Introduction

MBBS III Sem

Dr.U.P.Rathnakar
MD.DIH.PGDHM

[Pharmacology]

ANS

[Skeletal muscles ]

[Cholinergic system] [Adrenergic system] 2

Sympathetic out flow:Thoraco-lumbar

Para-sympathetic outflow:Cranio-sacral

 N.Transmitter Receptor N.Transmitter Receptor

Parasympathetic Sympathetic Enteric Synapse

Synapse

Synapse

Synapse

Somatic
[Not ANS]
N.Transmitter Receptor

Synapse

Autonomic Supplies all innervated structures Synapses outside CNS Ganglia + Peripheral plexus + Spontaneous activity in effectors+ Interruption of nerve supply-No atrophy

Somatic Sk.Muscles Inside C.S.axis No ganglia No peripheral plexus None

Interruption of nerve supply-Disuse atrophy

NA, Adrenaline, acetylcholine

Acetylcholine

Flight, Fight and Fright

Sit & Digest

Sympathetic[Ex., Emergency, embarrassment]

P.Sympathetic [Energy saving & restorative] 8

Organ
Survival Eye Heart Bronchi GIT Sphincters UB

Sympathetic [Fight, flight]

Possible Mydriasis Stimulation Dilatation

Motility,Secretion Contract
Relaxes detrusor contracts trigon, & sphincter Ejaculation

P.Sympathetic [Sit, digest] Not possible Meiosis Depression Spasm Motility,Secretion

Relax
Contracts detrusor, Relaxes trigon & sphincter Sexual arousal
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Sexual organs

Drugs acting on the ANS

Cholinergic drugs [P.S.Mimetic] Anticholinergic drugs[P.S.lytic] Neuromuscular blockers Adrenergic drugs [Symp.mimetic] Blockers[antiadrenergic] [Symp.lytic]

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ANS Pharmacology
[Targets of drug action]

Receptors Neurotransmitters

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Adrenergic receptors
Receptors: 1, 2 1, 2, 3

Neurotransmitter- Nor adrenaline, Adrenaline

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Receptors- Parasympathetic CHOLINERGIC

Muscarinic= M1, M2, M3, M4, M5 Nicotinic= N N , NM

Neurotransmitter = Acetylcholine
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Neurotransmitters
Nerve impulses elicit responses in effector organs and post synaptic neurones through liberation of specific chemical transmitters

Junctional transmission conduction

Vs

Nerve
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Junctional [synaptic] transmission Otto Loewis experiment

Electrical VS Humoral
Bradycardia

Flow of Chemical substance

Bradycardia

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Criteria: Neurotransmitter
1. Should be neurones

present in Presynaptic

2. Should be

Released on nerve impulse

3. Application of sub. Produces Similar response to nerve stimulation 4. Effects are antagonised or

potentiated by other sub. Which also have similar effect on nerve 16 stimulation.

Steps in neurotransmission:
Impulse conduction Arrival of impulse Synthesis Storage & release of transmitter Combination of transmitter with P.J. receptors Postjunctional activity: Excitatory[EPSP] or Inhibitory[IPSP] Termination of neurotransmitter action [Diffusion, destruction, reuptake]

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 Impulse conduction:

Na conductance DepolarizationInside (+)ve(K flows outRepolarization) Action potentialImpulse propogation.

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Storage & release of transmitter:

Neurotransmitter synthesized and stored in pre junctional nerve endings in Synaptic Vesicles Arrival of nerve impulseFuses vesicular and axonal membrane Ca entry fluidizes membraneContents of vesicle releasedExocytosis Other protiens also participate in docking and fusion. Presynaptic receptors modulate transmitter release
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 Combination of transmitter with P.J. receptors and P.J.potential:

Excitatory post synaptic potential(EPSP): permeability to cations-Na or Ca Depolarization EPSP

IPSP: permeability to K or Cl Hyperpolarization IPSP

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Termination
After a neurotransmitter molecule binds to a receptor molecule, it must be removed Processes: 1. The neurotransmitter may diffuse away 2. Enzymes within the subsynaptic membrane may inactivate/metabolize the neurotransmitter. 3. Reuptake pumps may actively pump the neurotransmitter back into the presynaptic axon terminal for reprocessing and re-release following a later action potential.
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Termination of neurotransmitter action

Cholinergic-Dissipation or destruction ACHE(acetylcholinesterase) Hydrolyzes Ach. if ACHE is inhibited action prolonged
Adrenergic-Diffusion, Reuptake, [enzymes-MAO, COMT]
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 NON-Electrogenic functions of neurotransmitter:

Continuos low grade releaseNo P.J. activity But important

Regulation of neurotransmitter biosynthetic and degradative enzymes Pre- and post-synaptic receptor density

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 Co-Transmitter: Other transmitters released along with principal transmitter Ach-VIP, NA-ATP Other cotransmitters- Adenosine, neuropeptide-Y, NO, Somatostatin etc.

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NANC: Nonadrenergic-noncholinergic transmission-exists in ANS. Principal transmitter is not Ach or NA. Eg. In GIT, GUT, (adenosine, ATP, NO)

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Neurotransmitters and receptors

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Neurotransmitters:Adrenergi c and Cholinergic

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Adrenergic system
[Drug targets]

- Agonists and antagonists [Blockers] Agonists and antagonists [Blockers] Distribution?????

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Cholinergic system
[Drug targets]

Cholinergic drugs
*Directly acting [Cholinomimetics] *Indirectly acting [Anticholinesterases]

Anticholinergic
Distribution of receptors???
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ANS-exceptions
Only symp. innervation Only P.symp. Innervation Adrenergic receptors-no symp.innervation Cholinergic receptors-no P.symp. Innervation Fibers symp. In origin-cholinergic in character
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Questions
Criteria for neurotransmitter Explain steps in neurohumoral transmission Enumerate cholinergic sites Enumerate the distribution of cholinergic/ adrenergic receptors.

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