Autonomic Nervous System

Agents:
ADRENERGICS
AND
ANDRENERGIC
BLOCKERS
 Adrenergic agonists
 Sympathomimetics/ Adrenomimetics
 Drugs that stimulate the sympathetic
NS.
 They act on one or more adrenergic
receptor sites located in the cells of
the different body organs.
Found on organs stimulated by
sympathetic fibers (using NE).
Two types :
a. Alpha : excitatory
b. Beta : inhibitory, except in
cardiac muscle where it is excitatory
Both types are found in many organs
 ALPHA 1 – adrenergic receptor
> Located in the vascular tissues
 Increase cardiac contractility, vasoconstriction
 Dilate pupils
 Decrease salivary gland secretion
 Increase bladder and prostate contraction
ALPHA 2 – adrenergic
receptor
> Located in the
postganglionic sympathetic
nerve endings.
 Inhibit norepinephrine
release
 Promotes vasodilation
 Decrease GI motility and
tone
BETA 1 –
adrenergic receptor
> Located primarily
in the heart
 Increase cardiac
contractility and
heart rate
 Increase renin
secretion, BP
 BETA 2 – adrenergic receptor
> Found mostly in the smooth muscles of the
lung, arterioles of skeletal muscle and uterine
muscle.
 Decreases GI tone and motility
 Bronchodilation
 Increases blood flow in skeletal muscles
 Decreases uterine tone
 Activates liver glycogenolysis
 Increases blood glucose
 DOPAMINERGIC
> Located in the renal, mesenteric, coronary,
and cerebral arteries.
* Vasodilation – increase blood flow
 According to their effects on organ cells:
1. Direct-acting Sympathomimetics
> Directly stimulate the adrenergic receptor.
* Epinephrine * Albuterol
* Norepinephrine * Clonidine
* Dobutamine * Dopamine
* Isoproterenol * Metaproterenol
* Methoxamine * Phenylephrine
* Ritodrine * Terbutaline
 According to their effects on organ cells:
2. Indirect-acting Sympathomimetics
> Stimulate the release of norepinephrine from the
terminal nerve endings.
* Amphetamine
* Tyramine
3. Mixed – acting Sympathomimetics
> Stimulate the adrenergic receptor sites and stimulate
the release of norepinephrine from the terminal nerve
endings.
* Ephedrine * Metaraminol
 According to important structural features:

1. CATECHOLAMINES - Are chemical structures of

substance that can produce a sympathomimetic
response.
 Contains the 3,4-dihydroxybenzene group.
 Endogenous
catecholamines:
* Epinephrine
* Norepinephrine
* Dopamine
Synthetic
catecholamines:
* Isoproterenol
* Dobutamine
 According to important structural features:
2. NONCATECHOLAMINES
Compounds lacking the catechol hydroxyl groups.
Stimulate the adrenergic receptors
Have longer duration of action.
* Phenylephrine * Amphetamine
* Metaproterenol
* Albuterol
* Ephedrine
 According to Receptor specificity:

Alpha and Beta Alpha Beta

Receptor Receptor Receptor
Epinephrine Midodrine Albuterol
Ephedrine Phenylephrine Metoproterenol
Norepinephrine Methoxamine Dobutamine
Dopamine Clonidine Isoetharine
Amphetamine Terbutaline
Ephedrine Ritodrine
Isoproterenol
 EPINEPHRINE

Potent inotropic drug

Drug Class: Sympathomimetic
Action: Causes vasoconstriction,
increases heart rate, and
bronchodilator.
Therapeutic uses:
* Treatment of choice for
anaphylactic reactions
* To treat bronchospasm and
cardiac arrest.
 EPINEPHRINE

Side effects: Anorexia, nausea,

vomiting, nervousness, tremors,
agitation, headache, pallor,
insomnia, dizziness
Adverse reactions: Dysrhythmias,
pulmonary edema
Drug interaction
▫ Beta-blockers (βBs)
 Decreases epinephrine action
▫ Digoxin
 Causes cardiac dysrhythmias
 EPINEPHRINE

 Nursing Interventions
▫ Monitor BP, pulse rate, urine output
▫ Report tachycardia, palpitations, tremors, dizziness,
hypertension
▫ Monitor IV site for infiltration
 Antidote: phentolamine mesylate (Regitine)
▫ Avoid cold medications/diet pills if hypertensive,
diabetic, CAD, or dysrhythmias
▫ Avoid adrenergics when nursing infants
▫ Avoid continuous use of adrenergic nasal sprays
 ALBUTEROL

Selective for beta2-adrenergic

receptors
Response is purely
bronchodilation
Primarily use to prevent and
treat bronchospasms.
Oral and inhalation
preparations
Side effects and adverse
effects:
* High dose: Tremors,
restlessness and nervousness
 CLONIDINE & METHYLDOPA

Selective alpha2-adrenergic drugs

Used primarily to treat hypertension
Side effects and adverse effects:
* Hypertension
* Tachycardia
* Palpitations
* Dysrhythmias
* Tremors
* Urinary difficulty
* Dizziness, nausea and vomiting
Adrenergic blockers
Sympatholytics
 Drugs that block the effects of adrenergic
neurotransmitter
MOA: Blocks the effects of neurotransmitter either
directly by occupying the alpha- or beta- receptors or
indirectly by inhibiting the release of the
neurotransmitters norepinephrine and epinephrine.
 ALPHA- BETA-BLOCKERS
BLOCKERS
• Doxazosin • Acetabutolol
• Phenoxybenzamine • Atenolol
• Phentolamine • Labetalol
• Prazosin • Metoprolol
• Terazosin • Nadolol
• Pindolol
• Propanolol
• Timolol
 Drugs that block or inhibit a response at the alpha-
adrenergic receptor site.
 2 Groups of Alpha-adrenergic blockers:
1. Selective alpha-blockers – block alpha1.
* Tolazoline * Doxazosin
* Prazosin * Terazosin

2. Nonselective alpha-blockers – block alpha1

and aplha2.
* Phenoxybenzamine * Phentolamine
@ Therapeutic
Indications:

Helpful in
decreasing
symptoms of
benign prostatic
hypertrophy
(BPH).
@ Therapeutic indications:
Promote vasodilation:
decrease blood pressure
Used to treat peripheral
vascular diseases (E.g.
Raynaud’s disease)
Side effects and adverse
effects:
* Orthostatic hypotension
* Reflex tachycardia
 Commonly called beta-blockers
 Effect at receptor site:
*Decrease heart rate – decrease blood
pressure.
* Bronchoconstriction
 2 Groups of Beta-adrenergic blockers:
1. Selective beta-blockers – block either beta1 or
beta2
BETA 1 BLOCKERS BETA 2 BLOCKERS

•Acebutolol – has ISA • Albuterol

• Metoprolol • Isoetharine
• Atenolol • Terbutaline
• Betaxolol
• Esmolol
• Bisoprolol
2. Nonselective beta-blockers – block both beta1
and beta2.
* Propanolol * Nadolol * Timolol
* Labetolol * Sotalol
@ Nonselective beta-blockers with ISA
(intrinsic sympathomimetic activity)
* Carteolol * Carvedilol
* Penbutolol * Pindolol
@ Therapeutic applications:
Lower blood pressure in hypertension but does NOT
induce postural hypotension.
 Useful in treating cardiac dysrhythmias, mild
tachycardia and angina pectoris.
@ Therapeutic applications:
Effective in treating myocardial infarction, glaucoma,
migraine and hyperthyroidism.
 PROPANOLOL

• A non-selective beta-antagonist
• Blocks both beta1 and beta2 receptors.
• Actions:
* Cardiovascular – diminishes cardiac
output
* Peripheral vasoconstriction
* Bronchoconstriction
* Increased sodium retention
* Disturbances in glucose metabolism –
decrease glycogenolysis.
 PROPANOLOL
Therapeutic effects:
* Hypertension
* Glaucoma
* Migraine
* Hyperthyroidism
* Angina pectoris
* Myocardial infarction
 PROPANOLOL

Side effects and adverse effects:

* Bronchoconstriction
> Must never be used in treating any
individual with obstructive pulmonary
disease.
*Arrhythmias
> Must not be stopped quickly and
should be tapered off gradually for 1 week.
* Sexual impairment
* Disturbances in metabolism
• MOA: Block the release of stored NE
from sympathetic terminal
• Drugs: * RESERPINE
* GUANETHIDINE
* COCAINE
• Therapeutic application:
Hypertension
• Side effects and adverse effects:
Orthostatic hypotension, decreased
libido
Autonomic Nervous System
Agents:

CHOLINERGICS
AND
ANTICHOLINERGICS
• ACETYCHOLINE – is the neurotransmitter located at the
ganglions and the parasympathetic terminal nerve
endings.

• 2 Families of Cholinergic receptors:

1. Muscarinic receptors – found on ganglia of the
peripheral nervous system and on autonomic effector
organs ---heart, smooth muscle, brain and exocrine
glands.
2. Nicotinic receptors – located in the CNS, adrenal
medulla, autonomic ganglia, and the neuromuscular
junction.
 2 GROUPS OF DRUG THAT AFFECT THE
PARASYMPATHETIC NS
1. CHOLINERGICS – drugs that stimulate the parasympathetic
nervous system.
 Parasympathomimetic
 Cholinomimetics, cholinergic stimulants, or cholinergic
agonists.
 2 GROUPS OF DRUG THAT AFFECT THE
PARASYMPATHETIC NS

2. ANTICHOLINERGICS – drugs that

blocks or inhibits the
parasympathetic nervous system.
 Parasympatholytic
 Cholinergic blocking agents,
Cholinergic or muscarinic
antagonist, antiparasympathetic
agents, antimuscarinic or
antispasmodics
 EFFECTS
OF
CHOLINERGICS
MUSCARINIC NICOTINIC BOTH
RECEPTOR RECEPTOR
 Muscarinic  Nicotine  Acetylcholine
 Pilocarpine  Succinyl-  Carbachol
 Betanechol choline
 Mimics the effects of acetylcholine by binding directly to
cholinoceptors.
 Act on the receptors to activate a tissue response.
 Primarily selective to the muscarinic receptors.
* Synthetic esters of choline:
> CARBACHOL – use as miotic agent and decrease
intraocular pressure.
> BETHANECHOL – used primarily to increase urination
 > PILOCARPINE – naturally occurring alkaloids
- used to treat glaucoma by relieving fluid pressure in the
eye.
Side effects and adverse effects:
* Hypotension * Diarrhea
* Excessive salivation *Bronchoconstriction
* Increase gastric acid secretion * Bradycardia
* Cardiac dysrhythmias
 Inhibit or inactivate the
enzyme --- Cholinesterase ACETYLCHOLINE
– permitting acetycholine
to accumulate at the Cholinesterase
receptor site.
 Cholinseterase inhibitors
 Anticholinesterases or
Acetylcholinesterase CHOLINE + ACETIC ACID
inhibitors
 Indications:
* Primary use is to treat Myasthenia
gravis
* Glaucoma
* Alzheimer’s disease
* Muscarinic antagonist poisoning
 2 TYPES OF CHOLINESTERASE
INHIBITORS
REVERSIBLE CHOLINESTERASE

1. REVERSIBLE CHOLINESTERASE INHIBITORS

INHIBITORS

SHORT-ACTING * Neostigmine
* Edrophonium
MODERATE-ACTING * Pyridostigmine

LONG-ACTING * Ambenonium
 @ PHYSOSTIGMINE – ophthalmic anticholinesterase
REVERSIBLE CHOLINESTERASE

drug.
* Indications:
> Increases intestinal and bladder motility
> Produces miosis and lowers intraocular pressure.
INHIBITORS

> Also used in treatment of overdose of drugs ---

Atropine, phenothiazines, and tricyclic
antidepressants.

* Side effects and adverse effects:

> Convulsions > Bradycardia
> Paralysis of skeletal muscles
 @ NEOSTIGMINE
REVERSIBLE CHOLINESTERASE

* Indications:
> Can stimulate contractility before it paralyzes.
> Used to stimulate the bladder and GI tract
INHIBITORS

> An antidote for tubocurarine

> Use in the symptomatic treatment of myasthenia
gravis

* Side effects and adverse effects:

> Salivation > Decreased blood pressure
> Flushing > Nausea and diarrhea
> Abdominal pain > Bronchospasm
 @ PYRIDOSTIGMINE – used in the chronic
REVERSIBLE CHOLINESTERASE

management of myasthenia gravis

@ EDROPHONIUM – used in the diagnosis of

myasthenia gravis.
INHIBITORS
 2 TYPES OF CHOLINESTERASE
IRREVERSIBLE CHOLINESTERASE
INHIBITORS
* Potent agents –long lasting effect
* Used to produce pupillary constriction and to
manufacture organophosphate insecticides.
INHIBITORS

@ ISOFLUROPHATE – produces intense miosis

> Actions: Generalized cholinergic stimulation,
paralysis of motor function and convulsions.
> For chronic treatment of an open-angle glaucoma
 CHOLINERGIC ANTAGONISTS
• Parasympatholytics or Anticholinergic blocking agents
• Muscarinic antagonist or Antimuscarinic agents
• Antiparasympathetic or Antispasmodic agents

• MOA: Selectively block the muscarinic sysnapses of the

parasympathetic nerves.
• Affects the following major body tissues and organs:
* Heart * Gastrointestinal tract
* Respiratory tract * Urinary bladder
* Eyes * Exocrine glands
 CHOLINERGIC ANTAGONISTS
 By blocking the parasympathetic nerves, the
sympathetic NS dominates.
Major response to Anticholinergics are:
* decrease GI motility * decrease in salivation
* dilation of pupils * increase in pulse rate
* decrease bladder contraction
* decrease rigidity and tremors
Act as an antidote to the toxicity caused by
cholinesterase inhibitors and organophosphate
ingestion.
 CHOLINERGIC ANTAGONISTS

* Has high affinity for muscarinic receptors.

* Derived from belladona plant (Atropa
belladona)
* Actions:
> Mydriasis
> Bradycardia
> Used as an antispasmodic to reduce
activity of the GI tract.
> Blocks the salivary glands ---produce
drying effect on the oral mucous
membranes.
 CHOLINERGIC ANTAGONISTS

* Indications:
> A preoperative medication to decrease salivary secretions
> An antispasmodic drug to treat peptic ulcers
> An agent to increase heart rate when bradycardia is
present
> Use an antidote for muscarinic agonist poisoning
* Side effects:
> Dry mouth > Tachycardia
> decrease perspiration > Constipation
> Blurred vision > Urinary retention
 CHOLINERGIC ANTAGONISTS

* A belladona alkaloid has greater action on the CNS and has

longer duration.
* One of the most effective anti-motion sickness drugs
available.
* Produces sedation but at higher doses can produce an
excitement.

* Useful in treating asthma and chronic obstructive pulmonary

disease.
MOA: Specifically act on the nicotinic receptors --- by
blocking the ion channels of the autonomic ganglia.
NICOTINE – depending on the dose, nicotine depolarizes
ganglia—stimulation first followed by paralysis of all
ganglia.
> Higher dose – BP falls because of ganglionic blockade
TRIMETHAPHAN – short-acting, competitive nicotinic
ganglionic blocker
> Given intravenously
> Used for emergency lowering of blood pressure