ADRENERGIC AGENTS

GROUP 3:
Dumalaog
Florin
Gadia
Galicha
Hilbero
Leuterio

Objectives:
Understand the central and peripheral nervous systems,
their functions, and their relationship to drugs.
Become aware of the role of neurotransmitters.
Learn how adrenergic drugs affect body systems and
where they work in the body.
Define the action of neuromuscular blocking agents in
reducing muscle activity.
Distinguish between narcotic and nonnarcotic analgesia.
Become familiar with the various types of agents for
migraine headaches.

Divisions of the Nervous System

Central Nervous System
Brain
Spinal cord

Peripheral Nervous System

Nerves
Sense organs

Divisions of the Nervous System

Central Nervous System
Peripheral Nervous System
Somatic Nervous System
Voluntary action: skeletal muscle contraction and
movement

Autonomic Nervous System

Involuntary activities: respiration, circulation,
digestion, sweating

Autonomic Nervous System

Review
The nervous system has two components. What
are they?

Answer
Central nervous system (CNS)
Peripheral nervous system (PNS)

Adrenergic Neurotransmitters

Major Neurotransmitters
Acetylcholine (ACh)
Smooth muscle, cardiac muscle, and
exocrine glands
Anticholinergics block ACh receptors

GABA (gamma-aminobutyric acid)

Regulates message delivery system of
the brain

Major Neurotransmitters
Dopamine
Acts on the CNS and kidneys
Epinephrine
Acts on cardiac and bronchodilator receptors
Known as Adrenaline
Serotonin
Acts on smooth muscle and gastric mucosa
(causes vasoconstriction)
Emotional responses: depression, anxiety

Communication by
Neurotransmitters

Neurotransmitters are released from one

axon and received by another neurons
dendrites.

Adrenergic Agents
Drugs that stimulate the sympathetic nervous system
(SNS)
Also known as
adrenergic agonists or sympathomimetics
Mimic the effects of the SNS neurotransmitters:
norepinephrine (NE) and epinephrine (EPI)

Adrenergic Receptors

The three important types of adrenergic

receptors in the study of drugs:

Alpha
Beta-1
Beta-2

Adrenergic Receptors
Located throughout the body
Are receptors for the sympathetic
neurotransmitters
Alpha-adrenergic receptors: respond to NE
Beta-adrenergic receptors: respond to EPI

Alpha1
-They are located in the vascular tissues of smooth muscles.
-When it is stimulated, arterioles and venules are
constricted, thereby increasing peripheral resistance and
blood return to the heart.
Alpha 2
-Alpha2 receptors also exist presynaptically associated with
nerve terminals.
-Activation of these receptors inhibits the release of
norepinephrine.

Beta1
-Located primarily in the heart.
-Stimulation increases myocardial contractility and heart rate.

Beta2
-Found mostly in the smooth muscle in the lungs,
arterioles of skeletal muscle and uterine muscle
-Stimulation can cause bronchodilation, inc. blood
flow to the skeletal muscle, relaxation of the
uterine muscle

Dopaminergic
-Located in the renal, mesentric, coranary and cerebral arteries
-When stimulated can increase blood flow due to vessels
dilation
-Only dopamine can activate this receptors.

The predominant alphaadrenergic agonist responses are:

Vasoconstriction and CNS stimulation

The beta-adrenergic agonist

response results in:
Bronchial, GI, and uterine smooth muscle
relaxation
Glycogenolysis
Cardiac stimulation

Dopaminergic Receptors
An additional adrenergic receptor
Stimulated by dopamine
Causes dilation of the following blood vessels,
resulting in INCREASED blood flow

Renal
Mesenteric
Coronary
Cerebral

Drugs Affecting Adrenergic

Neurotransmission

Sympathomimetic Agents

I.

Sympathomimetics:

A. Directly acting sympathomimetics, which directly

stimulate adrenergic receptors. They are either:
1.

Non-selective -agonists such as norepinephrine and epinephrine.

2.

Non-selective -agonists such as isoprenaline and epinephrine.

3.

Selective -agonists such as phenylephrine.

4.

Selective -agonists such as clonidine.

*Clonidine- useful in the treatment of hypertension

5.

Selective -agonists such as dobutamine

6.

Selective 2-agonists such as salbutamol

*Salbutamol and other 2-agonists- useful in the treatment of bronchial
asthma

Note:
epinephrine
all & all
norepinephrine
all , 1 & 3
isoproterenol (isoprenaline) all

I. Sympathomimetics:

B.Indirectly acting sympathomimetics- agents that elevate

the concentration of norepinephrine at neuroeffector
junctions
The effectiveness of such indirect sympathomimetics diminishes or disappears
(tachyphylaxis) when vesicular stores of norepinephrine are depleted

C.Dual (mixed) acting sympathomimetics- It enters

noradrenergic neurons and cause norepinephrine release
and also activates receptors
e.g. ephedrine

II. Sympatholytics:

A.Noradrenergic receptor blockers which include

1.Drugs which antagonize the effects produced by bothand -receptor stimulation

e.g. labetalol - and -receptor antagonist

- it is effective in hypertension
2. Drugs which antagonize the effects produced by -receptor stimulation
3. Drugs which antagonize the effects produced by -receptor stimulation

B.Drugs that prevent noradrenergic transmission which

include:
1.Noradrenergic neuron blockers
e.g guanethidine- used in the treatment of hypertension
2. Drugs that deplete NE from noradrenergic neurons
e.g. reserpine - used in the treatment of hypertension
3. Drugs that interfere with the synthesis of NE
e.g. methyldopa- used in the treatment of hypertension,
its use during pregnancy appears to
be relatively safe

Catecholamines
Substances that can produce a
sympathomimetic response
Endogenous:
epinephrine, norepinephrine,dopamine

Synthetic:
isoproterenol, dobutamine, phenylephrine

Sympathomimetic Agent
Mechanism of Action:

Direct-acting sympathomimetic:
Binds directly to the receptor and causes a physiologic response
Indirect-acting sympathomimetic:
Causes the release of catecholamine from the storage sites (vesicles)
in the nerve endings
The catecholamine then binds to the receptors and causes a
physiologic response
Mixed-acting sympathomimetic:
Directly stimulates the receptor by binding
to it and indirectly stimulates the receptor by causing
the release of stored neurotransmitters from
the vesicles in the nerve endings

Adrenergic Agents:
Therapeutic Uses
Bronchodilators: treatment of asthma and
bronchitis
Agents that stimulate beta2-adrenergic receptors
of bronchial smooth muscles causing relaxation
Examples:
albuterol
ephedrine
epinephrine
isoetharine
isoproterenol levalbuterol
metaproterenol
salmeterol
terbutaline
These agents may also affect uterine and vascular
smooth muscles.

Adrenergic Agents:
Therapeutic Uses
Reduction of intraocular pressure and
mydriasis (pupil dilation): treatment of
open-angle glaucoma
Examples:

epinephrine and dipivefrin

Adrenergic Agents:
Therapeutic Uses
Nasal decongestant:
Intranasal (topical) application causes constriction
of dilated arterioles and reduction of nasal blood
flow, thus decreasing congestion.
Examples:
epinephrine
ephedrine
naphazoline
phenylephrine tetrahydrozoline

Adrenergic Agents:
Therapeutic Uses
Ophthalmic
Topical application to the eye surface affects
the vasculature of the eye, stimulating alpha
receptors on small arterioles, thus relieving
conjunctival congestion.
Examples:

epinephrine
phenylephrine

naphazoline
tetrahydrozoline

Adrenergic Agents:
Therapeutic Uses
Vasoactive sympathomimetics (pressors,
inotropes), also called cardioselective
sympathomimetics
Used to support the heart during cardiac failure
or shock.
Examples:
dobutamine
dopamine
ephedrine
epinephrine
fenoldopam
isoproterenol
methoxamine norepinephrine phenylephrine

Adrenergic Agents: Side Effects

Alpha-Adrenergic Effects
CNS:
headache, restlessness, excitement, insomnia, euphoria
Cardiovascular:
palpitations (dysrhythmias), tachycardia,
vasoconstriction, hypertension
Other:
anorexia, dry mouth, nausea, vomiting, taste changes
(rare)

Adrenergic Agents: Side Effects

Beta-Adrenergic Effects
CNS:
mild tremors, headache, nervousness, dizziness

Cardiovascular:
increased heart rate, palpitations (dysrhythmias),
fluctuations in BP

Other:
sweating, nausea, vomiting, muscle cramps

Adrenergic Receptor
Antagonists (Blockers)

Adrenergic-Blocking Agents
Bind to adrenergic receptors, but inhibit or
block stimulation of the sympathetic
nervous system (SNS)
Have the opposite effect of adrenergic
agents
Also known as
adrenergic antagonists or sympatholytics

Alpha-Blocker Mechanisms

Adrenergic-Blocking Agents:
Drug Effects and Therapeutic
Uses

Alpha-Blockers

Cause both arterial and venous dilation, reducing

peripheral vascular resistance and BP
Used to treat hypertension
Effect on receptors on prostate gland and bladder
decreased resistance to urinary outflow, thus
reducing urinary obstruction and relieving effects
of BPH

Adrenergic-Blocking Agents:
Drug Effects and Therapeutic
Uses

Alpha-Blockers
Phentolamine

Quickly reverses the potent vasoconstrictive effects of

extravasated vasopressors such as norepinephrine or
epinephrine.
Restores blood flow and prevents tissue necrosis.

Adrenergic-Blocking Agents:
Side Effects
Alpha Blockers
Body System
Side/Adverse Effects
Cardiovascular

Palpitations, orthostatic
hypotension, tachycardia,
edema, dysrhythmias, chest
pain

CNS

Dizziness, headache, drowsiness,

anxiety, depression, vertigo,
weakness, numbness, fatigue

Adrenergic-Blocking Agents:
Side Effects
Alpha Blockers
Body System
Side/Adverse Effects
Gastrointestinal

Nausea, vomiting, diarrhea,

constipation, abdominal pain

Other

Incontinence, nose bleeding,

tinnitus, dry mouth, pharyngitis,
rhinitis

Beta Receptors
Beta1 Receptors
Located primarily on the heart
Beta blockers selective for these receptors
are called cardioselective beta blockers

Beta2 Receptors
Located primarily on smooth muscles
of bronchioles and blood vessels

Nonspecific Beta Blockers

Beta blockers that block both beta1 and
beta2 receptors
Mechanism of Action:
Nonspecific (Beta1 and Beta2)
Effects on heart: Same as cardioselective
Bronchioles:
Constriction, resulting in
of airways and
shortness of breath
Blood vessels: Vasoconstriction

narrowing

Beta Blockers: Therapeutic Uses

Anti-angina:

Cardioprotective:

decreases demand for

myocardial oxygen
inhibits stimulation by
circulating catecholamines

Class II antidysrhythmic

Antihypertensive
Treatment of migraine headaches
Glaucoma (topical use)

Beta Blockers: Side Effects

Body System

Side/Adverse Effects

Blood

Agranulocytosis,

Cardiovascular

AV block, bradycardia, congestive

heart failure, peripheral vascular
insufficiency

CNS

Dizziness, mental depression,

lethargy, hallucinations

thrombocytopenia

Adrenergic-Blocking Agents:
Side Effects
Beta Blockers
Body System

Side/Adverse Effects

Gastrointestinal

Nausea, dry mouth, vomiting,

diarrhea, cramps, ischemic colitis

Other

Impotence, rash, alopecia,

bronchospasms

Adrenergic Blocking Agents:

Implications
Avoid OTC medications because of
possible interactions.
Possible drug interactions may occur with:

Antacids (aluminum hydroxide type)

Antimuscarinics/anticholinergics
Diuretics and cardiovascular drugs
Neuromuscular blocking agents
Oral hypoglycemic agents

Sympathomimetics
Ephedrine hydrochloride It is an alkaloid of plants of
Ephedra family, which has indirect a-, b-adrenomimetic
(sympathomimetic) action

Administration
collapse conditions, for prophylaxis of decreasing of blood pressure before spinal
anesthesia, infectious diseases
treatment of rhinitis (2 %, 3 % solution to drop into nose).
prophylaxis and elimination of bronchial spasm (inhalations 0,5 %-1 % solutions
of drug)

SIDE EFFECTS
excitement, tremor, inconsiderable euphoria, insomnia, seizures
drug addiction
tachyphylaxy

Alpha-adrenoblockers
Phentolamine, tropaphen
are synthetic a1, 2-drenoblockers
administration
diagnostics and symptomatic treatment of
feochromocytoma
disturbances of peripheral blood circulation in case
of endarteritis, Reinos disease, trophic ulcers,
decubitus
complex treatment of hypertensive crises, acute
cardiac insufficiency
complex therapy of hypovolemic and cardiogenic
shock

Prazosin
Selective a1- adrenoblocker

Administration
treatment of essential hypertension
stabile cardiac insufficiency
Side effects
phenomenon of first dose: sudden decreasing of blood
pressure and even development of orthostatic collapse
after first administrations of the drug
Prophylaxis: administration of half-dose before sleep

Atenolol (tenormin)

cardioselelctive -adrenoblocker of long action

Indications for administration

ischemic

heart disease
essential hypertension
cardiac arrhythmias
acute myocardium infarction

Acebutolol (sectral)
1-adrenoblocker with internal
sympathomimetic activity

Indications
disorders of cardiac rhythm
(tachyarrhythmias)
hypertension
ischemic heart disease

Labetolol
-, -adrenoblocker. The drug blocks 1, 2, 1 and
2-adrenoreceptors

Administration
treatment of patients with essential hypertension
hypertensive crisis

Contraindications
Atrio-ventricular blockade,
cardiac insufficiency

Thank you!