Autonomic Nervous System

Question 0

What are drugs that increase the parasympathetic system called?

Answer 0

Parasympathomimetic - a drug which MIMics the PARASYMPATHetic system

Question 1

What are drugs which increase sympathetic function called?

Answer 1

Sympathomimetic - drugs that MIMIc the SYMPATHetic system

Question 2

What are drugs that decrease sympathetic function called?

Answer 2

Sympatholytic - a drug which Limits the SYMPATHetic system

Question 3

What are drugs which reduce the parasympathetic function called?

Answer 3

Parasympatholytic - a drug which Limits the PARASYMPATHetic system

Question 4

What is the general action of anitcholinesterases?

Answer 4

Increase the availability of acetylcholine

Increase post synaptic stimulation, which is mostly parasympathetic as this is the path that has most of the acetylcholine receptors.

The side effects that can be predicted are:
M2 - cardiac, decrease in heart rate which then causes a drop in blood pressure
When there is inhibition of peripheral cholinesteraises, there is increased risk of activation of endothelial cholinergic receptors, which stimulates nitric oxide production, causing vasodilation which will contribute to a hypotension response.
M3 - VSMC contraction, ie increased peristalsis, bronchoconstriction
Stimulation of secretory receptors

Large doses of will initially stimulate, then block as the receptors are desensitised.

This is very useful, as drugs which can cause this can be used as muscle relaxant.

Question 5

What is a short acting anticholinesterases ?

Answer 5

Edrophonium is a short active anticholinesterase, which is used a diagnostic tool for myasthenia gravies ( reduces nicotinic cholinergic receptors in skeletal muscle). When given, it increases acetylcholine available, so if weakness was present this will provide a maximum response.

Question 6

What is a medium acting anticholinesterase?

Answer 6

Neostigmine is a medium acting cholinesterase, which increases acetylcholine present for a longer time, allowing it to outcompete any drug which is competing for receptor activity. This can be used to reverse any blocking effect which is preventing contraction, ie muscle relaxants. It is only used in skeletal muscle, not used in any neural disorders as it doesn’t cross the blood brain barrier.

Question 7

What is myasthenia gravis?

Answer 7

Autoimmune disorder which causes muscle weakness as there is loss of nicotinic receptors at the neuromuscular junction.

Edrophonium can be used to determine if treatment is required/is suitable.

If there is no response, this means that the acetylcholine is causing a block which is preventing contraction, and the treatment is too high.

If there is an improvement, it suggests that the current treatment is too low as higher acetylcholine has produced an improvement.

Over time more receptors are lost, and treatment ceases to be effective.

Question 8

What are the common side effects to drugs that increase acetylcholine avalibility and why?

Answer 8

As acetylcholine stimulates receptors most commonly associated with the parasympathetic system, we expect to see common side effects in relation to where those receptors are located.

Increased GI motility
Increased salivation
Nausea & vomiting - no credit for this as common to most drugs
Bronco-constriction - cautionin people who suffer from ASMA!!!
Brady aria and hypotension

It can be administered with an anti-muscarinic drug to reduce side-effects

Question 9

Which medium term anticholinesterases are used in Alzheimer’s and their properties.

Answer 9

Donepezil is 24 hrs duration, has some side effects
Rivastigmine has 8hrs duration, side effects subside over time

These can help improve cholinergic transmission in the cns, which helps to ameliorate the deficits caused by the disease.

Common side effects include
Nausea and vomiting 
Increased Gi motility
Incontinence 
Bradycardia

Caution in ASTHMA and irregular heart beat.

It can also be hepatotoxic

Question 10

What are irreversible anticholinesterases?

Answer 10

Organophosphate poisoning
Remove ability for acetylcholinesterases to work protectively
Large problems its breathing, bradycardia
If it crosses the brain blood barrier it causes severe peripheral nerve demyelination
Can be treated and symptoms relived with atropine ( which blocks receptors thus limiting the amount of excessive stimulation that can occur) however this does not treat any cns damage

Question 11

What effects does excessive acetylcholine have on the CNS?

Answer 11

Initially excitation ie convulsions

Then depression of system leading to unconsciousness and respiratory failure.

Question 12

What general actions do muscarinic receptor antagonists exhibit?

Answer 12

Antagonists block the normal function of the receptor, so the general effects are opposite of those that would be caused by normal activation.
Secretion will be reduced, including salivary,sweat and gastric.
Blocking muscarinic receptor in the heart will switch on pathways that are associated with the sympathetic system, ie elevation of heart rate/ tachycardia.
Gi motility will be reduced, increase risk of constipation.
Bronco dilation so can be used for short term asthma relief, although beta blockers are preferred.

Question 13

What are the examples of muscarinic receptor antagonists?

Answer 13

Atropine is readily absorbed from gut and can cross blood brain barrier.
Relatively selective for m2, but not specific.

Hyosine can be used to prevent motion sickness.

Question 14

What is the difference between muscarinic and nicotinic acetylcholine receptors?

Answer 14

In the nervous system, most pathways have a pregangleonic neuron and a post gangleonic neuro, with the exception of the somatic system which has only one.

The first of these neurons is the nicotinic acetylcholine receptor, and is a ligand gated ion channel. This means it operated very quickly, and is often responsible for the release of the first neurotransmitter. In the somatic system this is the type present.

The second neuron is the muscarinic receptor, which is a GCPR, which takes longer to act. All muscarinic receptors are this type.

Question 15

Describe how nicotine and DMPP affect transmitter release.

Answer 15

If the receptor is nicotinic, it can be affected by nicotine. This can affect any nicotinic receptor and can cause a variety of symptoms in smokers.

Question 16

What is a non-depolarising blocking agent?

Answer 16

This is a competitive antagonist, which blocks reaction by decreasing the number of receptors that are activated by actylcholine by filling the receptors. This can be reversed by increasing the concentration of acetylcholine at the receptor.

Question 17

What is a depolarising blocking agent?

Answer 17

This is a drug that activated the receptor and initially causes some contraction, however the maintained depolarisation which they cause means that the NA+ channels in the membrane to enter an inactive stat which prevents any AP propagation. Because of this increasing acetylcholine will only prolong the block.

Question 18

What is autonomic ganglia stimulation?

Answer 18

This is when a drug stimulates the first post synaptic receptors, which is sensitive to acetylcholine, but also nicotine as it is a nicotinic receptor. This then causes further release of secondary neurotransmitters,which is acetylcholine in the parasympathetic, and Noradrenaline in the sympathetic neurons. The side effects are varied as the pathway activated could be either sympathetic or parasympathetic.

These can be both excitatory or inhibitory and included GI disturbances, dizzyness( high or low blood pressure) palpitations.

Because of the varied effects they should be used with caution in anyone with cardiovascular disease or diabetes.

Question 19

What are autonomic ganglia blockers

Answer 19

These are drugs which block the first post gangleonic receptors (nicotinic), which means there is less release of the second neuro transmitters. Dependant on whether the neuron in question is parasympathetic or sympathetic, this will reduce the release of acetylcholine or noradrenaline. They indiscriminately block both pathways and the effect will be dependant on the location of the receptor and receptor type in that area.

The most common side effect is vasodilation and hypotension, as the main regulator of blood vessels is noradrenaline, and with a reduction of noradrenaline there is a dilation of bloodvessels.

Question 20

Uses of adrenaline and administration

Answer 20

Cardiac arrest can be treated with adrenalin given by IV Central line

Anaphylactic shock can be treated by intramuscular injection as first line, can be given by IV in an emergency

Question 21

What is the general use of alpha adrenoceptor agonists

Answer 21

The main use of alpha agonists is as VSMC constriction. It is very important for regulating vascular constriction, which in turn can affect blood pressure - initial increase in BP as venous return increases. It can affect different vascular beds differently, depending on receptor density- both apha and beta receptors can be affected by adrenaline/noradrenaline, so if the number of alpha receptors is greater, the overall effect will be VSMC contraction. If the number of beta receptors is greater than the number of alpha receptor, it will cause VSMC relaxation.

Question 22

What is an example of an a1 agonist and how does it work?

Answer 22

Phenylephrine is a decongestant that mimics noradrenaline and causes vasoconstriction.

When someone is congested, the bloodvessels in the sinus dilate. When they dilate, there is an increased pressure in the capilary bed, and there is a higher diffusion of fluid into the surrounding tissue, which causes swelling of the nasal passage.

The activation of the a1 causes constriction of the blood vessel, and there is then less diffusion of fluid, and the nasal passage feels less swollen.

Question 23

Which vascular beds have Higher beta density than alpha density?

Answer 23

Cerebral, coronary and pulmonary beds

Question 24

What is an example of an a2 receptor, and it’s uses and side effects?

Answer 24

Clonidine is a centrally acting anti hypertensive which can be used to treat high blood pressure.

A2 receptors located presynaptically on the synapses where the nt noradrenaline is released from act as inhibitory self regulation receptors.

On stimulation, they cause inhibition of AC in the synaptic bulb, which reduces cAMP. CAMP promotes ca2+ influx in response to membrane depolarrisation, which then promotes the release of noradrenaline into the post synaptic space. With a decrease of cAMP there is a reduction of release noradrenaline.

Noradrenaline is the main regulator of vascular cells, and an increase of noradrenaline causes contraction. As this causes a reduction of NA there will be a relaxation of blood vessels, and a decrease in blood pressure.

Because it is a sympathetic pathway it can cause constipation and dry mouth as well as sedation.

Question 25

What are the general actions of beta adrenoceptors in VSMC?

Answer 25

Gs, increase in AC, increase in cAMP,increase in PKA. PKA a prevents MLCK from phosphorylating MLC, so contraction cannot occur. Thus relaxation.

This pathway also increases expression of sodium/potassium pumps( 2 sodium out for 3 potassium in) so if there are more pumps, there is more potassium going into the cell, and less external potassium. This means there is risk of extra cellular hypokalemia.

Question 26

What is the effect of beta adrenoceptor in the heart?

Answer 26

Both beta 1 and 2 cause increased rate and force contraction. This increases cardiac output and increases the oxygen consumption of the heart, both of which could be a problem in someone with heart problems.

Question 27

What affect does beta receptor activation have on metabolism?

Answer 27

This is a sympathetic pathway, associated with fight/flight.
Stimulates increase of glucose avalibility, increased breakdown of stored glycogen, and reduces conversion of glucose to glycogen. Hyperglycaemia

Question 28

What is b3

Answer 28

Mostly involved in lipolysis, the breakdown of fat products for energy.

Question 29

What affect does beta agonists have on skeletal muscle?

Answer 29

B2 increases twitch, shakiness

Question 30

What is an example of a b1 agonist drug and its effects?

Answer 30

Dobutamine is a b1 agonist, which causes increased contractility in the heart. It is a racemic mix, so effectiveness can be varied depending on mix.

Used in carcinogenic shock, IV administration.

Question 31

What parts of the body are the different beta receptors found and their functions?

Answer 31

B1 located mostly in the heart, causes increased contraction rate and force.
B2 found in the heart and in VSMC such as the lungs, as well as skeletal muscle
Increased contraction rate and force in the heart.
Bronchodilation/smooth muscle relaxation
Skeletal muscle twitch.
B3 causes lipolysis.
B1 and b2 also cause increase in blood glucose levels.

Question 32

What is an example of a b2 agonist and its effects?

Answer 32

Salbutamol is a b2 agonist, which causes bronchodilation. It is very important for treating asthma.

It can also be used to delay labour as agonists of b2 causes dilation in uterine smooth muscle.

Question 33

What is the general uses of andrenoceptor antagonists?

Answer 33

Beta blockers are very useful for cardiovascular problems such as angina, which reduced the amount of work the heart has to do, as it slows rate and force of contractions.

Beta blockers can also be used to relieve anxiety but can cause tremors or palpitations.

Alpha blockers can be used for vasodilation ( blocking a1 reduces contraction)

Question 34

What is angina?

Answer 34

This occurs when there is a blockade or reduced blood flow through the coronary artery which means the oxygen demand of the heart is not being met, and there is sensation of pain and symptoms similar to heart attack. These symptoms are relieved when the demand on the heart is decreased.

Question 35

What is an example of an a1 adrenoceptor antagonist?

Answer 35

Prazosine is the first selective a1 antagonist (doxazosine has a longr half life and so only needs once a day dosing.)

It is an anti hypertensive drug,which causes vasodilation by blocking a1 receptors.

There is a possibility of tachycardia due to the baroceptor reflex causing the heart to pump faster to try and restore the initial blood pressure.

There may also be some blockage of a2 receptors, which normally reduce noradrenaline release. This extra noradrenaline in the system can also contribute to the probability of tachycardia.

Question 36

What is a problem associated with b1 blockers?

Answer 36

Blocking b1 reduced the amount of renin in the body, which in turn reduces the volume of fluid reabsorbed into the body. This reduces the volume of of blood, which will cause a gradual drop in arterial pressure.

It also reduces sympathetic output in the cns, which then causes further vasodilation, which reduces blood pressure.

Question 37

What is one of the first beta blockers?

Answer 37

Propranolol is one of the first beta blockers, and is non selective for b1 or b2 so effects them both.

Question 38

What is a second generation beta blocker/ selective beta blocker?

Answer 38

Atenolol is a b1 selective beta blocker

Question 39

What is a benefit of third generation beta blockers?

Answer 39

They also have an influence on nitric oxide, which causes relaxation in blood vessels, so it causes further dilation.

Question 40

What effect will beta blockers have on healthy individuals?

Answer 40

There is very little effect on healthy individuals, which suggest there is something different in the receptors in those in diseased state.

Question 41

What side effect are expected from beta blockers?

Answer 41

One of the main things to be careful with in beta blockers is for anyone who suffers from asthma. As beta blockers are selective but not specific, activation in VSMC causes bronchoconstriction, which could cause breathing difficulties.

It is possible that for patients that have heart failure that a depression in heart function will occur before any benefits will be seen.

They can block symptoms of hypoglycaemia, which is something that would normally be apparent due to activation on the sympathetic system. By blocking this, the symptoms are masked, and this is especially dangerous in anyone who has poorly managed glucose levels such as diabetes.

Low energy levels/ fatigue due to lower heart output.

Cold extremities can be problematic in anyone with peripheral vascular disease, as they already have poor circulation, and lowering BP further reduces the circulation of blood.

Question 42

What causes nausea and vomiting?

Answer 42

The medulla causes the vomiting, or reverse peristalsis. This is stimulated by chemo triggers, which are feedback from the body. Many different substances in the circulation can cause this feedback, including histamine,dopamine,acetycholine and serotonin, so nearly all drugs have the possibility of causing these side effects.

Question 43

What is the cholinergic pathway.

Answer 43

Once released into the post synaptic space, acetycholine is rapidly hydrolysed by acetylcholinesterases.
The choline is then transported back into the cell, where is needs to be re acetyl-ized.
In the cell there is choline acetyltransferase, which takes the acetyl group from acetyl coenzyme A, and attaches it to the choline.
The new acetycholine is then packaged into vesicles which migrate to the synapse and are ready for release.

Question 44

What is an agonist?

Answer 44

An agonist binds to a receptor and triggers changes in cell function that would be caused by that receptors normal neurotransmitter.

Question 45

What is an antagonist?

Answer 45

An antagonist binds to a receptor and blocks activation by an agonist.

Question 46

What is an inverse agonist?

Answer 46

An inverse agonist binds to a receptor and causes the opposite action to what would be caused by an agonist, this is not blocking, this is activating in reverse.

Question 47

What is a partial agonist?

Answer 47

This binds and causes an effect at the receptor, but this is less than the full effect that would be caused if an agonist was bound.