cholinergic agonists and antagonists
TRANSCRIPT
-
8/13/2019 Cholinergic Agonists and Antagonists
1/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
2/21
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:
-
8/13/2019 Cholinergic Agonists and Antagonists
3/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
4/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
5/21
-
8/13/2019 Cholinergic Agonists and Antagonists
6/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
7/21
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 -
8/13/2019 Cholinergic Agonists and Antagonists
8/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
9/21
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.
-
8/13/2019 Cholinergic Agonists and Antagonists
10/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
11/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
12/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
13/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
14/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
15/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
16/21
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:
-
8/13/2019 Cholinergic Agonists and Antagonists
17/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
18/21
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.
-
8/13/2019 Cholinergic Agonists and Antagonists
19/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
20/21
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
-
8/13/2019 Cholinergic Agonists and Antagonists
21/21
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.