autonomic physiology and pharmacology

Question 1

what’s the difference between autonomic and somatic nervous system efferent pathways?

Answer 1

somatic - to skeletal muscle

autonomic
- ganglion split into pre-ganglionic (small myelinated) fibre and post-ganglionic (unmyelinated) fibre
- goes to smooth muscle, cardiac muscle, glands, GI neurones

Question 2

whats the difference between autonomic and somatic nervous system target connection?

Answer 2

somatic
- specialised neuron muscular junction

• alpha motor neurons release ACh directly onto the nicotinic receptors on the end plate
• ionotropic receptors with integral ion channels, depolarization always excites the skeletal muscle

autonomic
- neurotransmitter released from varicosities

• metabotropic receptors (G-protein coupled), they either depolarize or hyperpolarize

Question 2

describe the outflow from CNS and location of ganglia of parasympathetic nervous system (rest and digest system):

Answer 2

Cranio-sacral outflow (in the brain and sacrum)

Ganglia lie close to or near the target

(long preganglionic fibres & short postganglionic fibres)

Question 3

what are 2 autonomic neurotransmitters?

Answer 3

Acetylcholine acts on cholinergic receptors

e.g. Nicotinic receptors (ionotropic) & Muscarinic receptors (metabotropic)

Noradrenaline acts on adrenergic receptors

e.g. alpha receptors & beta receptors

Question 3

describe the outflow from CNS and location of ganglia of sympathetic nervous system (fight or flight system):

Answer 3

Thoracolumbar outflow (in thoracic and lumbar segments)
(T1-T12 & L1-L2)

Ganglia close to the spinal cord in the sympathetic trunk
(para-vertebral ganglia)

(short preganglionic fibres & long postganglionic fibres)

Question 4

all preganglionic fibers release acetylcholine, which acts on nicotinic cholinergic receptors.

Question 5

what do parasympathetic and sympathetic post ganglionic fibers release?

Answer 5

parasympathetic - acetylcholine which acts on cholinergic muscarinic receptors on the target.

Sympathetic postganglionic fibres release noradrenaline, which acts on either alpha or beta-type adrenergic receptors.

Question 6

What is the one exception to preganglionic fibres that go straight through?

Answer 6

There is one exception of preganglionic fibres that go straight through
sympathetic trunk → celiac ganglia → postganglionic cells on adrenal gland

This releases adrenaline & noradrenaline into the blood.
(mass hormonal activation if this works)

Question 7

what are 2 exceptions to the rule in sympathetic post-ganglionic fibres?

Answer 7

There are two exceptions to the rule in sympathetic postganglionic fibres:

1- Sympathetic cholinergic fibers that innervate sweat glands

2- Non-adrenergic non-cholinergic (NANC) transmitters e.g. peptides

Question 8

using the eye as an example, describe what the sympathetic system does:

Answer 8

Noradrenaline activates a1 receptors on the radial muscle of the iris

Radial muscle contracts & makes the pupil larger

• Noradrenaline activates b2 receptors on ciliary muscle around the lens

The ciliary muscle relaxes & eye focuses far away

Question 9

using the eye as an example, describe what the sympathetic system does:

Answer 9

Acetylcholine activates muscarinic receptors on the sphincter (circular) muscle of the iris

Contracts sphincter muscle & makes pupil smaller

• Acetylcholine activates muscarinic receptors on ciliary muscle around the lens

Ciliary muscle contracts & eye focuses close-up

An example of two different types of antagonistic actions

Question 10

using the heart as an example, describe what the sympathetic system does:

Answer 10

Noradrenaline activates {{c1::b1 receptors}} on the pacemaker cells

Increases heart rate

• Noadrenaline activates {{c1::b1 receptors}} on the myocytes

Increases strength of contraction

Question 11

using the heart as an example, describe what the parasympathetic system does:

Answer 11

• Acetylcholine activates muscarinic receptors on pacemaker cells
  > Decreases heart rate
• Little effect on myocytes
  > Little effect on the strength of contraction

Question 11

Explain the sympathetic and parasympathetic effect on the lungs

Answer 11

Sympathetic system

• Noradrenaline activates b2 receptors on the smooth muscle of airways
  > Makes smooth muscle relax & dilates airways

Parasympathetic system

• Acetylcholine activates muscarinic receptors on the smooth muscle of airways
  > Makes smooth muscle contract & constricts airways

Question 11

Why do patients with asthma and heart problems take salbutamol?

Why do patients with hypertension and lung problems take atenolol?

Answer 11

Because salbutamol is a b2 agonist

→ dilates airways, but does not affect the heart.

Because atenolol is a b1 antagonist

→ decreases heart rate, but does not affect airways.

Question 12

Explain the redirection of blood during exercise

Explain the sympathetic and parasympathetic effects on the blood vessels

Answer 12

Sympathetic System

Tissues that contain b2 receptors e.g. heart and skeletal tissue

→ vasodilation & increase in blood flow during fight or flight

Tissues that contain a1 receptors e.g. kidneys, GI tract …etc.

→ vasoconstriction & decrease in blood flow during fight or flight

Parasympathetic System

Does not affect the majority of blood vessels

Exceptions - salivary glands & genitalia

Question 12

Explain the sympathetic and parasympathetic effects on the salivary glands:

Answer 12

Sympathetic system

• Noradrenaline activates b receptors
  Stimulates thick secretion rich in enzymes

Parasympathetic system

• Acetylcholine activates muscarinic receptors
  Stimulates profuse watery secretion

An example of dual innervation with non-antagonistic actions i.e. no relax vs contract

Question 12

Explain the sympathetic and parasympathetic effect on the blood vessels:

Answer 12

Sympathetic system

• Noradrenaline activates a1 receptors on the smooth muscle of vessels
  > Makes smooth muscle contract (vasoconstriction) & blood flow decreases
• Noradrenaline activates b2 receptors on the smooth muscle of vessels
  > Makes smooth muscle relax (vasodilation) & blood flow increases

Parasympathetic system

Usually no effect, except in genitalia and salivary glands. (EXCEPTIONS)

i.e. the response depends on what receptors each tissue expresses

Single-system (sympathetic) innervation of the blood vessels means that a tone is continually maintained, so you either increase activity or decrease it.

Question 12

using the bladder as an example explain the sympathetic and parasympathetic effects:

Answer 12

Sympathetic system

• Noradrenaline activates a1 receptors on the smooth muscle of the sphincter
  Contracts smooth muscle and stops urination
• Noradrenaline activates b2 receptors on the smooth muscle of the bladder wall
  Relaxes smooth muscle and reduces pressure

Parasympathetic system

• Acetylcholine activates muscarinic receptors on the smooth muscle of the sphincter
  Relaxes smooth muscle and causes urination
• Acetylcholine activates muscarinic receptors on the smooth muscle of the bladder wall
  Contracts smooth muscle and increases pressure

Question 13

explain the effects of parasympathetic & sympathetic on the reproductive tract as an example:

Answer 13

Sympathetic system

• Noradrenaline activates a1 receptors on the smooth muscle of the urethra
  Contracts smooth muscle and causes ejaculation

Parasympathetic system

• Acetylcholine activates muscarinic receptors on the smooth muscle of the corpus cavernosum
  Relaxes smooth muscle & causes erection

An example of dual innervation with complementary effects

Question 14

what is the baroreceptor reflex?

Answer 14

a type of autonomic reflex that detects blood pressure, and sends info to the integrating centre in the brain, then that centre coordinates sympathetic and parasympathetic outflow to the tissues accordingly..

Question 14

what does the hypothalamus do?

Answer 14

it’s a portion of the brain responsible for central control, it coordinates autonomic, somatic, and endocrine activity.

Both of them together control the sympathetic and parasympathetic systems

Question 15

what type of receptors does the neuromuscular junction use?

Answer 15

nicotinic

Question 16

what are the 8 steps of synaptic transmission?

Answer 16

1. Synthesis and packaging of neurotransmitters (usually) in presynaptic terminals
2. Na+ action potential invades the terminal
3. Activates voltage-gated Ca2+-channels
4. Triggers Ca2+-dependent exocytosis of pre-packaged vesicles of transmitter
5. Transmitter diffuses across cleft and binds to ionotropic and metabotropic receptors to evoke
   a postsynaptic response
6. Presynaptic autoreceptors inhibit further transmitter release by closing calcium channels
7. The transmitter is (usually) inactivated by an enzyme or is uptaken into glia or neurones
8. Transmitter is metabolised within cells

Question 17

what are the 5 ways to inhibit AP transmission, targeting NMJ transmission?

Answer 17

1- inhibit choline transporter e.g. hemicholinium 2- Block voltage-gated Ca2+ channels e.g. black widow spider venom 3- Block vesicle fusion e.g. botulinum 4- Use non-depolarising nicotinic receptor blockers (competitive antagonists → high affinity & low/zero efficacy) e.g. d-tubocurarine 5 - Use depolarising nicotinic receptor blockers (keep muscle depolarised and stop voltage-gated sodium channels from working again) e.g. succinylcholine

Question 18

How does an anticholinesterase work? e.g. eserine

Answer 18

An anticholinesterase blocks acetylcholinesterase → stops breakdown of ACh so it hangs around in the synaptic cleft for longer.

Question 18

when targeting postsynaptic parasympathetic transmission, what do muscarinic receptors do?

Answer 18

Muscarinic receptor agonists - e.g. carbachol, pilocarpine * mimic the effect of the parasympathetic system (slow heart rate, contract smooth muscle in airways and bladder, increase gut motility, increase bronchial secretions and salivation, constrict pupil) Muscarinic receptor antagonists - e.g atropine * will block effects of the parasympathetic system i.e. mimic the effect of the sympathetic system (increase heart rate, relax smooth muscle in airways and bladder, reduce gut motility, bronchial secretions and salivation, dilate pupil)

Question 19

What is Glaucoma and how are muscarinic agonists used to relieve it?

Answer 19

Glaucoma is raised intraocular pressure. Muscarinic agonists contract the ciliary muscle supporting the lens and the sphincter muscle of the pupil to increase drainage of the aqueous humour through the canal of Schlemm

Question 19

what are 5 ways to inhibit AP transmission when targeting postganglionic sympathetic transmission?

Answer 19

1- Blocking the enzymes that produce NA e.g. carbidopa 2- Blocking the transporter that fills the vesicles with NA e.g. reserpine 3- introducing a “false” transmitter e.g. methyldopa * looks like NA but doesn't bind to receptor 4- Activating inhibitory presynaptic (α2) autoreceptors * inhibits voltage gate Ca2+ channels, so reduces the release of vesicles. e.g. methyldopa 5- Blocking α or β postsynaptic receptors e.g. doxazosin or propranolol

Question 19

how does the mechanism of removing neurotransmitters differ in NMJ than in postganglionic cleft?

Answer 19

NMJ - usage of an enzyme called acetylcholinesterase to break down acetylcholine and then it's taken up the presynaptic terminal Postganglionic cleft - usage of a reuptake molecule to take noradrenaline back into the presynaptic terminal

Question 20

what are 3 ways to potentiate AP transmission when targeting postganglionic sympathetic transmission?

Answer 20

1- Stimulate NA release e.g. amphetamine 2- Inhibit uptake into: Neurones e.g. cocaine & tricyclic antidepressants Glia e.g. phenoxybenzamine * Allows NA to hang out around the cleft longer 3- Activate postsynaptic receptors e.g. phenylephrine and salbutamol All of the above-mentioned drugs are known as sympathomimetics

Question 20

summary: Mention some clinical applications of alpha and beta agonists:

Answer 20

α1 agonists (contraction of muscle) can be used as decongestants and dilate the pupil (mydriatics) * α2 agonists can be used in the treatment of hypertension * β2 agonists (relaxation of muscle) can be used in the treatment of asthma * β1 antagonists can be used in the treatment of hypertension, angina and cardiac arrhythmias