Herni Suprapti

What are adrenergic agonists?


 Drugs or endogenous catecholamines that activate 
and/or  receptors.

 These drugs are also knows as sympathomimetics.

 classified

 mechanism of action (direct vs indirect)

 receptor site specificity (1, 2, 1, 2)

  selective direct-acting
agonists

 Phenylephrine
 Methoxamine
 Clonidine
 Methyldopa
  selective direct-acting
agonists

 Dobutamine
 Isoproterenol
 Albuterol
 Metaproterenol
 Terbutaline
  and  direct-acting agonists

 Epinephrine
 Norepinephrine
 Dopamine
 direct-acting agonists are-
considered catecholamines

 Epinephrine
 Norepinephrine
 Isoproterenol
 Dopamine
 Dobutamine
 
 indirect-acting adrenergic agonists.
 Tyramine
 Amphetamine

 mixed (direct and indirect) agonists.

 Ephedrine
 Metaraminol
DIRECT-ACTING  SELECTIVE
RECEPTOR AGONISTS

1 and 2 receptors located

 1 receptors are located on the effector organ’s
postsynaptic membrane.
 2 receptors are predominantly located on the
presynaptic membrane.
 Postsynaptic 2 receptors are limited to the CNS and
blood vessels.
 physiologic responses occur when 
receptors are stimulated

 1 stimulation

 2 stimulation
 1 stimulation

  release of intracellular calcium from the
endoplasmic reticulum via inositol triphosphate
(IP3) 
 vascular constriction
 decreased intestinal tone and motility
 contraction of the bladder’s internal sphincter
 ejaculation
 contraction of the pregnant uterus
 mydriasis.
 2 presynaptic membrane receptors are
stimulated

 intracellular cyclic adenosine monophosphate (cAMP)
production is inhibited.
 2 receptors function primarily as part of a negative
feedback loop.
 When norepinephrine is released from nerve terminals,
some will circulate back to the presynaptic membrane and
bind to the 2 receptor. This will subsequently inhibit
further norepinephrine release.
 Other actions mediated by 2 receptors include increased
vagal tone, platelet aggregation, and suppressed insulin
secretion.
direct-acting agonists that are selective for 1- and
2 adrenergic receptors


 1 receptors
 phenylephrine and methoxamine

 2 receptors
 clonidine and methyldopa
 physiologic actions
 Primarily vasoconstriction. The subsequent rise in
blood pressure also leads to a reflex bradycardia.

adverse effects
Rebound mucosal swelling and
hypertensive headache
 therapeutic use

 As a nasal decongestant (primary use)
 To treat hypotension
 For ocular examinations (mydriasis)
 To terminate episodes of paroxysmal atrial
tachycardia (PAT)
 METHOXAMINE

 What receptors does methoxamine work on?
 As with phenylephrine, methoxamine is fairly specific
for 1 receptors.

 therapeutic uses.
 Treatment of hypotension and PAT

 adverse effects
 similar to those of phenylephrine.
 CLONIDINE

 What receptors does clonidine work on?
 Clonidine stimulates 2 receptors in the CNS, which reduces sympathetic
nervous system outflow from the brain.

 therapeutic uses.
 Treatment of hypertension
 Withdrawal from benzodiazepines and opiates
 Treatment of diarrhea in diabetic patients who have autonomic neuropathies

 Toxicities
 Sedation
 Dry mouth
 Sexual dysfunction
 Orthostatic hypotension
 DIRECT-ACTING 
SELECTIVE AGONISTS

 Where are the  receptors
located?

  1 receptors are primarily located on the
postsynaptic membrane.

 2 receptors are found on both the pre-and

postsynaptic membranes.
 the physiologic responses once 
receptors are stimulated

 1 stimulation activates adenylate cyclase  opens calcium
channels  cardiac stimulation with both increased inotropic and
chronotropic effects.

 1 stimulation  increased lipolysis.

 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 1 and 2 receptors produce decreased intestinal tone and
motility (just as the -adrenergic receptors do).
 DOBUTAMINE

 A dopamine analogue
 Primarily act on 1 but it does have some action on
2 receptors as well

 physiologic effects
 Increased heart rate and contractility (1)
 Smooth muscle relaxation (2)

 therapeutic use
 Treatment of unstable CHF and shock
 DOBUTAMINE

 route of administration?
 IV

 adverse effects?
 Arrhythmias
 Headache
 Hypertension
 Palpitations
 Angina
 Nausea
 ISOPROTERENOL

 Which receptors mediate the effects of isoproterenol?
 1 and 2 receptors

 physiologic actions
 Increases cardiovascular inotropic and chronotropic response (1)
 Lowers peripheral vascular resistance (2)
 Relaxes smooth muscles (2)

 In what clinical situations is it appropriate to use isoproterenol?

 Stimulation of heart rate in patients suffering from heart block and
bradycardia
 In the past, used for treatment of asthma
 ISOPROTERENOL

 What is the route of administration?
 IV

 What are the toxicities of isoproterenol?

 Arrhythmias
 Palpitations
 Tachycardia
 Headache
 ALBUTEROL, METAPROTERENOL,
AND TERBUTALINE

 What are the pharmacologic actions of these 2
direct-acting agonists?
 Stimulation of smooth muscle dilatation
 Can stimulate 1 receptors at higher doses

 What is the route of administration?

 Albuterol and metaproterenol are usually inhaled.
 Terbutaline can be given orally or subcutaneously.
 ALBUTEROL, METAPROTERENOL, AND
TERBUTALINE

 List the therapeutic uses.
 Treatment of bronchospasm/asthma
 Treatment of chronic obstructive pulmonary disease
 Treatment of bronchitis
 Terbutaline and ritodrine can be used to relax the uterus
during premature labor.

 What are the potential adverse effects of the 2 selective drugs?

 Arrhythmias
 Tachycardia
 Headache
 Nausea and vomiting
DIRECT-ACTING 
AND  AGONISTS

 EPINEPHRINE

 Which receptors does epinephrine act upon?
 It stimulates 1, 2, 1, and 2 receptors.
 At low doses epinephrine stimulates  receptors and
at high doses it stimulates  receptors.
physiologic responses to epinephrine

 Cardiovascular
 increased heart rate and contractility;
 vasoconstriction of arterioles in the skin, viscera, and
mucous membranes
 Respiratory
 bronchodilation through activation of 2 receptors
 Metabolic
 increased glycogenolysis and release of glucagon and
a decreased release of insulin results in hyperglycemia
 therapeutic uses

 Given for bronchospasm secondary to acute asthma
or anaphylactic shock
 Used in anaphylaxis and cardiac arrest to increase
cardiac electrical activity
 Used in conjunction with local anesthetics to prolong
effects via vasoconstriction
 Used to achieve hemostasis
 Epinephrine’s adverse effects

 Cardiac arrhythmias
 Hypertension
 Palpitations
 Dizziness, anxiety, headache
 Tremor
 Myocardial infarction due to increased cardiac work
 Pulmonary edema
 epinephrine reversal

 When epinephrine is administered alone, it will
cause an increase in systemic blood pressure because
of its  activity.
 When given in conjunction with an  blocker such as
phenoxybenzamine, epinephrine will cause a
decrease in blood pressure because of its 2 activity.
 This effect is knows as epinephrine reversal.
 NOREPINEPHRINE

 What receptors does nor-epinephrine stimulate?
 α1, α2, and β1 receptors. Norepinephrine has a stronger affinity for α receptors than
for β receptors.

 physiologic effects
 Vasoconstriction
 Reflex bradycardia

 therapeutic use
 It is one of the last-line agents in the treatment of shock.

 adverse effects
 Tissue hypoxia secondary to potent vasoconstriction
 Decreased perfusion to the kidneys
 Tissue necrosis due to extravasation during intravenous administration
 Arrhythmias
 DOPAMINE

 Where is this agonist found?
 It is synthesized in the CNS, sympathetic ganglia, and
adrenal medulla.

 What receptors does dopamine act on?

 α1, β1 and β2. It also stimulates its own dopamine (D1
and D2) receptors located in the peripheral mesenteric
and renal vascular beds. Dopamine receptors are
stimulated at low dose, β receptors at moderate dose,
and α1 receptors at higher doses. Dopamine does not
cross the blood-brain barrier.
 DOPAMINE

 therapeutic uses
 Treatment of shock—it raises blood pressure by stimulating the β1 receptors of
the heart
 Used in acute renal failure to increase renal blood flow
 Treatment of acute congestive heart failure

 How is it administered?
 IV

 adverse effects
 Decreased renal perfusion at higher doses
 Arrhythmias
 Tachycardia
 Hypertension
 Tissue necrosis can occur if dopamine extravasates during infusion.
 TYRAMINE

 What is tyramine?
 Tyramine is a by-product of tyrosine metabolism; tyrosine is a precursor to
dopamine, epinephrine, and norepinephrine.

 mechanism of action
 Tyramine is taken up by sympathetic neurons, which causes a release of
catecholamines.

 Is there a therapeutic use for tyramine?

 No

 adverse effects
 It can cause a hypertensive emergency in patients who take MAO inhibiting
drugs since MAO is responsible for the 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.
 AMPHETAMINE

 pharmacologic actions
 It releases stores of norepinephrine and dopamine. It can enter the CNS.

 When is it appropriate to administer amphetamine?

 Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and
narcolepsy. It is also used for appetite suppression.

 adverse effects
 Psychological and physical dependence
 Psychosis
 Confusion
 Insomnia
 Headache
 Restlessness
 Palpitations
 Tachycardia
 Impotence
 MIXED (DIRECT &
INDIRECT) AGONISTS

 EPHEDRINE

 How does ephedrine work?
 It stimulates the release of norepinephrine from nerve
terminals. It also acts as a direct adrenergic agonist.

 therapeutic uses
 Ephedrine is used in the treatment of urinary incontinence,
bronchospasm, and hypotension.

 adverse effects
 Arrhythmias
 Palpitations
 Insomnia
 Hypertension
 METARAMINOL

 drug’s actions
 Metaraminol acts indirectly by releasing norepinephrine. It
can also directly stimulate a receptors.

 therapeutic uses
 Treatment of hypotension and termination of PAT
episodes

 adverse effects
 Similar to those of norepinephrine