1. Chapter 6: Introduction to Autonomic Pharmacology
Autonomic Drugs
Chapter 6: Introduction to Autonomic
Pharmacology

2. Q1: How Many Parts are there in Human Nervous System? What are they?
Central Nervous System (CNS)
Peripheral Nervous System (PNS)

3. Q2: How does the CNS Consist of?

4. Q3: How does the PNS Consist of?
Afferent Nervous System (In)
Efferent Nervous System (Out)
Autonomic Nervous system (ANS)
(two neurons)
Somatic Nervous System (SNS)
(single neuron)

5. Q4: What Is the Basic Cell of NS?
Cell Body
Neuron
Neurite
Dendrite
Cell Body
Axon

6. Q5: What is the Connection between neurons?
Synapse

7. Q6: What is the Collection of axon fibers?
Nerve

8. Q7: What are Collections of neuron cell bodies in the CNS and PNS?
Ganglion (PNS)
Nuclei(CNS)

9. Q8: What is a Neurotransmitter?
Endogenous chemical
released from neurons
to communicate with
target cells of muscles,
organs, or neurons
across synapses

10. Q9: What is a Receptor? Receptor A molecular structure
or site on the surface
or interior of a cell
that binds with
substances such as
hormones, antigens,
drugs, or
neurotransmitters

11. FUNCTIONS OF THE NERVOUS SYSTEM
1. Control center
2. Responds and adapts to changes that occur both inside and outside the body
Ex: pain,
temperature,
pregnancy

12. Summarization of the Nervous System
PNS
ceptor
AFNS
CNS
ANS
ENS
effector
SNS
PNS
Accidents
Drugs
Alcohol
Disease
Factors that can change the function of NS:

13. Efferent Nervous System

14. Autonomic Nervous System (ANS)
Autonomic means automatic.
Auto: self Nomos: law (functioning by its own law, not under conscious control)
You DO NOT control your Autonomic Nervous System, it works automatically.

15. Autonomic Nervous System (ANS)
ANS controls the functions of MANY organs automatically.
That is why many drugs affecting the ANS affect many organs
eyes, pupils, lacrimal glands, salivary glands, heart, blood vessels, lung airways, bowels, pancreas, ureters, bladder

16. Classification of Autonomic Nervous System (ANS)

17. Classification of Autonomic Nervous System (ANS)
Sympathetic Division:
Adrenaline Rush
Fear, Flight, Fight
Prepare body for
stress

18. Sympathetic Division
Can you guess what is happening to Poor Jerry’s organ functions?
Running is voluntary, but everything else is automatic!

19. Sympathetic Division Heart: Pounding, HR BP: Sky High
Lung Airway: Wide Open
Blood to Muscles: Increased
Blood to GI: Decreased
Digestion: Stopped
Pupils: Dilated

20. Classification of Autonomic Nervous System (ANS)
Parasympathetic Division:
Rest, Repair,
Digest
Recover body
from stress

21. Parasympathetic Division:
Can you guess what is happening to her when she is relaxing by doing Yogo?

22. Parasympathetic Division
HR: Dropping
BP: Normal
Lung Airway:
Constricted
Blood to Muscles:
Decreased
Blood to GI:
Increased
Digestion: Increased
Pupils: Constricted

23. Autonomic Nervous System (ANS)

24. Transmission of ANS
Synapse
neurotransmitters
Receptors

25. Transmission of ANS Five Steps Impulse conduction Transmitter release
Transmitter combine with specific receptors on postsynaptic membrane
Postsynaptic activity
Termination of transmitters action

26. Neurotransmitters of Autonomic Nervous System (ANS)
Acetylcholine: Ach
Catecholamines
-- Dopamine
-- Norepinephrine (NE) = Noradrenaline (NA)
-- Epinephrine (EP) = Adrenaline (AD)
Serotonin, GABA

27. Neurotransmitters of Autonomic Nervous System (ANS)
Two primary neurotransmitters
Acetylcholine: Ach
Norepinephrine: NE = Noradrenaline (NA)

28. Where is Acetylcholine
Acetylcholine is made from
AcetylCoEnzyme A
made by mitochondria as part of energy transfer
Choline
Lecithin has fatty acids that contains choline

29. Where is Acetylcholine
Neuromuscular Junction
-- the neurotransmitter that signals voluntary muscle movement is acetylcholine (N-R) A P
Axon
Acetylcholine
Neuron Terminal
N-R
Synapse
Voluntary Muscle

30. Where is Acetylcholine
Autonomic Nervous System
-- the neurotransmitter that signals parasympathetic smooth muscle movement is acetylcholine (M-R) A P
Axon
Acetylcholine
Neuron Terminal
M-R
Synapse
Heart, Lung, Pupils, GI

31. Where is Acetylcholine
Central Nervous System (CNS)
We will discuss cholinergic and anticholinergic medications when we talk about Parkinson’s Disease

32. Where is Acetylcholine
Autonomic Nervous System
-- the neurotransmitter that signals parasympathetic smooth muscle movement is acetylcholine (M-R) A P
Axon
Acetylcholine
Neuron Terminal
M-R
Synapse
Heart, Lung, Pupils, GI

33. Where is Norepinephrine
Norepinephrine is a member of
catecholamine family, which is made
from
Amino Acid Tyrosine
Chemical Steps
Dopamine Norepinephrine Epinephrine

34. Where is Norepinephrine
Autonomic Nervous System
-- the neurotransmitter that signals sympathetic smooth muscle movement is norepinephrine (α/β-R) A P
Axon
Norepinephrine
Neuron Terminal
α/β -R
Synapse
Vascular Smooth Muscle (α-R) Heart, Lung Smooth Muscle(β-R)

35. Autonomic Nervous System

36. Biosynthesis, storage, release and termination of Acetylcholine (Ach)
mitochodria
inhibitor

37. Biosynthesis, storage, release and termination of Norepinephrine (NE)
mitochodria

38. Termination (pump and enzyme)
Ach: diffused into choline and acetate by acetylcholinesterase (AchE) in synapse, very efficient

39. Termination (pump and enzyme)
NE: diffused into vanillylmandelic acid (VMA)
and homovanillic acid (HVA)
I. uptake1 (neuronal uptake ) 75%-90%
storage in vesicles\ MAO (monoamine
oxidase)
II. uptake2 (non-neuronal uptake) 10-25%
COMT(catechol-methyltranferase)\MAO

40. Receptors of ANS Classification: Cholinoceptor: stick to acetylcholine
Adrenoceptor: stick to norepinephrine
(noradrenaline)

41. Acetylcholine Receptor (Cholinoceptor)
Two Types
Muscarinic receptors (M-R) : muscarine
Nicotinic receptors (N-R) : nicotine

42. Acetylcholine Receptor (Cholinoceptor)
Muscarinic receptors (M-R):
Five Subtypes
M1-R: ganglion, CNS
M2-R: heart, presynaptic sites (negative
feedback), CNS
M3-R: exocrine glands, smooth muscle,
endothelium, CNS
M4 –R: exocrine glands, smooth muscle, CNS
M5 -R: CNS

43. Acetylcholine Receptor (Cholinoceptor)
Nicotinic receptors (N-R):
Two Subtypes
NM-R: skeletal muscle
NN-R: ganglion and CNS

44. Norepinephrine Receptor (Adrenoceptor)
Two Types:
Alpha receptors (α-R):
Beta receptors (β-R)

45. Adrenoceptor α-R: Two Subtypes α1-R: postsynaptic effector cells α2-R:
(especially smooth muscle)
α2-R:
presynaptic nerve terminals (negative feedback),
platelet, smooth muscle, lipocytes

46. Adrenoceptor β-R: Three Subtypes β1-R: postsynaptic effector cells,
(especially heart, lipocytes,)
presynaptic nerve terminals
β2-R: postsynaptic effector cells,
(especially smooth muscle)
β3-R: postsynaptic effector cells,
(especially lipocytes)

47. Important Points Many drugs affecting ANS affect many organs
The sympathetic and parasympathetic divisions of ANS have opposing effects in many organs

48. Important Points
Acetylcholine (Ach) and Norepinephrine (NE) are two primary neurotransmitters in ANS
Ach is the primary neurotransmitter at parasympathetic and somatic neuroeffector junctions
NE is the primary neurotransmitter at sympathetic junctions

49. Important Points
Chemicals or sites bind with acetylcholine at postsynaptic membranes are called cholinergic receptors. They are muscarinic receptors (M-R) and nicotinic receptors (N-R).
Chemicals or sites bind with norepinephrine at postsynaptic membranes are called adrenergic receptors. They are alpha (α-R ) and beta receptors (β-R).

51. Biosynthesis Choline and Tyrosine neuron terminal cytoplasm
Transport
Choline and Tyrosine neuron terminal cytoplasm
In the cytoplasm
1. choline + acetyl-coenzymeA Ach
2. tyrosine neuron terminal DOPA
Dopamine
Na+-dependent membrane carrier
Catalytic action
Choline acetyltransferase, ChAT
Transport
Tyrosine hydroxylase
Na+-dependent membrane carrier
dopa decarboxylase

52. Storage 1. Ach vesicles 2. Dopamine vesicles NE (in the vesicles )
Ach, ATP, Peptide
Transport
Antiporter
Transport
dopamine hydroxylase
Antiporter
NE, ATP, Peptide

53. Release
Calcium-dependent process: AP triggers sufficient influx of calcium ions
Exocytosis: fusion of the vesicular membrane with the terminal membrane
Quantal release: several hundred quanta of Ach/NE into the synaptic cleft
Cotransmission: ATP, peptide, dopamine-β-hydroxylase are also released into the synaptic cleft

54. General Actions of Acetylcholine
Promotes transmission in postganglionic autonomic fibers
Promotes release of epinephrine and norepinephrine from the adrenal medulla
Promotes transmission in skeletal muscle fibers
Promotes the functions of the parasympathetic nervous system at cardiac muscle, smooth muscles and glands
Promotes sympathetic thermoregulatory sweating

55. Acetylcholine Receptor (Cholinoceptor)
Receptor Name
Tissue
Action
Muscarinic
Receptors
CNS neurons, sympathetic postganglionic neurons, some presynaptic sites
Myocardium, smooth muscle, some presynaptic sites
Exocrine glands, vessels (smooth muscle and endothelium)
Formation of IP3 and DAG, increased intracellular calcium
Opening of potassium channels, inhibition of adenylyl cyclase
Nicotinic
Postganglionic neurons, some presynaptic cholinergic terminals
Skeletal muscle neuromuscular end plates
Opening of sodium, potassium channels, depolization M1 M2 M3 NN NM