Exam 1: Cholinergics Flashcards by Anthony Carli

What are the 2 basic classes of cholinergic agents?

cholinomimetics

anticholinergics

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Cholinomimetics include which drug classes?

direct agonists

AChE inhibitors

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Anticholinergics include which drug classes?

cholinergic antagonists

NMJ Blockers

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This receptor is a ligand gated sodium channel that responds to acetylcholine and what other substance?

Nicotinic receptor

nicotine

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A patient had an initial muscle twitch followed by a depolarizing blockade and paralysis. This occured after nicotine administration. What just happened?

desensitization

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These receptors have the following characteristics:

GCPR
Located on PNS effectors
Resond to ACh

Muscarinic receptors

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Stimulation of muscarinic receptors on the eye have what 3 effects?

miosis

blurred vision

decreased intraocular pressure

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What is responsible for the miosis when eyes are stimulated by a muscarinic agonist?

contraction of the circular muscle

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What is responsible for the blurred vision that occurs during stimulation by a muscarinic agonist?

contractin of the ciliary muscle leading to a round lens

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Muscarinic agonists will have what effect on glands?

increased secretion

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What happens to the GI system with muscarinic stimulation?

increased motility, secretion, peristalsis and relaxed sphincters

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When a muscarinic agonist is administered, will the bladder favor physiologic conditions for filling or voiding?

voiding (i.e. detrusor contraction, sphincter relaxation)

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What is responsible for the bradycardia induced by muscarinic stimulation?

slowing of the SA node

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what effects should be expected on injection of ACh?

decreased HR and BP

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What causes the decreased BP from ACh injection since the vessels generally don’t directly respond to PNS stimulation?

endothelial M3 release of NO

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What happens in the respiratory system with muscarinic stimulation?

increased secretions

bronchoconstriction

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Muscarinic agonists have what effects on the brain?

increased memory, cognition, alertness, arousal

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What drug class has the following adverse effects?

N/V
bladder tightness
sweating
salivation
bronchoconstriction
constricted pupils
blurred vision

muscarinic agonists

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What drugs are considered direct muscarinic agonists?

ACh, bethanechol, pilocarpine

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What conditions are contraindicated for muscarinic agonists?

Asthma/COPD
Peptic Ulcer
Bowel Obstruction
CAD/Heart Disease

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SLUDGE is an acronym that describes muscarinic agonist toxicity. what does it stand for?

salivation
lacrimation
urination
defecation
GI distress
Emesis

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In addition to SLUDGE, what adverse effects can be seen in muscarinic agonist toxicity?

HA
visual disturbance
bronchospasm
bradycardia
shock

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describe the half life and clinical use of acetylcholine

no clinical use due to short half life

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What two major effects will be seen on acetylcholine administration?

decreased BP, decreased HR

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these two drugs are nonspecific muscarinic agonists

bethanechol and pilocarpine

What therapeutic effects does bethanechol have?

increased GI motility decreased urinary retention

Can bethanechol cross the BBB?

Why doesn't bethanechol have CNS activity?

quaternary ammonium salt, charged

which ammonium salts can cross the BBB?

tertiary ammonium salts

Pilocarpine is used as a drug of last resort for which condition?

acute angle closure glaucoma

Pilocarpine is useful for treating what conditions via what routes?

topical for glaucoma PO for xerostomia

What is an adverse effect for pilocarpine when administered PO?

profuse sweating

What is an adverse effect for pilocarpine when administered topically in the eye?

blurred vision

Nicotine causes IPSPs/EPSPs

EPSPs

The central effects of low doses of nicotine include...

increased alertness and attention

What are the effects on the central body with high dose nicotine?

tremor, vomiting, tachypnea

What cardiac sxs can occur with nicotine poisoning?

HTN, tachycardia with alternating vagal bradycardia

What are the GI/GU side effects of nicotine?

vomiting, diarrhea, urination

at the NMJ, overdose of nicotine can have what effects?

convulsions leading to receptor desensitization and flaccid paralysis

How do you treat nicotine toxicity?

anticonvulsants and assisted respiration

This drug is a partial nicotinic receptor agonist that stimulates dopamine release, and stimulates the reward center.

Varenicline

What therapeutic effect does varenicline have?

Tx for smoking cessation

Describe the adverse effects of varenicline...

N/V, constipation, flatulence nightmares, psychosis, suicidal ideation

What six drugs are considered cholinesterase inhibitors?

neostigmine, pyridostigmine, physostigmine, edrophonium, donepezil, organophosphates

What is the common suffix for AChE inhibitors, and what are two exceptions?

"stigmine" suffix edrophonium, donepezil exceptions

What is the general mechanism of cholinesterase inhibitors?

inhibit ACh breadown leading to increased time in the cleft and increased receptor activation

Are AChE inhibitors depolarizing or non-depolarizing blockers?

non-depolarizing

Muscle Twitch and Fasciculation NMJ Blockade Paralysis These are signs of poisoning via high-dose _____

cholinesterase inhibitors

What are three clinical uses for low dose cholinesterase inhibitors?

Tx of Myasthenia Gravis Reverse NMJ Blockade Nicontine antagonism

What are three severe, serious side effects of cholinesterase overdose/toxicity?

SLUDGE sxs Respiratory Arrest Death

These Cholinesterase inhibitors have the following indications... Tx of ileus Tx of bladder atony Tx of Myasthenia Overcome Post-op NMJ Block

Neostigmine & Pyridostigmine

Which cholinesterase inhibitors form covalent bonds with AChE?

Neostigmine and pyridostigmine

Do Neostigmine and pyridostigmine cross the BBB? why or why not?

no... quaternary ammonium compound

Neostigmine and Pyridostigmine dosing needs to be titrated. What happens if the dose is too high?

receptor desensitization, patient weakness

Which Cholinesterase Inhibitor is a tertiary ammonium compound and can therefor cross the BBB?

Physostigmine, Donepizil

What is physostigmine used for?

treat atropine (m antagonist) poisoning

Edrophonium is useful for what two processes

diagnosis and dose determination for myasthenia

Donepizil is useful in treating what?

alzheimers

How do you treat organophosphate poisoning?

atropine, +/- 2-PAM, diazepime, ABCs

In OP poisoning, describe the dosing regime for atropine

titrate atropine until pupils dilate only use if known OP poisoning

When can 2-PAM be administered with OP poisoning?

if < 3-4 hours of exposure

Why can you only use atropine if confirmed OP poisoning?

atropine is an AChE inhibitor itself, but is more attracted to OP

Describe the "aging"process of OP and AChE

occurs within 4 hours covalent phosphorylation that breaks O-P bond from drug to make AChE bond irreversible

The following are SFx of what drug class? Dry mouth Dry eyes Midriasis Cycloplegia Tachycardia Reduced GI motility Urinary Retention

Cholinergic antagonists

Rank PNS tone/antimuscarinic affinity of the following tissue types salivary/sweat/bronchioles heart/eye GI/GU CNS

Salivary, Sweat, Bronchioles > Heart, Eye > GI/GU > CNS

Rank the following tissue types from most-sensitive to least-sensitive to cholinergic antagonists... salivary/sweat/bronchioles heart/eye GI/GU CNS

Salivary, Sweat, Bronchioles > Heart, Eye > GI/GU > CNS

What mnemonic is helpful for remembering the adverse effects of atropine?

"hot as a hare, dry as a bone, blind as a bat, red as a beat, mad as a hatter"

In the eye, atropine has what three effects?

mydriasis cycloplegia increased IOP

In the CV system, atropine has what effects, particularly on what patient population?

healthy young adults increased vagal tone Tachygardia

Atropine has what three effects on the glads?

xerostomia dry eyes increased skin temperature

What effect does atropine have on the lungs?

bronchodilation

What effect does atropine have on GI/GU?

GI: decreased motility and secretion GU: decreased motility/activity

What adverse effects of atropine occur in the CV system?

tachycardia cardiopulm collapse

In the heart, where does atropine exert its effects?

the atria

What are the mechanisms by which atropine can increase HR?

Block post-synaptic M2 receptors, decrease PNS, increase HR Block pre-synaptic SNS M2 receptors, increased NE, increased Beta 1 stimulation, increased HR

Atropine exerts what therapeutic effects on the heart?

tx for bradycardia tx for heart block post-MI therapy

Which cholinergic antagonist is used to dilate the eyes for eye exam?

topicamide

This cholinergic antagonist is delivered transdermally to treat motion sickness...

scopalamine

Which cholinergic antaagonist acts as a bronchodilator, and therefor is useful in treating COPD and Acute Asthma Attack?

ipratropium

how is ipratropium administered?

inhalation

Which four cholinergic antagonists are M3 selective, and what are they used to treat?

Tolderodine, Fesoterodine, Darifenacin, Solifenacin Tx of overactive bladder

This drug is a cholinergic antagonist that is useful in treating bladder spasm...

oxybutynin

Which cholinergic antagonist decreases GI spasm/cramping making it a tx for diarrhea predominant IBS?

dicycloamine

What is an adverse effect of onabotulinumtoxinA?

asthenia

What are three indications for IM injection of onabotulinumtoxin A?

urinary incontinence migraine prophylaxis wrinkles

______ blocks the release of ACh to the synaptic cleft,

botox

This drug causes a depolarization, which causes initial contraction, then receptor desensitization and NMJ block...

succinylcholine

Which NMJ blocker is useful as a paralytic for short surgical procedures and ET intubation?

succinylcholine

What are the two major adverse effects of succinylcholine?

cardiac arrest secondary to hyperkalemia in burn patients malignant hyperthermia

how do you treat malignant hyperthermia?

dantrolene

What are the 3 contraindications of succinylcholine?

burns hx of malignant hyperthermia soft tissue damage

Rank the order of effects felt by non-depolarizing NMJ blockers...

small muscles > large muscles > diaphragm

If strength improves after edrophomium administration, what do you need to do to the daily dose of neostigmine/pyridostigmine?

increase it

If strength is worsened with edrophonium administration, what do you need to do to the daily dose of neostigmine/pyridostigmine and why?

decrease it, causing desensitization