisoning, which is characterized by vomiting and nausea 6-12 hours after ingestion

Moderate to high doses of atropine in children and infants can cause death due to hyperthermic effects

Nonselective antimuscarinic agents (atropine) should be avoided in patients with acid-peptic disease (potential to slow gastric emptying and increase discomfort)

Question 31

dicyclomine

Answer 31

not found anywhere in dsa

Question 32

glycopyrrolate

Answer 32

gi disorders, antimuscuarinic, quaternary and charged, with neostigmine to block parasympathetic effects during reversal of skeletal muscle relaxation

Question 33

hyoscyamine

Answer 33

gi disorders, antimuscarinic

Question 34

cyclopentalate

Answer 34

antimuscarinic used for ophthalmology

Question 35

homatropine

Answer 35

antimuscarinic used in ophthalmology, used to prevent synechia formation (the iris adheres to either the lens or the cornea) in uveitis and iritis

Question 36

tropicamide

Answer 36

antimuscarinic used in ophthalmology, tertiary amine

Question 37

ipratroprium

Answer 37

antimuscurinic used in copd and asthma, quaternary

used as an inhalational agent in the treatment of COPD and is currently a first-line therapy (use in asthma is off-label and should be done in combination with a short-acting beta-adrenergic agonist)

Question 38

tiotropium

Answer 38

antimuscurinic used in copd and asthma

has a longer bronchodilator action than ipratropium (half life 120 hrs vs. 2 hrs) and can be dosed once daily (vs. 3-4 times/day) in patients with COPD

Question 39

darifenacin

Answer 39

antimuscurinic used to treat urinary urgency, selective for the M3 subtype and are advantageous because of their longer half-lives and reduced incidence of xerostomia and constipation

Question 40

desoterodine

Answer 40

antimuscurinic used to treat uriary disorders (urgency?)

Question 41

oxybutynin

Answer 41

antimuscurinic used to treat urinary urgency
The prototype agent used in disorders of the genitourinary tract is oxybutynin, which is somewhat selective for M3 mAChRs with side effects that include dry mouth, dizziness, constipation, blurred vision, dry eyes, and urinary tract infections among others

Question 42

solifenacin

Answer 42

antimuscurinic used to treat urinary frequency

selective for the M3 subtype and are advantageous because of their longer half-lives and reduced incidence of xerostomia and constipation

Question 43

tolterodine

Answer 43

antimuscurinic used to treat urinary frequency selective for the M3 subtype and are advantageous because of their longer half-lives and reduced incidence of xerostomia and constipation

Question 44

trospium

Answer 44

nonselective antagonist that is comparable in efficacy and side effects with oxybutynin

Question 45

benztropine

Answer 45

antimuscurinic used for movment disorders, tertiary so sued in cns, parkinsons

Question 46

biperiden

Answer 46

antimuscurinic used for moement disorders

Question 47

orphenadrine

Answer 47

antimuscurinic used for movment disorders

Question 48

procyclidine

Answer 48

antimsucurinic sued for movement disorders

Question 49

trihexyphenidyl

Answer 49

antimuscurinic used in movement disorders, tertiary amine used for parkinsons

Question 50

mecamylamine

Answer 50

from initial ganglion blockers and has improved GI tract absorption

can cross the blood-brain barrier and cause sedation, tremor, choreiform movements, and mental aberrations

approved for use to treat hypertension and is being investigated for use in smoking cessation therapy