cholinergic agonists and antagonists

8/13/2019 Cholinergic Agonists and Antagonists

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The nervous system works continuously to keep the body

functioning properly and to maintain homeostasis. The nervous

system consists of the central nervous system (CNS) and the

peripheral nervous system (PNS). The CNS consists of the brain

and spinal cord.

Nerves or neurons throughout the body transfer messages to and

from the CNS in order to elicit a response. These nerves are part

of the PNS, which has two divisions, sensory and motor:

Afferent neurons in the sensory division carry sensory impulsesto the brain and spinal cord. Examples include:

Sense of touch Pain Body position Chemicals in body fluidsEfferent neurons in the motor division carry impulses away from

the brain and spinal cord to the muscles and glands

(periphery). The motor division has two main parts:

Somatic nervous systemvoluntary control of skeletalmuscles (example: ability to scratch your arm if it itches)

Autonomic nervous systeminvoluntary control of vitalfunctions in muscles and glands, including the

cardiovascular, respiratory, digestive, and genitourinary

systems. The autonomic nervous system has two

branches:

Sympathetic


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ParasympatheticMany drugs are available for treating a variety of problems in

target organs and glands associated with the autonomic nervous

system. Therefore, it is essential that you understand the

physiology of this system and the vital functions it affects.

The autonomic nervous system (ANS)maintains homeostasis in

the body by controlling involuntary functions. This continual

process is accomplished by balancing signals from its two

branches: sympathetic nervous system (fight-or-flight response)and parasympathetic nervous system (rest-and-digest response).

The sympathetic nervous system (SNS)is activated when the

body perceives some sort of threat or stressor. The SNS prepares

the body to react immediately by:

Increasing blood pressure

Increasing heart rateDilating bronchiolesDilating pupils Increasing perspiration Increasing glucose productionDecreasing peristalsis, thereby decreasing defecationThe parasympathetic nervous system (PNS)returns the body to

a restful state after a fight-or-flight response is no longer needed,

and then it continues to maintain the body at rest. Therefore, the

PNS has the opposite effect of the SNS by:


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Decreasing blood pressureDecreasing heart rateConstricting bronchiolesConstricting pupils Increasing peristalsis Increasing urination and salivationMedications used to treat disorders in targeted organs and glands

associated with the autonomic nervous system typically elicit either

a sympathetic response or a parasympathetic response.

The CNS and the PNS communicate with each other through nerve

cells called neurons. Chemicals, called neurotransmitters, help

accomplish this communication process. Norepinephrine (NE) and

acetylcholine (ACh) are two major neurotransmitters of the ANS.

The following steps describe how a message is transmitted from

one neuron to another:

When an action is required within the body, an impulsecalledan action potentialis initiated by the CNS.

In order for the action potential to transmit, it must get acrossthe synaptic cleft, the physical space between two neurons.

When the action potential reaches the synaptic cleft,neurotransmitters are released from vesicles in the

presynaptic neuron.

Neurotransmitters cross the synaptic cleft through themechanism of diffusion. They bind with receptors in the


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postsynaptic neuron to elicit the needed response.

The neurotransmitters are then either broken down or returned to

the presynaptic neuron, where they wait to respond again when

needed.

Mechanisms of Action of Autonomic Drugs

In the ANS, messages are transmitted along a pathway made of

preganglionic neurons and postganglionic neurons. The

preganglionic neurons transmit the action potential from the spinalcord to a junction called the ganglionic synapse. On the other side

of this synapse, postganglionic neurons receive the action

potential. They send the message on to muscle or glandular cells

to initiate a response.

Many medications affect the autonomic nervous system. Some act

between two communicating neurons, whereas others act at

muscle or glandular tissue sites. Medications are not generally

prescribed to correct problems associated with the autonomic

nervous system. Rather, they are targeted to affect the muscular or

glandular tissues instead.

Medications may also affect synaptic transmission by:

Increasing or decreasing neurotransmitter synthesis Inhibiting the storage of neurotransmitters in synaptic vesicles Increasing or decreasing the release of neurotransmittersBinding to the postganglionic cells to stimulate or inhibit the


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Cholinergic antagonists, also called anticholinergics, are mostly

used to inhibit the parasympathetic nervous system. However,

some are used to treat conditions in target organs related to the

sympathetic nervous system. Anticholinergics block ACh from

binding at these receptor sites:

Muscarinic receptorsare found in sweat glands, cardiac muscle,blood vessels of skeletal muscles, and the neuroeffector

junction of the parasympathetic nervous system.

Nicotinic receptorsare found in the adrenal medulla, skeletal

muscle cells, and ganglia of the sympathetic and parasympathetic

nervous systems.

Direct-Acting Muscarinic Agonists

Muscarinic agonists are drugs that mimic the effects of ACh.

Direct-acting muscarinic agonists work in one of two ways:

Entering the synaptic cleft and binding directly to ACh receptorsto produce a greater effect

Increasing the amount of ACh that is released from the neuronterminals, so that more ACh reaches the receptor sites

Examples of direct-acting muscarinic agonists are:

Generic

Names

Brand

NamesIndications for Use/Therapeutic Effects

bethanechol

chloride

Duvoid,

Urecholine

Stimulates peristalsis Increases urinary output


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carbachol Miostat Induces miosis during and after eyesurgery to lower intraocular pressure

Treats glaucoma by lowering intraocularpressure

cevimeline

hydrochlorid

e

Evoxac Treats xerostomia (dry mouth) in clientswith Sjogren syndrome (excessively

dry mucous membranes)

pilocarpine

hydrochlorid

e

Isopto

Carpine,

Ocusert,

Salagen

Reduces intraocular pressureTreats glaucoma by constricting pupilsPrescribed for xerostomia (Salagen)

To learn more, click to review the prototype drug bethanechol

chloride.

Indirect Acting Muscarinic Agonists

Indirect-acting muscarinic agonists work by blockingacetylcholinesterase (AChE). In other words, these drugs prevent

AChE from destroying ACh. As a result, the action of ACh is

prolonged at receptor sites, lengthening its effect on the body.

Because of their mechanism of action, indirect-acting muscarinic

agonists are often called AChE inhibitors. Examples of these drugs

are:

Generic NamesBrand

NamesIndications for Use/Therapeutic Effects

donepezil Aricept Treatment for mild to moderate
http://media.pearsoncmg.com/ph/chet/chet_readypoint_1/phar/module_02/lesson_02/BethanecholChloride.pdfhttp://media.pearsoncmg.com/ph/chet/chet_readypoint_1/phar/module_02/lesson_02/BethanecholChloride.pdfhttp://media.pearsoncmg.com/ph/chet/chet_readypoint_1/phar/module_02/lesson_02/BethanecholChloride.pdfhttp://media.pearsoncmg.com/ph/chet/chet_readypoint_1/phar/module_02/lesson_02/BethanecholChloride.pdfhttp://media.pearsoncmg.com/ph/chet/chet_readypoint_1/phar/module_02/lesson_02/BethanecholChloride.pdf


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hydrochloride Alzheimer disease

galantamine

hydrobromide

Razadyne

rivastigmine

tartrate

Exelon

tacrine Cognex

echothiophate

iodide

Phospholin

e Iodide

Treats glaucoma by constricting pupils,reduces intraocular pressure

physostigmine

salicylate

Antilirium

pyridostigmine

bromide

Mestinon Treatment for chemical warfare agents Improves muscle strength in myasthenia

gravis

Cholinergic Agonists: Myasthenia Gravis TX

Myastenia gravis (MG)is an autoimmune disorder that affectsskeletal muscle. Although MG is not a condition of the autonomic

nervous system, AChE inhibitors are the primary treatment for this

disease. Characteristic symptoms of MG are:

Excessive muscle fatigue and general tirednessDifficulty in chewing, swallowing, and speechPtosis and diplopiaThe diagram on this screen compares a normal neuromuscular

junction with one that exhibits MG. In the MG image, note the

widened synaptic cleft and the decreased number of acetylcholine


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receptors that hinder the transfer of impulses to the muscle.

Diagnosis of MG is determined by administering edrophonium

chloride (Enlon, Reversol, Tensilon), an AChE inhibitor. A client withMG will show an improvement in symptoms immediately after

receiving this drug.

Pharmacotherapy of MG consists of the following:

Treatment begins with administration of AChE inhibitors such aspyridostigmine bromide (Mestinon).

Corticosteroids, such as prednisone (Deltasone, Orasone), areadded when the disorder progresses.

Immunosuppressants that may be administered with, or in placeof, corticosteroids include:

Azathioprine (Imuran)

Cyclosporine (Sandimmune)

Mycophenolate mofetil (CellCept)

Nicotinic Agonists

Nicotinics, also known as nicotinic agonists, can have varied effects

on the body. For that reason, their use is limited. Nicotinic

agonists, such as nicotine, can produce both sympathetic and

parasympathetic responses in the body. Increased blood pressure,

pulse, and mental alertness are examples. An increased feeling of

nausea, due to triggering of the emetic centers of the CNS, is

another potential response.


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Nicotine is sometimes used as a drug in tobacco cessation

programs. Nicotine replacement therapy (NRT) helps relieve

nicotine withdrawal symptoms as the client gradually uses less and

less tobacco. Examples of symptoms associated with nicotine

withdrawal are:

Depression or sadness InsomniaLoss of concentrationHeadaches Increased appetiteNRT products are available in a variety of forms:

Delivery Systems Brand Names

transdermal

patch

Habitrol,

NicoDerm

chewing gum Nicorette Gumlozenge Nicorette Lozenge

inhaler Nicotrol Inhaler

nasal spray Nicotrol NS

Cholinergic Antagonists

Cholinergic antagonists, also known as anticholinergics orparasympatholytics, produce many of the same effects in the body

as adrenergic agonists. However, cholinergic antagonists elicit

those body responses in different ways than adrenergic agonists

do. In other words, the mechanisms of actions are different even


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though many of the results are similar.

Cholinergic antagonists block the action of the neurotransmitter

acetylcholine (ACh) in the cholinergic synapses, and prevent AChfrom binding at receptor sites. This prevents a cholinergic effect

from occurring and allows the sympathetic nervous system

response to dominate.

The two main types of cholinergic antagonists are classified

according to their specific mechanisms of action:

Muscarinic antagonistsblock ACh from binding to muscarinicreceptor sites in the parasympathetic nervous system and

inhibit some transmission in the sympathetic nervous system.

Nicotinic antagonistsblock ACh from binding to nicotinic

receptor sites located in the ganglia of both the sympathetic and

parasympathetic nervous systems.

General effects

Because cholinergic antagonists have the opposite effect of

cholinergic agonists, their actions predominately affect the body in

the following ways:

Increase blood pressure and pulse rate Increase bronchial dilationProduce mydriasis (dilated pupils) and cycloplegia (paralysis of

ciliary muscle)

Decrease sweating


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Reduce secretions and dry out mucous membranesDecrease gastric motility Increase urinary retentionMuscarinic antagonists are not considered the first drugs of choice

because of their potential for adverse effects, such as:

Tachycardia and arrhythmiasMydriasis and cycloplegia, resulting in photophobia and

increased intraocular pressure

Dry eyesDry mouth (xerostomia)Urinary retention, which poses a threat to males with prostate

problems

Decreased sweating that can lead to hyperthermia if the body

cannot regulate its temperature

Muscarinic antagonists (anticholinergics) can be used to treat a

wide variety of conditions. However, they are used infrequently

because many clients do not tolerate them well. Examples of

anticholinergics include:

Generic Names

Brand

Names Indications for Use/Therapeut

atropine and

atropine sulfate

AtroPen Treatment for bradycardia, irritable bowel organophosphate insecticide poisoning

AChE inhibitors


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Useful for ophthalmic exams due to the drdicyclomine

hydrochloride

Bentyl Treatment for irritable bowel syndrome

glycopyrrolate Robinul Decreases oral and GI tract secretionsTreatment for peptic ulcer diseasemethscopolamin

e bromide

Pamine

hyoscyamine

sulfate

Cystospaz Treatment for spasms in GI tract conditionTreatment for colic and enterocolitis in infaGiven preoperatively to reduce oral and ga

ipratropium

bromide

Atrovent Relaxes bronchial smooth muscle; dilates atiotropium

bromide

Spiriva

benztropine

mesylate

Cogentin Reduces symptoms of muscular tremors aParkinson disease

trihexyphenidylhydrochloride

Artane

cyclopentolate

hydrochloride

Cyclogyl Dilates pupils for ophthalmic exams

scopolamine Transderm

Scp

Prevents motion sickness

oxybutyninchloride

Ditropan Decreases bladder spasms and involuntary

tolterodine

tartrate

Detrol


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Cholinergic Crisis

Cholinergic crisis is a serious condition that can result from

overdosage of AChE inhibitors. This condition is also caused by

poisoning from chemical agents such as:

Sarin, a toxic nerve agent used in chemical warfareMalathion, parathion, and other organophosphate insecticidesOverstimulation of the parasympathetic nervous system causes the

symptoms of cholinergic crisis, including:

Nausea, vomiting, and abdominal crampingMiosis (constriction of pupils)TachycardiaHyperglycemiaMuscle twitching, followed by muscle weaknessCentral nervous system effects such as headache, delirium,

convulsions, and coma, especially with organophosphateinsecticide poisoning

Atropine sulfate, an anticholinergic and muscarinic antagonist, is

the primary drug used to treat cholinergic crisis. Pralidoxime

chloride (2-PAM, Protopam Chloride) is administered concurrently

with atropine (AtroPen) as an antidote for sarin or insecticide

poisoning. Pralidoxime chloride is classified as a cholinesterase

receptor agonist and a detoxification agent. It helps restore normal

transmission at neuromuscular junctions.

Nicotinic Antagonists


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Nicotinic antagonists are classified as either ganglionic blockers or

neuromuscular blockers. Ganglionic blockers interfere with

receptors of both the sympathetic and parasympathetic nervous

systems. Ganglionic blockers are used to elicit a vasodilation effect

to treat hypertension.

Neuromuscular blockers do not produce an effect on the

autonomic nervous system, but instead block ACh from binding to

receptor sites at the neuromuscular junction. Neuromuscular

blockers are used to:

Produce relaxation of the diaphragm, skeletal muscles, andabdominal muscles

Relax muscles during endotracheal tube insertionHelp manage mechanical ventilationExamples of both ganglionic and neuromuscular blockers are:

Drug Names Indications for Use/Therapeutic Effects

ecamylamine hydrochloride

nversine)

Ganglionic blocker used in the past to treat severe ormalignant hypertension

Not often used today because other drugs with fewereffects are available

Approved for treatment of Tourette syndromeuccinylcholine chloride

Anectine)

Neuromuscular blocker for short medical-surgical procDepolarizing skeletal muscle relaxantUsed during endotracheal tube insertion

racurium besylate (Tracrium) Longer-acting neuromuscular blocker


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Nonpolarizing skeletal muscle relaxantLasts for 2045 minutes1

Assessment

During the assessment phase of the nursing process, information is

gathered regarding the clients past and present health history to

enable planning for safe and effective drug administration.

Before administering either cholinergic agonists or antagonists,

you should:

Conduct a health history and question the clients past orpresent drug use, including prescription drugs, herbal

products, and over-the counter drugs.

Assess for any drug allergies that the client has experienced.Complete a head-to-toe physical assessment.Obtain a baseline set of vital signs.Before administering cholinergic agonists, be sure to:

Assess for history of urinary retention.Observe for symptoms associated with myasthenia gravis:

Ptosis (refer to the photo on this screen)

DiplopiaDifficulty chewing

Decreased muscle strength

Before administering cholinergic antagonists, be sure to:


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Assess for history of glaucoma.Assess bowel and bladder habits.Planning

During the planning phase of the nursing process, you will work

with clients to develop their individualized plans of care by:

Discussing goals and outcomes that clients would like to achievePlanning goals that are realistic, to increase client compliance

with the drug regimen

Assessment

Myasthenic vs Cholinergic Crisis

Before, during, and after administering cholinergic agonists, it is

important to assess your clients. A critical part of this process

involves the ability to distinguish between a myasthenic crisis anda cholinergic crisis, and treat them appropriately.

A cholinergic crisis occurs when the parasympathetic nervous

system is overstimulated, as in the case of an AChE inhibitor

overdose. In contrast, a myasthenic crisis can occur if a client

suddenly stops taking his/her AChE inhibitor medication for MG.

Because some symptoms of a myasthenic crisis are similar to those

of a cholinergic crisis, a diagnosis must be carefully made. For

example, the following signs may be present in both conditions:

Tachycardia


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Muscle weaknessRespiratory distress

To make a diagnosis, a very small dose of edrophonium chloride

(Enlon, Reversol, Tensilon) is administered. If the client shows signs

of improvement, then he/she is treated with drugs that support

MG. However, if there is no symptomatic improvement, then a

cholinergic crisis is diagnosed and atropine sulfate is administered

as an antidote. A diagnosis of cholinergic crisis also requiresdiscontinuing any AChE inhibitors that the client was taking.

Interventions for Cholinergic Agonists

Cholinergic agonists can produce serious adverse effects. During

the implementation stage of the nursing process, it is imperative

that you continually monitor and assess for any complications

related to drug administration.

All cholinergic agonists:

Monitor vital signs before, during, and after administration.Notify the health care provider if there is a significant change

from the baseline.

Check serum laboratory liver enzymes to rule out hepatotoxicity.Monitor for cholinergic crisis and notify the health care provider

immediately if you observe signs of this condition.


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Administer atropine sulfate as an antidote, as directed by the

health care provider.

Direct-acting cholinergic agonists:

Evaluate the client for orthostatic hypotension.Obtain daily intake and output (I & O).Palpate the clients bladder to assess for distention related to

urinary retention.

Evaluate the clients ability to see clearly. Implement safetyprecautions to prevent injury.

Indirect-acting cholinergic agonists:

Assess for muscle weakness or any neuromuscular changes.Administer medications 30 minutes prior to mealtime to promote

chewing and swallowing.2

Interventions for Cholinergic Antagonists

During the implementation stage of the nursing process, you

should continually check for complications or serious adverse

effects related to anticholinergics, by:

Monitoring vital signs and reporting significant changes to thehealth care provider

Recording daily urinary intake and output (I & O)Monitoring for the following adverse effects:

Adverse Effects Nursing Interventions

Dry mouth Provide frequent mouth


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care.

Hyperthermia due to decreased

sweating

Maintain comfortable

room temperature.

Dry eyes Apply artificial tears.

Symptoms associated with overdose of

an anticholinergic agent:

DysphagiaAgitation, confusion Increased heart rateFeverUrinary retentionLoss of coordinationHallucinations

Immediately contact

health care provider.

Client Education

Part of your role as a nurse is to provide education on cholinergic

agonists and cholinergic antagonists and their use. Both the client

and his/her family members who help provide care should be

included in teaching sessions. Instruct the client to:

Take his/her vital signs every day and report any significantchanges to the health care provider.

Take all medications as directed.Keep all follow-up appointments with the health care provider.Refrain from taking any over-the-counter medications or herbal


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products until the health care provider is consulted.

Do the following if taking a cholinergic agonist: Immediately report adverse effects, such as GI distress and

difficulty breathing, to the health care provider.

Avoid GI distress by taking medication prior to eating. Keep scheduled appointments for laboratory studies per

health care providers instructions.

Avoid driving until blurring of vision clears after drugadministration.

Prevent falls due to orthostatic hypotension by changingbody positions slowly.

Do the following if taking a cholinergic antagonist: Minimize symptoms associated with dry mouth by

increasing fluids, sucking on sugar-free candy, and

maintaining good oral hygiene.

Immediately report adverse effects, such as difficultyswallowing, fever, tachycardia, dizziness, excessive

tiredness, and difficulty breathing, to the health care

provider.

Avoid excessive exercise, because the medication decreasesthe ability to sweat.

Contact the health care provider if the client experiences adecrease in urinary output or constipation.

cholinergic agonists and antagonists

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