Pharmacology- I

Course CodeNumber 201311

Prof. Dr. Abdulrahim Abu Jayyab
Basic Principles of Pharmacology
 Introduction to Pharmacology
Pharmacology: is derived from the Greek terms
• Pharmacon which means a drug or medicine and logo
which means learning, Knowledge or science.

Definition of Pharmacology: Study of the manner in

which the function of living systems is affected by
chemical agents. Other term pharmacology the effect of a
drug (chemical) on the body (living system).
Drug is derived from the French word Drogue which means
dry herb.
Pharmacotherapy: term very close to Pharmacology and in
fact practical application of Pharmacology
- causal (it is possible to treat the cause of disease:
antimicrobial therapy, substitution of some enzymes,
hormones ..)
Pharmacodynamics : mechanisms of the
effects of drug on the body which deal with
1. Actions
2. Mechanism of action
3. Uses
4. Dose
5. Frequently of administration
6. Side effects
7. Contraindications
•Pharmacokinetics: the way the body
affects the drug during (with) time
(absorption, distribution, metabolism,
excretion) that means it deals with
1.Route of administration
2.Absorption
3.Distribution (2,3,4,5) ADME
4.Metabolism
5.Elimination
6.Excretion
General pharmacology: describes
general actions which determine the
action and activity of a drug
Special pharmacology: description of
individual drugs and therapeutic groups of
drugs - Molecular pharmacology concerns
with the effects of drugs from the point of
view of their molecular action
- Pharmacogenetics deals eith the genetic
aspects of the action
- Clinical pharmacology which covers
the clinical use and trial of drugs
- Toxicology The Area of pharmacology
that deals with the adverse (reaction)
effect of chemicals and drugs on
biological systems. On other term
toxicology is the study of adverse
reactions of chemicals or physical agent
on living organisms.
Definition of Drug : Any substance that
brings about a change in biologic function
through its chemical action. Alters state in
the body in other term
Drug: That is a substance that produced
by various sources which when
administered into the body restores the
normal body function that have disturbed
by a disease.
Drug Sources:-
•Plants e.g. alkaloids, morphine, digoxin
quinine and pilocarpine.
•Animal: insulin, vitamins, sera, vaccines and
thyroxine.
•Mineral e.g. magnesium, iron, Zn sulphate
Ca+2 and selnum.
•Synthetic eg. Aspirin, chloroquine,
sulphonamides and procaine.
•Biosynthesis microorganism, antibiotics e.g.
Penicillin, streptomycin and ….
•Genetic engineering (recombinant DNA
technology) insulin, growth hormone,
interferone and erthropoeitin.
ROUTES OF DRUG ADMINISTRATION
Absorption of Drugs:
Absorption is the transfer of drug from it site of
administration to the blood stream. The rate and
efficiency of absorption depend on the route of
administration I.V. administration absorption is
complete, that is the total dose of drug reaches
the systemic circulation. Drug administration by
other routes may result in only partial absorption.
For example, oral administration requires that a
drug dissolve in the gastrointestinal fluid and
then penetrate the epithelial cells of the intestinal
mucosa
Transport of drug from the GI tract drugs
may be absorbed from the GI tract by either passive
diffusion or active transport.
•Passive diffusion: NO energy is required and
diffusion means drugs moves from region of high
concentration to a region of low concentration.
Diffusion does not involve a carrier. Lipid-soluble
drugs readily move across most biological
membranes where as water soluble drugs penetrate
the cell membrane through aqueous channels.
•Active transport: that is required energy and
involve specific carrier proteins. Active transport is
energy dependent and is driven by the hydrolysis of
ATP. It is capable of moving drugs against a
concentration gradient.
Fate of Drugs:-
Drug absorption into general circulation
•binding to the receptors (reversible)
•binding to tissues (fats)
•binding to plasma protein
•metabolism
•liver b)kidney c) intestine d) blood e)
lungs of tissues
•Elimination
a) nasal secretions b) milk c) urine d)
tears e) stool f) sweat g) saliva
h) exhaled air
 Chemical signaling between cells:-
1. Hormones
Specialized endocrine cells secrete hormones into the blood
stream. Where they travel throughout the body exerting effect
on target cells distributed in the body.
2. Neurotransmitters
Each neurons release certain chemical signals called
neurotransmitters from the nerve terminals. These substances
rapidly diffuse across gap (synapse) between nerves endings
and combine with specific receptors.
3. Local mediator
Most cells in the body secrete chemicals that act locally. These
chemicals signals are rapidly destroyed or removed. They do
not enter the blood and are not distributed throughout the
body. Histamines and prostaglandins are examples of local
mediators
Receptor: Specific molecule that drug
may interact with that plays a regulatory
function role
Nature of Receptors
These are macromolecules composed of :
Proteins
Glycoproteins
Phospholipids
In anther means Receptor binds to specific
drugs. For each drug there may be more
than one specific binding site depending
upon the organ involved.
Binding of drugs to receptors by involve:
•H-bond
•Ionic bond
•Vander Waals bond
•Dipole-dipole bond
•Covalent bond which is the strongest
Generally, we select drug that binds with
other than types of covalent binding.
 Membrane receptors
All neurotransmitters and most
hormones and local mediators are too
hydrophilic to penetrate the lipid bilayer
of target-cell plasma membrane.
Instead, their signal is mediated by
binding to specific receptors on the
cell surface.
Types of neurotransmitters
Although over 50 chemical signal
molecules in the nervous system have
been tentatively identified, only 6
signal compounds, NE, E, actylcholine,
dopamine, seretonin, histamine, and
gama amine butyric-acid – are mostly
commonly involved in the action of
therapeutically useful drugs, which
have clinical applications
Types of Receptors
Cholinergic receptors
a) Muscarinic receptors (Atropine-
sensitive) Blocked by atropine
•M1, M2, M3 , M4 And M5
b) Nicotine (N) receptors classified
according to the blocking agent
•neuronal (Nn) Etamon sensitive
receptors
•muscle (Nm) curare sensitive
receptors
•Adrenergic receptors
•Alpha-receptors classified into
•Alpha 1
•Alpha2
•Beta - adrenoreceptors classified
into
•Beta1 adreno receptors
•Beta2 adreno receptors
•Beta3 adreno receptors
•Histaminergic receptors
•H1 receptors
•H2 receptors
•H3 receptors
•H4 receptors
•Serotonin receptors
Three types :
a) 5-HT1
b) 5HT2
c) 5HT3
•Dopaminergic receptors
•D receptors
1

•D receptors
2

•D receptors
3

•D4 receptors
•Purioreceptors
•Purine (P1) receptors
•Adenosine A1
•Adenosine A2
•Purine P2 receptors
 •GABA receptors
•GABAa
•GABAb
•Glycine receptors
•Glutamic receptors
•Asparate receptors
•Opioide receptors
•Receptors for endocrine hormones
•Bonzadiazaphine receptors
•Prostanoid receptors – five types
Drugs
Also drug can be defined as the following
It is any chemical substances that alters
body functions by interaction at the
molecular level and can be used for
diagnosis, prevention or treatment of
disease.
According to the mode of action Drugs are
divided into:
•Agonist
•Antiagonist
•Dudlist (partial agonist)
Agonist: It is a chemical which when
added to tissues produces an observable
or a measurable effect.
Antagonist: Is a chemical which has no
an observable or a measurable effect. But
block or antagonises the action of agonist.
Dulist (partial agonist): Is a chemical
which has the ability to induce an initial
effect which can be observed or
measured and it also has the ability to
block the action of an agonist acting on
the same receptors.
Types of Antagonists:-
1. Competitive antagonist:-
It is a drug which blockage can be overcome by
increasing the concentration of agonist.
e.g. Hyoscine against Ach.
2. Non-competitive antagonists:-
It is a drug which blockade cannot be overcome by
increasing the concentration of agonist.
e.g. Phenoxybenzamine against NA
3. Chemical antagonist:-
4- Pharmacokinetics anatagonist
5- Physiological antagonists or pharmacological
anatagonists: It is a drug which decreases the effect of
an agonist by producing an equal opposite effect.
Definition of Some Concepts
1 . Half-life of drugs (t1/2) = It is
the time required for maximum level of
drug concentrated to drop 50% of
maximum concentration.
•Continuous absorption > metabolism
+Excretion
•Balance between absorption and
metabolism + excretion
•Due to absorption < metabolism and
excretion
 2. Therapeutic plasma level (TPL):
Concentration. Of drug which is required to
obtain an optimal effect of that drug.
•For most drugs TPL is half the max.
concentration. can be obtained of the drug (i.e.
at the t1/2 of drug).
•For most drugs the interval between doses
(frequency of administration) is equivalent to
t1/2 of the drug.
N.B. For some drugs, there is no relation
between therapeutic plasma level and the effect
e.g. locally acting drug in GIT – Anti-cancer
drugs.
 ED50

3 . Effective Dose 50 ED50 : It is the dose

required to produce 50% of the maximum
effect.
4 . Lethal Dose 50 or Toxic 50 LD50: the
dose that produces death in 50% of a group.
5 . Therapeutic index:-
It is the ratio between toxic or lethal dose 50
(TD50 or LD50) and effective dose 50 (ED50).
( i.e. T.I. LD50 )
For each drug we must determine
therapeutic index
The higher the therapeutic index, the
safer the drug.
•Therapeutic Index (T.I) of cardiac
glycosides = 2 therefore not safe.
•T. I of most drugs = 10, therefore is safe.
•For several drugs, in comparison, conc.
must be in moles and effect in % of
maximum.
The potent drug is that drug which produce
Ed50 at lower conc. (in moles).
The smaller the ED50 in moles for a certain
group of drugs the more potent the drug.
Metabolism of Drugs
Some drugs are unmetabolised, they are excreted
unchanged (in urine or faeces)
Metabolism:-
•Microsomal enzymes : Mostly present in the liver
•Nonmicrosomal enzymes : Present at any site of
cell (cytoplasm, mitochondria, plasma)
The most important microsomal enzyme is
Cytochrome P-450.
Microsomal enzymes can be inhibited or
stimulated by certain drugs.
Non Microsomal enzymes can be inhibited only by
certain drugs.
If we administer drug x which is
metabolised by microsomal enzymes
and drug B which stimulates
synthesis of metabolising enzymes.

Thus, the t1/2 of drug X in present

of drug B will be decreased (i.e.
metabolised faster).
 Factors which effect the drug t1/2 or duration:
1. Co-administration of other drugs:-
e.g. a) Microsomal enzymes inducers   synthesis
e.g. phenobarbitone, Rifampicin, Nicotine. These drugs
decrease t1/2 of all drugs that are metabolised by
microsomal enzymes. In this case, increase frequency of
administration or increase the dose.
b) Microsomal enzymes inhibitors
e.g. Oral contraceptives (estrogen + progestin),
chlorampehnicol, erythromycin, cimetidine, (Tagamet).
Coadministration of these drugs with other drugs  
t1/2 of drug that are metabolised by microsomal
enzymes.
 2. Health

In case of liver disease , t1/2 will be

increased in those case of drugs
that are metabolized in the liver.
In renal disease t1/2 will be
increased in case of drugs that
are excreted unchanged in the urine .
2. Age
Persons who are considered are:-
Newborn  the quantity of
metabolizing enzymes is low therefore
t1/2 is high.
Children and adults  metabolizing
enzymes activity is similar between
children and adult.
Elderly  the activity of enzymes is low
therefore t1/2 is high.
•Genetical factors:-
In some people, the enzyme activity is
low . So, t1/2 is high and more toxicity
occur. So, reduce the dose or change
the drug.
In others, the enzyme quantity is high.
So, t1/2 is low. Therefore,
the dose should be increased or should
be changed the drug.
Urine PH
•In take of urine acidifiers:-
i.e. acidic urine occur.
Renal reabsorption of non-metabolized
drugs usually occur in the non-ionized form.
•In presence of acid, bases will be ionized.
Therefore, no reabsorption happen.
Therefore,  duration of action.
•If a patient took a toxic dose of basic drug,
the best way to induce the excretion of the
drug is to acidify the urine.
Means to control urine PH
To acidify urine:-
By taking 1) Ascorbic acid 2) NH4Cl
Which facilities elimination of basic
drugs or basic poisons
To alkalinize urine administer: NaHO3.
The akalinization of urine hastens the
excretion of acidic drugs or acidic
poisons that are excreted in urine
unchanged.
.
Definition of some terms
1 . Tolerance:- It is decrease in
effect of a certain drug after chronic
administration.
•The cause for the loss of activity:
•The increase in metabolizing enzymes
(induction)
•Changes affinity of the drug to the
receptors
Therefore , we should increase the
dose of the drug.
2 . Tacchyphylaxis:
It is tolerance on isolated tissues or
organs or It is loss of drug activity or
effect following rapid exposure of the
tissue to a drug.
Tacchyphylaxis may be due to :
•Effects are probably due to release of
another substance (indirect simulation)
High affinity of the drug to the receptor
might be due to increase in the number
of the receptors
3 . Receptors:- A specific cellular
site that interacts with an endogenous
substance or a drug molecule and
mediates that compound’s action.
Receptors are located in or on the cell
membranes or within the cell itself.
They are affected by micromolar or
nanomolar concentrations, demonstrate
relative stereospecificity, and be
selectively blocked by antagonists.
4 . Affinity: the ability of a chemical
compound to combine with a specific
receptors.
5 . Efficacy:- The ability of a
compound to produce a
physiologic/pharmacologic response.
Also referred to as intrinsic activity.
6 . Potency
The ability of a compound to produce
an effect relative to its concentration.
The more potent a drug is, the less
concentration (dose) required to
produce a maximal effect.
7 . Potentiation The process
that occurs when administration of a
second drug increases the effectiveness
of a first drug that is minimally effective
or ineffective when given alone.
8. Additivity
The process that occurs when co-
administration of two drugs causes a
therapeutic effect equal to the sum of
effects obtained by administration of either
drug individually.
9 . Synergism:
The process that occurs when co-
administration of two drugs causes a
therapeutic effect that is greater than the
sum of effects obtained by administration of
either drug individually.
10 . Anaphylaxis
An acute systemic (commonly
characterized by urticaria,
respiratory distress, and vascular
collapse) that occurs in a previously
sensitized individual after exposure
to the sensitizing antigen.
 Intoduction to the General
mechanisms of action of Drugs
 The drug may stimulates or inhibits an
organ:
•1- Stimulation: a) Contraction of
smooth, cardiac or skeletal muscles
• b) Release of hormones,
neurotransmitter or local mediator
2- Inhibition: a) Relaxation of smooth,
cardiac or skeletal muscles
b) Inhibition of release of hormones,
neurotransmitter or local mediator
The cation Ca+2+ is very important for the
activity of drugs.
 Sites of Ca+2 ions
a) Extracellular Ca+2
b) Intracellular
1- Mitochondria
2- Sarcoplasmic reticulum
3- Microsomes
4- Inner side plasma membrane
Drug should stimulate or inhibit influx
of Ca+2 inside cells.
Mechanisms of contraction in smooth muscles
Smooth muscles: In all muscles we have two
contractile proteins (actin, myosin)
Actin + Myosin  Actomycin [this means
shortening of muscles (contraction)]
The steps are as follows:-
•Ca+2 interacts with Ca+2 binding protein known as
calmodulin to produce a complex called Ca-
calmodulin complex.
•Then this complex activates light chain
myosinkinases which in presence of ATP
phosphorylates myosine.
•The activated myosin interact with actin to
produce Actomysine  contraction.
Mechanisms of contraction in cardiac muscles
 In cardiac muscles there is no calmodulin
Actin + Myosin  Actomycin
This reaction is controlled negatively by Troponine
(which is a calcium-binding proteins)
The importance of Ca+2 is to reliefe the inhibition
effect of Troponine.
•The interaction between actin and myosin is
controlled negatively by the protein troponine.
 free intracellular Ca+2+ leads to interaction
between Ca+2 troponine.
Therefore, formation of Actomycin  contraction.
Skeletal muscles contracts like cardiac muscles .
Drug or mediator-receptors interactions:-
Drugs, neurotransmitters, hormones, or local
hormone bound to their receptors that gives
changes in the structure of the receptors
. This process is known as receptor conformation
which gives DR-Complex
D + R  DR Complex
This complex might cause direct action via
changes the permeability of ions such as
Na+ and K+ without interference of
intercellular messenger systems which usually
require second messenger generation.
Therefore we have to classify the
receptors according to its location
Classification of the Receptors
1. Located in the membrane and directly to an ion-
channel. These receptors activate the cell with a time-
scale of milli-seconds, e.g. the actylcholine-nicotinic
receptors.
2. Located in the membrane and attached via G-protein
to ion channel or an enzyme, e.g.
(a) Adrenaline 2 receptors in smooth muscles
activates Adenylate Cyclase.
(b) Noradrenaline -receptors in smooth muscles
activates phospholipase C .
(c) Bradykinin in fibroblasts activates phospholipase A2.
All of the above receptors attached to their specific
enzymes by G-protein whereas Muscurinic receptors are
coupled by G-protein to K+ channels.
3. Located in the membrane and part of the receptors
as protein kinase which has integral tyrosine kinase
activity, e.g. Insulin receptors and receptors of growth
hormone. Also could be linked to tyrosine kinase (e.g.
Cytokine receptors). These receptors usually cause
slower cell stimulation with a time-scale of minutes,
e.g. Insulin receptors.
4. Located in the cytosol or nucleus with the Ligand-
receptor Complex acting on DNA that gives inhibition
of protein synthesis via inhibition expression of certain
genes or transcription and translation of mediator
proteins, e.g. the glucocorticoid, hydrocortisone; in
the case, the activation of cell is with a time-scale of
minutes to hours.
Second Messengers
IntracellularReceptor-Enzyme Systems
(second messenger)
Phospholipase C (PLC) and Phospholipase (D)
PLC acts on Phosphatidyl Inositol 4,5 bi-
phosphate (PIP2) gives Inositol 1,4,5
triphosphate (which cause influx Ca+2 from
intracellular storage site leads to increase the
level of Ca+2)
and other compound called Diacylglycerol DAG
(which stimulates protein kinase).
PLD acts on phosphatidyl choline (PC) to produce
phosphatidic acid (PA).
Phospholipase A2 (PLA2)
This enzyme produces arachidonate
which might function as second
messenger in some cells. And these
arachidonate are considered as
prostaglandine precursors.
There are 5 main prostanoid receptors on
each for five natural prostanoids, PGE2,
PGF2, PGD2, PGF2 and TXA2 termed
as EP, IP, DP, IP, IP receptors respectively.
•Adenylyl Cyclase enzyme
Which increase the synthesis of CAMP
from ATP
•Guanylyl Cyclase enzyme
Which increase CAMP production from
GTP
Mechanism of Action of Drugs
1) Drug Mediator Actions on their Receptors:-
•Drug + Receptor  DR Complex
•This complex interacts with G-protein which is bound to GTP to
give final complex.
•The final complex activates the enzyme Phospholipase C (PLC).
•The activated enzyme (PLC) hydrolysis a compound called
phosphatidyl inositol 4,5 bi-phosphate resulting in compound :
inositol 1,4,5 triphosphate (IP3) + diacylglycerol DAG
•IP3 mobilizes intercellular Ca+2 and activate Ca+2 regulated
enzymes and cell process. IP3 acts directly on a calcium channel
on the membrane of sarcoplasmic reticulum to release stored
Ca+2 in a sense of bursts. Examples: The receptors which
coupled to Diacylglycerol and Inositol triphosphate (a) 1
Adrenoreceptors (b) Cholinergic muscarinic receptors M1 &. M3
•Ca+2 I nteract with Ca+2 binding protein in smooth muscles and
cardiac muscles @@@@ see the mechanism action of Ca+2 in
these muscles.
2- Depolarization (open of Ca+2
channels)
Some drugs interact with receptors to
increase influx of Na+ ions  increase
in electrical potential within the cell.
This increase in E.P. opens membrane
Ca+2 channels through which
intracellular Ca+2 ion influx inside the
cell : increase in intacellular level of
Ca+2 ion. Such as nicotinic receptor
 Modulation of Cyclic Nucleotides
(cAMP, cGMP)
Drugs either decrease or increase in
levels.
•Increase cAMP in smooth muscles 
Relaxation.
•Increase cAMP in cardiac muscles 
Contraction. )
 Role of cAMP in Smooth Muscles:-
•D + R  Complex.
•Complex then interacts with Gs protein (s:
stimulatory), this protein is usually linked to
enzyme adenylyl cyclase which converts ATP into
cAMP.
•Guanosine is the same thing, (guanylyl cyclase).
•cAMP activates protein kinases which in
presence of ATP, phosphorylates the protein
phospholamban.
•The negativelly charged phosphate ions attract
the +vely charged Ca+2 ions.
…decrease in intracellular Ca+2,  relaxation.
(opposite to that of contraction
Role of cAMP in Cardiac Muscles:-
•Drug + Receptor  Complex.
•This complex interacts with Gs protein. This
protein is usually linked to the enzyme adenylyl
cyclase which converts ATP into cAMP.
•CAMP activates protein kinases which in the
presence of ATP phosphorylates calcium channels
resulting of influx of extracellular Ca+2.
…increase in level of free
intracellular Ca+2
 +ve inotropic and
contraction. Such as Beta adrenergic receptors
•The effect of cGMP is the same.
•Gene Transcription
i.e. synthesis or inhibition of specific
proteins.
•This mechanism is specifically for
corticosteroids, e.g. Cortisone, Sex
hormones, Thyroxine…
•The receptors are present in cytoplasm.
•The drug must penetrate the cell
membrane and interact with receptor.
•It will take time for action (min.  1 hour)
•Blockade of some Channels
•If we block K+ channels the E.P.
will become less negative and
make partial depolarization.
•Thus, drugs induce blockade of
K+ channels will lead to decrease
in the intracellular –ve potential
leading to relative depolarization
and stimulation in muscles or
heart.
 •Blockade of Na+ Channels
Ion channels can be affected by some
drugs. This lead to decrease in
depolarization that cause inhibition
of cell e.g. local anesthetics which
physically block the sodium channel.
 •Calcium Channel Antagonists
Which bind to specific sites in the
Ca+2 Channel protein inhibiting
channel opening leads to
decrease in intracellular Ca+2 ions
that cause inhibition.
•Chloride Channel Opening
Other agent such as
Benzodiazopines
bind on the receptor-channel
complex of the chloride
channel facilitating its opening
resulting in hyperdepolarization
by the neurotransmitter GABA.
•Interaction with Carrier
Molecules
Carrier molecules which transport
ions and small inorganic molecules
into or out of cells can be affected
by drugs which inhibit their
transports, e.g. loop diuretics on
the Na+/K+/2Cl- co-transporter in
the loop of Henle.
 •Inhibition of some Enzymes
Drug action on enzyme is usually inhibitory, e.g.
neostigmine on acetylcholinestrase (an ext
racellular enzyme) The action is usually directly
•often by substrate competition
•but sometimes by inactivation, e.g.
• aspirin on cyclo-oxygenase.
•Some drug inhibit enzymes indirectly,
• e.g. heparin inhibits the coagulation
•enzymes by speeding up
• the action of a natural inhibitor,
•antithrombin III.
•Some drugs can themselves develop enzyme
•activity, e.g. antistreplase.
•Some Drugs Produce their Action
without Interaction with Specific
Receptors
•Examples:
•Antacids, chelating agents,
•Kaolen, pectin and tannins,
Introduction to Autonomic
Pharmacology
Prof. Dr. Abdulrahim Abu Jayyab
The nervous system is divided
into two anatomical divisions
. Central nervous system
I) Brain a) Forebrain
- Cerebrum - Diencephalons
b) Cerebellum
c) Brain Stem - Midbrain
-Medulla oblongata - Pones
II Spinal cord- Cervical
- Thoracic
- Lumber – Sacral
2- Peripheral Nervous System
a) Afferent Division
b) Efferent Division
Efferent Nervous System
The Efferent Nervous System Consist of
the following
a) Autonomic nervous system.
b) Somatic nervous system
Somatic nervous system
•One motor neuron extends from the
CNS to skeletal muscle
•Axons are well myelinated, conduct
impulses rapidly
Control voluntary activity. It innervates
and controls the motor function of the
body. It consists of long neurons
originated or starts from the spinal
cord and directly innervated skeletal
muscles.
Autonomic nervous system

Other names
a) Visceral
b) Vegetative
c) Involuntary
The Autonomic Nervous System
A system of motor neurons
•Innervates smooth muscle
•Cardiac muscle,
•Glands
Regulates
-Visceral functions
-Heart rate
- Blood pressure
- Digestion,
- Urination
Function of ANS:
- Therefore, we can say in other
term regulates activity of
structures not under voluntary
control
a) Smooth muscle
b) Cardiac muscle
c) Secretory glands
III. Structural arrangements
a) Connections — 2 neurons
- 1 Neuronal fiber leaving brainstem
and spinal cord synapses outside the CNS
at a ganglion -- preganglionic neuron
1) Second neuron impacts on effectors
organ -- postganglionic neuron
b) Two divisions in ANS
1.based on differences in
a- Anatomy
b- Function
Can be further divided into two
parts:-
a) Sympathetic.
b ) Parasympatheticic .
I- sympathetic (thoracolumbar) division
a) Fibers originate in the thoracic and
lumbar regions (T1-L3) of the spinal cord
b) Ganglia are located near the spinal cord
(distant from effectors organ)
c) Other than a second neuron,
preganglionic neurons innervate the adrenal medulla
which is embryologically and anatomically analogous to
other sympathetic ganglia
d) One preganglionic neuron may act on
many postganglionic neurons (up to1:20)
e) Diffuse distribution pattern leads to
widespread massive responses
1- Desirable if organism is confronted with a sudden
emergency (e.g. pain, asphyxia, strong emotions)
2- Fight or flight” response
II- parasympathetic (craniosacral) division
a). Fibers originate in tectal region (Cranial)
of the brain stem (oculomotor [III], facial[VII],
glossopharyngeal [IX] and vagus [X]) and sacral
segments (S2-S4) of the spinal cord
b) Ganglia are located near the end effectors
organs (distant from spinal cord)
c) Generally
1 preganglionic:1 postganglionic neuron
d) Discrete distribution leads to fine and limited
responses
e) Functionally important in protection,
conservation and restoration of bodily resources
III. Innervations
a) Some tissues receive only
parasympathetic innervations
1 - Parotid gland
2- Lachrymal gland
3- Nasopharyngeal glands
b) Some tissues receive only
sympathetic innervations
1) Sweat glands
2) Adrenal medulla
3) Piloerectors
4) Most blood vessels
c) Some tissues are innervated
by both
1) Salivary glands
2) Heart
3) Lungs (bronchial muscle)
4) Abdominal and pelvic viscera
relative degree of innervations

Characteristic Sympathetic
Parasympathetic
Spinal Cord
Origin Thoracic-Lumbar Cranial-Sacral
Length of
Postganglionic Fiber Long Fiber Short
Innervations Diffuse(1:20) Discrete(1:1)
Function Fight or Flight Minute-to-
Minute Control
1) Neurotransmitter of Preganglioinc of
Parasympatheticis ACh
2) Neurotransmitter of Postganglionic
of Parasympathetic is Ach
3) Neurotransmitter of Preganglionic of
Sympathetic is Ach
4) Neurotransmitter of Postganglionic
of Sympathetic is NE
5) Neurotransmitter of somatic neurons
is Ach
Neurotransmitters
Neurotransmitters
Endogenous chemical mediators that transmit
never impulse across junction such as synapse.
Neurotransmitters in the ANS are
1. Acetylcholine (ACh)
2. Norepinephrine (NE)
3. Since epinephrine (Epi) is released into the
circulation it is referred to as neurohormone
rather than a neurotransmitter
Neurons which release ACh are called
cholinergic
Neurons which release NE are called adrenergic
Neurotransmitters associated with the
autonomic nervous system
•Sympathetic division
•Preganglionic neurons release ACh
• postganglionic neurons release NE (ACh -->NE)
• At sweat glands (ACh --> Ach)
•Adrenal medulla releases Epi, NE (ACh --> Epi,
b) Parasympathetic division
a. Preganglionic neurons release Ach
b.Postganglionic neurons releaseACh (ACh->Ach)
c) Caution: a. Cholinergic? Parasympathetic
b. Adrenergic? Sympathetic
1- Acetylcholine
It is a neurotransmitter of both
sympathetic and Parasympathetic at the
ganglionic synapse. Also Acetycholine
is the parasympathetic neurotransmitter at
the postganglionic synapse of
parasympathatic.
It is also a neurotransmitter of some
postganglionic of sympathetic such as sweat
glands ,as well as it is a neurotransmitter
of somatic neurons
2-Norepinephrine
It is the neurotransmitter of
sympathetic at the postgangtionic
synapse .
Except sweat gland and some blood
vessels , which is Acetylcholine .
In addition the preganglionic fiber to
the adrenal medulla is acetycholine
and also the somatic ( motor) nerve
to Skeletal muscles .