This document discusses the autonomic nervous system. It begins by defining the sympathetic and parasympathetic nervous systems, their functions, and the types of receptors they act on. It then covers cholinergic and adrenergic neurotransmission in more detail. The rest of the document discusses cholinergic and adrenergic drugs, including cholinomimetics, anticholinesterases, antimuscarinics, adrenomimetics, and adrenoceptor antagonists. Key therapeutic uses and side effects of various drugs are provided as examples.

1. Chapter-2
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By: Ebrahim M. (B. Pharm., MSc.), Assist. Prof. of
Pharmacology

2. Nervous System
Peripheral nervous Central nervous
system (PNS) system (CNS)
Afferent Efferent Brain Spinal
(sensory) (motor) cord
Somatic nervous Autonomic nervous
system (SNS) system (ANS)
Sympathetic Parasympathetic Enteric nervous system
(thoraco-lumbar) (Cranio-sacral)
2

3. Difference between Somatic NS and ANS
Somatic NS
 concerned with
consciously controlled
functions
e.g. Movement , Respiration
 Innervate skeletal muscle
 consist of a single motor
neuron
 Has no peripheral ganglia
 Effect is always excitation
Autonomic NS
 activities are not under conscious
control
*concerned primarily with visceral
functions: Regulation of the heart,
temp., secretary glands, digestion,
metabolism
 Innervate visceral organs
 consist of two motor neurons in
series
 Has ganglia b/n pre-synaptic and
post synaptic
 Effect is both excitatory &
inhibitory 3

4. ANS Functions
Sympathetic nervous system functions
1. Regulating the cardiovascular system
 Increase cardiac output
 Causes vasoconstriction
2. Regulate body temperature
 By regulating blood flow to the skin
 By promoting secretion of sweat, thereby helping the body
to cool
 By inducing piloerection (erection of hair) can promote
heat conservation
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5. Sympathetic nervous system functions……..
3. Implementing the “ fight – or – flight” reaction which consists
 Increasing heart rate and blood pressure
 Shunting blood away from the skin and viscera into skeletal
muscles
 Dilating the bronchi to improve oxygenation
 Dilating the pupil to enhance visual acuity
 Mobilizing stored energy
 thereby providing glucose for the brain and fatty acids for
muscles
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6. 6

7. Parasympathetic nervous system functions
 maintains essential bodily functions
• such as digestive processes, elimination of wastes and is
required for life
 usually acts to oppose or balance the actions of the sympathetic
division
– Is dominant over the sympathetic in “rest and digest”
situations
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8. Functions of parasympathetic nervous system
• Slowing the heart rate
• Increase gastric secretion
• Emptying of the bladder
• Emptying of the bowel
• Focusing the eye for near vision
• Constricting the pupil
• Contracting bronchial smooth muscle
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9. 9

10. Important terminology
 Cholinergic neurons
– are neurons which synthesis, store & release Ach
 Cholinomimetics
– are those agents which mimic the activity of Ach
– Are also called parasympathomimetics
 Chlinoreceptors
– are binding site for Ach & cholinomimetics
 Cholinoreceptor antagonists (anticholinergic or parasympatholytics)
– are agents which block/ oppose the actions of Ach
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11.  Adrenergic neurons
– are neurons which synthesis, store & release EP and NE
 Adrenomimetics
– are agents which mimic the activities of NE
– Are also called sympathomimetics
 Adrenoceptors
– are binding sites for NE, EP & adrenomimetics
 Adrenoceptor antagonists
– are agents which antagonize the activities of NE, EP
– are also called sympatholytics/sympathoplegics
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12. Autonomic receptors
• Includes cholinergic and adrenergic receptors
Cholinergic receptors
• Two types: muscarinic & nicotinic cholinoceptors
Muscarinic receptors
• Are activated by muscarine (plant alkaloid)
• Found in many visceral organs such as smooth muscle cells,
cardiac cells, exocrine glands, CNS, Autonomic ganglia
• Further classified into M1, M2, M3, M4 & M5
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13. Muscarinic Receptor Activation
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14. Muscarinic Receptor Activation
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15. Cholinergic receptors ………..
Nicotinic receptors
• Activated by nicotine (tobacco alkaloid)
• Based on their location nicotinic Ach receptors are grouped
into two types
– Nn (at ganglia)
– Nm (at neuromuscular junction)
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16. Adrenoceptors
– Interact with NE, EP & other related drugs
– Two types
1. α-adrenoceptors (α-1, α-2)
2. β-adrenoceptors (β-1, β-2, β-3)
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17. Adrenoceptors
Receptor Location Effect
Alpha1 (α1) Effector tissues: eys,
smooth muscle, glands
↑ Ca2+, causes contraction,
secretion, mydriasis
Alpha2 (α2) Nerve endings, some
smooth muscle
↓ Transmitter release (nerves),
causes contraction (muscle)
Beta1 (β1) Cardiac muscle,
juxtaglomerular
apparatus
↑ Heart rate, ↑ force; ↑ renin
release
Beta2 (β2) Smooth muscle, liver Relax smooth muscle; ↑
glycogenolysis
Beta3 (β3) Adipose (fat) cells ↑ Lipolysis
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18. Neurotransmission
• Involves
– Synthesis
– Storage
– Release
– Interaction
– removal
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19. Steps in cholinergic neurotransmission
1. Synthesis of acetyl choline (ACh)
 From choline and acetyl CoA which catalyzed by choline
acetyl transferase
2. Up take to storage vesicle
3. Release of acetyl choline by exocytosis
4. Binding to receptor
5. Degradation of acetyl choline by acetylcholinesterase /AChE
 To acetate & choline
6. Recycling of choline
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20. Cholinergic neurotransmission
20

21. Adrenergic neurotransmission
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22. Cholinergic Drugs
1. Cholinomimetic drugs
• Similar effects to acetylcholine (Ach)
• Elicit all or some of the effects of Ach
• Classified as
1. Direct acting
 Cholinergic receptor agonists
2. Indirect acting
 Acetyl cholinesterase enzyme inhibitors (AchEIs) also
called anticholinesterase
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23. 23
Cholinomimetic drugs

24. Direct Cholinergic Agonists
 Choline esters: Methacholine, Carbachol, Bethanechol
 Alkaloids: Muscarine, Pilocarpine, Arecholine
 Differ from Ach
Have longer duration of action
Effective orally & parenterally
Relatively more selective in their actions
But, still less potent than Ach
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25. Cholinomimetic drugs: therapeutic use
a) Pilocarpine
• Use: Glaucoma, xerostomia, reverse mydriatic effects of
atropine
• Dose: 1–2 gtts TID in eye 1–6 times/d
• SE: Temporary reduction in visual acuity, headache
b) Bethanecol
• Use:
1) Urinary retention - because relax urinary sphincter
2) Gastric atony
3) Paralytic ileus
• CI: gastric ulcer, recent surgery of the bowel, asthma
• Dose: 10-15mg po tid or QID, 5mg SC QID
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26. Anticholinesterases drugs
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Reversible
• Carbamates
• Physostigmine
• Neostigmine
• Pyridostigmine
• Demecarium
• Rivastigmine
• Donepezil
• Phenol
• Edrophoniuim
Irreversible
• Organophosphates
• Diisoproyl fluorophosphates
• Echothiophate
• Parathion
• Malathion
• Diazinon (Tlk-20)
• Tabun
• Sarin
• Soman
Nerve gases for
chemical warfare

27. Anticholinesterases: therapeutic uses
1) Paralytic illeus or bladder atony - Neostigmine 0.5mg sc
2) Glaucoma: Physiostigmine
3) Alzheimer's disease: donepezil, rivastigmine
4) Mayesthenia glavis
– Pyridostigmine: 30-60mg oral
– Neostigmine: 7.5-15mg oral
– Ambenonium: 2.5-5mg oral
5) Insecticide (irreversible ACEI)
– Result in bradycardia, hypotension, bronchospasm
– Parathion, malathion
Note: poisoning with anticholinesterase can be treated by
anticholinergic drugs like atropine.
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28. Properties of Indirect-Acting Cholinomimetics
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29. 29
Treatment
– Maintenance of respiration
– Atropine parenterally in large doses
– Pralidoxime chloride (2-PAM, or 2-
pyridine aldoxime methyl chloride)
effective as an antidote for
poisoning by phosphate ester
AChEIs

30.  Contraindication to cholinomimetics
– Bronchial asthma
– GIT hyper-motility
– Peptic ulcer disease
– Coronary artery disease
– Hypotension
– Bradycardia
– Hyperthyroidism: may cause atrial fibrillation
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31.  Adverse effects of cholinomimetics
• Choline esters can cause (SLUDGE BBB):
– Nausea
– Abdominal cramps
– Salivation
– Diarrhea
– Baradycardia
– Hypotension
– Reflex tachycardia
– Bronchoconstriction
– Sweating/ diaphoresis
– Lacrimation
– Urination
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32. 2. Cholinergic antagonists
Cholinergic blockers or anti-cholinergic drugs
Bind to cholinergic receptor but do not trigger the usual
receptor mediated intracellular effects
These drugs are classified as:
– Anti-muscarinic agents
– Ganglionic blockers (Nn)
– Neuromuscular blocking drugs (Nm)
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33. 33
Target Effect Use Drug
Glands secretion PUD Pirenzepine, Telenzepine
Eye Mydriasis Ophthalmic
examination
Atropine, Tropicamide,
Cyclopentolate
Urinary
bladder
 tone with
constriction
Urinary
incontinency
Tolferodine, Darifenacin,
Fesoterodine
GI smooth
muscle
 motility with
tone
Hyper motility Hyoscine
CNS Block all
muscarnic
-motion sickness
-parkinsonism
-Hyoscine/ scopolamine
-Benzotropine
Respiratory Relaxation Asthma Ipratropium, Tiotropium
Antimuscarinics…

34. Neuromuscular blocking drug
• Succinyl choline, Vecuronium, Mivacurium, Pancuronium,
Rapacurium, Gallamine
• These drugs generally block the action of acetylcholine and
produce different effect.
1) Adjuvant in general anesthesia: muscle relaxation
2) Control ventilation i.e. facilitation of endotracheal intubation
3) Prevention of trauma in electro shock therapy of psychiatric
disorder E.g. Succinyl choline
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35. Contraindications
– Glaucoma, Cardiac diseases
– Hyperthyroidism, Reflux esophagitis
– Prosthetic hypertrophy
Side effects
 Dry mouth
 Urinary retention
 Constipation
 Confusion
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36. Adrenergic drugs
1. Adrenomimetics
• Drugs which activate the effects of adrenergic SN
stimulation
• Also called sympathomimetics
• Have a wide range of effects
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37. 37

38. – Adrenomimetics can be classified into three groups
1. Direct acting adrenomimetics
– Directly interact & stimulate adrenoceptors
– Their effects are not reduced by prior treatment with
reserpine or guanethidine
– Prior treatment with reserpine or guanethidine can increase
their effects due to receptor upregulation
Examples: NE, EP, DA, IP, Dobutamine, phenylephrine,
albuterol, salmeterol, metaraminole, terbutalin, clonidine,
oxymethazoline
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39. 2. Indirect acting adrenomimetics
• Don’t interact with the adrenoceptors
• Increase availability of NE/EP to stimulate the adrenoceptors
• Their action emanates from one of the following
– Displace stored neurotransmitters from the vesicles
E.g. amphetamine, tyramine, methamphetamine
– Inhibit reuptake of neurotransmitters into the neuron
E.g. cocaine, TCAs
– Inhibit the metabolizing enzymes (MAO & COMT)
E.g. selegiline, rasagiline, entacapone, tolcapone
• Their response is abolished by prior administration of reserpine or
guanethidine
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40. 3. Mixed acting adrenomimetics
– Work by both direct & indirect mechanisms
– Increase release of NE & also activate adrenoceptors
E.g. ephedrine
– Their responses are blunted but not abolished by prior
treatment with reserpine or guanethidine
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41. 41

42. Catecholamines
Derivatives of β-phenyl ethylamine
When 3,4 OH is added to phenyl ring (3,4 OH)→ catechol ring
Hence, catechol ethyl amine→catecholamines
Phenyl ring
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Ethyl amine

43. Catecholamines…..
 These compounds share the following properties:
 High potency: by activating α or β receptors
 Rapid inactivation: metabolized (MAO&COMT)
- have a brief of action when given parentrally, and are
ineffective when administered orally because of
inactivation
 Poor penetration into the CNS
- Catecholamines are polar & do not cross BBB
- Nevertheless have some clinical effects that are
attributed to the action of CNS.
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44. Adrenaline/Epinephrine
• Stimulate both α with β receptor
Use:
1) Asthma (β2 - selective are better)
2) Anaphylactic shock
3) Potentiation with prolongation of action of local anesthetic
(by  absorption)
4) Restore normal cardiac rhythm in case of cardiac arrest
5) Topical hemostatic agent (control superficial bleeding)
• Dose:
SC, IM 0.1mg - 0.5mg
IV - 0.25mg (in emergency an IV can be used but should be
diluted and given by IV infusion because of cardiac
arrhythmia. 44

45. α1 adrenergic agonists
• Phenylephrine
• Xylomethazoline
• Methoxamine
• Use:
1) Nasal decongestant
2) To raise BP in hypotensive state & shock
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46. Alpha 2 - adrenergic agonist
Methyldopa (aldomet)
• MOA -  sympathetic outflow,
• Use: moderate to severe hypertension in pregnant mom.
• Dose: initial 250mg 2-3X/day
– Usual dose range 250mg -1000mg po bid.
• AE:
– headache, fatigue, sleep disturbance
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47. β2 Agonist
Include
• Salbutamol/albuterol – rapid acting
• Terbutaline
• Formetrol & Salmetrol – long acting (nocturnal asthma)
• Ritodrine-for Preterm Labour
Use
1) Asthma, albuterol 2 puffs every 4-6 hours as needed (90
mcg/inhalation)
2) Premature labour, terbutaline 2.5-5 mcg/minute over 12hrs
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48. Ephedrine
• Both α with β agonist (mixed acting)
Use:
1) Asthma - 25-50mg PO 3-4 PRN
2) To treat hypotension
3) Used to relieve broncho-constriction with mucosal
congestion (incorporated in cough syrup)
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49. 2. Adrenoceptor antagonists
 Works by competing with adrenomimetics for access to
adrenoceptors
– Reduce effects produced by both sympathetic nerve
stimulation & exogenous adrenomimetics
• Adrenoceptor antagonists
– Don’t prevent release of NE/EP from adrenergic neurons
– Are not catecholamine depleting agents
– Are also called, sympathoplegics, sympatholytics
49

50. 50

51. 51

52. α1 - Blockers
• Use:
– Hypertensive crisis
– Short term control of BP in pheochromocytoma
– Drug choice for HTN with benign prostate hyperplasia
(BPH)
• SE:
 orthostatic hypotension, headache, water retention
(relaxation), first dose syncope (fainting)
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53.  -Blockers
A. Non selective -Blockers
– Are also called 1st generation -blockers
– Propranolol, Timolol, Nadolol, Pindolol
B. Cardio selectives [1Blockers ]
– Are called 2nd generation -blockers
– Atenolol, Bisoprolol, Esmolol, Metoprolol
C. Non-selective adrenergic blockers( &  Blockers)
– Are also called 3rd generation -blockers
– Carvedilol, Labetalol, Bucindolol, Nebivolol
Longest half life: Nadolol, Cartelol (24 hrs)
Shortest half life: Esmolol (10 min) 53

54. • Some of the β-blockers have some intrinsic activity &
membrane stabilizing activity
– May be considered as partial antagonists
– Examples
• Pindolol
• Acebutolol
• Bucindolol
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55. β – Blocker: Therapeutic use
 Hypertension- alone or with diuretic
 For angina treatment: by decreasing cardiac work with
oxygen demand
 For chronic heart failure… only metoprolol, bisoprolol & carvedilol
 For cardiac arrhythmia
 Glaucoma treatment: Timolol
 Anti anxiety related to performance: Propranolol
 Prophylaxis of migraine
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56. 56

57. Adverse effects of β-blockers
 CVS
– Bradycardia
– hypotension
– AV block
 Bronchoconstriction
 Hypoglycemic effect
 Affect lipid profile
 Muscle pain & fatigue
 Sleep disturbances, nightmares
 Impaired sexual activity
 Reduce peripheral blood flow  cold extremities
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More pronounced with 1 selectives
Produced by non-
selective blockers

58. Contraindications to β-blockers
 Acute Heart failure
 Bradycardia
 Slow AV-node conduction
 Asthma & COPD
 Diabetes mellitus
 Hypothyroidism
 Combination with Ca++-channel blockers
 Some general anesthetics- cardiac depression
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59. Thank You!
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60. Assignment
1. Management of Shock (types, pathophysiology of shock
and their management).
2. Pharmacology of anesthetics (local anesthetics and
general anesthetics)
3. Management of Neurodegenerative disorders
(Alzheimer’s disease, Huntington disease, multiple
sclerosis….)
4. New drug development process (preclinical trial and
clinical trials)
5. Management of selrected cardiovascular disorders
(myocardial infraction, ischemic stroke, haemorrhagic
stroke, valvular heart disease).
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