Adrenergic agonists
Samuel Aguazim (MD)
What are adrenergic agonist
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Drugs that mimic the effects of
adrenergic nerve stimulation (or
stimulation of the adrenal medulla)
Mimic the effects of norepinephrine or
epinephrine
These drugs are known as
adrenomimetics or sympathomimetics
Remember the actions of the SNS are
mediated through alpha and beta
receptors.
Remember
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Alpha 1: most vascular smooth
muscle, agonist contract
Beta 1: heart, agonist increase rate
Beta 2: respiratory and uterine
smooth muscle, agonists relax.
Name alpha selective direct –
acting agonists
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Phenylephrine
Methoxamine
Clonidine
methyldopa
Identify the major beta
selective direct-acting agonist
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Dobutamine
Isoproterenol
Albuterol
Metaproterenol
Terbutaline
List the major alpha and beta
direct-acting agonists
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Epinephrine
Norepinephrine
dopamine
Direct- acting agonists
considered catecholamines
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Epinephrine
Norepinephrine
Isoproterenol
Dopamine
Dobutamine
The direct acting drugs bind to the
receptors. So specificity of action is a
possibility.
INDIRECT ACTING
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The indirect-acting
sympathomimetic agents acts by
releasing previously stored
norepinephrines, their effects are
widespread and non specific
Amphetamine
Tyramine
TWO MIXED AGONISTS
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DIRECT & INDIRECT ACTING
Ephedrine
Metaraminol
Where are alpha 1 and alpha 2
receptors located
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Alpha 1 receptors are located on the
effector organ’s postsynaptic
membrane.
Alpha 2 receptors are predominantly
located on the presynaptic
membrane.
Postsynaptic alpha 2 receptors are
limited to the CNS and blood vessels
RESPONSES ASSOCIATED WITH
TYPES OF ADRENOCEPTORS
Alpha1
Stimulation leads to release of intracellular
calcium from the endoplasmic reticulum
via inositol triphosphate (IP3 ). This leads
to
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Arterial and arteriolar constriction
(cutaneous, visceral, skeletal & pulmonary)
Venous constriction
Uterine contraction
Pupillary dilation ( mydriasis )
(contraction of radial smooth muscle of iris)
Contraction of ureter
Contraction of pilomotor muscles
Alpha 2
When alpha 2 presynaptic membrane receptors
are stimulated, intracellular cyclic adenosine
monophosphate ( c CAMP ) production is
inhibited.
 Inhibition of NE release
 Inhibition of ganglionic transmission
 Reduction of BP and heart rate
 Vasoconstriction (quantitatively less important
than α1)
 Decrease insulin secretion
 Platelet aggregation
Name the direct-acting agonists that
are selective for α1 and α2
adrenergic receptors
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Alpha 1 receptorsphenylephrine and methoxamine
Alpha 2 receptors- clonidine and
methyldopa
Phenylephrine
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Physiologic action( alpha 1 agonist)
Primarily vasoconstriction
Therapeutic uses
Nasal decongestant**
Treat hypotension
For ocular examinations( mydriasis)
To terminate episodes of paroxysmal atrial
tachycardia( PAT)
SE: REBOUND MUCOSAL SWELLING AND
HYPERTENSIVE HEADACHE
METHOXAMINE
THERAPEUTIC USES:
 Treatment of hypotension and
paroxysmal atrial tachycardia
( PAT)
 Adverse effect: similar to those of
phenylephrine
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Alpha 2 selective agonists
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Clonidine --- it activates alpha 2 in the CNS to
reduce sympathetic stimulation to the heart
and activates presynaptic alpha 2 receptors on
the peripheral nerve endings to inhibit the
release of norepinephrine
Therapeutic use – treat essential HTN,
withdrawal from benzodiazepines and opiates,
treatment of diarrhea in diabetic patients who
have autonomic neuropathies
Adverse Effects:
• dry mouth
• sedation
• sexual dysfunction
Direct – acting beta selective
agonists
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LOCATION:
β1 receptors are primarily located on
the postsynaptic membrane.
β2 receptors are found on both the
pre and postsynaptic membranes
Beta 1
Beta 1 stimulation activates adenylate cyclase,
which opens calcium channels leading to:
cardiac stimulation with both increased
chronotropic(HR), inotropic( contraction),
dromotropic(conduction) effects.
stimulation of lipolysis
 stimulation of renin secretion
Beta 2
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Beta 2 receptors work via adenylate cyclase
stimulation as well.
In this case, however, bronchial smooth
muscle as well as skeletal muscle
vasculature are dilated.
The uterus, ciliary and detrusor muscles are
relaxed and glucagon release is increased.
Both beta 1 and beta 2 receptors produce
decreased intestinal tone and motility.
DOBUTAMINE
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A dopamine analogue that acts primarily on beta 1
but it does have some action on beta 2 receptors as
well.
Physiologic effects: increased heart rate and
contractility (β1) and smooth muscle relaxation
(β2)
Uses: treatment of unstable CHF and shock
Route: iv
Adverse effects: arrthymias, headache, hypertension,
palpitation, angina and nausea
Isoproterenol
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Activates ß adrenergic receptors (both
ß1 - and ß2 -receptor subtypes)
Activation of cardiac ß1 - adrenergic
receptors: increased contractility and
heart rate.
Activation of ß2 - adrenergic receptors:
Bronchial and GI smooth muscle
relaxation
Isoproterenol: Limited
therapeutic uses
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Emergency settings to treat heart
block or severe bradycardia
Management of torsade de pointes (a
ventricular arrhythmia)
Beta 2 selective agonists
Drugs used as medication for broncho-dilation
due to smooth muscle dilatation
1. Albuterol
2. Salmeterol – long acting with late onset
3. Metaproterenol
4. Terbutaline
Therapeutic uses: rx of bronchospasm/asthma
COPD, bronchitis.
Adverse effect: arrhythmias, tachycardia,
headache and vomiting
NOR EPINEPHRINE(NE)
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Through stimulation of alpha
receptors, NE causes constriction of
all major vascular beds.
This, in turn, causes an increase in
resistance and pressure.
The increase in blood pressure
causes a reflex increase in
parasympathetic output to the
heart, which acts to slow the heart
down
NOR EPINEPHRINE
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Activates alpha and beta 1 receptors
physiologic effects: vasoconstriction
and reflex bradycardia
Therapeutic uses
 Shock
 Never used for asthma
 SE: TISSUE HYPOXIA
 DECREASED PERFUSION TO KIDNEY
 TISSUE NECROSIS
Catecholamines
Drug
Epinephrine
Norepinephrine
Isoproterenol
Dobutamine
Dopamine
Receptors
alpha1, alpha2 ß1, ß2
alpha1, alpha2, ß1
ß1 , ß2
ß1 (alpha1)
(alpha1 and ß1 at high doses)
Direct- acting alpha and beta
agonist
EPINEPHRINE
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Epinephrine is a potent activator of
alpha and ß adrenergic receptors
Prominent Cardiovascular Effects
Cardiac effects
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Heart rate increases
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Cardiac output increases
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Oxygen consumption increases
Vascular effects
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Over renal system – decreased blood flow
Renin – release
Respiratory system-Broncho - dilatation -Beta 2
Decreased secretions
Metabolic- increased glycogenolysis and release
glucagon and a decreased release of insulin
results in hyperglycemia
Epinephrine
Used mainly for bronchospasm
 Acute asthma
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Anaphylactic shock
Open angle glaucoma
Increase the duration of local anesthesia
SE: Cardiac arrhythmias, hypertension,
palpitations, dizziness, anxiety, headache
and tremor. etc
Dopamine
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Dopamine is the immediate precursor
of norepinephrine.
It is synthesized in the CNS,
sympathetic ganglia and adrenal
medulla
acts on alpha 1, beta 1 and beta 2 and
dopamine ( D1&D2) receptors
At high doses dopamine acts much
epinephrine
Cardiovascular Effects (Dopamine)
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Treatment of shock- raises BP by
stimulating the beta 1 receptors of the
heart
Acute renal failure to increase renal blood
flow
Treatment of acute CHF
Therapeutic use (Dopamine)
Drug of choice for shock
Both cardiogenic and hypovolemic shock.
Continuous infusion to be given.
Dopamine increases heart rate and
cardiac output while simultaneously
dilating the renal and coronary
arteries.
Adverse effects
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palpitations
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tachycardia
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arrhythmias
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coronary insufficiency
alpha methyl DOPA
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very effective alpha 2 agonist, and so
prevents the release of NE.
· It is used as an antihypertensive
OTHER ADRENERGIC
DRUGS
Ephedrine – alpha , beta and CNS
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Mainly used for treatment of asthma
and nasal decongestant.
Phenylpropanolamine – nasal
decongestant and bronchodilator
Tetrahydrozoline – related to
ephedrine used as topical nasal and
conjunctival decongestant.
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Naphazoline - used as topical
vasoconstrictor.
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Oxymetazoline – to reduce
congestion and swelling of the nasal
mucosa.
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Xylometazoline -- nasal
decongestant.
Indirectly Acting Sympathomimetics
-act by releasing NE -
Pharmacological
Effects
 Vasoconstriction
 Bronchodilation
 CNS effects:
stimulation
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anorexigenic
Applications
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Nasal decongestion
Asthma
Narcolepsy
Hyperkinetic
Syndrome
Obesity
Indirectly Acting drugs
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Amphetamine
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Tyramine
Amphetamine
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Alpha, beta . It releases stores NE
and dopamine. It can enter CNS
Used as CNS stimulant in
treatment of children with
attention deficit syndrome.
(hyperactivity is the feature)
Narcolepsy
Obesity
Side effects
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Headache, palpitations, dysphoria
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Appetite suppression
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Weight loss due to decrease food intake
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Psychological tolerance/dependence
TYRAMINE
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It is a by-product of tyrosine metabolism;
tyrosine is a precursor to dopamine,
epinephrine and norepinephrine
MOA: tyramine is taken up by
sympathetic neurons, which causes a
release of catecholamines.
Is there a therapeutic use: NO
What are tyramine’s adverse
effects ?
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It can cause a hypertensive emergency
in patients who take monoamine
oxidase (MAO) inhibiting drugs since
MAO is responsible for metabolism of
tyramine.
It is important to warn patients who are
taking MAO inhibitors not to eat foods
with high tyramine concentrations, such
as red wine, beer, chocolate and
cheese.
Drugs used as inhalation medication for
broncho dilation are
1.Epinephrine – short acting
2. Isoproterenol
3. Albuterol
4. Salmeterol – long acting with late
onset
5. Metaproterenol
6. Terbutaline
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Mixed action adrenergic agonists
Ephedrine
Stimulates both alpha and beta
receptors
Plant alkaloid now made synthetically
Used in asthma
Nasal decongestant