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Divisions of human
nervous system
Nervous system
ANS / SNS
Autonomic nervous system controls
involuntary activities of smooth muscle,
secretory glands and the visceral organs of
the body such as the heart (involuntary
activities of smooth muscle)
Somatic nervous system innervates the
skeletal muscles and controls voluntary
movement
Autonomic Nervous
System Sympathetic Nervous System
Para sympathetic System
Enteric System
Parasympathetic Nervous
System
75% of all parasympathetic nerve fibers are in
Parasympathetic Nervous
System
Also supply the muscles of the eyes, lacrimal,
Neurotransmitters
Neurotransmitters
Acetylcholine: skeletal muscle
Norepinepherine: stress response
Body Responses
Dilation of blood vessels in skin
Decrease heart rate (bradycardia)
Increase secretion of digestive enzymes
Constriction of smooth muscle of bronchi
Increase in sweat glands
Contraction of smooth muscles of urinary
bladder
Contraction of smooth muscle of skeletal
system
Cholinergic Agents
Direct acting - act on the receptors to
activate a tissue response
Indirect acting - inhibit the action of the
enzyme cholinesterase
(acetylcholinesterase - ACH)
: Major uses
, Stimulate bladder & GI tone
, constrict pupils (miosis)
neuromuscular transmission
Cholinergic Receptors
:Two types, determined by
Location
Action once stimulated
Nicotinic receptors
Muscarinic receptors
Nicotinic Receptors
Located in the ganglia of both the
PSNS and SNS
Named nicotinic because can be stimulated
by the alkaloid nicotine
Muscarinic Receptors
:Located postsynaptically
Smooth muscle
Cardiac muscle
Glands of parasympathetic fibers
Effector organs of cholinergic sympathetic
fibers
Named muscarinic because can be
Cholinergic Agent
(Parasympathomimetics)
Bethanechol (Urecholine) selective to
muscarinic receptors, mimic action of
acetylcholine
Use - For urinary retention
Take on an empty stomach d/t inc. peristalsis *
Alert- Never give IM or IV circulatory
*
collapse, hypotension, shock & cardiac arrest
.poss
Pilocarpine (Pilocar) - Ophthalmic - direct
acting
Parasympathetic Nervous
System
: Functions stimulated by PNS
, Resting
, reparative
vegetative function
Autonomic Drugs
Drugs used due to their ability to stimulate or
block activity of the sympathetic or
.parasympathetic nervous system
Effect of Drugs
Drugs that act of ANS usually affect
.the entire body
Effects depend on whether you are
.trying to stimulate or inhibit function
Receptor Activity
Drugs are developed to stimulate or inhibit
.particular subtypes of receptors
.More selective on particular body tissues
Decrease adverse effects on other body
.tissues side effects
Cholinergic Drugs
Parasympathomimetics or cholinomimetics
Stimulate parasympathetic nervous system in
Cholinergic Drugs
Useful in treating
Alzheimers Disease,
Myasthenia gravis,
atony of the smooth muscle of the GI system or
urinary system
Cholinergic Drugs
Normal neuromuscular function, acetylcholine
Cholinergic Drugs
Acetylcholine important neurotransmitter
Cholinergic DrugsGI
effects
Acetylcholine stimulates cholinergic receptors in the
Cholinergic DrugsGU
effects
Acetylcholine stimulates cholinergic receptors
Acetylcholine
One of the main neurotransmitters of the ANS is
acetylcholine
Acetylcholine is released at preganglionic fibers
of both the sympathetic and parasympathetic
nervous system
Also released from postganglionic sympathetic
neurons that innervate the sweat glands and
from motor neurons that innervate the skeletal
muscles
Acetylcholine
Sympathetic and parasympathetic divisions of
Acetylcholine
Nicotinic receptors are located in motor
Acetylcholine
Muscarinic receptors are located in :
most internal organs.
This includes the cardiovascular, respiratory,
gastrointestinal, and genitourinary. Stimulation of the
muscarinic receptors may result in either excitation or
inhibition, depending on the organ involved.
Mechanisms of ActionDirect
Acting Cholinergics
Direct acting cholinergics are lipid insoluble
Do not readily enter the CNS so effects are peripheral
Resistant to metabolism by acetylcholinesterase
Effects are longer acting than with acetylcholine
BP effects
Increased tone and contractility in GI smooth
muscle, relaxation of sphincters, increased
salivary gland and GI secretions
Increased tone and contractility of smooth
muscle in urinary bladder and relaxation of
the sphincter
smooth muscle
Increased respiratory secretions
Constriction of pupils (miosis) and contraction
of ciliary muscle
given IM or IV.
Used to treat urinary retention due to bladder
atony and for postoperative abdominal
distention due to paralytic ileus
Indirect-Acting Cholinergic
Drugs
Action is by decreasing the inactivation of
Indirect-Acting or
.Anticholinesterase Drugs cont
Anticholinesterase drugs are either reversible
or irreversible inhibitors of
acetylcholinesterase
Reversible agents are such drugs
as:edrophodium (Tensilon). Used to diagnose
myasthenia gravis and for reversal of nondepolarizing neuromuscular blockers
Indirect-acting agents
.cont
Neostigmine (Prostigmine)prototype
Indirect ActingReversible
.cont
Physostigmine (Antilirium)only
Specific Conditions
Distinction between cholinergic crisis and a
myasthenic crisis
Difficult to ascertain as both are characterized
by respiratory difficulty or failure
Need to distinguish as require opposite
treatment measures
Myasthenia Gravis
If s/s not clearly indicative of the problem,
Toxicity of Cholinergic
Drugs
Atropine is the specific antidote to cholinergic
agents
Atropine reverses only the muscarinic effects
of cholinergic drugs; heart, smooth muscle,
and glands.
Atropine cannot reverse the nicotinic effects
of skeletal muscle weakness or paralysis due
to overdose of indirect cholinergic drugs.
Toxicity of Irreversible
Anticholinesterase Agents
These agents are lipid soluble
Can enter the body by the eye,skin,
.Toxicity cont
Cholinergic crisis occurs because the
.Toxicity cont
Emergency tx includes:
1. Decontamination of clothing
2. Flushing poison from skin and eyes
3. Activated charcoal and lavage for GI
ingestion
4. Atropine to counteract the muscarinic
effects
.Toxicity cont
To relieve the neuromuscular blockade by
Nervous system
Nervous system
Neurotransmitter systems
System
Noradrenaline
system
Dopamine
system
Origin
locus coeruleus
Lateral tegmental field
arousal
reward
dopamine pathways:
mesocortical pathway
mesolimbic pathway
nigrostriatal pathway
tuberoinfundibular pathway
Cholinergic
system
Effects
Common neurotransmitters
Abbreviation
Category
Name
Small: Amino
acids
Aspartate
Neuropeptides
N-Acetylaspartylglutamate
NAAG
Small: Amino
acids
Glu
Small: Amino
acids
Gamma-aminobutyric acid
GABA
Small: Amino
acids
Glycine
Small:
Acetylcholine
Small:
Monoamine (
Phe/Tyr)
Metabotropic
Ionotropic
NMDA receptor,
Kainate receptor,
AMPA receptor
GABAB receptor
GABAA, GABAC
Gly
Glycine receptor
Acetylcholine
Ach
Nicotinic acetylcholine
receptor
Dopamine
DA
Dopamine receptor
Norepinephrine (noradrenaline)
NE
Adrenergic receptor
Epinephrine (adrenaline)
Epi
Adrenergic receptor
Octopamine
Tyramine
Serotonin (5-hydroxytryptamine)
Melatonin
Histamine
PP: Gastrins
Gastrin
PP: Gastrins
Cholecystokinin
PP: Neurohypophyseals
5-HT
5-HT3
Mel
Melatonin receptor
Histamine receptor
Cholecystokinin receptor
Vasopressin
Vasopressin receptor
PP: Neurohypophyseals
Oxytocin
Oxytocin receptor
PP: Neurohypophyseals
Neurophysin I
PP: Neurohypophyseals
Neurophysin II
PP: Neuropeptide Y
Neuropeptide Y
NY
Neuropeptide Y receptor
PP: Neuropeptide Y
Pancreatic polypeptide
PP
PP: Neuropeptide Y
Peptide YY
PYY
PP: Opioids
Corticotropin (adrenocorticotropic
hormone)
Corticotropin receptor
PP: Opioids
Dynorphin
PP: Opioids
Endorphin
PP: Opioids
Enkephaline
PP: Secretins
Secretin
Secretin receptor
PP: Secretins
Motilin
Motilin receptor
PP: Secretins
Glucagon
Glucagon receptor
CCK
ACTH
PP: Secretins
VIP
PP: Secretins
GRF
PP: Somtostatins
Somatostatin
Somatostatin receptor
SS: Tachykinins
Neurokinin A
SS: Tachykinins
Neurokinin B
SS: Tachykinins
Substance P
PP: Other
Bombesin
PP: Other
GRP
Gas
Nitric oxide
NO
Gas
Carbon monoxide
CO
Other
Anandamide
AEA
Cannabinoid receptor
Other
Adenosine triphosphate
ATP
P2Y12
P2X
receptor
Anticholinergics
Also called cholinergic blocking agents or
parasympatholytics
Again, focus is on the parasympathetic
nervous system
Parasympathetic system acts as a resting and
reparative function
Functions include digestion, excretion, cardiac
decelertion, anabolism and near vision
Anticholinergics
Most anticholinergic drugs interact with the
Cholinergic Blocking
Agents: Mechanism of
Competitive antagonists
Action
Compete with ACh
Block ACh at the muscarinic receptors in the
PSNS
As a result, ACh is unable to bind to the receptor
site
.and cause a cholinergic effect
Drug Effects of
Cholinergic Blocking
Cardiovascular
Agents
Small doses: decrease heart rate
CNS
Drug Effects of
Cholinergic
Blocking
Eye
Dilated
pupils
(mydriasis)
Agents
Decreased accommodation due to paralysis
of ciliary muscles (cycloplegia)
Gastrointestinal
Relax smooth muscle tone of GI tract
Decrease intestinal and gastric secretions
Decrease motility and peristalsis
Drug Effects of
Cholinergic
Blocking
Genitourinary
Agents
Relaxed detrusor muscle
Increased constriction of internal sphincter
Result: urinary retention
Glandular
Respiratory
Cholinergic Blocking
Agents: Nursing
Anticholinergics may lead to higher risk for
Implications
Use In GI Disorders
Helpful in treating irritable colon or colitis
Useful in gastritis, pylorospasm and ulcerative
Use in GU disorders
Antispasmotic effects seen in overactive
Ophthalmology
Mydriatic and cycloplegia for examinations
and surgery
Meiosis
Mydriasis
Respiratory
In bronchospasm whether related to asthma
or COPD
Atrovent very useful for its bronchodilating
effects
Cardiology
Atropine is used to increase heart rate in
Parkinsons Disease
Useful in those with minimal side effects
Those who cannot take Levodopa
Helpful in decreasing salivation, spasticity and
tremors
Preop
Help prevent vagal stimulation and potential
bradycardia
Reduce respiratory secretions as well
Contraindications
BPH
Myasthenia gravis
Hyperthyroidism
Glaucoma
Tachydysrhythmias
Not in situations whereby delaying of gastric
emptying is a concern
Individual Anticholinergic
Drugs
Atropineprototype. Antidote. Belladonna
alkaloid.
Ipratropium (Atrovent). Useful in
rhinorrhea. Also excellent bronchodilator.
Scopolamine, similar to atropine.
Depresses CNS and causes amnesia,
drowsiness, euphoria, relaxation and sleep.
Also good for motion sickness. Given
parenterally, orally and transdermally.
Centrally Acting
Anticholinergics
Urinary Antispasmotics
Flavoxate (Urispas)relieves dysuria, urgency,
Toxicity of
Anticholinergics
Anticholinergic overdose syndrome is
characterized by: Hyperthermia, delirium, dry
mouth, tacycardia, ileus, urinary retention.
Seizures, coma and respiratory arrest may
occur.
Txactivated charcoal, Antilirium, cooling
agents (ice bags, cooling blankets, tepid
baths).
Cholinergic Blocking
Agents: Chemical Class
Typical anticholinergic (cholinergic blocking) agents include :
Atropine sulfate
Benztropine mesylate
Biperiden hydrochloride
Dicyclomine hydrochloride
Ipratropium bromide
Propantheline bromide
Scopolamine hydrobromide
Scopolamine transdermal therapeutic system
Trihexyphenidyl hydrochloride
Cholinergic Blocking
Agents: Therapeutic
CNS
Uses
Decreased muscle rigidity and muscle
tremors
Parkinsons disease
Drug-induced extrapyramidal reactions
Cholinergic Blocking
Agents: Therapeutic
Cardiovascular
Uses
Affect the hearts conduction system
Low doses: slow the heart rate
High doses: block inhibitory vagal effects on
the SA and AV node pacemaker cells
Result: increased heart rate
Cholinergic Blocking
Agents: Therapeutic
Atropine
Uses
Cholinergic Blocking
Agents: Therapeutic
Respiratory
Uses
Blocking the cholinergic stimulation of the PSNS
.allows unopposed action of the SNS
:Results
Cholinergic Blocking
Agents: Therapeutic Uses
:Respiratory agents are used to treat
Exercise-induced bronchospasms
Chronic bronchitis
Asthma
Chronic obstructive pulmonary disease
Cholinergic Blocking
Agents: Therapeutic
Gastrointestinal
Uses
PSNS
controls gastric secretions and smooth
.muscles that produce gastric motility
:Blockade of PSNS results in
Decreased secretions
Relaxation of smooth muscle
Decreased GI motility and peristalsis
Cholinergic Blocking
Agents: Therapeutic
:Gastrointestinal
agents are used to treat
Uses
Peptic ulcer disease
Irritable bowel disease
GI hypersecretory states
Cholinergic Blocking
Agents: Therapeutic
Genitourinary
Usesdetrusor muscles of the bladder
Relaxed
Increased constriction of the internal
sphincter
Reflex neurogenic bladder
Incontinence
Cholinergic Blocking
Agents:
Side/Adverse Effectson Body System
Side Effects
CNS : excitation, restlessness, irritability, disorientation, hallucinations, delirium
Increased heart rate
Cardiovascular dyrrhytmias -
Cholinergic Blocking
Agents:
Side Effects
EYE :
Cholinergic Blocking
Agents:
Genito-Urinary
retention
Side
Effects
Glandular : decreased sweating
Respiratory : decreased bronchial secretions
Cholinergic Blocking
Agents: Interactions
Antihistamines, phenothiazines,
tricyclic antidepressants, MAOIs
When given with cholinergic blocking
agents, cause ADDITIVE cholinergic
effects, resulting in increased effects
Cholinergic Blocking
Agents: Nursing
Keep in mind that these agents will block
Implications
Cholinergic Blocking
Agents: Nursing
Medications should be taken exactly as prescribed
Implications
.to have the maximum therapeutic effect
. Overdosing can cause life-threatening problems
Blurred vision may cause problems with driving
.or operating machinery
Patients may experience sensitivity to light and
.may want to wear dark glasses or sunglasses
Cholinergic Blocking
Agents: Nursing
When giving ophthalmic solutions, apply pressure to
Implications
.the inner canthus to prevent systemic absorption
Dry mouth may occur; can be handled by chewing
.gum, frequent mouth care, and hard candy
Check with physician before taking any other
.medication, including OTC medications
ANTIDOTE for atropine is physostigmine salicylate
.(Antilirium)
Drug interactions
Amantadine / Additive anticholinergic side effects
Antacids / Lowered absorption of anticholinergics from GI tract
Antidepressants, tricyclic / Additive anticholinergic side effects
Antihistamines / Additive anticholinergic side effects
Atenolol / Anticholinergics increase effects of atenolol
Benzodiazepines / Additive anticholinergic side effects
Corticosteroids / Additive increased intraocular pressure
Cyclopropane / Increased chance of ventricular arrhythmias
Digoxin / Increases effect of digoxin due to increased absorption from GI tract
Disopyramide / Potentiation of anticholinergic side effects
Guanethidine / Reversal of inhibition of gastric acid secretion caused by
anticholinergics
Haloperidol / Additive increased intraocular pressure
Histamine / Reversal of inhibition of gastric acid secretion caused by
anticholinergics
Levodopa / Possible decreased effect of levodopa due to increased breakdown
of levodopa in stomach (due to delayed gastric emptying time)
Contralndicatlons:
Glaucoma, adhesions between iris and lens of the eye, tachycardia, myocardial
ischemia, unstable CV state in acute hemorrhage, partial obstruction of the GI
and biliary tracts, prostatic hypertrophy, renal disease, myasthenia gravis,
hepatic disease, paralytic ileus, pyloroduodenal stenosis, pyloric obstruction,
intestinal atony, ulcerative colitis, obstructive uropathy. Cardiac clients,
especially when there is danger of tachycardia; older persons suffering from
atherosclerosis or mental impairment. Lactation.
Special Concerns:
Use with caution in pregnancy. Infants and young children are more susceptible
to the toxic side effects of anticholinergic drugs. Use in children when the
ambient temperature is high may cause a rapid increase in body temperature
due to suppression of sweat glands. Geriatric clients are particularly likely to
manifest anticholinergic side effects and CNS effects, including agitation,
confusion, drowsiness, excitement, glaucoma, and impaired memory. Use with
caution in hyperthyroidism, CHF, cardiac arrhythmias, hypertension, Down
syndrome, asthma, spastic paralysis, blonde individuals, allergies, and chronic
lung disease.
Overdose Management:
Symptoms ("Belladonna Poisoning"): Infants and children are especially
susceptible to the toxic effects of atropine and scopolamine. Poisoning (dosedependent) is characterized by the following symptoms: dry mouth, burning
sensation of the mouth, difficulty in swallowing and speaking, blurred vision,
photophobia, rash, tachycardia, increased respiration, increased body
temperature, restlessness, irritability, confusion, muscle incoordination, dilated
pupils, hot dry skin, respiratory depression and paralysis, tremors, seizures,
hallucinations. and death.
Treatment ("Belladonna Poisoning"):
Gastric lavage or induction of vomiting followed by activated charcoal. General supportive
measures.
Anticholinergic effects can be reversed by physostigmine (Eserine), l 3 mg IV
(effectiveness uncertain; thus use other agents if possible). Neostigmine methylsulfate, 0.52 mg IV, repeated as necessary.
If there is excitation, diazepam, a short-acting barbiturate, IV sodium thiopental (2%
solution), or chloral hydrate (100-200 mL of a 2% solution by rectal infusion) may be given.
For fever, cool baths may be used. Keep client in a darkened room if photophobia is
manifested.
Artificial respiration should be instituted if there is paralysis of respiratory muscles.