Adrenergic Drugs

dr. Ave Olivia Rahman, M.Sc.

Bagian Farmakologi FKIK UNJA
2015
 Tujuan Pembelajaran
• Mengetahui definisi dan pembagian obat
adrenergik.
• Mengetahui mekanisme kerja dari masing-
masing obat adrenergik
• Mengetahui penggunaan klinis dari obat
adrenergik.
• Mengetahui efek samping yang dapat timbul
dari obat adrenegik
 Autonomic Nervous Systems

Symphatetic Parasymphatetic
Nervous System Nervous System
(fight-or-flight (the body is at
situations.) rest)
Typical Autonomic Nerve
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• Nerves release certain neurotransmitter

• Neurotransmitters bind to receptors on organ
 effects
• Each organ has different type of receptor
Effect of ANS on Effector Organs
Symphatic Nervous System
Norepinephrine synthesis & release
Effects of Binding to Adrenergik Receptor
Vascular Smooth Muscle
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 Drugs/Subtances

Symphato-
symphatolitics
mimetics
 Symphatomimetics

Direct Acting means Binding to Receptors

 SYMPATHOMIMETICS : DIRECT ACTING
• α dan β agonist : epinefrin, etilefrin, oksilofin

• α agonist : norepinephrine
• α 1 agonist : phenylephrine, methoxamine
• α 2 agonist : Clonidine, Brimonidine, guanabenz, guanfacine,
α methylnorepinephrine, Methyldopa, xylometazolin,
naphazoline, oxymathazoline

• β agonist : isoprenalin, oksiprenalin.

• β1 agonist : dobutamine
• β2 agonist : salbutamol, fenoterol, klenbuterol, salmeterol,
formoterol, terbutaline
 SYMPATHOMIMETICS : INDIRECT
ACTING
Mechanism of actions :
• Blocking reuptake
• Blocking degradation
• Inducing release of endogenous
catecholamines (NE/E)
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• Amphetamine
• Cocaine
• Phenelzine
• Meclobemide
• Ephedrine
• Tyramine
Indirect...Blocking Degeneration

MAO Inhibitors  Blocking degradation of NE

Example : Phenelzine, Meclobemide
Indirect ...Blocking Reuptake
 Mixed-Acting Agents
• Act indirectly to induce release and directly as
agonists.
• Ephedrine; pseudoephedrine
• Amphetamine and amphetamine-like
compounds have very weak agonist activity,
and as such are sometimes listed only as
indirect-acting agents.
Non selective: Epinephrine
 Epinephrine
• Low dose  largely vasodilation due to high
potency at vessel β2 receptors

• High dose  increased in systolic blood

pressure via action on vessel α receptors;
maintained decrease in diastolic pressure via
β2 receptors; increased cardiac output and
rate due to potent action on β1 receptors (rate
somewhat blunted due to vagal reflex)
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• For acute anaphylaxis.
Aqueous epinephrine 1:1000 dilution (1 mg in
1 mL), 0.2 to 0.5 mg (0.01 mg/kg in children;
maximum dose, 0.3 mg) administered
intramuscularly every 5 to 15 minutes or as
necessary, depending on the severity of the
anaphylaxis
• Complementer in local anesthetic
Epinephrine
 Dobutamine

• Selective action on β1 receptors

• Increase cardiac output
 Dopamine
• Low dose  vasodilation leading to drop in
blood pressure via D1 receptors; enhanced
renal perfusion due to pronounced renal
vasodilation

• High dose  small increase in cardiac output

via β1 receptors; vasocontriction due to
activation of vessel α receptors
 Salbutamol & others β2 agonist
• Highly selective action on β2 receptors and
long duration of action
• Effect : broncodhilation, relaxation of uterus
muscle, vasodilatation.
• Used for asthma, tocolitics, vasodilator in
pheripherial vascular disease.
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 Phenylephrine
• selective action α1 receptors
• Effect : vasocontrictor, dilatation pupil
• Used : effective as mydriatic and decongestant
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Decongestan

Vasoconstriction reactive hyperemia

 α1
α1

β2
β2
SALBUTAMOL
β1

UTERUS β2
DILATATION

α1
β2
 Symphatolitics/Blocker

α symphatolitics β symphatolitics

Selective Non Selective Non

α1 selective β1 selective
 α- and β Blockers

• Example : Labetalol
• Works by blocking both α- and β receptors in
the body, which lowers blood pressure
• Used for treating high blood pressure
• Contraindication : heart block, heart failure,
asthma, obstructive airway disease, severe
slow heartbeat, severe low blood pressure
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 α Blockers Non selective
• Phentolamine, tolazoline, phenoxybenzamine
• Block at postsynaptic α1-adrenoceptors and
presynaptic α2-receptors.
• Block of α2-receptors results in uncontrolled
release of NE
 α1 Blockers
• Prazosin, terazosin, alfuzosin, doksazosin
• Used in hypertension (side effect is postural
hypotension because it prevent reflex
vasoconstriction.
• Improve mictutition in benign hyperplasia of
the prostate (terazosin, alfuzosin, tamsulosin)
 α2 Blockers
• Yohimbine
• Evergreen tree. It’s bark contains a chemical
called yohimbine.
• Used to arouse sexual excitement, for erectile
dysfunction (ED), sexual problems caused by
medications for depression called selective-
serotonin reuptake inhibitors (SSRIs), and
general sexual problems in both men and
women (Lack of evidence)
 α blocker

Physiologic event Non selective α blocker α1 blocker

 Non selective β Blockers
• Proponolol, oksprenolol, metoprolol, atenolol,
nadolol, sotalol.
• Blocking both the β1 and β2 receptor.
 β1 Blockers
• Metoprolol
• Cardioselective
• Relative selectivity. In high dose, also block β2.
• More prefer in co-morbid with DM, asthma.
Inhibitors of simpathetic tone (transmitter output from
simpathetic nerves)
 Clonidine
• Short-term action as vasocontrictor due to
direct action on α2 receptors in blood vessels
• Long-term vasodilation likely resulting from
action on presynaptic α2 receptors in brain
reducing sympathetic discharge
• Clonidine is used to treat hypertension (high
blood pressure).
 Indirect
Symphatolitics
Summary: Sympathomimetics Drugs
 Post Test
1. Simpatolitik adalah .....
2. Simpatomimetik adalah ....
3. Cara kerja obat agonist adrenergik adalah ....
4. Efek obat golongan β2 agonis pada saluran nafas
adalah ....
5. Efek obat golongan β blocker non selektif pada
saluran nafas adalah ....
6. Efek obat golongan α1 agonis pada pembuluh
darah adalah ...., pada mata adalah .....
7. Mekanisme kerja reserpine adalah ....
8. Mekanisme kerja amphetamine adalah ....
9. Salah satu penggunaan klinis epinefrin adalah .....
 Tugas
No. Nama Obat Mekanisme Penggunaan Dosis
Kerja Klinis