PHARMACOLOGY (LECTURE)
2B
AUTONOMIC NERVOUS SYSTEM
P-05 Dr. PAGUIRIGAN | September 9, 2018
*NOTE: This only includes the additional notes
during our first meeting on ANS. Please refer to
topnotch review for the full discussion.
CATECHOLAMINES
DOPAMINE
 Immediate metabolic precursor
Norepinephrine and Epinephrine
 Central neurotransmitter with intrinsic
pharmacologic activities
 Substrate for both Monoamine Oxidase
(MAO) and Catechol-O-methyl transferase –
thus it is not effective when administered
orally
 Cardiovascular effects:
o Positive inotropic effect on the
myocardium, acting as an agonist on
the Beta 1 receptor
o Capable of releasing Norepinephrine
from Nerve Terminals
 Tachycardia effect is less than Isoproterenol
 Can cause increased:
o systolic and pulse pressure
o Glomerular Filtration Rate
o Renal Blood Flow and Sodium
excretion
 The untoward effects due to overdosage are
generally attributable to excessive
sympathomimetic activity – Nausea,
Vomiting, Tachycardia, Anginal pain,
Arrhythmias, Headache, Hypertension,
Vasoconstriction may be encountered
during IV infusion of Dopamine
 Should not be used in patients who have
received Monoamine Oxidase Inhibitors
(MAO Inhibitors)
 Therapeutic uses:
o Tx of some types of shocks
o Beneficial for patients with Oliguria and
with low or normal Peripheral vascular
resistance
o Tx of Cardiogenic and Bacteremic
(septic)shock
o Tx of profound hypotension following
removal of Pheochromocytoma
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DOBUTAMINE
 Directly acting agent with selectivity for Beta
1 receptor(leads to increased inotropic and
chronotropic effects)
of  Relatively more effective in enhancing the
contractile force of the heart than in
increasing the heart rate
 It does not affect the Atrial conduction
velocity but it augments the conduction
velocity through the AV node
 There’s little to no effect on the ventricular
impulse conduction
 Does not produce Renal vasodilation
 Plasma half-life: 2 mins
 Not effective when given orally
 Usual dose: 2.5-10 nanograms/kg/min
 Rapidly metabolized in the Liver to an
inactive conjugate with Glucoronic acid and
3-o-methyl dobutamine
 Should not be used in patients with Atrial
Fibrillation
 Side effects:
o May be less frequent
o Can be in the form of Nausea,
Headache, Palpitation, Shortness of
Breath and Anginal Pain
 Therapeutic uses:
o Congestive Heart Failure
o Cardiogenic Shock
 Contraindication/s:
o Patients with marked obstruction to
Cardiac ejection (like in Idiopathic
Hypertrophic Subaortic Stenosis)
NON CATECHOLAMINES
AMPHETAMINE
 Has a powerful CNS stimulant action in
addition to the peripheral alpha and beta
action that is common to indirectly acting
sympathomimetic drugs
 Effective after oral administration and its
effect may last for several hours
 P-05 AUTONOMIC NERVOUS SYSTEM
 The effect increases both the systolic and
diastolic blood pressure, the heart rate is
reflexively slowed and cardiac arrhythmias
may occur
 The L-isomer form is slightly more potent
that the D-isomer as far as the
Cardiovascular action is concerned
 One of the most potent Sympathomimetic
amines with respect to stimulation of the
Central Nervous system
 Depression of Appetite: It can cause weight
loss in obese humans but the weight loss is
almost entirely due to reduced food intake
and only small measure in increased
metabolism
EPHEDRINE
 Stimulate both alpha and beta receptors
 Minimal uses related to both types of action
 Its cardiovascular action intercedes 10x
longer than epinephrine
 Bronchial muscle relaxation is less
prominent but more sustained compared
with epinephrine
 Mydriasis occurs after local application of
the drug to the eyes
 The activity of the human uterus is usually
reduced by ephedrine
 Less effective than epinephrine in elevating
the concentration of Glucose in the blood
 The CNS effects are similar to those of
Amphetamine but are considerably less
marked
 Therapeutic uses:
o For bronchospasm
o Stokes Adams syndrome
o Nasal Decongestion
o Allergic disorders
o Pressor agent during Spinal Anesthesia
o Central Stimulant in cases of
Narcolepsy
MEPHENTERMINE
 One of several pressor agents that can be
used various Hypotensive conditions
 Prolonged duration of action – up to 4 hours
 Cardiac contraction is enhanced; Cardiac
output, Systolic and Diastolic pressures are
also increased
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 Marked mucosal vasoconstriction can be
produced by local application of the drug but
it is used clinically mainly as a pressor
agent in various hypotensive states
HYDROXYAMPHETAMINE
 Actions are similar to that of Ephedrine with
the exception that this drug almost entirely
lacks CNS stimulant activity
 Its only current clinical use is as a Mydriatic
METARAMINOL
 Used almost exclusively for the treatment of
Hypotension
 Has both a direct and an indirect action
 Overall effects are similar to those of
Norepinephrine but it is much less potent
and has a more prolonged action
 Also lacks CNS stimulant effect
 It is absorbed after oral administration but
for equal effects the oral dose to be given
must 5 or 6 times greater than the dose that
should be given by IM and IV
 The pressor effect of an IM dose of 5mg will
last for about 15hours
 Principal use: Pressor agent in certain
hypotensive states
PHENYLEPRINE
 Powerful alpha 1 receptor stimulant with
little effect on the Beta receptors of the
heart
 The direct action on receptors accounts for
the greater part of its effect, only a small
part is due to its activity to release
Norepinephrine
 The CNS stimulant action is minimal
 The response to the drug will persist for
20mins after an IV dose and as long as
50mins after subcutaneous administration
 The effects of the drug are marked reflex
bradycardia, slight increase in heart race,
the cardiac output is slightly decreased and
peripheral resistance is considerably
increased. Coronary blood flow is also
increased. The pulmonary BV is constricted
 P-05 AUTONOMIC NERVOUS SYSTEM
so there is a rise and increase in pulmonary
arterial pressure
 Therapeutic uses: nasal decongestant,
hypotension, mydriasis and as local
vasoconstrictor in local anesthesia. It is also
used as a relief of paroxysmal atrial
tachycardia.
METHOXAMINE
 The pharmacologic properties of
methoxamine are almost exclusively those
that are characteristic of alpha receptor
stimulation and it acts directly on this site.
The effects are thereof the same as
phenylephrine.
 Its effects are increased in the blood
pressure due entirely to vasoconstriction.
There is no stimulant action in the heart.
And it lacks beta receptor action on the
smooth muscles. There is also no central
nervous system stimulation.
 Reflex bradycardia is prominent so it used
clinically to relief paroxysmal atrial
tachycardia. It does not appear to
precipitate cardiac arrhythmias. It prolongs
ventricular muscle action potential and
refractory period and slows the AV
conduction.
 Therapeutic uses: used as pressor agent in
hypotensive states and ends attacks
paroxysmal tachycardia.
SELECTIVE BETA-2 ADRENERGIC
STIMULANTS
METAPROTERENOL
 Quite similar chemically to isoproterenol but
it is resistant to methylation by COMT. It is
effective and given orally and it has
somewhat long duration of action compared
to isoproterenol
 Primary beta-2 adrenergic agonist
 Inhalation: relative effect on the beta-1
receptors of the heart
 After oral or inhalation of metaproterenol,
there is an increased in the force expiratory
volume and maximal rate of force expiratory
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flow and there is decrease in the airway
resistance.
 After oral dose, there is an improvement in
airway function up to 4 hours
 After inhalation, the improvement in
respiratory function will become apparent
for 3-4 hours
 Approximately 40% is absorbed after oral
dose. It is excreted in urine primarily as
conjugate with glucuronic acid.
 Adverse reactions: tachycardia,
hypertension, nervousness, tremors,
palpitations, nausea and vomiting
 It is used clinically as a bronchodilator
TERBUTALINE
 is a synthetic sympathomimetic agent
 It is given orally, SQ, or by inhalation
 It used for the treatment of reversible
obstruction of the airway.
 It is relatively selective beta-2 agonist
 It is not methylated by COMT
 After oral dose of 5 mg, it produces
bronchodilation after about 1 hour and this
will persist for about 7 hours
 When it is given SQ, the effects will start
within 5 mins and will last for 4 hours
 Side effects: nervousness, muscle tremors,
headache, tachycardia, palpitation,
drowsiness, nausea, vomiting, sweating
ALBUTEROL
 it is a selective beta-2 adrenergic agonist
with pharmacologic properties and
therapeutic effects similar to terbutaline
 Inhalation: the effect will start after 15 mins
and will last for 3-4 hours
RITODRINE
 selective beta-2 adrenergic agonist
 It is used to delay or prevent premature
labor
 It is rapidly but it is completely absorbed
(about 30%) following oral administration
and 90% is excreted in the urine as an
inactive conjugate
 About 50% of the drug is excreted
unchanged after IV administration
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-MOA: -appears to exert its vasodilator action
ISOETHARINE thru the blockade of post synaptic a1 receptors
 for bronchospastic diseases -cause reversal of pressor responses to
epinephrine and blocks pressor responses to
PRENALTEROL norepinephrine
 selective beta-1 adrenergic agonist -reduces vascular tone in both the
 it is used for chronic congestive heart failure resistance and capacitance vessels
-associated with reduction of venous return
PROPYLHEXEDRINE and cardiac output
 used as an inhaler 4. Trimazocin
-clinically related exhibits similar
pharmacologic properties to Prazosin
NAPHAZOLINE HCl -has less potent inhibition on a1 adrenergic
 used as ophthalmic and nasal solution receptors
-Half life: 2hours
TETRAHYDROZOLINE -it is extensively metabolize in the liver
 used as ophthalmic and nasal solution 5. Ergot Alkaloids
-act to a varying degree as partial agonist or
OXYMETAZOLINE antagonist at the alpha adrenergic, and
dopaminergic receptors
 nasal spray or nasal drop
-ERGOTAMINE and
ERGONOVINE/ERGOMETRINE: -produce
XYLOMETAZOLINE
coronary vasoconstriction
 nasal spray or nasal drop
-associated with schemic changes in the ECG
and anginal pain in coronary artery disease
PSEUDOEPHEDRINE,
-induce BRADYCARDIA
PHENYLPROPANOLAMINE
-USE: stimulation of uterine contraction
 used orally as nasal decongestant (postpartum) and relive migraine
ALPHA-ADRENERGIC BLOCKING AGENTS 6. Chlorpromazine
-prolongs and enhances the pressor response
PHENOXYBENZAMINE, PHENTOLAMINE to Norepinephrine
7. Haloperidol
 blocks the alpha adrenergic receptors but -inhibits dopamine induce renal vasodilation
they don’t have agonistic activity 8. Yohimbine
1. Phenoxybenzamine and Diphenhydramine -produces competitive alpha-adrenergic
-drugs that block alpha adrenergic receptors blockade but limited duration only
but don’t have alpha agonistic activity -has little direct effect on smooth muscle but it
2. Phentolamine and Tolazoline readily penetrates the CNS
-they produce moderately effective
competitive alpha-adrenergic blocking that is NON-SELECTIVE BETA BLOCKERS
relatively transient 1.Propranolol
-USE: Cardiac stimulation, Stimulation of GI 2. Alprenolol
tract (those that are block by atropine), 3. Bunolol
Stimulation of Gastric secretion, Peripheral 3. Nadolol
vasodilation 4. Oxyprenolol
-AE: Tachycardia, cardiac arrythmias, anginal 5. Penbutolol
pain 6. Pindolol
-Note: Phentolamine (more potent) 7. Sotalol
3. Prazosin 8. Timolol
-USE: -popular antiHTN agent

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P-05 AUTONOMIC NERVOUS SYSTEM
SELECTIVE B1 BLOCKERS It causes a prolonged decrease on the
1. Metoprolol catecholamine content of the heart due to the
2. Atenolol destruction of sympathetic nerve endings. Most
3. Acebutolol peripheral sympathetic nerves are affected by
4. Bevandolol the drug. The Adrenal Medulla and the
5. Tolamolol Peripheral Cholinergic Neurons are not affected
6. Bisoprolol by this drug.
7. Esmolol
8. Betaxolol Ganglionic Stimulant Drugs:
- Nicotine
CENTRALLY ACTING - Tetramethyl Ammonium
1. Clonidine - Dimethylphenylpiperazine
2. Methyldopa
They are considered ganglionic stimulant drugs.
Adrenergic Neuron Blocking agent Stimulation of the ganglia by these drugs differs
1. Guanetidine from that produced by nicotine in that the initial
2. Guanadrel stimulation is not followed by a blocking action.
3. Betamidine While in that of nicotine the stimulation is
4. Bretylium followed a blocking action.
5. Debrisoquine
6. Reserpine Stimulation caused by Nicotine stimulates
markedly the Central Nervous System and the
Specific Inhibitors of Cathecolamine Cardiovascular System. It increases the heart
Synthesis rate and blood pressure.

1. Metyrosine GIT: It increases the tone and motor activity of

-competetive inhibitor of tyrosine hydroxylase the bowel.
that catalyzes synthesis of
dihydroxyphenylalanine which wil result in Exocrine Gland: Initial stimulation of the salivary
reduction in the synthesis of Noepinephrine and and bronchial secretion followed by inhibition.
Dopamine both in the PNS and CNS
Nicotine is readily absorbed in the respiratory
Tyrosine Hydroxylase - the enzyme that tract, on the buccal mucous membrane and on
catalyses the synthesis of the skin.
Dihydroxyphenylalanine from Tyrosine.
Approximately 80-90% of Nicotine is altered in
Inhibition of Tyrosine Hydroxylase will result in the body mainly in the liver but also in the
the reduction in the synthesis of Norepinephrine kidneys and in the lungs.
and Dopamine both in the peripheral and
central nervous system. Major Metabolite of Nicotine:
1. Cotinine – different from
Monoamine Oxidase Inhibitors 2. Nicotine N-Oxide
1. Phenelzine
2. Isocarboxazine Ganglion Blocking Drugs:
3. Tranylcypromine - Hexamethonium
- Mecamylamine
Drugs that destroy the Adrenergic Nerve - Trimethophan
Fibers: - Pentolinium
- 6-Hydroxydopamine
In the Cardiovascular System they cause
postural hypotension, sympathetically mediated

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P-05 AUTONOMIC NERVOUS SYSTEM
vasomotor reflexes are inhibited, and the cold
pressor response is reduced.

They cause mild tachycardia that usually

accompany the hypotension. Cardiac output is
also reduced as a result of diminished venous
return due to venous dilatation and peripheral
pooling of blood.

In hypertensive patients, the cardiac output,

stroke volume and left ventricular work are all
diminished so the total systemic vascular
resistance is decreased by these ganglionic
blockers but the blood flow and the vascular
resistance of the individual vascular beds are
variable.

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