Cholinergic Agonists and Antagonists Flashcards
In most organs, which mAChR receptor predominants?
Which predominates in the heart?
Which in smooth muscle?
1) M3
2) M2
3) M3, M2
What are the parasympathetic effects on the iris sphincter muscle?
On the ciliary muscles?
1) Contraction (miosis)
2) Contraction for near vision
What are the parasympathetic effects on the SA node?
What are the parasympathetic effects on the atria?
What are the parasympathetic effects on the AV node?
What are the parasympathetic effects on the ventricles?
1) Decrease HR
2) Decrease in contractile strength and refractory period
3) Decrease in conduction velocity and increase refractory period
4) Decrease in contractile strength
What are the parasympathetic effects on the arteries and veins?
Via what?
Dilation via EDRF
What are the parasympathetic effects on the bronchial muscles?
What are the parasympathetic effects on the bronchial glands?
1) Contraction
2) Stimulation
What are the parasympathetic effects on GI motility?
What are the parasympathetic effects on GI sphincters?
What are the parasympathetic effects on GI secretion?
1) Increase
2) Relax
3) Stimulate
What are the parasympathetic effects on the detrusor muscle?
What are the parasympathetic effects on the Trigone and sphincter?
1) Contraction
2) Relax
What are the parasympathetic effects on the sweat, salivary, lacrimal and nasopharyngeal glands?
Secretion of glands
Accommodative esotropia is a misalignment of the eyes that can be diagnosed and treated with?
Cholinomimetic agonists
What is the most widely used choline ester for GI/GU disorders, including postoperative ileus, congenital megacolon, urinary retention, and esophageal reflux?
What must the physician be certain of otherwise the drug may exacerbate the problem and may even cause perforation?
1) Bethanechol
2) No obstruction
Pilocarpine and cevimeline are used to do what?
What condition does it help?
1) Increase salivary secretion
2) Dry mouth from Sjögren’s syndrome
The overdose of what drug causes predictable muscarinic effects such as nausea, vomiting, diarrhea, urinary urgency, salivation, sweating, cutaneous vasodilation, and bronchial constriction?
What antimuscarinic compounds do you use to treat this?
1) Pilocarpine and the choline esters
2) Atropine
Mushrooms of the genus Inocybe can cause?
Muscarinic poisoning
What are the major contraindications to the use of mAChR agonists that are distributed systemically?
1) Asthma
2) Hyperthyroidism
3) Coronary insufficiency
4) Acid-peptic disease
CNS stimulation (convulsions progressing to coma), Skeletal muscle end plate depolarization, Respiratory paralysis, Hypertension, and Cardiac arrhythmias are all acute toxicity effects of?
Nicotinic stimulants
What are the treatments for acute toxicity effects of nicotinic stimulants?
1) Atropine ganglia
2) Parenteral anticonvulsants (diazepam)
What is approved for intraocular use during surgery and causes miosis (reduction in pupil size)?
Acetylcholine
What is administered by inhalation for the diagnosis of bronchial airway hyperreactivity in patients who do not have clinically apparent asthma?
Methacholine
What can be used to treat patients with urinary retention and heartburn?
What type of agonist is it?
1) Bethanechol
2) Selective mAChR agonist
What is a nonspecific cholinergic agonist that is used for the treatment of glaucoma or to produce miosis during surgery or ophthalmic examination?
Carbachol
What is given as an oral tablet used to treat dry mouth (xerostomia) in patients with Sjögren’s syndrome?
It is metabolized via what?
1) Cevimeline
2) P450 pathways
What is 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)?
What type of agonist is it?
1) Pilocarpine
2) mAChR agonist
Bethanechol may produce urinary tract infection if?
Sphincter fails to relax
What is FDA approved for smoking cessation?
Varenicline
Varenicline is a partial agonist that binds with high affinity and selectivity to what receptor located in the brain to stimulate receptor-mediated activity?
α4β2 nicotinic acetylcholine receptors
Varenicline causes a sustained release of what NT to reduce craving and withdrawal symptoms associated with smoking cessation?
Dopamine
What is the most common adverse effect of Varenicline?
What are some serious adverse effects?
1) Nausea
2) Changes in behavior, agitation, depressed mood,
and suicide
Acetylcholinesterase (AChE) inhibitors such as Alcohols and Carbamic acid esters have what type of charge?
What type of binding does it have to AChE?
Which is more longer lasting?
1) Positive or neutral charge
2) Noncovalent and reversible
3) Carbamic acid esters
What makes AChE inhibitors such as Organophosphates toxic to the CNS?
What type of binding does it have to AChE?
1) Neutral charge and highly lipid-soluble
2) Covalent and irreversible
What category of AChE inhibitors such as neostigmine, pyridostigmine, edrophonium, echothiophate, ambenonium are poorly absorbed?
What category of AChE inhibitors such as physostigmine, donepezil, tacrine, rivastigmine, galantamine are well-absorbed?
1) Quaternary and charged AChE inhibitor
2) Tertiary and uncharged AChE inhibitors
What is required in order to reestablish the termination of ACh signaling at the neuromuscular junction?
Regeneration of AChE
What is the mechanism of action for AChE inhibitors?
ACh accumulation throughout the body and activation of nAChRs and mAChRs
What do AChE inhibitors stimulate at autonomic effector organs?
What do AChE inhibitors stimulate at, followed by depression or paralysis, all autonomic ganglia and skeletal muscle?
What do AChE inhibitors stimulate, with occasional subsequent depression, in the CNS?
1) mAChRs
2) nAChRs
3) Cholinergic receptor sites
The eye, respiratory tract, GI tract, and urinary tract are innervated by what receptors?
mAChRs
What does moderate doses of AChE inhibitors do to HR?
How does it affect CO?
How does it affect atrial and ventricular contractility?
How does it affect BP?
1) Bradycardia
2) Decreased cardiac output
3) Decreased atrial and ventricular contractility
4) Increase in blood pressure
Some quaternary carbamate AChE inhibitors such as neostigmine have what additional effects at the NMJ?
Direct nicotinic agonist effects
What effect does AChE inhibitors have on paralysis induced by neuromuscular blocking drugs during surgical anesthesia?
Which drugs are preferred in this case?
1) Reverse the paralysis
2) Neostigmine and edrophonium
What condition is characterized by increased intraocular pressure?
AChE inhibitors can reduce intraocular pressure by?
Therapy with AChE inhibitors has largely been replaced by?
1) Glaucoma
2) Stimulating mAChRs of the ciliary body and
causing contraction, which facilitates outflow of aqueous humor
3) Topical β-blockers and prostaglandin derivatives
Patients with progressive dementia of the Alzheimer type are found to have a deficiency of?
Donepezil, rivastigmine, galantamine, and physostigmine are AChE inhibitors that benefit patients with what condition?
1) Intact cholinergic neurons
2) Dementia associated with Parkinson disease
Intoxication due to anticholinergic agents can produce cutaneous vasodilation, anhidrosis, anhidrotic hyperthermia, non reactive mydriasis, delirium, hallucinations, and a reduction of the desire to urinate which are all generally the result of?
What can reverse the above mentioned anticholinergic effects?
Why is it preferred?
1) Blocked mAChR stimulation
2) Physostigmine
3) It crosses the blood-brain barrier
Nondepolarizing neuromuscular blocking agents in combination with AChE inhibitors will cause diminished neuromuscular blockade however what is the one exception?
Mivacurium where neuromuscular blockade is prolonged
What drug in combination with AChE inhibitors will enhance phase 1 block and antagonize phase 2 block?
Succinylcholine
Cholinergic agonists act predominantly on?
mAChRs
What drug in combination with AChE inhibitors may enhance the bradycardic effects?
Beta-blockers
What drug in coadministration with AChE inhibitors may enhance muscle weakness seen in patients with myasthenia gravis?
Systemic corticosteroids
The SLUDGE symptoms of AChE intoxication are caused by stimulation of what receptor?
mAChR stimulation
What drug is the antidote recommended for cholinergic poisoning in combination with maintenance of vital signs (respiration in particular) and decontamination?
Why is this the antidote?
1) Atropine
2) It is a mAChR antagonist
Atropine is ineffective against what type of stimulation?
Peripheral neuromuscular stimulation (nAChRs)
Current antidotal therapy for organophosphate exposure resulting from warfare, terrorism, or other source includes?
1) Parenteral atropine
2) Pralidoxime
3) Benzodiazepine
Where do antinicotinic drugs elicit their effects at?
1) The neuromuscular junction
2) nAChRs in the ganglia
What are often called parasympatholytic because they block the effects of parasympathetic autonomic discharge?
mAChR blockers
What is the prototype antimuscarinic compound?
Atropine
What type of amines such as Atropine, tropicamide, benztropine are used for their effects on the eye or CNS?
Tertiary amines
What type of amines such as Ipratropium and glycopyrrolate are charged and elicit their antimuscarinic effects in the periphery?
Quaternary amines
How do tertiary compounds and quaternary compounds compare to one another?
Tertiary compounds are more readily absorbed and widely distributed while Quaternary compounds are relatively free of CNS effects at low doses
What are the tissues most sensitive to atropine?
Bronchial, salivary and sweat glands
How does Atropine distinguish between mAChR types?
It doesn’t because it antagonizes the actions of all 5 mAChRs
Although not as effective as dopaminergic therapy, tremor associated with Parkinson disease is reduced by?
What are some examples?
1) mAChR antagonists
2) Tertiary amines such as benztropine and trihexyphenidyl
Vestibular disturbances (motion sickness) appear to involve muscarinic cholinergic transmission and what is effective at prevention or reversal of these symptoms?
Scopolamine
Antimuscarinic agents have what effect on the eye?
1) Mydriasis (dilation)
2) Weak ciliary muscle contraction (poor near vision)
3) Reduced lacrimal secretion
Low doses of atropine result in what cardiovascular response?
Moderate to high doses of atropine cause?
1) Initial bradycardia before the effects of peripheral vagal block manifest
2) Tachycardia by blockade of vagal slowing
Blockade of airway mAChRs can cause?
Bronchodilation and reduce secretion
Antimuscarinic agents have what effect on salivary secretion?
What effect does inhibition of mAChRs have on gastric emptying time?
1) Decrease
2) Prolonged
How are antimuscarinic agents useful in the treatment of urinary incontinence?
Relax smooth muscle of the ureters and bladder wall and slow voiding
What effect does Atropine have on thermoregulatory sweating?
How does it do this?
What can it cause in children?
1) Suppresses
2) Inhibits sympathetic cholinergic nerve fibers
3) Atropine fever
How is atropine used in surgical manipulation of visceral organs as an anesthetic?
What is Atropine paired with to block parasympathetic effects during reversal of skeletal muscle relaxation?
1) Blocks vagal reflexes
2) Neostigmine
What should antimuscarinic agents never be used for unless cycloplegia or prolonged action is required?
Mydriasis
What mAChR antagonists is used to prevent synechia formation in uveitis and iritis (the iris adheres to either the lens or the cornea)?
Homatropine
What is used as an inhalational agent in the treatment of asthma and COPD and is currently a first-line therapy?
Ipratropium
What recently approved agent 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?
Tiotropium
What is the first drug of choice for symptomatic bradycardia in an advanced cardiac life support (ACLS) setting?
Atropine
The combination of atropine and diphenoxylate (trade name Lomotil) are used to treat?
Common traveler’s diarrhea
Agents with selectivity for what subtype of mAChR is preferred for agents that reduce urinary frequency due to presence in bladder wall and sphincter smooth muscle?
M3 subtype
Oxybutynin, Darifenacin, solifenacin, and tolterodine are all used in disorders of the genitourinary tract due it being selective for what mAChRs?
Which one comes with side effects such as xerostomia and constipation?
1) M3
2) Oxybutynin
What is utilized to treat both CNS and peripheral effects of excessive stimulation of mAChRs due to cholinergic poisoning?
What is a cholinesterase regenerator compound that can be used to treat organophosphate poisoning by breaking the bond between the organophosphate and
cholinesterase enzyme?
1) Atropine
2) Pralidoxime
Because Pralidoxime is charged it is only effective in regenerating cholinesterase at?
The neuromuscular junction
When is Atropine of no use in mushroom poisoning?
Delayed-onset
What may be adverse effects of antimuscarinic agents used to reduce GI secretion?
Mydriasis and cycloplegia
Moderate to high doses of atropine in children and infants can cause death due to?
What is the treatment?
1) Hyperthermic effects
2) AChE inhibitor
Antimuscarinic agents are contraindicated in patients with what condition?
It should be used with caution in elderly men with a history of?
1) Glaucoma
2) Prostatic hyperplasia
What should be avoided in patients with acid-peptic disease?
Non-selective antimuscarinic agents (atropine)
All ganglion-blocking drugs are?
Synthetic amines
What tertiary amine was developed from initial ganglion blockers and has improved GI tract absorption?
Mecamylamine
Ganglion-blocking agents competitively block the action of?
Does it block either parasympathetic or sympathetic autonomic ganglia?
1) ACh and similar agonists at nAChRs
2) Both, it blocks all autonomic outflow
Can mecamylamine cross the blood-brain barrier?
Why or why not?
1) Yes
2) It is uncharged
While the use of ganglion blockers is infrequent because more selective autonomic blocking agents are available, what is approved for use to treat hypertension?
Mecamylamine
