Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

LIFE207 > SAR in the Peripheral Nervous System > Flashcards

SAR in the Peripheral Nervous System Flashcards

1
Q

Peripheral nervous system

A

2 types:
Somatic efferent system:
- Innervates (supplies with nerves) skeletal muscle
- Voluntary, something we consciously take control of i.e. flexing a muscle, moving around

Autonomic system:
- Innervates smooth muscle e.g. blood vessels
- Involuntary
- Sub-types inc. sympathetic and parasympathetic (can work in same tissues to bring about opposite effects)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Neurotransmission in the Somatic Nervous System

A
  • Transmission of electrical signals from central nervous system > neurone > skeletal muscle fibre
  • Trigger release of neurotransmitters that act on receptors in skeletal muscle fibre
  • Leads to innervation of (supplying of nerves to) skeletal muscle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Sympathetic nervous system

A
  • Sympathetic nervous system signalling processes gather in the ganglion chain (tissue parallel to spinal chord) then come down into different tissues
  • Lots of connections from ganglion chain can come down into one tissue e.g. blood vessels
  • To manipulate system for particular outcome/benefit, need to target ganglia as there is a synaptic gap which electrical impulse can’t travel over (chemical mediator needs to be released into gap to act on receptors on other side)

FIGHT OR FLIGHT

Thoracic:
- Eye
- Salivary glands
- Heart
- Lungs
- Liver

Lumbar:
- GI tract

Sacral
- Bladder
- Blood vessels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Parasympathetic nervous system

A
  • Similar organs/tissues innervated as in the sympathetic system
  • Innervated from medulla and sacral region of CNS
  • Longer fibres come down to a junction, lead to different tissues
  • Electrical signals travel down fibres, reach ganglia then carry down into particular tissue to give desired effect

REST AND DIGEST

Medulla:
- Eye
- Lacrimal gland
- Salivary glands
- Heart
- Lungs
- Upper GI tract

Sacral:
- Lower GI tract
- Bladder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Somatic nervous system

A
  • somatic nerves innervate skeletal (voluntary) muscles
  • one single axon from the spinal cord to muscle (no ganglia)
  • acetylcholine (ACh) is the neurotransmitter
  • acts on nicotinic ACh receptors located on skeletal muscle membranes
  • nicotinic receptors linked to Na+ ion channel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Autonomic nervous system

A

Parasympathetic:
- long pre-ganglionic nerve, short post-ganglionic nerve
- post-ganglionic nerves release ACh to act on muscarinic receptors on effector cells

Sympathetic:
- short pre-ganglionic nerve, long post-ganglionic nerve
- most post-ganglionic nerves release noradrenaline (NA) to act on α and β adrenoreceptors on effector cells

Both:
- pre-ganglionic nerves release ACh to act on nicotinic receptors on post-ganglionic nerve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Nicotinic agonists

A

Acetylcholine
Nicotine
Carbachol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Nicotinic antagonists

A

d-Tubocurarine
Pancuronium
Suxamethonium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Ganglia

A
  • Relay station between neurones (not a synapse)
  • Information enters ganglion, excites neurone then exits
  • Give an opportunity to intervene pharmacologically
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

The Nicotinic Cholinergic Synapse (Ach)

A
  • Acetyl CoA and choline combine to form ACh (choline acetyl transferase)
  • ACh stored in vesicles
  • Action potential release ACh
  • ACh acts on nicotinic receptor, opening ion channel
  • ACh action terminated by acetylcholinesterase enzyme
  • Choline reclaimed by nerve ending (rate limiting step in ACh synthesis)
  • Empty vesicles are refilled with ACh
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Drugs that interfere with ACh process

A

Vesamicol
- Blocks transfer of ACh into vesicles

Botulinum toxin
- Blocks release of ACh from nerve endings

Anticholinesterases
- Prevent hydrolysis of ACh by the enzyme acetylcholinesterase

Hemicholinium
- Blocks uptake of choline by NMJ (slide7?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Synthesis of Noradrenaline

A

Occurs in noradrenergic nerves
Tyrosine hydroxylase is rate limiting step

  • Tyrosine > DOPA by tyrosine hydroxylase
  • DOPA > dopamine by DOPA decarboxylase
  • Dopamine > noradrenaline by dopamine β hydroxylase

NA in nerve terminals is contained in vesicles along with ATP and chromogranin A

ATP also has neurotransmitter function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Release of noradrenaline

A
  • Ca2+ enters nerve ending and activates exocytosis of NA from storage vesicles
  • Reduced by action of released NA on pre-synaptic α2-adrenoreceptors

Negative feedback inhibition of transmitter relase

Autoinhibitory feedback mechanism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Drugs affecting noradrenaline

A

Synthesis:
- Disulfiram (antabuse) inhibits dopamine β-hydroxylase, causing some depletion of NA stores
- mainly used for its action on metabolism of alcohol

Storage:
- Reserpine blocks mechanism that transports NA into vesicles

Release:
- Tyramine, amphetamine (indirectly acting sympathomimetics) increase release of NA from vesicles
-Nimodipine reduces release by blockade of Ca2+ channels in nerve terminals
- Any α_2 agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Actions of noradrenaline

A
  • Effector cells innervated by sympathetic nerves have receptors for NA
  • Some organs or tissues have only one type of adrenoreceptor, others have two or more
  • Different subtypes can mediate similar or different responses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Locations of adrenoreceptor subtypes

A

α1:
- Blood vessels
- Gut smooth muscle
- Uterus
- Liver

α2:
- Blood vessels
- Gut smooth muscle

β1:
- Heart

β2:
- Blood vessels
- Lungs
- Gut smooth muscle
- Uterus
- Kidney
- Liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

α1 activation effects

A
  • Contraction of smooth muscle generally (not gut) e.g. blood vessels, uterus
  • Relaxation of gut smooth muscle
  • Salivary secretion
  • Hepatic glycogenolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

α2 activation effects

A
  • Inhibition of transmitter release
  • Platelet aggregation
  • Contraction of vascular smooth muscle
  • Decrease in insulin release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

β1, 2 and 3 activation effects

A

β1:
- Increased cardiac rate and force

β2:
- Bronchodilation
- Vasodilation
- Relaxation of gut smooth muscle
- Hepatic glycogenolysis
- Muscle tremor

β3:
- Lipolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Adrenaline receptor sites

A

α1, α2, β1, β2

21
Q

Noradrenaline receptor sites

A

α1, α2, β1

22
Q

Isoprenaline receptor sites

A

β1, β2

23
Q

Adrenoreceptor agonists

A

α1:
- Phenlyephrine

α2:
- Clonidine (high blood pressure)

β1:
- Dobutamine (heart failure)

β2:
- Salbutamol, terbutaline (asthma)

24
Q

Adrenoreceptor antagonists

A

α (non-selective):
- Phentolamine, phenoxybenzamine

α1:
- Prazosin (ant-hypertensive)

α2:
- Yohimbine

β (non-selective):
- Propranolol (cardiovasculae, glaucoma, thyrotoxicosis, tremor, migraine prophylaxis, anxiety) (beta-blocker)

β1:
- atenolol (cardiovascular, anti-hypertensive, antianginal, antiarrythmic)

β2:
- Butoxamine

25
Q

Termination of noradrenaline action

A
  • Noradrenaline rapidly removed from synapses by active transport mechanisms

Uptake 1 (neuronal re-uptake):
- relatively selective for noradrenaline (tyramine)

Uptake 2 (extraneuronal re-uptake):
- takes up noradrenaline, adrenaline, and isprenaline

26
Q

Metabolism of noradrenaline

A

Endogenous and exogenous catecholamines are metabolised by two enzymes:
- monoamine oxidase (MAO)
- catechol-O-methyl transferase (COMT)

MAO is abundant in sympathetic nerve endings

COMT Is widely distributed in effector cells and also present in the extracellular space:
- more important for circulating adrenaline and some drugs e.g. isoprenaline

27
Q

Drugs affecting uptake of noradrenaline

A

Uptake 1 blocked by:
- Cocaine, despiramine

Uptake 2 blocked by:
- Phenoxybenzamine, corticosterone (and other steroid hormones)

28
Q

Drugs affecting metabolism of noradrenaline

A

MAO inhibited by:
- Tranylcypromine, iproniazid

MAOIs (?) used in treatment of depression

29
Q

Drug binding

A

Drug - Receptor
Hormone - Receptor
Substrate - Enzyme
Drug - Enzyme
Antibody - Antigen

30
Q

Stages of drug binding

A

1 - Chemical recognition
2 - Biological event:
- response (agonist)
- prevent response (antagonist)
- chemical change (substrate)
- prevent chemical change (inhibitor)

Optimize 1 & 2 for a specific effect

31
Q

Chemical bonds in drug action

A

Covalent - 150-600 (kJ/mol) - -
Ion-ion - 20-40 - 1/d (relationship between strength and distance)
Ion-dipole - 8-20 - 1/d^2
Dipole-dipole - 3-15 - 1/d^3
Hydrogen - 5-25 - 1/d^4
VdW - 0.5-5 - 1/d^5-8
Hydrophobic bonds - 3.4 per ethylene group

32
Q

Treatment of Myasthenia Gravis

A
  • Disease characterized by progressive muscle weakness
  • Antibodies against nicotinic receptors in the NMJ (neuromuscular junction)

1 - Increase ACh in the NMJ strengthens muscle contractions (anticholinesterases)

2 - Mimic the effect of of ACh at the NMJ (nicotinic agonists)

33
Q

Anticholinesterase effects

A

Increase ACh at nicotinic (skeletal muscle) and muscarinic (heart, gut motility) receptors

Increased skeletal muscle tension
Decreased heart rate
Increased gut motility

34
Q

Mimicking agonists and antagonists

A

Selectivity advantage:
- Nicotinic agonists for myasthenia gravis do not decrease heart rate
- Muscarinic antagonists reduce gut motility and don’t decrease skeletal tension

35
Q

Equipotent molar ratio (EMR)

A

EC50 of test compound / EC50 of Acetylcholine

EMR < 1 = more potent
EMR > 1 = less potent

Can be used to compare effects of variant molecules

36
Q

Assay of acetylcholine

A

Measure the response (%) of acetylcholine on a prepared tissue receptor (muscarinic or nicotinic) by measuring tension of contraction and compare to a test compound on the same tissue

37
Q

Structure of acetylcholine

A

Ether oxygen essential for muscarinic receptors

Ester oxygen essential for nicotinic receptors

38
Q

Rigid analogues of muscarinic receptors

A

Muscarine - 0.33 EMR
Methyl futrethonium - 0.34 EMR

39
Q

Rigid analogues of nicotinic receptors

A

Nicotine - 8 EMR

40
Q

Bisonium compounds

A

+N(CH3)3-(CH2)n-(CH3)3N+

n = 6 - ganglion blocker (hexamethonium)

n= 10 - neuromuscular blocker - decamethonium

41
Q

Morphine SAR

A
  • used to treat pain
  • potentially lethal side effects
  • mediated by μ-opioid receptors
  • β-arrestin signalling (side effects)
  • G-protein signalling (analgesia)
42
Q

Anticholinesterase drug examples

A

Edrophonium
- short acting
- diagnostic only

Neostigmine
- long acting
- carbamyl ester
- used to treat muscle weakness and reverse paralysis after surgery

Dyflos
- irreversible
- non-selective, block other serine hydrolases
- insecticides, chemical warfare

43
Q

Anticholinesterase as a treatment

A
  • used in neurodegenerative diseases (alzheimer’s, parkinsons) (i.e. rivastigmine, donepezil, galantamine)
  • loss of ACh producing cells leading to reduced cholinergic signalling in the brain
  • can develop cholinergic crisis (overstimulation of acetylcholine receptor): SLUDGE
44
Q

SLUDGE (cholinergic crisis)

A
  • Salivation
  • Lacrimation
  • Urination
  • Diaphoresis
  • GI upset
  • Emesis
45
Q

Adverse effects of anticholinesterases

A

Cholinergic crisis:
- SLUDGE
- Prolonged muscle contraction
- Seizures
- Respiratory depression

46
Q

Treatment of adverse effects of anticholinesterases (cholinergic crisis)

A
  • Some elements can be reversed with antimuscarinic drugs (atropine, diphenhydramine) but the most dangerous, respiratory depression, cannot
  • The NMJ (like the diaphragm) works by ACh activating nicotinic ACh receptors leading to a muscle contraction
  • Atropine only blocks muscarinic receptors, so will not improve muscle strength and ability breathe during a cholinergic crisis
  • Patient requires NM blocking drugs snd mechanical ventilation until crisis is resolved
  • Brings into question their use, concerns over long term problems and minimal efficacy
47
Q

Anticholinesterases, inhibitors of AChE, are used in treating Alzheimer’s disease but require careful monitoring and consideration for use. Describe the issues here in terms of the mechanisms of action of acetylcholine and its regulation (100 marks)

A

40-59%
- Simple descriptions of ACh synthesis, activity at nicotinic and muscarinic receptors, regulation of ACh activity by AChE, discussion of the cellular issues that AChE inhibitors could support

60-69%, as above but also:
- Discussion of how AChE could cause issues more broadly, a clear description of the receptor differences and their locations and interactions with comparisons, and discussion if how various AChEs can impact the enzyme (MoA(. Some evidence of critical evaluation

70%+, as above but also:
- Discuss the side effects of their use, what is know about AEs (adverse effects), how AEs may be treated, and what are the benefits vs. risks? Clear evidence of critical evaluation

48
Q

Acetylcholinesterase

A

2 types:
- True cholinesterase
- Acetylcholinesterase found at nerve endings, skeletal muscle
- Pseudo cholinesterase
- Butyrylcholinesterase found in plasma, liver, instestine

Both hydrolyse ACh, true AChE has greatest affinity for ACh

AChE is a globular protein that resemble bunches of balloons tethered to the postsynaptic membrane

1 molecule of cholinesterase hydrolyses 5000 molecules of ACh per second

LIFE207 (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions