Autonomic Nervous System Agents

Central Nervous System

(CNS)


Consists of brain and spinal cord


Peripheral Nervous System
(PNS)

Located outside the brain and spinal cord
Made up of 2 divisions : Autonomic and Somatic


Autonomic Nervous System

Also called Visceral system
Innervates (acts on) smooth muscles and glands
An involuntary nervous system over w/c a person has little or no control
2 sets of neurons : afferent and efferent


Afferent Neurons (sensory)

Send impulses to the CNS where they are interpreted


Efferent Neurons (motor)

Receive the impulses from the brain ,transmit through spinal cord to the effector organ cells
Efferent pathways are divided into 2 branches : Sympathetic and Parasympathetic


Sympathetic Nervous System

Also called adrenergic system
It is the neurotransmitter Norepinephrine that innervates smooth muscle
Norepinephrine is released from the terminal nerve ending and stimulates cell receptors to produce a response

Parasympathetic Nervous
System

Also called cholinergic system
It is the neurotransmitter acetylcholine at the end of the neuron that innervates the muscles
The cholinergic receptors at organ cells are either nicotinic or muscarinic (stimulated by alkaloids nicotine and muscarine)
The enzyme acethylcolinesterase may inactive acetylcholine before it reaches the receptor cell


Somatic Nervous System

A voluntary system that innervates skeletal muscles over w/c there is control
Central Nervous System
Brain Spinal Cord
Peripheral Nervous System
Autonomic NS Somatic NS
Afferent neurons
(sensory)
Efferent neurons
(motor)
Sympathetic NS/ Adrenergic
system
Parasympathetic NS/
Cholinergic system























SYMPATHETIC STIMULANTS


PARASYMPATHETIC STIMULANTS


SYMPATHETIC DEPRESSANTS

PARASYMPATHETIC DEPRESSANTS

Adrenergics
Increase BP
Increase pulse rate
Relax bronchioles
Dilate pupils of eyes
Relax uterine muscles
Increase Blood sugar


Direct-Acting (Parasympathomimetics)
Decrease BP
Decrease pulse rate
Constrict bronchioles
Constrict pupils of eyes
Increase urinary contraction
Increase peristalsis

Indirect-Acting (Cholinesterase
Inhibitors/Anticholinesterase)
Increase muscle tone

Sympatholytics (Adrenergic blockers)
Decrease pulse rate
Decrease BP
Constrict bronchioles

Parasympatholytics (Anticholinergics)
Increase pulse rate
Decrease Mucous secretions
Decrease GI motility
Increase urinary retention
Dilate pupils of eyes





























Body tissue organ

Sympathetic response

Parasympathetic response

Eye

Dilates pupils

Constricts pupils

Lungs

Dilates bronchioles

Constricts bronchioles
Increases secretions

Heart

Increases heart rate

Decreases heart rate

Blood vessels

Constricts blood vessels

Dilates blood vessels

GI

Relaxes smooth muscles

Increases peristalsis

Bladder

Relaxes bladder muscle

Constricts bladder

Uterus

Relaxes uterine muscle



Salivary gland

Increases salivation


Adrenergic and Adrenergic blockers

Adrenergics


Definition

Drugs that stimulate the sympathetic NS
Also known as :
o Adrenergic agonists
o Sympathomimetics
o Adrenomimetics
Mimic the sympathetic neurotransmitters i.e norepinephrine and epinephrine
Act on one or more adrenergic receptor sites located in the cells of muscle


Adrenergic receptors


Alpha1
Located in the vessels of muscle
Arterioles and venules constrict , increasing peripheral resistance and blood return to the heart
Circulation is improved , BP increase
Too much stimulation causes decreased blood flow to the vital organs

Alpha2
Located in the postganglionic sympathetic nerve endings
Inhibits the release of Norepinephrine leading to a decrease in vasoconstriction
BP decrease

Beta1
Located primarily in the heart
Increases myocardial contractility and heart rate

Beta2
Located mostly in the smooth muscles of the lung, arterioles of skeletal muscles, and uterine muscle
Causes relaxation of smooth muscles of lungs = Bronchodilation
Increase in blood flow to the skeletal muscles
Relaxation of the uterine muscle = Decrease uterine contraction

Dopaminergic
Located in the renal, mesenteric, coronary, and cerebral arteries
Vessels dilate, blood flow increases
Only dopamine can activate this receptor


Inactivation of Neurotransmitters

After the transmitter has performed its function, the action must be stopped to prevent prolonging the effect
Transmitters are inactivated by..
o Reuptake of the transmitter back into the neuron (nerve cell terminal)
o Enzymatic transformation or degradation
o Diffusion away from the receptor
Enzymes that inactivate the metabolism of Norepinephrine
o Monoamine oxidase (MAO) inside the neuron
o Catechol-O-methyltransferase (COMT) outside the neuron
Drugs can either stop the termination of neurotransmitter by either :
o Inhibiting the norepinephrine reuptake w/c prolongs the action of transmitter
o Inhibiting degradation of norepinephrine by enzyme action

Classification of
Sympathomimetics/Adrenomimetics

Direct acting sympathomimetics
o Directly stimulate the adrenergic receptor
Indirect-acting sympathomimetics
o Stimulate the release of Norepinephrine from the terminal nerve endings
o eg. amphetamine
Mixed-acting sympathomimetics
o Both direct and indirect acting
o Stimulate the adrenergic receptor sites and stimulate the release of Norepinephrine from the terminal nerve
endings
o eg. Ephedrine

Ephedrine
- Acts indirectly by stimulating the release of Norepinephrine
- Acts directly on the alpha1, beta1 and beta 2-receptors
- Ephedrine-like epinephrine increases the heart rate and BP but is not as potent a vasoconstrictor as epinephrine
- Treat idiopathic orthostatic hypotension and hypotension that results from spinal anesthesia
- Dilate bronchial tubes and useful to treat mild forms of bronchial asthma

Catecholamines
Chemical structures of a substance either endogenous or synthetic that can produce a sympathomimetic response
Endogenous
o Epinephrine
o Norepinephrine
o Dopamine
Synthetic
o Isoproterenol
o Dobutamine

Noncatecholamines
Stimulate the adrenergic receptors
Most have a longer duration of action than endogenous or synthetic cathecolamines
Example :
o Phenylephrine
o Metaproterenol
o Albuterol




ALPHA1-RECEPTOR

ALPHA2-RECEPTOR

BETA1-RECEPTOR

BETA2-RECEPTOR

Blood vessels
Vasoconstriction
Increased BP
Increased contractibility of heart

Blood vessels
Decreased BP (reduced
Norepinephrine)

Heart
Increased heart contraction
Increased heart rate

GI tract
Smooth muscles
Decreased GI tone and motility

Eye
Mydriasis (Pupil dilation)

GI tract
Smooth muscles
Decreased GI tone and motility

Kidney
Increased renin secretion
Increased angiotensin
Increased BP

Lungs
Bronchodilation

Bladder
Contraction



Uterus
Relaxation of uterine smooth
muscles

Prostate
Contraction

Liver
Activation of glycogenolysis
Increased blood sugar

Meds :


Epinephrine (adrenalin)


Acts on alpha1, beta1, beta2
Increase BP, pupil dilation, Increase heart rate, Bronchodilation
Useful in certain types of shock (i.e., cardiogenic, anaphylactic)
Because it affects 3 diff adrenergic receptors , it is nonselective w/c excites all receptors app. equally


Albuterol sulfate (Proventil)


Selective for beta2 , response is purely Bronchodilation
High dosage may affect beta1 receptor causing an increase in heart rate


Clonidine (Catapres) and
Methyldopa (Aldomet)


Selective alpha2-adrenergic drugs
Used primarily to treat hypertension
Regulate the release of Norepinephrine by inhibiting its release












Adrenergic Blockers (Antagonists)


Definition

Drugs that block the effects of adrenergic neurotransmitters
Also known as :
o Adrenergic antagonists
o Sympatholytics
Block the alpha and beta receptor sites
Block the effects of neurotransmitter either :
o Directly by occupying the alpha or beta receptors
o Indirectly by inhibiting the release of neurotransmitters
The 3 sympatholytic receptors :
o Alpha1
- vasodilation
- decreases BP
- reflex tachycardia might result
- miosis / constriction of pupil
- suppresses ejaculation
- reduces contraction of smooth muscle in bladder neck and prostate gland
o Beta1
- decreases heart rate
- reduces force of contractions
o Beta2
- constricts bronchioles
- contracts uterus
- inhibits glycogenolysis w/c can decrease blood sugar


Alpha-Adrenergic
blockers

Drugs that block or inhibit a response at the alpha-adrenergic receptor site
2 groups :
o Selective alpha blockers
- Block alpha1
o Nonselective alpha blockers
- Block alpha 1 and alpha2
Can cause orthostatic hypotension and reflex tachycardia thats why theyre not frequently prescribed
Helpful in decreasing symptoms of benign prostatic hypertrophy (BPH)
Promote vasodilation causing decrease in BP
As BP decreases, pulse rate usually increases to compensate for the low BP and inadequate blood flow
Can be used to treat peripheral vascular disease (eg. Raynauds disease)


Beta-Adrenergic
blockers

Effects:
o Decrease heart rate
o Decrease BP
o Bronchoconstriction
Nonselective beta blockers (beta 1 and beta 2) should be used w/ extreme caution in any client who has COPD
or asthma
Selective beta1-blocker (metaprolol tartrate [Lopressol]) may be ordered to decrease BP and pulse rate
Useful in treating cardiac dysrhythmias, mild hypertension, mild tachycardia and angina pectoris
Side effects
o Bradycardia
o Hypotension
o Palpitations
o Headache
o Dizziness
o Hyperglycemia
o Hypoglycemia
o Bronchospasm
o Agranulocytosis

Intrinsic sympathomimetic activity (ISA)
Causes partial stimulation of beta receptors
Nonselective beta blockers that have ISA
o carteolol
o carvedilol
o penbutolol
o pindolol
Selective beta blocker that has ISA
o acebutolol

Propanolol Hydrochloride (Inderal)
First beta blocker prescribed to treat angina, cardiac dysrhythmias, hypertension, and heart failure
Has many side effects partly because of its nonselective response
Contraindicated for clients w/ asthma or second or third degree heart block
Extensively metabolized by the liver so only a small amt of drug reaches the systemic circulation
Drug interactions
o Phenytoin, Isoproterenol, NSAIDs , barbiturates, and xanthenes = Decreased the drug effect
o If taken w/ digoxin or calcium blocker = Atrioventricular (AV) heart block
o If taken w/ another Antihypertensive = BP can be decreased


Adrenergic Neuron
Blockers

Drugs that block the release of Norepinephrine from the sympathetic terminal neurons
Classified as subdivision of adrenergic blockers
Clinical use is to decrease BP

Guanadrel sulfate (Hylorel)
Ex of adrenergic neuron blocker
A potent antihypertensive agent



















































Cholinergics and Anticholinergics

Cholinergics


Definition

Drugs that stimulate the parasympathetic system
Also known as
o Parasympathomimetics
o Cholinomimetics
o Cholinergic stimulants
o Cholinergic agonists
Mimic the parasympathetic neurotransmitter acetylcholine
Acetylcholine (ACh)
o Located at the ganglions and parasympathetic terminal nerve endings
o Innervates receptors in organs, tissues and glands
2 types of cholinergic receptors :
o Muscarinic receptors
- stimulate smooth muscle and slow heart rate
o Nicotinic receptors (neuromuscular)
- affect skeletal muscles
Nonselective
o Affect both muscarinic and nicotinic receptors
Selective
o Affect muscarinic receptor only

Direct-Acting Cholinergics


Act on the receptors to activate a tissue response
Primarily selective to the muscarinic receptors but are nonspecific because the muscarinic receptors are
located in the smooth muscles of the GI and Genitourinary tracts, glands and heart
Muscarinic agonist
o Contraindicated for clients with intestinal or urinary tract obstruction and for those with active asthma
o Mild to severe side effects :
- Hypotension
- Bradycardia
- Excessive salivation
- Increased gastric acid secretion
- Abdominal cramps
- Diarrhea
- Bronchoconstriction
- Cardiac dysrhythmias
o Should be prescribed cautiously for pt with low blood pressure and heart rates

Bethanechol chloride (Urecholine)
Acts on the muscarinic receptor
Used primarily to increase urination

Metoclopramide HCl (Reglan)
Treat Gastroesophageal reflux disease (GERD)
Increases gastric emptying time

Pilocarpine
Constricts the pupils of eyes thus opening the canal of Schlemm to promote drainage of aqueous humor (fluid)
Used to treat glaucoma by relieving fluid (intraocular) pressure in the eye


Indirect-Acting
Cholinergics

Also known as :
o Cholinesterase (ChE) inhibitors
o Acetylcholinesterase (AChE) inhibitors
o Anticholinesterases
2 types : reversible and irreversible
Do not act on receptors instead they inhibit the action of the enzyme cholinesterase (ChE)/
acetylcholinesterase by forming a chemical complex thus permitting acetylcholine to persists and attach to the
receptor
Binds with cholinesterase allowing acetylcholine to activate the muscarinic and nicotinic cholinergic receptors
w/c permits skeletal muscle stimulation that increases the force of muscular contraction
Useful to increase muscle tone for pt myasthenia gravis
By Increasing acetylcholine , additional effects occur :
o Increase in GI motility
o Bradycardia
o Miosis
o Bronchial constriction
o Increased micturition
Treat :
Myasthenia gravis (neuromuscular disorder)
Glaucoma
Alzheimers disease
Muscarinic antagonist poisoning

Cholinesterase (ChE)
- Acetylcholinesterase
- Function is to break down into choline and acetic acid
- May destroy acetylcholine before it reaches the receptor or after it has attached to the site



Reversible Cholinesterase
Inhibitors

Bind the enzyme cholinesterase for several min to hours
Used to :
o Produce papillary constriction in the treatment of glaucoma
o Increase muscle strength in clients w/ myasthenia gravis
Drugs used with myasthenia gravis :
o neostigmine (Prostigmin) Short acting
o pyridostigmine bromide (Mestinon) Moderate acting
o ambenonium chloride (Mytelase) Long acting
o edrophonium chloride (Tensilon) Short acting
Physostigmine (Antilirium)
o A reversible ophthalmic Anticholinesterase
Caution in clients who have :
o Bradycardia
o Asthma
o Peptic ulcers
o Hyperthyroidism
Contraindicated in clients w/
o Intestinal or urinary obstruction


Irreversible
Cholinesterase Inhibitors

Bond bet. irreversible inhibitors and cholinesterase is considered permanent
But bond can be broken w/ the use of pralidoxime (Protopam) an antidote to reverse the irreversible
organophosphate and it has effect at the neuromuscular junction
Potent agents because of their long-lasting effects
The enzyme cholinesterase must be regenerated before the drug effect diminishes, process may take days or
weeks
Used to :
o Produce papillary constriction
o Manufacture organophosphate insecticides


Anticholinergics


Definition

Drugs that inhibit the actions of acetylcholine by occupying the acetylcholine receptors
Also known as:
o Parasympatholytics
o Cholinergic blocking agents
o Cholinergic or Muscarinic antagonists
o Antiparasympathetic agents
o Antimuscarinic agents
o Antispasmodics
Major body tissues and organs affected by Anticholinergics are :
o Heart
o Respiratory tract
o GI tract
o Urinary bladder
o Eyes
o Exocrine glands
Major responses to anticholinergics :
o Decrease in GI motility
o Decrease in salivation
o Dilation of pupils/ mydriasis
o Increase in pulse rate
o Decreased bladder contraction = urinary rention
o Decreased rigidity and tremors r/t neuromuscular excitement
By blocking the parasympathetic nerves, the sympathetic (adrenergic) nervous system dominates
Muscarinic receptors are involved in tissue and organ responses to anticholinergics because anticholinergics
inhibit actions of acetylcholine by occupying these receptor sites
Can act as an antidote to the toxicity caused by cholinesterase inhibitors and organophosphate ingestion
May block the effect of direct-acting Parasympathomimetics and of indirect Parasympathomimetics
Can increase intraocular pressure , so should not be administered to clients diagnosed w/ glaucoma


Atropine Sulfate

First derived from the belladonna plant (Atropa belladonna) ; Purified in 1831
A classic anticholinergic drug or muscarinic antagonist
Usage :
o As a preoperative medication to decrease salivary secretions
o As an antispasmodic drug to treat peptic ulcers because it relaxes smooth muscles of the GI tract
and decreases peristalsis
o As an agent to increase heart rate when bradycardia is present
o As an antidote for muscarinic agonist poisoning caused by an overdose of a cholinesterase inhibitor
or a muscarinic drug such as Bethanechol
Atropine and Atropine-like drugs side effects /adverse reactions :
o Dry mouth
o Decreased perspiration
o Blurred vision
o Tachycardia
o Constipation
o Urinary retention
o Nausea
o Headache
o Dry skin
o Abdominal distention
o Hypotension
o Hypertension
o Impotence
o Photophobia
o Coma

Synthetic Anticholinergic drugs
Also used to treat peptic ulcers and intestinal spasticity
Not frequently used to decrease gastric secretions since the introduction of histamine (H2) blockers
Propantheline bromide (Pro-Banthine)
o Decreases gastric secretion and GI spasms

Antiparkinson-Anticholinergic Drugs

Anticholinergic drugs affect the CNS by suppressing the tremors and muscular rigidity of parkinsonism
o trihexyphenidyl hydrochloride (Artane)
o procyclidine (Kemadrin)
o biperiden (Akineton)
o benztropine (Cogentin)
May be used in combination w/ levodopa to control parkinsonism
May also be used alone to treat Pseudoparkinsonism w/c results from the side effects of phenothiazines in
antipsychotic drugs

Antihistamines for treating motion
sickness

Scopolamine
Available topically as a skin patch that is placed behind the ear
Delivered over 3 days and is frequently prescribed for activities such as flying, cruising on the water, and
bus or automobile trips
dimenhydrinate (Dramamine)
cyclizine (Marezine)
meclizine hydrochloride (Bonine)

SiDe Effects :
o Dry mouth
o Visual disturbances esp. blurred vision resulting from papillary dilation
o Tachycardia
o Constipation s/t decreased GI persitalsis
o Hypotension
o Urinary retention r/t decreased bladder tone
o Skin rash
o Muscle weakness
o Flushing