Drugs Affecting Peripheral
Nervous System #2
Fight or Flight versus the
Parasympathetic Pig
Adrenergic Nerve Endings
• The adrenergic nerve ending
synthesizes and releases
norepinephrine (NE)
• Released norepinephrine stimulates
adrenergic receptors located on cardiac
and smooth muscle membranes to
initiate sympathetic responses
• In emergency situations the adrenal
medulla releases epinephrine (EPI)
which also stimulates adrenergic
receptors and sympathetic activity
• NE and EPI are inactivated by neuronal
reuptake back into the nerve ending for
reuse or metabolism by monoamine
oxidase (MAO)
– MAOI??
• How do the various tissues distinguish a
response to norepinephrine?
• Why does the Fight or Flight response
excite some tissues and inhibit others?
Alpha-Adrenergic Receptors
• Alpha-adrenergic receptors are located
on smooth muscle membranes and
cause smooth muscle contraction when
stimulated by NE, EPI, or drugs
• Alpha receptor stimulation causes
vasoconstriction of most arteries and
veins
Alpha-Adrenergic Receptors
Cont’d
• Alpha receptor stimulation of the radial
muscle of the pupil causes pupillary
dilation or mydriasis
• Contraction of the smooth muscle
sphincters in the urinary and intestinal
tracts inhibit urination and intestinal
motility
Beta-Adrenergic Receptors
• Beta-1 receptors are located primarily in
the heart and cause increased heart rate,
force of contraction, and atrioventricular
conduction
• Beta-2 receptors are mostly located on
smooth muscle and cause relaxation of
smooth muscle, especially bronchiolar and
uterine smooth muscle
• Beta-3 receptor stimulation also causes
vasodilation and increased blood flow to
coronary and skeletal muscle blood
vessels
Table 2.2
Sympathomimetics
Norepinephrine
and Epinephrine (Catecholamines)
• Norepinephrine is released from adrenergic
nerve endings and primarily stimulates alpha
and beta-1 receptors, it is not effective at
beta-2 receptors
• Epinephrine is released from the adrenal
medulla into the blood where it travels as a
hormone to stimulate all alpha and beta
receptors
Alpha-Adrenergic Drugs
• Alpha-adrenergic drugs are used clinically to
cause vasoconstriction of blood vessels
• In hypotensive states, drugs such as
norepinephrine and metaraminol, are given
by IV injection to raise blood pressure
• In allergies and colds, drugs such as
phenylephrine (non-catecholamine) are
administered as nasal sprays or drops, and
oral tablets to decongest nasal and ocular
tissues
Alpha Adrenergic Drugs and
Indications
Ephedrine
Nasal Decongestant
Methoxamine (Vasoxyl)
Increase blood pressure
Norepinephrine
(Levophed)
Increase blood pressure
Pseudoephedrine
(pseudaphed)
Nasal decongestant
Tetrahydrozoline (Visine) Opthalmic decongestant
Beta-Adrenergic Drugs
• Beta drugs are used clinically to stimulate the
heart, bronchodilate respiratory
passageways, and relax the uterus during
preterm labor
• Selective beta-2 drugs are usually
administered by oral inhalation for the control
of asthma
• Epinephrine is injected subcutaneously in
allergic and cardiac emergencies to stimulate
the heart, promote bronchodilation, and
maintain blood pressure
Beta Adrenergic Drugs and
Indications
Epinephrine
(Adrenaline)
Isoproterenol
(isuprel)
Albuterol
(Ventolin)
Salmeterol
(Serevent)
α, β-1,
β-2
β
β
Vasopressor, cardiac
stimulant, bronchodilation
Cardiac stimulant,
bronchodilator
Bronchodilator
β
bronchodilator
Indirect and Mixed Agents
• Indirect Agents cause release of
norepinephrine from nerve ending
– Do not bind directly to adrenergic receptor
• Mixed Agents cause release of
norepinephrine from nerve ending and bind
directly to adrenergic receptor
• Table 2.1
Adverse Effects Caused
by Adrenergic Drugs
• The main adverse effect caused by alpha
drugs is excessive vasoconstriction resulting
in hypertension or excessive dryness of the
eyes and nasal sinuses when used as
decongestants
• Overstimulation with beta drugs causes
excessive cardiac stimulation and increased
blood pressure
• Adrenergic drugs can also cause CNS
stimulation resulting in tremors, restlessness,
and anxiety
Cholinomimetics
Cholinergic Nerve Endings
• Cholinergic nerve endings synthesize and
release acetylcholine (ACH)
• Released ACH stimulates cholinergic
receptors located on smooth, cardiac, and
skeletal muscle membranes to initiate a
variety of effects
• ACH is inactivated by the enzyme
acetylcholinesterase
Classification of Cholinergic
Receptors
• There are three main types of cholinergic receptors
• Cholinergic receptors, also referred to as
muscarinic, are associated with the
parasympathetic nervous system
• Nicotinic-neural receptors are located on
autonomic ganglia
• Nicotinic-muscle receptors are located on skeletal
muscle
Cholinergic Receptor Actions
• Cholinergic receptors are located on smooth and
cardiac muscle membranes in association with
parasympathetic nerve endings
• Parasympathetic nervous activity is associated
with body functions during rest and restoration of
energy such as eating and digestion
• Parasympathetic activity also controls the
elimination of waste products from the urinary and
intestinal tracts
Direct Cholinergic Agonists
Direct-Acting Cholinergic Drugs
• Direct-acting cholinergic drugs are similar to ACH
and stimulate receptors like ACH
• Direct-acting drugs have longer durations of
action than ACH and are clinically useful
• These drugs are used in opthalmology as miotics
and in the treatment of glaucoma
• Bethanechol stimulates urinary bladder
contraction and is taken orally to treat
nonobstructive urinary retention
Indirect-Acting Cholinergic
Drugs
• Indirect-acting drugs increase ACH levels at
receptors by inhibiting the enzyme
acetylcholinesterase
• These drugs primarily increase ACH at cholinergic
and nicotinic-muscle receptors
• Drugs classified as reversible inhibitors of
acetylcholinesterase are the most widely used
• These drugs are also referred to as
anticholinesterase drugs
Adrenergic Blockers
Cholinesterase Inhibitors
Cholinergic Antagonists
Ganglion Blockers
Autonomic Ganglia
• The neural synapses between autonomic pre- and
postganglionic nerve fibers are referred to as
autonomic ganglia
• ACH is the neurotransmitter released at all preganglionic fibers and functions to transmit the
nerve impulse to the postganglionic fibers
• The receptor on the postganglionic nerve
membrane at the ganglionic site is the nicotinicneural (Nn) receptor
Drug Actions
on Autonomic Ganglia
• Drugs that bind to and stimulate Nn ganglionic
receptors activate both sympathetic and
parasympathetic autonomic nerves
• Drugs that block the Nn receptors inhibit the
activity of both autonomic divisions
• With the exception of nicotine, there are few
ganglionic drugs of clinical importance
Nicotine and Ganglionic
Stimulation
• Nicotine, the main active ingredient in tobacco
products, is a mild ganglionic stimulant
• Both sympathetic and parasympathetic ganglionic Nn
receptors are stimulated by nicotine
• The main effects of nicotine via smoking are an
increase in cardiac and gastrointestinal activity
• Nicotine also produces effects in the brain related to
the pleasures of smoking and the development of
drug dependency
Smoking Deterrents
• Nicotine containing gum (Nicorette) and
transdermal patches (Habitrol, Nicoderm,
Nicotrol, ProStep) are used to aid in quitting
the smoking habit
• The gum or patches are used in decreasing
amounts over an 8–12 week time period
• Tobacco products should not be used while
using these products
Ganglionic Blocking Drugs
• Ganglionic blocking drugs bind to the Nn receptor
and block the effects of ACH at the ganglia
• The activity of both autonomic divisions is
decreased
• The main effects of blockade are decreased blood
pressure, heart rate, gastrointestinal, and
genitourinary activity
• The only clinical use of ganglionic blockers is to
lower blood pressure during surgery or in the
treatment of severe hypertension
Adverse Effects
• Ganglionic blockers reduce the activity of the
entire autonomic nervous system to produce a
wide variety of adverse autonomic effects
• Adverse effects include hypotension, decreased
cardiac output, constipation, urinary retention,
blurred vision, and dry mouth
• A significant number of patients cannot tolerate
these drugs, which accounts for the limited clinical
use
Neuromuscular Transmission and
Blockade
Local Anesthetics