THE PHARMACOLOGY OF THE

AUTONOMIC NERVOUS
SYSTEM

Dhita Evi Aryani, M.Farm.Klin., Apt.

Laboratorium Farmakologi FKH UB
 Sistem saraf otonom:
• Bekerja tanpa pengaruh sistem
saraf pusat: otak/ sumsum tulang
belakang
• Mengatur kerja otot polos dan
kelenjar secara tidak sadar
• Dibagi menjadi dua: simpatik dan
parasimpatik
• Pada beberapa aktivitas
berlawanan, antara simpatik dan
parasimpatik
KONDISI V.S ISTIRAHAT
TERANCAM
 PROVE IT!!
• Apa yang kita lakukan ketika
kondisi kita terancam?
• Bagaimana pupil kita ketika
kita sedang berada di gedung
yang menakutkan?
• Bagaimana nafas kita ketika
ada anjing yang mengejar
kita?
• Bagaimana denyut jantung
kita ketika kita melihat suatu
tawuran?

SIMPATIK
 EFEK
SIMPATIK EFEK
PARASIMPATIK

ADRENERGIK
KOLINERGIK
Comparison of Divisions

7 SSP_faal/ikun/2006
Autonomic Nervous System (Obat Saraf Otonom)
 Obat ini berkerja seperti neurotransmitter atau mengganggu
pelepasan neurotransmitter.

 Mereka bisa mempengaruhi system saraf simpatik atau

parasimpatik.
• Perbedaan struktur antara saraf simpatik dan
parasimpatik terletak pada posisi ganglion.
• Saraf simpatik mempunyai ganglion yang terletak di
sepanjang tulang belakang menempel pada
sumsum tulang belakang sehingga mempunyai urat
pra ganglion pendek,
• sedangkan saraf parasimpatik mempunyai urat pra
ganglion yang panjang karena ganglion menempel
pada organ yang dibantu.
 Sinaps adalah struktur yang terdapat diantara neuron. Impuls
ditransmisi dari neuron ke neuron lain dan pada organ tubuh
yang berhubungan. Sinaps adalah titik pertautan antara dua
neuron.
 Neurotransmitter adalah agen kimiawi yang berperan dalam
mentransmisi impuls melalui sinaps.
 Neurotransmitter yang bersifat eksitasi adalah acetylcholine,
norepinephrine, dopamine, glutamate dan histamine.
 Sedangkan neurotransmitter yang pada umumnya
menginhibisi adalah gamma aminobutyric acid (GABA) pada
jaringan otak dan glycine pada medula spinalis.
 Serotonin menghambat dan mengontrol tidur, lapar dan
mempengaruhi kesadaran
Sinapsis
Neuron
Neuron Pasca sinaps
pra sinaps

Vesikel Membran Na+

sinapsis Neuro-
paska K+
mengandung transmitter
sinaps
neurotransmitter Membran
neuron
Ligan

Celah sinaps

Ligan (pintu gerbang ion)

Penerimaan impuls oleh saraf aferen/sensorik

 Neuron kolinergik
 Asetilkolin
 Berperan pada pengendalian sistem motorik
 Neuron dopaminergik
 Dopamin
 Berperan pada gerakan dan kerja obat antipsikotik
 Neuron nor adrenergik
 Nor adrenalin
 Berperan pada regulasi TD dan kerja obat antidepresan
 Neuron adrenergik
 Adrenalin
 Berperan = nor adrenergik
Penerimaan impuls
Penerimaan oleh saraf
impuls oleh aferen/sensorik
saraf aferen/sensorik
 Neuron gabaergik
 GABA (asam g–aminobutirat)
 Ada pada CNS, sebagai neuron inhibitorik
 Berperan pada regulasi motorik
 Neuron serotoninergik
 Serotonin
 Tidak banyak terdapat di CNS
 Serotonin dibentuk dari asam amino triptofan
 Sympathetic Nervous
System Drugs
 Adrenergic Drugs/Sympathomimetics
 Adrenergic Blocking Agents/Sympatholytics
 Adrenergic Drugs/Sympathomimetics
 Drugs that simulate the action of the sympathetic nervous
 Adrenergic nerves have either alpha (a) or beta (b) receptors
 Catecholamines are
chemicals that can cause a
sympathomimetic response.
Examples of naturally
occurring catecholamines
are epinephrine,
norepinephrine, and
dopamine.
Adrenergic Receptors
 Adrenergic nerves have either alpha
(a) or beta (b) receptors
 They act on one type (either alpha or
beta receptors only; these are called
selective drugs) or both types (both
alpha and beta receptors; these are
called nonselective drugs) of
adrenergic receptors located on the
cells of smooth muscles.
Midriasis (dilatasi pupil)

 Miosis (kontriksi pupil)

 Direct-acting sympathomimetics

 Dopamine, dobutamine, norepinephrine, phenylephrine, and

epinephrine:
 Vasopressor as well as inotropic (affecting the force of heart
muscle contraction) and chronotropic (affecting the heart
rate) support.
 Used in treatment of shock (anaphylactic, septic) to increase
blood pressure
Dopamine as direct-acting sympathomimetics
Ephedrine
 Indirect-acting: Depletes NE stores in sympathetic nerve
endings, so that tachyphylaxis to cardiac and pressor
effects of the drug may develop.
 Direct-acting: Stimulates alpha and beta receptors.

 The central effects of ephedrine (similar to those of

amphetamine drugs but less pronounced) are
overshadowed to a large extent by its peripheral actions.
 Used for treatment of asthma and as nasal decongestant.
 Side effect: raise blood pressure.
Xylazine
 Alpha2-adrenergic agonist used for its sedative and
analgesic in a variety of species. Sometimes used as an
emetic in cats.
 Contraindicated: animals receiving epinephrine or having
active ventricular arrhythmias. Extreme caution:
preexisting cardiac dysfunction, hypotension or shock,
respiratory dysfunction, severe hepatic or renal
insufficiency, preexisting seizure disorders, or if severely
debilitated. Should generally not be used in the last
trimester of pregnancy, particularly in cattle
Efek Samping
 Side effects include tachycardia, hypertension,
and cardiac arrhythmias.
 Adrenergic Blocking Agents/
Sympatholytics : Inhibitors of simpathetic
 tone
Drugs that block the effects of the adrenergic neurotransmitters
 They act as antagonists to the adrenergic agonists by blocking
the alpha- and beta-receptor sites.
 They can block the receptor site
either by occupying the receptor or
by inhibiting the release of the
neurotransmitter.
 Alpha blockers usually promote
vasodilation and a decrease in blood
pressure.
 Side effects of alpha blockers include
tachycardia and hypotension.
Clonidine (α2-agrenergic agonist):
 Activates presynaptic α2-receptors  decreased release of both NE
and ACh.
 Indication. hypertension.
 Adverse effects. Dry mouth; rebound hypertension after abrupt
cessation of clonidine therapy.
α-methyldopa:
 Competes for dopa decarboxylase  decreases the rate of
conversion of L-dopa to NE (via dopamine).
 Generates the false transmitter α-methyl-NE  a higher
affinity for α2-receptors  effects similar to those of clonidine.
 Indication. hypertension.
 Adverse effects. Fatigue, orthostatic hypotension, cutaneous
reactions.
 Alpha-adrenergic blockers

Non-selective α-blockers, e.g., phenoxybenzamine

Their blockade leads to uncontrolled release of norepinephrine with an overt
enhancement of sympathetic effects at β1-adrenoceptor-mediated myocardial
neuroeffector junctions, resulting in tachycardia and tachyarrhythmia. Used in small
animals to decrease urethral sphincter tone and in horses to prevent or treat
laminitis. It should not be used in horses with colic.

Selective α1-blockers, e.g., prazosin

Used to treat animals with heart failure and hypertension
 Yohimbine
 Pharmacology - Yohimbine is an alpha2-adrenergic antagonist
that can antagonize the effects of xylazine. Alone, yohimbine
increases heart rate, blood pressure, causes CNS stimulation
and antidiuresis, and has hyperinsulinemic effects. By blocking
central alpha2-receptors, yohimbine causes sympathetic
outflow (norepinephrine) to be enhanced. Peripheral alpha2-
receptors are also found in the cardiovascular system,
genitourinary system, GI tract, in platelets, and adipose tissue.
 Uses/Indications - Yohimbine is indicated to reverse the effects
of xylazine in dogs, but it is being used clinically in several other
species as well. Yohimbine may be efficacious in reversing some
of the toxic effects associated with other agents as well (e.g.,
amitraz).
 Beta-adrenergic receptor
Recep- Blocker/antagonist
Organ Effect Agonist aplication
tor aplication
Heart β1 ↑ contractility Hypertension:
Congestive heart • Cardioselective blocker
↑ heart rate
failure: Dobutamine (atenolol, betaxolol,
↑ automaticity bisoprolol, metoprolol)
JG cells- β1 ↑ renin release • Non-selective β-blocker
kidney (propanolol, timolol)
Bronchial β2 Bronchodilation Asthma attack: β2-
smooth agonist (short-acting:
muscle salbutamol, albuterol,
terbutaline; long-
acting: salmeterol,
formoterol)
Eye-ciliary β2 ↑ aqueous Glaucoma: topical non-
epitheli- humor selective β-blocker
um production by (timolol), β1-selective
the ciliary blocker (betaxolol, β1 > β2)
epithelium
 Beta-adrenergic blockers

Blood Pressure = Cardiac Output x Peripheral Resistance

Decrease in cardiac output/stroke volume  decrease in blood pressure
 Beta-adrenergic blockers

 Cardioselective blockers: inhibit β1 receptors at low to

moderate dose, higher doses also inhibit β2 receptors.

 Abrupt discontinuation may cause withdrawal rebound

phenomena (palpitation, sweating, hypertension) 
gradually tapering off for 14 days to prevent the rebound.
 Beta blockers decrease heart rate and blood
pressure. Side effects of beta blockers
include bradycardia and hypotension.
Examples of beta blockers used in veterinary
practice include the following:
 propranolol (Inderal®), which blocks beta-1
and beta-2 receptors and is used to treat
cardiac arrhythmias and cardiac disease in
animals.
 metoprolol (Lopressor®) and atenolol
(Tenormin®), which block beta-2 receptors
and are used to treat hypertension.
 timolol (Timoptic®), which blocks beta-1 and
beta-2 receptors and is used as an
ophthalmic preparation to treat glaucoma.
Glaucoma
Aqueous humor formation:
 Stimulation of β2-receptors formation ciliary epithelium
 increases aqueous humor formation
Topical treatment:
 β-adrenergic blocker: timolol, betaxolol
Side effects:
 Timolol:
 Ocular: irritation
 Systemic: headache, dizziness, bronchospasm,
bradycardia, hypotension
 Betaxolol: Reduced side effects compared to timolol
Glaucoma

Aqueous humor formation:

 Stimulation of α2-receptors  reduces NE release 
reduces aqueous humor formation
Topical treatment:
 α2-adrenergic agonist: apraclonidine, brimonidine (more
selective than apraclonidine)
Side effects:
 Allergic reaction (redness, itching, tearing of eye)
 Limited blood-brain barrier penetration  reduced CNS
and cardiovascular side effects
 Side effects of beta-adrenergic blockers
Organ Recep- Effect Side effect due to beta-adrenergic
tor blockade
Heart Β1 ↑ contractility Myocardial insufficiency in HF
↑ heart rate Bradycardia
↑ automaticity AV block
Blood β2 Vasodilation Vasodilating effect of epinephrine is
vessel abolished, leaving the α-receptor-
mediated vasoconstriction
unaffected: “cold hands and feet”
Bronchial β2 Bronchodilation Bronchial asthma
smooth
muscle
Liver β2 ↑ gluconeogenesis Hypoglycemia in diabetic patient
↑ glycogenolysis treated with oral antidiabetic or
↑ lipolysis insulin
Dyslipidemia
Adipose β3 ↑ lipolysis Dyslipidemia
Parasympathetic Nervous
System Drugs
 Cholinergic Drugs/
Parasympathomimetics
 Anticholinergic Drugs/
Parasympatholytics/
Antimuscarinic/Antispasmodic
 Sistem saraf parasimpatik
berkaitan dengan:
• Peningkatan aktivitas saluran
cerna seperti peningkatan
pengeluaran air liur,
pengeluaran asam lambung,
peningkatan motilitas usus,
peningkatan defekasi
• Peningkatan aktivitas saluran
urin urinasi lebih tinggi
• Penyempitan pupil
• Penurunan denyut jantung
• Penyempitan saluran nafas
(bronkokonstriksi)

Senyawa neurotransmiter atau penghantar pesan yang penting

dalam sistem saraf parasimpatik adalah asetilkolin
Terdapat enzim yang dapat
menguraikan asetilkolin yaitu:
asetilkolinesterase

Obat parasimpatomimetik dapat

bekerja secara langsung ataupun
tidak langsung

Secara langsung melalui ikatan

dengan reseptor asetilkolin.
Terdapat dua reseptor: nikotinik
dan muskarinik

Obat parasimpatomimetik tidak

langsung bekerja dengan cara
menghambat penghancuran
asetilkolin oleh
asetilkolinesterase sehingga
konsentrasi asetilkolin tetap tinggi
Beberapa insektisida merupakan senyawa yang bekerja parasimpatomimetik secara
tidak langsung

INSEKTISIDA
 Cholinergic Drugs/Parasympathomimetics
 Bekerja dengan cara meniru system parasimpatis
 Bisa bekerja dengan cara langsung (meniru efek asetilkolin)
atau tidak langsung (menghambat kerusakan asetilkolin)
Reseptor Cholinergic
Effect Cholinergic Drugs
 Contoh Obat dan Indikasinya
Direct acting cholinergic
 Metoclopramide HCl

DOSIS
Indirect acting cholinergic
Endrophonium
Neostigmine, Physosthigmine
Efek Samping Obat Kolinergik
Side effects of cholinergic drugs include bradycardia,
diarrhea and vomiting, and increased secretions (intestinal,
bronchial, and ocular).
Anticholinergic Drugs/
Parasympatholytics

 Anticholinergic drugs inhibit the actions of acetylcholine by

occupying the acetylcholine receptors
 These drugs are also referred to as parasympatholytics,
antimuscarinic agents, or antispasmodics.
 The major body tissues
affected by the
anticholinergic drugs
are the heart,
respiratory tract,
gastrointestinal tract,
urinary bladder, eye,
and exocrine glands.
 By blocking the
parasympathetic
nerves, the sympathetic
or adrenergic nervous
system dominates.
Contoh Obat dan Indikasinya
Efek samping obat Antikolinergik
 Side effects of anticholinergics may include
tachycardia, constipation, dry mouth, dry eye,
and drowsiness.