AUTONOMIC NERVOUS SYSTEM

 Governs all the whole body

Nervous System  Enteric (Aurbach and Meissener’s)

Anatomical Two subsystem:
 Central Nervous system- only involves
brain and spinal cord
 Peripheral Nervous system- anything
other neurons or nerve cells aside brain and
spinal cord; outside the central
Physiologic divisions:
 Efferent (motor)
- All the neuron who branch outside
the central; coming from the brain or
direction toward the periphery
Two branch:
Autonomic Nervous system
 Sympathetic
 Parasympathetic
Somatic Nervous system
 Afferent (sensory)
-Toward the brain
Example: One person slaps you and it you feel the
pain so there will be an afferent sensory that will
signal the brain (ay nasampal ka) and the brain will
react to slap him/her too so signal coming from the
brain to your hand and that is efferent.
Sympathetic Nervous System
 Under fight or flight such as adrenaline rush
 Masturbation and once semen is out
Parasympathetic Nervous System
 Rest or digest
 Masturbation but still under erection

DIFFERENCES BETWEEN THE SOMATIC AND AUTONOMIC NERVOUS SYSTEM

SNS ANS
Anatomy 1 neuron set-up 2 neuron set-up Ganglion -------- collection of neuron’s cell bodies located
(From NS, the outside the CNS (an exclusive feature of ANS)
signal will notify (Brain or spinal cord receive the signal---axon-releases signal-receive by
the organ using 1 dendrites---axon---release and stimulate)
neuron set-up;
Dendrites---axon Ganglion/Ganglia – Junction
—then release
and stimulate the Preganglionic: before ganglion; nearer to NS
Skeletal muscle)
Postganglionic: After the ganglion; nearer to effector organ
Myelin sheath is
heavier (heavily Myelin sheath is lighter (light myelinated)
myelinated)
Neurotransmitter:
Preganglionic
(acetylcholine-all Ganglion)

Postganglionic (epinephrine and acetylcholine)

Function Voluntary Involuntary Movement

Movement Ex. Ex. Heartbeat, Contraction of the e blood vessels, sweat glands
Contraction of the
Skeletal Muscle

Neurons Myelin Sheath

 Dendrites receive the signal-- nucleus to  It helps to speed-up the transmission of

process information—nucleus will fire a
signal—then it will go to the axon –lalabas
sa axon terminal---then lalabas ulit and
receive again by other dendrites
signal (it makes the signal jump)
 Clinical correlation: Multiple Sclerosis
(inability to create myelin sheath); Vitamins
(Fish oil rich in Docosahexaenoic acid
(DHA), Vitamin B complex high dose)

PARASYMPATHETIC AND SYMPATHETIC

 Special ganglia: Adrenal Medulla (located in

kidney)
Parasympathetic
 Neurotransmitter of Adrenal medulla:
 longer preganglionic and shorter Epinephrine or Adrenaline (have presence
postganglionic of CH3 (methyl group) which have faster
effect); Norepinephrine or Noradrenaline
Sympathetic
Similarities:
 Shorter preganglionic and longer
postganglionic  Both of them do not possess myelin sheath
in the postganglionic axon but preganglionic
is myelinated.
Synaptic Neurotransmission

 Transmission of neural impulses

Pre-synapse----Synaptic cleft----Post-synapse

Explanation:

 First neuron sends a signal to the receiving neuron or second neuron which is called ganglion or
synapse, after that signal will be receive by receiving neuron.

 Neurotransmitter is contained in vesicle which releases the acetylcholine (neurotransmitter) then

second neuron have a receptor where acetylcholine will bind then receptor response or action will take
place
 Parts of the spine Origin Receptors Neurotransmitter

Cranial (Cervical) Parasympathetic N, M Acetylcholine

Sacral Parasympathetic N, M Acetylcholine

Thoracic Sympathetic A, B, D Catecholamines
Lumbar Sympathetic A, B, D Catecholamines

Summarize:

Sympathetic Parasympathetic
Location of neuronal Thoracic & lumbar nerves Cranial (III, VII, IX, X) and sacral (2-4)
exit from CNS (T1-L3) nerves
(roots; source of the
nerves)
Preganglionic axon Short, myelinated Long, myelinated Terminate at ganglia
Terminate at ganglia within or near target organ
(sympathetic chain)
Postganglionic axon Long, unmyelinated Short, unmyelinated
Ratio of pre to 1:15 (diffuse outflow) 1:1 (decrease outflow)
postganglionic fibers

Synaptic
neurotransmitter
• Between pre & Acetylcholine
postganglionic
neurons Acetylcholine
•At neuroeffector Norepinephrine
junction

Exception from rule:

1. If you are parasympathetic, your neurotransmitter postganglionic is acetylcholine
2. If you are sympathetic, your neurotransmitter postganglionic is epinephrine, Norepinephrine, and dopamine.
But sweat gland is an exception wherein its post ganglionic neurotransmitter is acetylcholine but classified as
sympathetic.

Receptor Location Mechanism Major Functions

M1 Nerve endings Gq-coupled ↑ IP3, DAG cascade
(Muscarinic)
M2 Heart, some nerve GI--coupled ↓ cAMP, activates K+
endings channels
M3 Effector cells: Gq -coupled ↑ IP3, DAG cascade
smooth muscle,
glands, endothelium
NN ANS ganglia Na+-K+ ion channel Depolarizes, evokes
(Nicotinic Neural) action potential
NM Neuromuscular end Na+-K+ ion channel Depolarizes, evokes
(Nicotinic Muscular) plate action potential

Receptor Location G Protein Second Messenger Major Functions

2+,
Alpha, (a,) Effector tissues: Ga T IP3, DAG ↑ Ca , causes contraction,
smooth muscle, secretion
glands
Alpha2 (a2) Nerve endings, G cAMP ↑ Transmitter release
some smooth (nerves), causes contraction
muscle (muscle)
Beta, (B,) Cardiac muscle, G, T cAMP ↑ Heart rate, ↑ force; ↑ renin
juxtaglomerular release
apparatus
Beta2 (B2) Smooth muscle, G, T cAMP Relax smooth muscle; ↑
liver, heart glycogenolysis; ↑ heart rate,
force
Beta, (B2) Adipose cells G, T cAMP ↑ Lipolysis
Dopamine, Smooth muscle G, T cAMP Relax renal vascular smooth
(D2) muscle

Sympathetic Nervous System Parasympathetic Nervous System

Eye
 Pupils Dilation Constricts
 Ciliary Muscles (Far Vision) (Near Vision)
Bronchial Smooth Muscles Bronchodilation Bronchoconstriction
Heart (+) Inotropic (-) Inotropic
(+) Chronotropic (-) Chronotropic
GIT
 Sphincters Closed Opened
 Intestinal Wall Muscles ↓ Motility ↑ Motility
 Secretions ↓ ↑

Loparamide (antiparasympathetic Diarrhea

or anticholinergic)
Bladder
 Sphincter Closed Opened
 Wall Muscles Relaxed Contraction
Male Genitalia Ejaculation Erection
Uterus Relaxation Contraction
Salivary Glands Thick, viscid secretion Copious, watery secretion
Lacrimal Glands Secretion
Skin
 Pilimotor Smooth Muscles Contraction
 Sweat Glands ↑ Sweating
Skeletal Muscles Relaxation Contraction
Metabolic Functions
 Liver Gluconeogenesis
Glycogenolysis
 Fat Cells Lipolysis
 Kidneys Renin Release

Blood sugar is increase

Gluconeogenesis (Creation of
Glucose coming from non-
 carbohydrates)

Glycogenolysis (breakdown of
glycogen to convert to glucose
therefore glucose level is
increased)

Lipolysis (breakdown of fat)

SYMPATHETIC NERVOUS SYSTEM

Three aromatic amino acid (PTT):
 Phenylalanine
 Tryptophan (with indole ring)
 Tyrosine (aromatic and alcoholic because of
presence benzene ring and OH on its
structure)
TYROSINE (precursor of Catecholamine)
Hydroxylase and it will further have converted to
Dopamine by DOPA Decarboxylase. After that,
dopamine will now enter in the vesicle and will
abruptly convert to norepinephrine by Dopamine
Hydroxylase.
Note: Vesicle is needed so that it can be fused with
cell membrane then release norepinephrine in the
bloodstream.

 SEND (Serotonin, Epinephrine,

Norepinephrine, Dopamine) Norepinephrine fate to:
 END (Tyrosine) 1. Bind to receptor of adrenoreceptor (Alpha, Beta,
 Serotonin (Tryptophan) Dopamine)
2. Convert to Epinephrine (PNMAT- Phenylalanin-
Pathway to create Epinephrine: n-methyltransferase)

Tyrosine will enter the nerve cell (cytoplasm) and 3. Reuptake or it will back to the cell maybe
then it will have converted into DOPA by tyrosine because of excess.
(Note: Norepinephrine cannot have diffused right
away with cell membrane so it needs a vehicle
called norepinephrine transporter.
4. Metabolize or destroy
 MAO (Monoamine Oxidase)
 COMT (Catechol-O-metyltransferase)
Summary:
Step 1. Uptake of tyrosine
Step 2. Tyrosine à DOPA (hydroxylation)
Step 3. DOPA à Dopamine (decarboxylation)
Step 4. Transport of Dopamine into vesicles.
Step 5. Dopamine à Norepinephrine (hydroxylation)
In the adrenal medulla…
Step 6. Norepinephrine à Epinephrine (methylation)
Receptors of sympathetic nervous system
 Alpha 1
-present in blood vessel (smoot muscle)
means when one neurotransmitter binds to
it either epinephrine or norepinephrine, the
blood vessels will vasoconstrict.
-Post-junctional Nerve terminal
-GI relaxation
-mydriasis (dilated pupil)
 Alpha 2
-Prejunctional Nerve Terminal
-there is an inhibition of release of
norepinephrine which should not be done
because it must promote it.
Note: The difference between Alpha from Beta
receptor is distinguish by their interaction. Example,

 Beta 1
-Positive inotropism (force of constraction
After release of Norepinephrine…
or malakas ang tibong nang puso)
1. Bind to receptors to elicit response -Positive Chronotropy (Rate of
constraction or mabilis ang tibok nang puso)
2. Removed by the following mechanisms:
a) reuptake  Beta 2
b) diffusion into body fluids and blood -salbutanol (to loosen the breath)
c) destruction by certain enzymes (monoamine
oxidase, COMT)

ALPHA1 ALPHA2 BETA1 BETA2

All blood vessels Presynaptic Heart Blood vessels (pulmonary,
 vasoconstriction  reduce  increase rate coronary)
 increase TPR release  increase force  vasodilation
of contraction
Mucosa CNS  increase Bronchial muscle
 decongestion  reduce velocity of  bronchodilation
sympathetic conduction
Eye outflow Uterus
radial muscle, iris  relaxation
 mydriasis
DA receptor BETA3 Hyperglycemia
Skin Splanchnic area Adipose tissue Lactic acidemia
 contraction of pilomotor  vasodilation  thermogenesi
muscles s
 lipolysis
Hyperglycemia

Note: decrease heart rate (beta blocker)

Type Tissue Actions

A1 Most vascular smooth muscle Contraction
(innervated)
Pupillary dilator muscle Contraction (dilates pupil)
Pilomotor smooth muscle Erects hair
Prostate Contraction
Heart Increases force of contraction
A2 Postsynaptic CNS neurons Probably multiple
Platelets Aggregation
 Adrenergic and cholinergic nerve Inhibits transmitter release
terminals
Some vascular smooth muscle Contraction
Fat cells Inhibits lipolysis
B1 Heart, juxtaglomerular cells Increases force and rate of contraction; increases
renin release
B2 Respiratory, uterine, and vascular Promotes smooth muscle relaxation
smooth muscle
Skeletal muscle Promotes potassium uptake
Human liver Activates glycogenolysis
B3 Bladder Relaxes detrusor muscle
Fat cells Activates lipolysis
D1 Smooth muscle Dilates renal blood vessels
D2 Nerve endings Modulates transmitter release

Among the three, epinephrine binds to alpha receptors the most

Isoproterenol has the highest affinity

Alpha-1 Receptors
Location:

 Blood Vessels
 Eyes
 Piloerector Muscles
 Urinary Bladder
Alpha-2 Receptors
Location:

 Presynaptic
 Post-synaptic
Beta-1 Receptors
Location:

 Heart
 Kidney (There will be renin secretion which
regulates blood pressure if one person is A.A.1. Non-selective direct-acting agonist
hypotensive) • Epinephrine (a1=a2, B1=B2)
 First line cardiac Stimulant where it is
Beta-2 Receptors used for cardia life support
Location:  First line agent in Anaphylactic shock
 Vasoconstrictor or Adjunct drug to
 Lungs Lidocaine or Local doses anesthesia
 Uterus  Epinephrine at low doses though beta
 Potassium Level (deacrese-hypokalamia) receptor it causes vasodilation
Dopamine Receptors  Epinephrine at high doses through alpha
receptor, it causes vasoconstriction
Location:  It promotes glycogenolysis through beta
2 receptor (lysis of ponomer to become
 D1 → Increased Urination
monomer)
 D2-D4 → Nausea, Vomiting due to loss of
 It also promotes lipolysis
peristalsis Stomach Distention
• Norepinephrine (a1 > a2, B1 > B2)
Sympathetic Nervous System  First line agent for septic shock
• Dopamine (Kidney Disease)
• Agonist (Sympathomimetics; adrenergic)
 Also a drug for a shock
• Antagonist (Sympatholytic Anti-andrenergic)
 At low doses stimulate the heart
 At high doses causes vasoconstriction
 Disadvantage: Dopamine is the fastest
to metabolize or destroy MAO and
A. Sympathetic Agonist
COMT
• Isoproterenol (Partially)
 Just classified as non-selective

A.A. Direct Acting

A.A.2. Selective direct-acting agonist  Used in CHF (does not significantly
increase oxygen demand in the
• Selective to a1 receptors
myocardium)
• Phenylephrine
 AE = used with caution in AF because it
 Binds primarily to alpha but favors increases
alpha-1
 Vasoconstrictor but has no effect on the Selective to B2 receptors
heart
• LABA
 Often used topically and ophthalmic
solutions for mydriasis  Formoterol
 Used as nasal decongestants  Bambuterol
 Large doses can cause hypertensive  Salmeterol
headaches and cardiac irregularities
• Oxymetazoline • SABA
• Tetrahydrozoline  Salbutamol
• Propylhexedrine  Terbutaline
• Methoxamine
 Binds primarily to alpha but favors Albuterol (Salbutamol), pirbuterol and
alpha-1 terbutaline
 Raises BP by vasoconstriction  Short acting β2 agonists used as
 Used to relieve attacks of paroxysmal bronchodilators
supraventricular tachycardia  Adm inistered by a m etered-dose
 Overcome hypotension during surgery inhaler
involving  Produce equivalent bronchodilation
 Halothane anesthetics and less cardiac action
 AE= hypertensive headaches and
Salmeterol and formoterol
vomiting
 β2 selctive agonists, long-acting
bronchodilators
 Lasts for twelve hours

Selective to a2 receptors

• Clonidine --> DOC for Hypertensive Urgency, A.B.1. Indirect-acting

Antihypertensive for Dialysis Patients, Adjunct
in ADHD MOA
 Alpha-2 agonist used in essential HTN
 Release norepinephrine
 Can be used to minimize withdrawal
 Inhibit re-uptake of norepinephrine
symptoms from opiates or
benzodiazepines Amphetamine, Tyramine, Epehdrine -->
 Acts centrally to inhibit sympathetic Stimulates Release of NE
vasomotor centers
• Methyldopa Cocaine, TCA (Imipramine), Duloxetine, and
Venlafaxine --> Inhibits re-uptake of NE
 Methyldopa “false neurotransmitter”,
DOC for gestational hypertension
(Methyldopa, Hydralazine, Labetalol,
Nifedipine)
 Adverse Effect: Hepatotoxicity
 False (+) Coom’bs Test (Test for
hymolytic anemia)
Selective to B1 receptors
• Dobutamine

 DOC for Cardiogenic Shock

 Increases cardiac rate and output •
 • Phenmetrazine

ADHD - methylphenidate (DOC), amphetamine

ANOREXIA-Phentermine, Phenmetrazine à Dec
Appetite
AE-Addiction (Amphetamine), Primary Pulmonary
Hypertension

A.C.1. Centrally Acting

• Phenylpropanolamine
• Methylphenidate
• Amphetamine
• Phentermine

Drug Receptor Clinical Use

Epinephrine Direct: a1=a2; b1=b2 Anaphylaxis
(Adrenaline) Cardiac arrest
Adjuvant to local anesthesia
Norepinephrine Direct: a1=a2; b1>>b2 Hypotension
(Noradrenaline)
Isoproterenol Direct b1=b2 CHF
Dopamine Direct: D1=D2>b1>>a Shock
Dobutamine Direct: b1>b2 Shock CHF

Drug Receptor Clinical Use

Phenylephrine Direct a1>a2 Ocular redness
Mydriasis
Tetrahydrozoline Direct: a1>a2 Ocular redness
Naphazoline
Methoxamine Direct: a1>a2 Adjuvant to general
anesthesia
Clonidine Direct: a2>a1 Hypertension
Metaproterenol Direct: B2>>B1 Asthma
Albuterol Labor (Terbutaline)
Terbutaline
Ritodrine Direct: B2 >> B1 Premature labor

Drug Receptor Clinical Use

Tyramine Indirect
Amphetamine Indirect ADHD
Metamphetamine Narcolepsy
Weight reduction
TCA's Indirect Clinical depression
Cocaine Indirect Mucosal anesthetic &
 vasoconstrictor
Ephedrine Mixed: direct on a1, B2, Hypotension secondary to
and indirect spinal anesthesia
PPA Mixed: direct on a.1. 81, Weight reduction
B2, and indirect

B. SYMPATHETIC ANTAGONIST Alpha blockers (1;2)

 We are blocking the sympathetic nervous
system actions
Examples: Blood vessels are constricting if it is under
sympathetic nervous system, and if we antagonize the
sympathetic action of epinephrine, norepinephrine to
that blood vessels what would be the resulting action?
Answer: Vasodilation
Note: This blockers or antagonist will block or reverse
the original action of sympathetic or adrenergic or
noradrenergic system.
B.A. Alpha blockers (1;2)
 Selective (specific)
 Non-selective
 Non-selective- anywhere between the two, I
can block or bind the effects.
 Selective- it can choose who will it block
Beta Blockers (1;2;3)
 Non-selective- any of the three I can bind or
antagonize the effect.
 Selective-there are only one beta receptors
subtype I can bind and antagonize its effect.
B.A.1.Non-selective Alpha Blockers
 Phenoxybenzamine
 it is irreversible
 Example: When the drugs binds to
receptor and it does not loosen up
again so the effects are permanent
therefore it is irreversible
 It is also non-competitive
 Allosteric binding site- it can bind aside
from the active site

 Phentolamine
B.B.Beta Blockers (1;2;3)
 It is reversible
 Non-selective  It is competitive (will take precedence
 Selective over the active site)
 ISA
B.A.2. Selective Alpha Blockers
 MSA
 Mixed Note: all who have the word “sin” in their last syllable is
under Selective Alpha Blockers
  Alpha-1 Blockers Nadolol Nebivolol
 Prozosin, Doxazosin, Terazosin, Sotalol Bisoprolol
Alfuzosin, Tamsulosin Timolol Betaxolol
 Indication: In actual setting, it is first Propranolol Esmosol
line in the treatment of patient with Pindolol Acebutolol
benign prostatic hyperplasia (BPH) or Atenolol
the enlargement of prostate gland of Metoprolol
males. (Tamsulosin for treatment)
 Alpha-2 Blockers Note:
 Yohimbine and Rauwolscine
 It is still under research they have  Beta-1
started with human effects those two.  One heart
 Action in the heart: When it is agonized there
ALPHA BLOCKERS USES will increase force and rate of the heart
 Pheochromocytoma  Beta-2
 Adrenal medulla has a tumor and  Two lungs
means there is abnormal firing of  Action in the lungs: When it is agonized, there
epinephrine. It means there will will be Bronchodilation
hypersecretion of epinephrine and  Non-Selective
therefore there is abundant  Beta 1 & 2
epinephrine in the blood and it will  Can block heart and lungs
readily bind to receptors.  Selective
 Question: What will happen to blood  Only Beta-1
vessels? There will be vasoconstriction  Can only block actions in the heart
 Alpha-1 (vasoconstriction)  Propranolol
 Beta-1 ( +Inotropy and +Chonotropy)  Brand name: Inderal
 If you have Pheochromocytoma, there  Drug of choice for stage fright (it blocks the
will be sympathetic storm. action of beta-1 which the increase rate of the
 Alpha blockers which block Alpha-1 and heart)
there will be vasodilation.
 Reynaud’s Syndrome
 Decrease blood supply to the tip of the Example: Asthma attack (The patient is already assessed
fingers and the best medicine is beta blockers)
 No blood supply, no delivery of oxygen Question: What will you choose, non-selective or
 Why blood cannot flow? Because there selective?
is vasoconstriction
 If alpha blockers are effective, it will Answer: Selective beta -1 addresses the increased rate
block the alpha-1 or the of the heart. But if you choose non-selective where if
vasoconstrictive effects of alpha-1. the beta-2 is blocked, there will be bronchoconstriction
Therefore, there will be deliverance of which is not appropriate for the asthmatic episode
blood and supply of oxygen. because it may stimulate the asthma of the patient. So,
 Hypertension and Urinary Retention in BPH therefore, we resort to Selective beta-1 blockers
 Erectile Dysfunction because there will be no effect on the lungs.
 There is no blood flow in the penis Intrinsic Membrane Stabilizing
 Alpha blockers will help to block the Sympathomimetic Activity
vasoconstriction as this is the reason Activity
why blood cannot flow to the penis. If Carteolol Propranolol
we use alpha blockers, it will block Labetalol Pindolol
again the effect of alpha-1 which is Acebutalol Acebutolol
vasoconstriction therefore will now Pindolol Labetalol
provide now a vasodilation. Metaprolol
 Carcinoid Syndrome

BETA BLOCKERS Note:

Non-Selective Selective  Intrinsic Sympathomimetic Activity

  They are beta blockers but they can cause
sympathetic activity or effects.
 Membrane Stabilizing Activity
 They possess local anesthetic activity or
stabilize the membrane if only if the dose of this
beta blockers exceeded the therapeutic level.

BETA BLOCKERS USES

 Hypertension
 Angina Pectoris (Chest pain; radiating to your left
arm)
 Stable Heart Failure
 Arrhythmia (abnormal rhythm of the heart)
 Glaucoma
 Sympathetic Symptoms of Hyperthyroidism
(exophthalmos, increase rate and force of heart)
 Stage Fright Note:
SIDE EFFECTS OF BETA BLOCKERS  The precursor of Acetylcholine (the end product)
is Acetyl-CoA and Choline.
 Bradycardia (slow heart rate due to overdose of
beta blockers) STEPS:
 Can mass Hypoglycemic Effect
1. Acetylcholine is already inside of the neuron or
RESTRICTION OF TAKING BETAL BLOCKERS nerve cell and Choline comes from the blood.
2. When Choline enters, the neuron will bind directly
 If patients heart or pulse rate is less than 60
to Acetyl-CoA.
bpm.
3. Acetyl-CoA through the enzyme Choline acetyl
 If you have reduce exercise tolerance (you get
transferase (ChAT), It will now transform into
tired easily)
acetylcholine.
B. PARASYMPATHETIC NERVOUS SYSTEM 4. Then, acetylcholine will be stored in the vesicle
and then it will have fused with cell membrane of
OVERVIEW the neuron and release acetylcholine in the
 Drugs affecting Autonomic Nervous System synapse.
 Cholinergic Drugs 5. What will happen to Acetylcholine?
 Adrenergic Drugs  It can bind to receptors (cholinoceptor)
and there will be parasympathetic effect
THE CHOLINERGIC DRUGS  If it is not bind to receptor, there will be
degradation or metabolize or destroy.
 Neurotransmitter: Acetylcholine (Ach)
Under parasympathetic nervous system,
THE CHOLINERGIC NEURON the one enzyme that degrades or
metabolize acetylcholine is
 Steps of neurotransmission
acetylcholinesterase.
1. Synthesis of Acetylcholine
2. Storage of Acetylcholine in vesicles
 Hemicholinium
3. Release of Acetylcholine
 Prevents the entry of choline to the
4. Binding to receptors
neuron
5. Degradation of Acetylcholine
 Vesamichol
6. Recycling of Choline
 Prevents or block the storage of choline in
the vesicles
 Botulinum
 Prevents the release of acetylcholine

What is parasympathetic action of skeletal muscle?

 Answer: Contraction (if there are many

acetylcholine that binds to receptor, possibly
there will be contraction of skeletal muscle)
  Botolinum toxin MUSCARINIC
 Botox or this used for wrinkles Type Tissue Response
 Mechanism action: It prevents or M1 Autonomic ganglia Depolarization(excitatory
inhibited the release of acetylcholine and postsynaptic potential)
then if inhibited, there will no
acetylcholine that will bind in the M2 Heart Dec. HR, contractility and
receptors and when there is no conduction
acetylcholine in the receptors, there will
M3 Circular & ciliary Contraction (miosis) and
be no contractions and there is relaxation.
muscles of the eye dec. accommodation
GI smooth muscle Contraction (inc.motility
and tone)
Urinary bladder Contraction (micturition)
smooth muscle
GI and GU Relaxation
Sphincters
Bronchlolar smooth Contraction
muscles (bronchoconstriction)
Secretory glands Increased secretion

CHOLINORECEPTORS

 Two (2) Families

 Muscarinic Receptor
 Nicotinic Receptor

NICOTINICS
Type Tissue Response
NM Muscle Contraction of
(Neuromuscular skeletal muscle
junction)

NN Neuronal Depolarization and

firing of
postganglionic
neuron
Autonomic
Ganglia

Adrenal Medulla Secretion of

catecholamine

Difference between Nicotinic Muscular and Nicotinic

Neural

 Nicotinic Muscular
 It is between neuromuscular junction
 Nicotinic Neural
 It neuronal because it is between
neuron
ANS DRUGS
Enhance neurotransmission
• Receptor agonists
• Agents that induce neurotransmitter release
• Drugs that prevent neurotransmitter
degradation
Suppress neurotransmission
• Presynaptic nerve blockers
• Receptor antagonists
• Ganglion blockers
CHOLINERGIC AGONISTS
Direct Acting Agonist
• Acetylcholine
• Bethanecol
Indirect Acting Agonist (reversible)
• Edrophonium
• Neostigmine
Indirect Acting Agonist (irreversible)
• Physostigmine
• Pyridostigmine
• Echothiophate
• Isoflurophate
Reactivates Acetylcholinesterase
• Pralidoxime
A. PARASYMPATHETIC AGONIST

A.A.Direct-acting

 Choline Esters
 Alkaloids

A.B. Indirect Acting

 Reversible
 Irreversible

Note:
Direct acting
 They bind directly to the receptor (muscarinic &
nicotinic receptors)
Indirect Acting
  It has this mechanism aside from interacting
directly to the receptors
A.A.1. CHOLINE ESTERS (DIRECT ACTING)
• Carbachol
 Used for Glaucoma
• Acetylcholine
 Possesses and can stimulate both
muscarinic and nicotinic activity
 Major neurotransmitter of
parasympathetic nervous system
 Disadvantage: It cannot penetrate
membranes (It means it needs vesicle in it
synthesis in order to release the
acetylcholine)
• Metacholine
• Betanechol
 Used for urinary retention
ACETYLCHOLINE
• Decrease in heart rate and cardiac output
 Vagal stimulation
 Question: On what mechanism does
acetylcholine makes the heart decrease in
rate and also decreases cardiac output?
 Answer: Vagal stimulation
 Therefore, (BP=CO x TPR) Blood
pressure = cardiac output x total
peripheral resistance (This formula can be
interpreted: ↑CO=↑BP ; ↓CO=↓BP
(Direct relationship)
• Decrease in blood pressure
 Vasodilation
 ↓CO + Vasodilation (work together to
give you significant drug is blood
pressure)
• GIT
 Increases salivary secretion (naglalaway)
 Stimulates salivary secretions and motility
 Question: What happen to the wall of GIT
during parasympathetic stimulation?
Contraction
 How about Sphincter? Open
• Bronchioles
 Stimulates bronchiolar secretion
 An individual can have mucus
• Genitourinary Tract
 The tone of the detrusor urinae muscle is
increased (Therefore there is contraction
of bladder and cause urination)
• Eye
 Miosis – constriction of the pupil
BETANECHOL
• Structurally related to Ach
 But they are little bit difference to their
attachment
• Acetate is replaced by Carbamate; Choline is
methylated
 How I will make this acetylcholine as
Betanechol?
 Answer: (1) Replaced CH3COO- (Acetate)
with Carbamate. ; (2) Methylate the
choline or put an attachment of methyl
(CH3)
 What is the advantage of replacing acetyl
with carbamate and attaching methyl to
the choline? Why it is needed to do?
 Answer: Acetylcholine has a problem
(sobra siyang namemetabolize
acetylcholinesterase, so therefore even if
you inject acetylcholine, it will be
worthless because it is readily
metabolized or degraded siya ni
acetylcholinesterase)
• Therefore, it is not hydrolyzed by
Acetylcholinesterase
• Muscarinic (M3+); Nicotinic (-)
• Duration of action – 1 hour
• Actions:
 Increased intestinal motility and tone
 Causes expulsion of urine
• Therapeutic Applications
 Urologic treatment
 Used to stimulate the atonic bladder
 Postpartum or post-operative non-
obstructive urinary retention
• Adverse Effects
 Cholinergic stimulation
 Sweating
 Salivation
 Flushing (Due to vasodilation)
 Decreased BP
 Nausea
 Abdominal pain
 Diarrhea
 Bronchospasm
CARBACHOL
• Muscarinic (+); Nicotinic (+)
• Ester of carbamic acid
• Actions
 Can cause the release of Epinephrine (Nn)
 Question: It parasympathetic but why it does
support the release of epinephrine? The
 action of nicotinic neural which can cause • Cevimeline
release of epinephrine  M receptors; tx of xerostomia associated with
 It is instilled into the eye causing miosis Sjogren’s syndrome

CONTRAINDICATION
• Therapeutic uses • Asthma
 It is rarely used therapeutically  Increase bronchial constriction & secretions
 Miotic agent • Hyperthyroidism
• Adverse Effect: Little or No SE
• Coronary insufficiency
A.A.2. ALKALOIDS (DIRECT ACTING)
 Stimulation of M receptors in coronary
 Nicotinic arteries à vasoconstriction
 Nicotine • Peptic ulcer disease
 Lobeline Smoking deterrent for smoking cessation
SIDE EFFECTS
 Varenicline
Muscarinic poisoning = Parasympathetic overdrive
Note: How do we address if you want to stop smoking?
Administer a nicotine but the problem is, it was smoke. So • Salivation & lacrimation
we had tartar and benzopyrene (both are carcinogenic • Nausea and vomiting
components of cigarette where benzopyrene can cause a • Headache and visual disturbances
mutation to the lungs and other cells which can cause • Bronchospasm
malignant tumor or cancer) • Bradycardia and hypotension
 Muscarinic • Shock
 Muscarine • Diarrhea These symptoms are reversed with the
 Pilocarpine (Botanical source: Jaborandi; • Urination administration of ATROPINE.

DOC for glaucoma)

PILOCARPINE A.B.1. REVERSIBLE

• Muscarinic (+) • Physostigmine

• Primarily used in ophthalmology for glaucoma
• Actions
 Produces rapid miosis and contraction of the
ciliary muscle
 One of the most potent stimulators of
secretions but it is not used for this purpose
OTHER AGENTS
Arrow poison & atropine poison
• Neostigmine
• Edrophonium
 Used in Diagnosis of Mysathenia gravis
• Demecarium
• Rivastigmine
• Tacrine
• Donepezil
• Galantamine
 Alzheimer’s Disease
Note: Why it changes from Physostigmine to
Neostigmine? Physostigmine is lipid soluble and
Neostigmine is water soluble. Like vitamins, if it is Lipid
soluble, the more time it takes to stay in the body while if
it water soluble, it will be excreted immediately. So if
Physostigmine is the DOC, it will stay in body for a long
time which cause parasympathetic effects such as
salivation, sweating, diarrhea, urination, and all that can
be uncomfortable to the patient. On the other hand, using
Neostigmine which have effect just like Physostigmine but
It can have excreted immediately therefore there will be
no pronounced parasympathetic effects

• Muscarine PHYSOSTIGMINE
 M; more of a toxic substance; from Amanita • Therapeutic uses
phalloides  Glaucoma
  Antidote for overdoses with anticholinergics • Short duration of action – 10-20 minutes
(Atropine, Phenothiazines, TCADs) • Used in the diagnosis of Myasthenia gravis
• Adverse Effects • Excess drug may provoke cholinergic crisis
 Convulsions • Antidote: Atropine
 Bradycardia • (Tensilon®, Enlon ®)
 Paralysis of the skeletal muscle • A cholinergic crisis is an over-stimulation at a
neuromuscular junction due to an excess of
NEOSTIGMINE
acetylcholine (ACh), as of a result of the inactivity
• It is more polar than Physostigmine, (perhaps even inhibition) of the AChE enzyme,
therefore it does not enter the CNS which normally breaks down acetylcholine.
• Duration of Action: 2-4 hours
• Used to stimulate bladder and GIT
• Antidote for Tubocurarine and other
competitive neuromuscular blocking
agent
• Used in the symptomatic treatment of
Myasthenia gravis
 Auto-immune disorder
 Caused by Ab to the nicotinic
receptor that bind to the ACh A.B.2. IRREVERSIBLE
receptors of neuromuscular junctions
• Organophospahtes
 This results to the degradation of the
• Parathion and Malathion (Spray for plants such
receptors
as corn, mango, rice field, bubula rin and
• Adverse effects
maguurinate sila once na inhaled)
 Cholinergic stimulation
• Tabun, Sarin, Soman (gas warfare’s where once
you inhaled this, bubula at maguurinate ka)
Note: Accident na nalanghap (within 24-48 hours, we
can use pralidoxime for post-exposure)

ANTICHOLINESTERASES (IRREVERSIBLE)
• Organophosphates
• Covalently binds to Acetylcholinesterase
• Long-lasting increase in Ach
ISOFLUROPHATE
• Mechanism of Action
 It covalently binds to the serine-OH at the
active site of Acetylcholinesterase
 The enzyme is permanently inactivated
• Actions
 Generalized cholinergic stimulation
 Paralysis of motor functions
 Intense miosis
• Therapeutic uses
 Ophthalmic ointment – chronic treatment of
PYRIDOSTIGMINE open-angle glaucoma (may last up to 1
week)
• Used in the chronic management of Myasthenia  Echothiophate is a newer agent
gravis • Reactivation of Acetylcholinesterase
• Duration of Action: 3-6 hours  Pralidoxime
EDROPHONIUM ORGANOPHOSPHATES (IRREVERSIBLE)
• Similar actions with Neostigmine • Echothiophate
  2nd line agent for glaucoma
• Malathion; Parathion - insecticides
• Sarin and Soman – nerve gases

B.A.1. MUSCARINIC BLOCKERS

• Atropine
• Scopolamine
• Biperiden
• Benztropine
• Trihexyphenidyl
POISONING SYMPTOMS • Cyclopentolate
• Homatropine
• D – diarrhea
• Tropicamide
• U – urination
• Ipratropium
• M – miosis
• Tiotropium
• B – bradycardia
• Oxytropium
• E – emesis; excitation
• L – lacrimation ATROPINE
• S – salivation and sweating
Question: Can Atropine cause mydriasis? YES, because
SIDE EFFECTS you block the miosis

Organ Side Effects • Belladona alkaloid (constituent plant)

Eye Miosis, loss of accommodation • It binds competitively to muscarinic receptors
CNS (if BBB Excitation, apathy, ataxia, respiratory (central and peripheral blocker)
is crossed) Depression • General actions – lasts for 4 hours (therefore the
administration is every 4 hours or 3 hours)
• Eyes – may last for days
Lungs Bronchoconstriction
• Eyes
Heart Bradycardia
GI & GU Diarrhea, involuntary micturition  Mydiasis (dilation of the pupil)
Glands Sweating, lacrimation, salivation  Unresponsiveness to light
 Cycloplegia (inability to focus for near vision)
 Increase in intraocular pressure (It can cause
B. PARASYMPATHETIC ANTAGONIST
glaucoma)
• Gastrointestinal
 Antispasmodic (one of the most potent)
 HCl production is not significantly affected
B.A. Muscarinic Blockers
 Pirenzepine – M1-muscarinic antagonist,
reduces gastric acid secretion at doses that
do not antagonize other systems
B.B. Nicotinic Receptor Blockers • Urinary System
• Non-depolarizing  Reduce hypermotility states of the urinary
• Depolarizing bladder
 Occasionally used in Enuresis in children
(involuntary voiding of the urine)
 A-adrenergic agonists are more
effective with fewer side effects
• Cardiovascular
 Low doses: decrease cardiac rate
(Bradycardia)
 High doses: cardiac rate increases modestly
(tachycardia)
  Arterial BP is unaffected but at toxic levels, • It has an unusual effect of blocking short-term
atropine will dilate the cutaneous vasculature memory
• Secretion • Scopolamine produces sedation
 Xerostomia – blocks the salivary glands to • High doses – produces excitement
produce a drying effect on the oral mucous
SCOPOLAMINE (THERAPEUTIC USES)
membranes
 Sweat and lacrimal glands are also affected • Prevention of motion sickness
 Inhibition of sweat – can cause elevation in • Blocks short-term memory
body temperature • Amnesic action is used in anesthetic procedures
ATROPINE (THERAPEUTIC USES)
• Ophthalmic IPRATROPIUM
 Topical atropine exerts mydriatic and
• Inhaled: treatment of Asthma and COPD in
cycloplegic effects
patients unable to take adrenergic agonists
 Phenylephrine: preferred for pupillary dilation
(together with salbutanol)
if cycloplegia is not required
• Used in the management of COPD
 It may induce attacks in individuals with
narrow angle glaucoma GANGLIONIC BLOCKERS
• Antispasmodic agents
• Specifically act on the nicotinic receptors
 Relaxes GIT and bladder
• Antidote for cholinergic agonists NICOTINE
 Tx of overdoses of Organosphosphates,
• Nicotine depolarizes ganglia, resulting first in
Mushroom Poisoning
stimulation of and followed by paralysis of all
• Antisecretory Agent
ganglia.
 Blocks secretions in the upper and lower
• Stimulatory Effects
respiratory tracts prior to surgery
 Increase BP
ATROPINE (PHARMACOKINETICS)  Increase cardiac rate
 Increase peristalsis
• Readily absorbed
 Increase secretions
• Partially metabolized by the liver
• At higher doses
• Eliminated primary in the urine (caution: px with
renal problems)  Decrease BP
• Half-life: 4 hours TRIMETHAPHAN
ATROPINE (ADVERSE EFFECTS) • Short-acting
• Dry mouth • Must be given by IV infusion
• Blurred vision • Used for the emergency lowering of BP (e.g.
• “Sandy eyes” Hypertension caused by Pulmonary edema or
dissecting aortic aneurysm) when other agents
• Tachycardia
cannot be used
• Constipation
• CNS: restlessness, confusion, hallucination, MECAMYLAMINE
delirium
• Duration of action: 10 hours after single
• It may exacerbate an attack of glaucoma in
administration
someone with latent conditions
• Has good oral absorption
SCOPOLAMINE
NEUROMUSCULAR BLOCKING DRUGS
• Belladona alkaloid
• Drugs that block cholinergic transmission
• It has greater action on the CNS and a longer
between motor nerve
duration of action than Atropine
• endings and the nicotinic receptors
• Note: Twilight Sleep (Component: Scopolamine &
• Structural analogs of ACh
Morphine-given to cancer patients in terminal end
 Nondepolarizing Type (Antagonists)
to ease symptoms)
 Depolarizing Type (Agonists)
SCOPOLAMINE (ACTIONS)
NONDEPOLARIZING (COMPETITIVE) BLOCKERS
• For motion sickness
 • Curare – first drug that was found capable of
blocking the skeletal neuromuscular junction
• Mechanism of action
 At low doses: They combine with Nicotinic
ATRACURIUM
receptors and prevent the binding of
Acetylcholine
 Their action can be overcome by increasing
the concentration of Ach at the synaptic gap
(Neostigmine)
 At high doses: blocks the ion channels at the
end-plate (weakens the neuromuscular
transmission)
• Therapeutic Uses
 Adjuvant drugs in anesthesia during surgery
to relax skeletal muscle
ROCURONIUM
• Pharmacokinetics
 All neuromuscular blocking agents are
administered intravenously since their uptake
via oral absorption is minimal
 Penetrate membranes very poorly
DEPOLARIZING AGENTS
 Many of the drugs are not metabolized
 Excreted unchanged in the urine and in the
bile
• Adverse Effects
 Tubocurarine may induce histamine release
and promote ganglionic blockade
 It may also lower BP
 Pancuronium: Vagolytic (increases heart
rate)
 Succinylcholine: Post-operative muscle pain,
Hyperkalemia, increased intraocular and
intragastric pressure; may trigger malignant
hyperthermia
• Drug Interactions
 Cholinesterase Inhibitors (Neostigmine,
Physostigmine, Edrophonium)
 Can overcome the actions of
nondepolarizing neuromuscular
blockers
 Halogenated HC anesthetics (Halothane)
 Enhances neuromuscular blockade
by exerting a stabilizing action at the
neuromuscular junction
 Aminoglycoside Antibiotics (Gentamycin,
Tobramycin)
 Inhibit ACh release from cholinergic
nerves by competing with Calcium
ions
 They synergize with Calcium ions,
enhancing blockade
 Calcium channel blockers
 It may increase the neuromuscular
block
MIVACURIUM
• Has a rapid recovery from blockade making it
useful for short surgical procedures
• The drug is hydrolyzed by plasma cholinesterase
• Useful in mechanical ventilation of critically ill
patients
• It is the only nondepolarizing neuromuscular
blocking drug whose dose need not be reduced
in patients with renal failure.
• Short duration of action suitable for short surgical
procedures.
• Rapid onset of action
• Useful for tracheal intubation in patients with
gastric contents
• Mechanism of action
 Succinylcholine attaches to the nicotinic
receptor and acts like ACh to depolarize the
junction
 These agents persists at high concentrations
in the synaptic cleft, remaining attached to
the receptor (stimulation) for a relatively long
time.
 Phase I: membrane depolarizes resulting in
an initial discharge which produces transient
fasciculation followed by flaccid paralysis
 Phase II: membrane repolarizes; the sodium
channel closes which causes resistance to
depolarization and a flaccid paralysis
• Actions
 Short-lasting muscle fasciculation followed by
paralysis
 Weak histamine-releasing action
• Therapeutic Uses
 Succinylcholine is useful when rapid
endotracheal intubation is required during the
induction of anesthesia
 It is also employed during electroconvulsive
shock treatment
• Pharmacokinetics
 Succinylcholine is injected by intravenous
infusion
 Brief duration of action because it is
hydrolyzed by plasma cholinesterase
• Adverse Effects
 Hyperthermia
 This is treated by rapidly cooling the
patients
 Dantrolene – blocks release of Calcium,
thus producing heat production and
relaxing muscle tone
 Apnea
 Paralysis of the diaphragm