By T.D.

Tesfa
April, 2018
Introduction
 The autonomic nervous system (ANS) regulates the vital body
functions without the conscious participation of the mind
 The ANS is composed of efferent neurons that innervate
smooth muscle of
 the viscera - cardiac muscle,
 vasculature, and - the exocrine glands

 control digestion, cardiac output, blood flow, and glandular

secretions

 Autonomic drugs act either by stimulating or by blocking the

action of the autonomic nerves
2
3
 Anatomy of the autonomic
nervous system
 Anatomically, they originate in the CNS and emerge from
different spinal cord regions

 The autonomic nervous system carries nerve impulses from the

CNS to the effector organs by way of two types of consecutive
efferent neurons

 The first nerve cell is called a preganglionic neuron, and its cell body
is located within the CNS

 Preganglionic neurons emerge from the brainstem or spinal cord

and make a synaptic connection in ganglia (an aggregation of
nerve cell bodies located in the peripheral nervous system)
4
 These ganglia function as relay stations between a
preganglionic neuron and a second nerve cell, the
postganglionic neuron

 The latter neuron has a cell body originating in the

ganglion

 It is generally non-myelinated and terminates on

effector organs, such as smooth muscles of the
viscera, cardiac muscle, and the exocrine glands

5
6
 Divisions of the Peripheral
Autonomic System
 Three divisions:
(1) the sympathetic or thoracolumbar outflow and
(2) the parasympathetic or craniosacral outflow
(3) enteric Nervous System

7
 1. Sympathetic neurons
(thoracolumbar outflow)
 The preganglionic neurons of the sympathetic system
come from thoracic and lumbar regions of the spinal
cord

 The preganglionic neurons are short in comparison to the

postganglionic ones

 Axons of the postganglionic neuron extend from these

ganglia to the tissues that they innervate and regulate

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9
 Effects of stimulation of the
sympathetic division (fight or flight)

 Eye: mydriasis (contraction of radial

muscles that dilate the pupil)

 Heart: increase in heart rate and

contractility

 Blood vessels to skin & mucous membranes: constriction

 Blood vessels to skeletal and heart muscles: dilatation

10
 Lung: dilatation of bronchioles

 GIT: decrease in tone and motility

 Salivary gland: thick, viscous secretion

 Bladder: relaxation of detrusor muscles &

contraction of sphincter – inhibit urination

 Uterus: relaxation

 Many of the effects results primarily from, or

are reinforced by, actions of epinephrine,
secreted by adrenal medulla
11
 2. Parasympathetic neurons (cranio-sacral
outflow)
 preganglionic fibers arise from the cranium (from cranial
nerves III, VII, IX, and X) and from the sacral region of the
spinal cord

 preganglionic fibers synapse in ganglia near or on the effector

organs

 the preganglionic fibers are long and the postganglionic ones

are short, with the ganglia close to or within the organ
innervated

 in most instances there is a one-to-one connection

between the preganglionic and postganglionic neurons,
enabling the discrete response of this division
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Parasympathetic divisions

13
 Effects of stimulation of the
parasympathetic division (rest and digest)
 Eye: miosis (contraction of circular muscles that contract the
pupil)

 Heart: decrease in heart rate and contractility

 Lung: constriction of bronchioles and increased bronchiolar

secretions

 GIT: increase in tone and motility

 Salivary gland: copious and watery secretion

 Bladder: contraction of detrusor muscles & relaxation of

sphincter – facilitate urination

 on the whole→ the organism is in “a rest and digest condition”

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 Cooperative Effects of SNS &
PSNS
 The effects of sympathetic and parasympathetic stimulation
are cooperative on the:

Reproductive systems

 Erection of the penis, for example, is due to vasodilation

(mediated by NO) resulting from action potentials through
parasympathetic nerves

 ejaculation is due to action potentials through sympathetic

nerves (peristaltic contractions of smooth muscle of the
male reproductive tract results in ejaculation)
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 Antagonistic
Control
• Most internal organs are
innervated by both branches
of the ANS which exhibit
antagonistic control

A great example is heart

rate. An increase in
sympathetic stimulation
causes HR to increase
whereas an increase in
parasympathetic stimulation
causes HR to decrease 16
3. The enteric nervous system
(ENS)
 The enteric nervous system (ENS) is sometimes
considered a third division of the ANS

 It is a collection of nerve fibers that innervate the

gastrointestinal tract, pancreas, and gallbladder

 And it constitutes the brain of the gut

 Control the processes of mixing, propulsion, and

absorption of nutrients in the GI tract

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 This system functions independently of the CNS and
controls the motility, exocrine and endocrine
secretions and microcirculation of the gastrointestinal
tract

 As indicated by the observation, deprivation of input

from both ANS divisions does not completely halt
activity neither in the plexuses nor in the smooth
muscle and glands innervated by them

 It is modulated by both the sympathetic and

parasympathetic nervous systems

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 Autonomic Transmission

Two types of fibers of ANS:

 Cholinergic fibers use Ach
 Acetylcholine is neurotransmitter:-
 All preganglionic autonomic fibers,
 All postganglionic parasympathetic fibers, and
 A few postganglionic sympathetic fibers

 Adrenergic fibers comprise

 majority of postganglionic sympathetic fibers;
 transmitter is norepinephrine (noradrenaline)

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20
Neurotransmitters
 There are two important neurotransmitters in
the autonomic nervous system
 These are
 Acetylcholine(Ach) and
 noradrenaline (norepinephrine) and epinephrine

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Neurotransmitters in the peripheral nervous system

22
Synthesis and Metabolism of Acetylcholine &
noradrenaline

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Acetylcholine
 Acetylcholine is the chemical transmitter at:
 all post-ganglionic parasympathetic neurons
 post-ganglionic sympathetic neurons to sweat
glands
 all autonomic ganglia (sympathetic &
parasympathetic)
 adrenal medulla
 neuromuscular junction
 CNS
• Norepinephrine ?

24
Drugs Acting on the Autonomic
Nervous System
I. Cholinergic Agonists (parasympathomimetics)

II. Cholinergic Antagonists (parasympatholytics)

III. Adrenergic Agonists (sympathomimetics)

IV. Adrenergic Antagonists (sympatholytics)

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Cholinergic Agonists
(Parasympathomimetics)
 Drugs that stimulate the parasympathetic nervous
system (PSNS)
 opposing system to the SNS
 Known as: cholinergic agonists or
parasympathomimetics
 Mimic the effects of the PSNS neurotransmitter:
acetylcholine (Ach)

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Cholinergic receptors
1. Muscarinic receptors

2. Nicotinic receptors

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Muscarinic receptors
 Subtypes
 M1, M2, M3, M4, M5
 M1, M3 and M5 are excitatory
 M2 & M4 are inhibitory
 Only M1, M2, M3 are pharmacologically important.
 Location
 M1 ------Gastric parietal cells
 M2 ------Cardiac cells, smooth muscles
 M3 ------Bladder, Exocrine glands, smooth muscle, CNS
 Agonists and Antagonists
 Pirenzepine----selective M1 blocker (peptic ulcer)
 Darifenacin-----selective M3 blocker (overactive
bladder)
 Atropine -----non-specific
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Nicotinic Receptors
 Subtypes –
 NN (neuronal nicotinic receptors)
 NM (muscular nicotinic receptors)
 Location
 NN----------CNS, adrenal medulla, autonomic ganglia
 NM----------Neuromuscular junction
Agonists and Antagonists
 Hexamethonium, ----selective NN blocker (Ganglion
blocker)
 Tubocurarine.-----selective NM blocker
(Neuromuscular blocker)
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Cholinergic Drugs
Mechanism of Action
 There are two groups of cholinergic drugs:

1. Direct-acting
 bind to and activate muscarinic or nicotinic
receptors

 include the following subgroups:

 A) Esters of choline: Ach, methacholine, carbachol,
betanechol
 B) Cholinergic alkaloids: pilocarpine, muscarine, arecoline,
nicotine
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2. Indirect-acting:
 inhibit the action of acetylcholinesterase
enzyme- which breaks down ACh - more ACh
is available at the receptors

a. Reversible: bind to cholinesterase for a period of

minutes to hours
 E.g. neostigmine, physostigmine, edrophonium

b. Irreversible: bind to cholinesterase and form a

permanent covalent bond
 E.g. Organophosphate compounds: echothiophate
 The body must make new cholinesterase to reverse
the effect
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Classification of cholinergic
agonists

32
1. Direct-Acting Cholinergic
Agonists
A. Acetylcholine (M&N)
 Has no clinical use b/c of
 its extreme short duration
 Non specific action
 Cannot be given orally (rapid hydrolysis)

 Pharmacological actions
 Heart: Decrease in heart rate and cardiac output
 Blood Pressure: Decrease in blood pressure due to
NO-mediated vasodilatation
 Gastrointestinal tract: Increase tone, motility and
secretions 33
 Salivary glands: Increase secretions
 Lung: Bronchoconstriction and increased bronchiolar
secretions
 Bladder: facilitate urine expulsion
 Eye:
 Enhance lacrimation
 constrict the circular muscle causing miosis, and
constrict the ciliary muscle (accommodation for near
vision)
 Open canal of Schlem - decrease intraocular pressure
(IOP)
 CNS: ACh modulates sleep, wakefulness, learning, and
memory
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B. Bethanechol (M only)
 is structurally related to acetylcholine, can be taken
orally
 has only muscarinic activity
 Actions: (Its major actions are on the bladder and
GIT)
 Bethanechol increases intestinal motility and tone
 cause expulsion of urine via acting on urinary bladder
 Therapeutic applications
 Used to reverse postsurgical atony of the bladder
and GI tract
 Adverse effects:
 Sweating, salivation, flushing, decreased blood pressure,
nausea, abdominal pain, diarrhea, and bronchospasm
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 C. Pilocarpine (M only)
 exhibits muscarinic activity and is used primarily in
ophthalmology
 Actions:
 Eye (locally): Miosis and contraction of the ciliary muscle
 Secretions (sweat, tears, saliva): increase
 Therapeutic use:
 Glaucoma (both narrow-angle and wide-angle)
 By opening of the trabecular meshwork around Schlemm's canal,
increase drainage of aqueous humor (decrease intraocular
pressure)
 Also, it may be used in hair lotion to promote growth of hair
 Adverse effects: sweating, salivation and CNS
disturbances
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Contraindications to the use
of choline esters
1. Bronchial asthma:- because they may induce
bronchoconstriction and increase bronchial
secretions
2. Peptic ulcer disease:- b/c increase gastric acid
secretion
3. Coronary insufficiency:- because the
hypotension produced will further compromise
coronary blood flow
4. Mechanical intestinal and urinary outlet
obstruction
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 2. Indirect-Acting Cholinergic Agonists
Reversible Anticholinesterases
A. Physostigmine
 It is a substrate for and reversibly inhibits
acetylcholinesterase enzyme
 potentiate cholinergic activity
 It can be absorbed orally and pass BBB
 Actions:
 It has a wide range of effects due to its action on both
the M and N sites of the ANS

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 Therapeutic uses:
 The drug increases intestinal and bladder motility
(for atony of either organ)
 Placed topically in the eye to treat glaucoma
 As antidote in overdoses of anticholinergic drugs
(atropine, phenothiazines, tricyclic antidepressants
(TCAs))
 For symptomatic treatment of myasthenia gravis
 Adverse effects:
 CNS: convulsions
 Heart: badycardia and decrease cardiac output

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B. Neostigmine
 reversibly inhibits acetylcholinesterase in a
manner similar to that of physostigmine
 it is more polar and does not enter the CNS
 Uses:
 It is used to stimulate the bladder and GI tract
 Myasthenia gravis
 An antidote for tubocurarine and other competitive
neuromuscular blocking agents
 Adverse effects:
 no CNS effects
 Salivation, flushing, decreased blood pressure,
nausea, abdominal pain, diarrhea, and bronchospasm
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C. Tacrine, donepezil,
rivastigmine, and galantamine
 Used to treat Alzheimer's disease
 Tacrine was the first to become available,
 but it has been replaced by the others because of
its hepatotoxicity
 Donepezil, rivastigmine, and galantamine can only
delay the progression of the disease, but cannot
stop it
 Side effects: GI distress

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Irreversible
Anticholinesterases
 combine with cholinesterase enzyme irreversibly
and thus hydrolysis is very slow
 Echothiophate, Isoflurophate,
 War gases (sarin, tabun),
 Organophosphate insecticides (malathion, parathion)

 They may be used in glaucoma

 Other organophosphates like parathion and
malathion are used as insecticides
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 Irreversible Anticholinesterases…

 Poisoning with organophosphates is an important

cause of morbidity and mortality all over the
world
 It usually results from:
 Occupational exposure as in persons engaged in
spraying insecticides,
 Accidental exposure, and
 Ingestion of any of these compounds with suicidal
intent

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Management of toxicity:
 Artificial respiration

 Decontamination

 Atropine (for muscarinic symptoms)

 Acetylcholinesterase reactivator (Pralidoxime)

 Pralidoxime is an antidote for organophosphte

poisoning

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 Cholinergic Antagonists
(Parasympatholytics)
Anticholinergics
 block the effects of acetylcholine and other cholinergic drugs at
cholinergic receptors
 Anticholinergics fall into two major families:
1. Antinicotinics:- block at nicotinic receptor
a. ganglion blockers such as hexamethonium, trimethaphan, etc., and
b. neuromuscular blockers such as gallamine, tubocurarine,
pancuronium, etc.
2. Antimuscarinics:- block at muscarinic receptors
a. tertiary amines such as atropine, scopolamine, tropicamide, etc,
and
b. quaternary amines such as propantheline, ipratropium,
benztropine, etc.
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I. Antimuscarinic Agents
A. Atropine (3ry amine & blocks M
receptors)
Organ-system Effects:
 CNS: - lower doses produce sedation
- higher doses produce excitation, agitation
and hallucination
 Eyes: - relaxation of circular muscle (mydriasis)
- relaxation or weakening of ciliary muscle
(cycloplegia)
 CVS: - tachycardia

46
Organ-system Effects of atropine…
 Respiratory: - bronchodilation and reduction of
secretion
 GIT: - decreased motility and secretions
 Urinary system : - relaxation of detrusor muscle
and constriction of sphincter (urine retention)
 Atropine is occasionally used in enuresis
(involuntary voiding of urine) among children
 Sweat Glands: - suppresses sweating
 can cause elevated body temperature

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Therapeutic uses of atropine
(Cont.)
1.Ophthalmic:Mydriatic (for eye examination)
 But it suffers the following disadvantages:
 Cycloplegic effect
 Long duration (days)
 Increases IOP in patients with narrow angle glaucoma
2. Antispasmodic:
 To relax the GI tract and bladder
3. Antisecretory:
 to block secretions in the upper and lower respiratory
tracts prior to surgery
4. Antidote
 for organophosphates and drugs like physostigmine
poisoning

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 Side effects
 Dryness of the mouth, tachycardia and blurred
vision
 Retention of urine
 Contraindications
 Glaucoma
 exacerbate latent glaucoma
 Bladder outlet obstruction
 Especially in elderlies

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B. Scopolamine (Hyoscine)
 Scopolamine has greater action on the CNS and a longer
duration of action in comparison to those of atropine
Actions
 Parasympatholytic actions:
 Stronger on secretions & eye
 Weaker on heart & GIT compared to atropine
 CNS:
 Inhibits the vomiting center --------anti-motion sickness
 Blocks short-term memory (causing amnesia)
Therapeutic uses
 Prevention of motion sickness (i.e. used prophylactically)
 Pre-anesthetic medication (to produce amnesia & reduce
bronchial secretion)
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C. Ipratropium
 is a quaternary derivative of atropine
 It does not have CNS effects
 It is used as inhalation and useful in treating asthma
and COPD in patients who are unable to take
adrenergic agonists
D. Tropicamide, Cyclopentolate
 These agents are used as ophthalmic solutions for
similar conditions as atropine (mydriasis)
 Their duration of action is shorter than that of atropine
E. Emepronium, Trospium, Tolterodine, Darifenacin
 For urinary incontinence
F. Beztropine, Trihexphenidyl
 For Parkinson’s disease
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II. NICOTINIC ANTAGONISTS

 Two subclasses: Skeletal neuromuscular blocking

agents, and ganglionic blocking agents.
Neuromuscular blockers
Tubocurarine and derivatives
 Plant alkaloid from Chondodendron tomentosum

 Causes muscle paralysis (arrow poison)

 Rapid onset of action

 Metocurine is a semi-synthetic analog of

tubocurarine. More potent than the parent
compound

 Therapeutic Use: As a muscle relaxant in various

surgical procedures
Succinylcholine
 Very short duration of action (iv)
 Rapid recovery (fast hydrolysis)
 Use: Muscle relaxant
 Suitable for continuous iv drip.
Botulinum Toxin (Botox)
 Toxin produced by the bacterium Clostridium Botulinum
 Causes food poisoning; Large doses can be fatal

 Prevents Acetylcholine release from the nerve terminal

 Produces flaccid paralysis of skeletal muscle

 Inhibition lasts from several weeks to 3 to 4 months

 Rigorously purified & highly diluted for therapeutic use

Therapeutic Uses:
 Administered locally, via intramuscular or intradermal
injections, to control muscle spasms and to facilitate muscle
relaxation (eye; face; neck etc.)
Botulinum Toxin (Botox) (2)
 Dermatological / Cosmetic Uses:
 To treat facial wrinkles (forehead; under the eyes
etc.)
 Prevent excessive sweating (palm; armpit etc)

 Sales (USA): $200 Million (2000); $350 Million

(2002); $1 Billion (2005, projected).
Drugs Affecting the Sympathetic
Nervous System

Release
Adrenergic Receptor
NE NE NE

MAO NE NE Muscle
Membrane
Metabolism NE Reuptake
Adrenergic nerve ending

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ADRENERGIC RECEPTORS
Adrenergic
Receptors

Alpha Beta
Receptors Receptors

Beta 1 Beta 2
alpha 1
alpha 2 Receptors Receptors
Receptors
Receptors
Beta 3
Receptors 60
Classification of Adrenergic Receptors

61
62
63
Alpha-adrenergic Receptors

 Found predominantly on smooth muscle membrane

 When stimulated by NE or EP produce contraction

 Produces vasoconstriction of most blood vessels

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Beta-adrenergic Receptors
 Found on both cardiac and some smooth
muscle membranes

 In the heart, beta 1 receptors

predominates

 When stimulated by NE or EP, they

increase heart rate and force of
contraction

65
Beta-adrenergic Receptors

 In smooth muscle, beta 2 receptors predominates

 When stimulated by EP, they produce muscle

relaxation

 Found in smooth muscles of blood vessels supplying

skeletal muscle and the coronary arteries

 Found on smooth muscle in the bronchial tree

66
 Sympathetic
Drugs

Sympathomimetic Sympatholytic
Drugs Drugs

67
Drugs Affecting the Sympathetic Nervous
System

Sympathomimetic
Drugs

Alpha-adrenergic agonists Beta- adrenergic agonists

68
 General Mode of Action of
Adrenergic Agonists
 Direct-acting agonists:- act directly by binding
to the adrenergic receptors
o E.g. NE, EP, DA, phenylephrine & isoproterenol

 Indirect-acting agonists:- cause the release of

NE from intra-neuronal storage vesicles
o E.g. amphetamine and tyramine

 Mixed-action agonists
o ephedrine
69
 1. Direct-acting agonists
Alpha-adrenergic Drugs
a. Non- selective Alpha-adrenergic Drugs
NE (norepinephrine)
 is prototype
 Most important clinical effect is contraction of
smooth muscles
 Vasoconstriction of most blood vessels – increase BP
 Contraction of sphincter muscles – inhibit
evacuation
 vasoconstriction of nasal mucosal
vasculature-hence lowering congestion (Nasal
decogestant) 70
 Non- selective Alpha…

 Stimulation of α1-adrenoceptors:- mydriasis,

 block drainage of aqueous humor and increase of
IOP :- contraindicated with closed angle glaucoma

 α1-adrenoceptors stimulation results in

vasoconstriction,
 Decrease aqueous humor formation & lowering of
IOP:- for open angle glaucoma

 This latter effect usually predominates

71
b. Selective α1-Adrenergic Agonists
Phenylephrine & methoxamine
 Cause Vasoconstriction
 increase BP

Therapeutic uses of α1-adrenergic agonists:

 Local nasal decongestant by producing vasoconstriction of
nasal mucosal vasculature
 To overcome hypotension induced by some general
anesthetic agents
 Pupillary dilation (mydriasis) – eye examination

 They are less potent but longer acting than

norepinephrine, being non susceptible to metabolism
with COMT 72
Adverse Effects

 Hypertensive crisis

 Irritation of the nasal sinuses or eye

73
c. Selective α2 -adrenergic
agonists
Clonidine & α-methyldopa
 activate α2-adrenergic receptors in the lower
brain stem
 decrease central outflow of the sympathetic
nervous system
 Oral intake produces a prolonged hypotensive
response (Treatment of Hypertension)

74
Beta-adrenergic Drugs
- act on beta adrenergic receptors

 Stimulate the heart – β1 mediated

 Cause bronchodilation – β2 mediated

 Relaxes uterine smooth muscle - β2 mediated

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 Beta-adrenergic Drugs…
Drugs Classification Main Use
Epinephrine Alpha, Beta-1 and Vasopressor, Cardiac
Beta-2 stimulant, bronchodilator

Isoproterenol Beta-1 and Beta-2 Cardiac stimulant,

bronchodilator

Albuterol Beta-2 Bronchodilator

Ritodrine Beta-2 Arrest preterm labor

76
 Beta-adrenergic Drugs…
Epinephrine

 Drug of choice for allergic reactions

 Used in combination with local anesthetics

 Used as a cardiac stimulant in emergencies

 Used in the treatment of asthma

77
 Beta-adrenergic Drugs…

Adverse Effects
CNS stimulation – tremor, restlessness,
anxiety (beta effect)

Over-stimulation of the heart (beta 1

effect)

Lower blood pressure in coronary and

skeletal muscle blood vessels (beta 2
effect)
78
 Beta-adrenergic Drugs…
Dopamine
 Neurotransmitter in the brain

 Precursor in the synthesis of NE

 Stimulates dopaminergic, beta-1 and alpha-

receptors

 Use as a drug

 Dobutamine (a synthetic dopamine analog)

 similar to dopamine but with more Beta-1 effect
 used in cardiogenic shock and heart failure
79
 Beta-adrenergic Drugs…

NE
NE
NE
MAO
Tyrosine DOPA Dopamine
NE
NE

80
 Beta-adrenergic Drugs…
DOPAMINE RECEPTORS EFFECTS
DOSE STIMULATED

Low dose Stimulate dopaminergic Increased renal blood flow

(D1) receptors in the (vasodilatation)
renal blood vessels

Moderate dose Stimulates beta-1 Increase myocardial

receptors in the heart contractility

Higher dose Stimulate alpha- Produces vasoconstriction

receptors

81
 β2-adrenergic receptor
agonists
Terbutaline, albuterol (salbutamol), &
ritodrine
 are selective β2 adrenergic receptor agonists
 produce bronchodilation without cardiac stimulation
 They produce uterine relaxation
 given orally, IV or by inhalation
 Have long duration of action and possess no CNS
stimulation

82
Therapeutic uses of β2 adrenergic receptor
agonists
o Treatment of bronchial asthma

o Treatment of bronchospasm associated with

bronchitis and emphysema

o Delay delivery in premature labor and in

threatened abortion; ritodrine is frequently
used for this purpose

83
2. Indirect- & Mixed-Acting Adrenergic
Receptor Agonists

 Ephedrine
 stimulates release of NE
 It activates β2 as well as α- and β1-aderenergic
receptors
 It is used to treat mild cases of asthma
 It crosses BBB giving rise to CNS stimulant action

84
Pseudoephedrine & Phenylpropanolamine
 stimulate the release of NE

 used as over-the-counter (OTC) nasal

decongestants for symptomatic relief of hay fever
and rhinitis

 Pseudoephedrine has little β2 agonist activity,

limited CNS stimulation

 Phenylpropanolamine also used to relieve upper

respiratory conditions associated with common cold

85
Antiadrenergic
Drugs

86
 Terminology
Antiadrenergics
=
Sympatholytics
=
Sympathoplegic

87
1. Centrally acting Sympatholytics
Clonidine & Methyldopa
Methyldopa is metabolized to
Methyl- noradrenaline ( False NT)  2 Agonists

 Clonidine

They act centrally :

Stimulate pre-synaptic α2 receptors in
brainstem  sympathetic outflow   COP,
PR,  BP

88
 Clonidine & Methyldopa

Uses:
 Both for Hypertension
 Methyldopa: hypertension in pregnancy
Adverse effects:
Clonidine: Dry mouth, sedation , CNS depression
 BP on withdrawal after long use
Methyldopa: Nightmares, CNS depression,
extrapyramidal effects, lactation due to  prolactin
secretion

89
 2. Adrenergic Neuron
Blockers
Reserpine
 It depletes ( storages & release ) NT:
 noradrenaline   BP
 Uses:
 As second line drug for treatment of HTN

90
3. Adrenergic receptor blockers

1. Alpha blockers
2. Beta blockers

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 Alpha () Blockers

 Selective  1 blockers: Prazosin, Doxazosin , Alfuzosin

 Selective  2 blockers: Yohimbine

 Non selective  blockers: Phenoxybenzamine,

Phentolamine
 Mech. of Action:
Bind to  - receptors
Block actions of nor-adrenaline & adrenaline on  -
receptors

Blockage is either:
 Competitive (reversible): Prazosin, Doxazosin
 Non-competitive (irreversible): Phenoxybenzamine

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 Alpha Blockers (Actions)
1.CVS: on blood vessels ( 1 receptors )
 Dilatation of arteries & veins   BP
Use:
 hypertension
2. Eye:
 Radial muscle of iris (1 receptors)  relaxes 
miosis (Constriction of pupil)
3. Nose:
 Dilatation of blood vessels  nasal congestion

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 Alpha Blockers (Actions,
Cont.)
4. Genito-urinary:
  resistance to urine flow
 Inhibition of ejaculation
Use: to treat urine retention in prostatic
hypertrophy

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Alpha Blockers (Uses)
1. Hypertension:
 Essential hypertension: Prazosin , Doxazosin
 Pheochromocytoma (secondary hypertension):
Phenoxybenzamine

2. Benign prostatic hypertrophy (BPH)

 Alfuzosin
 Tamsulosin

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 Alpha Blockers (Pharmacokinetics)

 Duration of action is related to their reversible 

- blocking effect:
 Prazosin (3 hrs),
 Doxazosin (22 hrs)

 Phenoxybenzamine (irreversible  - blockers)

is long acting : 2 - 3 days

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Alpha Blockers (Adverse effects)

1. Orthostatic-hypotension
2. Reflex tachycardia
3. Nasal congestion
4. Inhibition of ejaculation

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 Beta ()-Blockers
A. Non-selective  Blockers(1+ 2 )
 Propranolol
 Nadolol ( long acting)
B. Cardio-selectives 1 Blockers
 Atenolol (intermediate )
 Betaxolol ( long acting)
 Esmolol ( short)
C. Mixed adrenergic blockers
( &  Blockers) : Carvedilol

 Longest half life: Nadolol (24 hrs)

 Shortest half life: Esmolol (10 min)
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 Pharmacological Actions
Beta Blockers
1. CVS:
a. Heart (1):
  myocardial contraction
  HR
  AV-conduction & automaticity
b. Blood Vessel to Sk. Muscle (2):
o Vasoconstriction, muscle pain & fatigue ( with non-
selective)

c. Jaxtaglomerular cells (1) of kidney:

 renin release,  aldosterone ,  angiotensin :
  Na & water retention,
 vasodilatation  ???
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 Actions (Cont.)

 EYE:
  IOP = to treat close angle glaucoma
 CNS/Neurological:
 Sedation ( with propranolol, carvedilol)
 Respiratory:
 Bronchoconstriction (with non-selective blockers)
 Metabolism:
  gluconeogenesis &  glycogenolysis

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Beta-Blockers…Clinical uses
Nonselective Blockers Main Use

Labetalol Hypertension

Nadolol Hypertension, Angina

Pectoris
Pindolol Hypertension

Propanolol Hypertension, Angina

Pectoris, arrhythmhias,
migraine

Timolol Hypertension, post

myocardial infarction.
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Beta-Blockers…Clinical uses

Selective Blockers Main Use

Acebutolol Hypertension, ventricular

arrhythmias.
Atenolol Hypertension, Angina
Pectoris
Bisoprolol Hypertension

Esmolol Supraventricular tachycardia

Metoprolol Hypertension, Angina

Pectoris

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 Adverse effects
1. CVS:
 Bradycardia,
 hypotension, heart failure, 1 blockers
 AV block
2. Bronchoconstriction, ( 2)
3. Muscle pains & fatigue
4. Increase hypoglycemic effect of anti-diabetic
drugs ( 2 blockers)
5. Sleep disturbances, nightmares ( with lipid
soluble  blockers)

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 Contra-indications

1. Heart failure
2. Peripheral vascular disease
3. Asthma
4. Diabetes taking hypoglycemic drugs
5. Combination with Ca-channel blockers

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