NEU 3 Flashcards
1
Q
What is a receptor?
A
Something that is able to respond to light, heat, chemical or other stimulus and is able to transmit a signal to a sensory nerve
2
Q
How do the terms drug target and receptor relate to each other?
A
All drug targets are receptors but not all receptors are drug targets
3
Q
What is an inverse agonist?
A
An agent that binds to the same receptor as an agonist but causes a pharmacological response oppostie to that of an agonist.
- e.g. GABA and benzodiazepines
4
Q
What is chemical antagonism?
A
When 2 substances combine in solutions such that the effect of the active drug is lost
5
Q
What is pharmacokinetic antagonism?
A
When an “antagonist” effectively reduces the concentration of the active drug (the agonist) at its site of action. This may be due to an increase in metabolism or renal excretion of teh agonist drug, or to decreased absorption o fthe drug from the gastrointestinal tract.
6
Q
What is a competitive antagonist?
A
An agonist that binds directly to the active site of the receptor, preventing the agonist from binding
7
Q
What is a non-competitive antagonist?
A
An antagonist that binds away from the active site and can change the shape of the inhibitor. Can be reversible or irreversible
8
Q
What is physiological antagonism?
A
When 2 drugs have opposing actions in the body which tend to cancel each other out (but bind at different sites)
9
Q
What is a dose response curve?
A
A curve that plots the concentration of a drug against its percentage efficacy
10
Q
What happens to a dose response curve if an antagonist is given with an antagonsit, provided this will be competitive antagonism
A
- Curve shifts to the right
- Higher concentration of the agonsit will be required in order to increase the efficacy and for a reaction to occur
11
Q
What are the structural and functional characteristics of the axon hillock?
A
- Are the areas where the axon emerges from the cell body and is unmyelinated
- Has few or no synapses of its own and a lower threshold than elsewhere in the cell
- Avoids the generation of action potentials elsewhere in teh cell as threshold for this region has to be reached as well
- Allows the neurone to evaluate and integrate a mix of positive and negative simultaneously converging on them
12
Q
Define pharmacodynamics
A
The effect of drugs on the functions of living systems
13
Q
Define pharmacokinetics
A
The effect of living systems on drugs
14
Q
Describe the drug targets in neuropharmacology and what the effect should be
A
- Receptors - drugs can act as agonists or antagonists
- Enzymes
- Transporters
- Effect should be to enhance or block effect of a neurotransmitter
15
Q
What are the 4 types of neurotransmitters based on chemical structure? Give examples for each
A
- Amino acids: aspartate, glutamate, GABA, gycine
- Acetylcholine
- Monoamines: dopamine, noradrenaline, adrenaline, serotonin
- Neuropeptides: NPY, endogenous opioids
16
Q
How do indirect agonists work?
A
- Increase the concentration of the NT by inhibiting ACh
- Do not act on receptor but are indirect as cause an action on the receptors
17
Q
Where are M1, M2 and M3 receptors found?
A
- M1 - autonomic ganglia
- M2 - heart
- M3 - smooth muscle and secretory glands
18
Q
List some muscarininc agonists
A
- Bethanechol
- Pilocarpine
- Acetylcholine
19
Q
Describe the pharmacodynamics of muscarinic agonists
A
- Cardiac slowing, decrease in cardiac output
- Contraction of smooth msucles (increased peristaltic acctivity in GI tract)
- Sweating, lacrimation, salivation and bronchial secretion
20
Q
Give clinical uses of muscarinic agonists
A
- Glaucoma
- Decreased gut motility
- Acetylcholine itself has no clinical uses as it is immediately metabolised (enzyme in the blood degrades it if injected)
21
Q
List some nicotinic agonists
A
- Acetylcholine
- Nicotine
- Suxamethonium
22
Q
Give the clinical uses of suxamethonium
A
- Blocks, as an agonist, nicotinic receptors at the neuromuscular junction
- Deplarisation block
- Useed during anaesthesia
23
Q
List some muscarinic antagonists
A
- Atropine
- Scopolamine
24
Q
What are the pharmacodynamics of muscarinic antagonists?
A
- Tachycardia
- GI motility inhibited
- Sweating, lacrimation, salivation and bronchial secretion inhibited
- Dilated pupil
- reflex bronchoconstriction inhibited
25
What are the clinical uses of atropine?
- Increase heart rate
- Reverse heart block due to increased tone in vagus nerve (e.g. pain)
- Adjunct in anaesthesia
- Anticholinesterase poisoning
26
What are the effects of nicotinic antagonists
- Block neuromuscular junction = paralysis
- Respiratoy failure
- Death
27
Describe the action of drugs that affect ACh release
- ACh release required influx of Ca2+
- Mg2+ inhibits release as it competes with Ca2+ for the cannel
- Aminoglycoside antibiotics also block Ca2+
- Ca2+ channel blockers relatively ineffective as they work on the wrong channel subtypes
- Botulinum toxin binds to nerve terminal (potent)
- Blocks ACh release
- Used to treat local muscle spasms, wrinkles
28
How do drugs that inhibit ACh metabolism acheive their function?
- Indirect agonists
| - Inhibit acetylcholinesterase and increase the half life of ACh (indirect cholinergic agonists)
29
What are teh 3 categories of anticholinesterases?
- Short actin
- Medium-duration
- Irreversible (organophosphates)
30
What are the effects of anticholinesterases?
- Enhance ACh at parasympathetic post-ganglionic synapses
- Bradycardia, hypotension, trouble breathing
- Nicotinic ganglionic effects are masked by muscarinic effects
- Usually ACh can only stimulate 1 AP due to fast metabolism
- Now lasts long enough to stimulate a train of APs (convulsions)
31
What are the clinical uses of anticholinesterases?
- Test for (edrophonium) and treat (neostrimine, pyridostigmine) myasthenia gravis
- Treat glaucoma
- Alzheimer's disease
- Reverse actin on non-depolarising neuromusclular blocking drugs
- Treat poisoning with atropine
32
Describe noradrenergic terminals and sites of drug action.
- No proper synapse system, largely same system as cholinergic, and drugs can still interfere
- Inactivation of the NT does not take place in the synaptic cleft
- NT needs to occur before release or at uptake (into pre- or postsynaptic)
- Any drug that interferes withe metabolism must do so in presynaptic site where NT is metabolised
- Negative feedback is taking place
- Any agonist that binds leads to a decrease in release
33
Describe clinical uses of drugs acting at adrenergic receptors.
Alpha adrenoceptor antagonists: alpha1, antihypertensive
| Beta adrenoceptor antagonists: beta1, myocardial infarction, anginapectoris, dysrhythmias, heart failure, hypertension
34
Describe the ways in which drugs can affect noradrenergic transmission.
- Drugs interfering with synthesis (MAO)
- Drugs stimulating synthesis (supply precurosor molecules for NT)
- Drugs affecting NA storage in the vesicles
- Incresing release
- Preventing reuptake
35
Describe the mechanism of action of drugs affecting noradrenergic storage in vesicles
- Reserpine: decreases transmitter availability (no clinial use)
- Monoamine oxidase inhibitors (MAO) increase transmitter availability
- selefiline = MAO-B (dopamine), used for cognitive dysfunction in dogs
36
Describe the general role of the ANS
- Maintain homeostasis within the body
| - Sympathetic and parasympathetic act in balance with each other (have opposing actions)
37
Describe the composition of the ANS
- GVE fibres (general visceral efferent): smooth and cardiac muscle, links with enteric NS, glands
- GVA fibres (general visceral afferent): blood pressure, gut distension
- Most are thinly myelinated
38
Outline the different ANS efferents and their actions
- To smooth muscle
- To cardiac muscle
- To glandular tissue
39
Outline the actions of ANS efferents on smooth muscle
- GIT: SNS decrease motility, PSNS increases
- Blood vessels (constriction by SNS, dilation by PSNS)
- Piloerectors (controlled by SNS only)
- Iris (SNS dilates, PSNS constricts)
- Lens (ciliary muscle, controlled only by PSNS)
40
Outline the actions of ANS efferents on cardiac muscle
- SA and AV nodes controlled by PSNS, decrease heart rate and contractility
- Whole heart innervated by SNS, increases heart rate and contracility
41
Outline the actions of ANS efferents on glandular tissue
- Control secretion quality and quantity
- PSNS - in charge of watery secretions e.g. salivary increased
- SNS - in charge of serous or hormonal secretions
42
What is the arrangement of ANS GVEs
- 2 neuron chain - preganglionic and postganglionic neuron
| - Autonomic ganglia contain the synapse between the 2 neurons and the postganglionic cell body
43
What do ANS afferents detect?
- Visceral pain/stretch
44
What is the ANS fibre pathway from abdominal organs?
- Follow SNS efferents
- For organs in contact with peritoneum
- From tissue to the sympathetic ganglion
- Sensory receptor -> ganglion where GVE synapses (but no synapse for GVA) -> splanchnic nerve to sympathetic trunk -> white ramus communicans -> ventral ramus -> mixed spinal nerve -> dorsal root into DRG -> cell body in DRG -> grey matter in dorsal horn of spinal column -> synapse to neuron in CNS
- Pseudounipolar cells where cell body is in DRG
45
What is the ANS fibre pathway from pelvic organs?
- Follow PSNS efferents
| - Organs not in contact with peritoneum
46
Describe the location of baroreceptors and the nerves signals travel in
- Carotid sinus - afferents use cr. n. IX
- Aortic arch - afferents use cr. n. X
- Forms part of negative feedback loop to keep bp constant (SNS and PSNS increase or decrease heart rate and vascular resistance)
47
Describe the location of chemoreceptors, the pathway of the afferent fibres and the chemicals detected
- Carotid body - afferents in IX
- Sense dissolved pO2 mainly
- High blood flow to area so no need to take oxygen from blood cells, if change number of blood cells then no change to dissolved oxygen, so not sense changes associated with anaemia
- Also sense pO2, pH and temperature to lesser degrees
48
Give the sites of the SNS ganglia
- Cranial cervical
- Middle cervical/stellate
- Cervicothoracic
- Coeliac
- Cranial mesenteric (unpaired)
- Caudal mesenteric (unpaired)
- Pelvic
49
Give the sites of the PSNS ganglia
- Ciliary ganglion
- Pterygopalatine ganglion
- Mandibular ganglion
- Otic ganglion
- Proximal and distal vagal ganglia
50
Describe the thoracolumbar outflow of the SNS from the CNS
- From sympathetic chain
- In chest follow blood vessels
- Into neck, hitch on vertebral nerve
- To get to head go to vagosympathetic trunk
- To gut, ganglionic chain extends down and supplies the gut
- Viscera - pelvic ganglion is combination of SNS and PSNS
51
What are the 3 things that can happen on entry to the sympathetic trunk?
- Immediate synapse in sympathetic trunk
- Run up or down sympathetic trunk prior to synapse
- Leave sympathetic trunk without synapsing
52
Describe what happens in the event that there is immediate synapsing in the sympathetic trunk upon entry
Return via the grey rami communicans to spinal nerves for distribution
53
Describe what may happen in the event that the signal runs up or down the sympathetic trunk before synapsing?
May go to the cranial cervical ganglion for distribution to the head or tail end of the body
54
Describe what hapens in the event of leaving the sympathetic trunk without synapsing
- Run to collateral or prevertebral ganglia close to abdominal organs
- Coeliac, cranial or caudal mesenteric
- Postganglionic fibres distribute to abdominal or pelvic organs
55
What is the general rule for the pathways of the SNS and PSNS?
The SNS follows arteries or capillaries
| The PSNS follows major nerves or forms its own nerves (vague as in vagus)
56
What cranial nerves contain parasympathetic fibres and what is their function?
- III, VII, IX, X
- III: iris smooth muscle, ciliary muscle attached to lens, focusing of the eye
- VII and IX: glands in the head region (salivary and lacrimal, mainly VII and parotid and zygomatic SG for IX)
- X: thoracic and abdominal viscera, glands and smooth msucle
- Also the sacral spinal nerve: pelvic nerve to pelvic viscera (including repro organs)
57
Describe the origin of the vagus nerve from the brain, its route of exit from the cranial cavity and its composition in terms of types of fibres
- Medulla oblongata
- Jugular foramen in the skull and exits via the tympano-occipital fissure
- Composition: mixed fibres, GVA, GVE, GSA, SVA, SVE
58
Describe the afferent components of the vagus nerve
- GSA: from skin of external acoustic meatus, meninges, cell bodies in proximal (jugular) ganglion
- GVA: pharynx, larynx, thoracic and abdominal viscera, cell bodies iin distal ganglion
- SVA: taste fibres from base of tongue adjacent to epiglottis, distal ganglion
59
Describe the efferent components of the vagus nerve
- GVE: PSNS - organs of thorax and abdomen
| - SVE: muscles derived from pharyngeal arches 4 and 6 (muscles of pharynx and larynx)
60
Describe the curse and distribution of the vagus nerve in the head and neck
- Below base of skull gives off auricular branch to ecternal accoustic meatus (sensory), pharyngeal branch (sensory and motor, all muscles except stylopharyngeus) and the cranial laryngeal nerve to the laryn (sensory as far as glottis, motor to cricothyroid muscle)
- Joins sympathetic trunk at cranial cervical ganglion
- Forms vagosympathetic trunk
- Joins sympathetic trunk at cranial cervical ganglion
- Lies in carotid sheath with common carotid artery and internal jugular vein
61
Describe the vagosympathetic trunk
- Several trunks
- Sympathetic fibres running cranially (GVE to head and neck)
- Parasympathetic fibres running caudally (GVE to heart and viscera)
- Parasympathetic fibres running cranially (GVA from receptors and viscera)
- Fibres that will form the recurent laryngeal nerve (SVE to laryngeal muscle)
62
Describe the course and distribution of the vagus nerve in the thorax
- Enters at thoracic inlet
- Separates from sympathetic tract at middle cervical ganglion
- Gives off recurrent laryngeal nerve, cardiac branches to cardiac plexus supplying heart, bronchial branches to pulmonary plexus supplying lungs
- To give off recurrent laryngeal nerve, right vagus hooks around right subclavian artery, left hooks around aortic arch, runs back cranilly along trachea
63
Describe the innervation of the larynx
- Cranial laryngeal nerve is sensory as far as glottis, motor to cricothyroid muscle
- Recurrent laryngeal nerve: sensory caudal to glottis, motor to all muscles except cricothyroid muscle
64
Describe the course and distribution of the vagus nerve in the abdomen
- Dorsal and ventral vagal trunks
- Provide preganglionic PSNS to abdominal plexi (receive postganglionic SNS), supply preganglionic PSNS to gut through transverse colon
- Dorsal vagal trunk: fibres to coeliac and cranial mesenteric plexi
- Ventral vagal trunk: fibres to gastic and hepatic plexi
65
Describe the course and distribution of the vagus nerve in the abdomen of ruminants
- Ruminant stomach classically described as having dorsa and ventral vagal supplies
- Crossover, resecting one trunk does not denervate a section of the rumen
- Dorsal vagal trunk: rumen and ruminal motor function
- Ventral vagal trunk: reticulum, omasum, abomasum, gastric plxus, branches to duodenum, pancreas, liver and hepatic plexus
66
Describe what laryngeal hemiplegia is, how it can be identified and the cause
- One side of the larynx collapses
- Usually not a problem in expiration
- Inspiration causes negative pressure in teh airway, sucking vocal cord into lumen, pressure drops and closure is more violent
- Poor performance
- Slap test can be used - slap thorax and opposite side of larynx should contract
- Roaring sound on inspiration, best seen with excercise endoscopy
- Occurs due to damage to recurrent laryngeal nerve from vagus nerve
- Usually affects left side
67
Define the term pain in relation to its effects
An unpleasant sensory and emotion experience associated with actual or potential damage, or is describe in terms of such damage. It is the conscious recognition of the nociceptive stimuli
68
List the 2 types of cutaneous pain.
- Fast - A
| - Slow - C
69
Relate the speed and quality of effect to the type of endings and axons which mediate fast A type pain
- A fibres detect initial, sharp pain
- Highly myelinated - faster speed of conduction
- Synapse in the dorsal horn of spinal cord
- Uses spinocervicothalamic tract
70
Relate the speed and quality of effect to the type of endings and axons which mediate slow C type pain
- C fibres transmit the "after pain"
- Poorly myelinated, slower speed of conduction
- More widespread receptors
- Pooly localised
- Project cranially in ipsilateral tracts, ascend C1 and C2 where they cross and synapse in lateral cervical nucleus
- Project through brain stem to thalamus and cortex
- Also used spinocervical thalamic tract
71
Compare cutaneous to deep pain and visceral pain and show how these are poorly localised.
- Cutaneous uses the spinocervicothalamic tract, visceral uses spinoreticular tract
Deep/visceral:
- Primary afferents enter cord and diverge cranially and caudally, spreads over several segments allowing intersegmental reflexes
- Second order afferents in dorsal horn are diffuse and bilateral
- Project to cortex via diffuse thalamic projections
- Activates limbic system = emotional response
72
Describe deep pain
- Multisynaptic
- Diffuse poor somatotropy (correspondence of receptors in regions or parts of the body via respective nerve fibers to specific functional areas of the cerebral cortex)
- Poorly localised
73
Describe visceral pain
- Very poorly localised
- Travel in sympathetic fibres
- Large overlapping receptor fields
74
What do deep an visceral pain respond to?
- Stretch
- Ischaemia
- Dilation
- Spasm
75
Explain how referred pain responses can occur in deep and visceral pain.
- Wide dynamic range neurons respond to both noxious and non-noxious stimuli
- Confuse patient as to source of pain
- Respond more vigorously to noxious
- Receive information from somatic and visceral fibres which converge
- Pain from viscera perceived as from somatic structures as are more used to somatic pain
76
List the substances or things which may stimulate or modify the sensitivity of pain endings
- Type of pain
- Type of fibre transmitting impulse
- Cognitive set of individual
- Chemica structure of transmitters and fibres
- Types of upbringing
- Emotional state
- Nociceptor sensitisers (leucotrienes, prostaglandins)
- Nociceptor activators
- Bradykinin
- Serotonin
- Potassium
- Adenosine
- Substance P
77
List the ongoing processes in the nervous system which can influence the perception of pain
- Peripheral modulation
- Dorsal horn modulation (gating)
- Dorsal horn modulation (referred pain)
78
Describe the process of peripheral modulation
- Silent receptors
- release of inflammatory mediators
- Decrease or increase the pain threshold and increase the perceived pain
79
Describe the process of dorsal horn modulation in gating
- One group of second-order neurons deals with nociception, another receives input from mechanoreceptors
- Modulate the first group
- Large diameter fibres transmit non-painful stimuli, thin transmit pain
- Transmission cells carry pain to brain
- Excitement of thin fibres inhibits inhibiting cells so more pain is felt (tranmissision fibres fire)
- If more thick fibres are stimulated, less pain is felt as the ratio between thin and thick and trnamission cells leads to less pain being sensed
80
Approximately how many times a day do I get the urge to throw my laptop out of the window and move somewhere hot?
At least once every half hour
81
Describe the general anatomy and function of the enteric nervous system
- Autonomic
- Consists of intramural ganglia and 2 major intramural plexuses
- Controls motility of the gut, endo and exocrine secretions, microcirculation of GIT and immune and inflammatory processes
82
Describe the enteric nervous system's spatial and functional relationships with the intestinal wall
- Have both afferent and efferent fibres
- Efferent excitatory branches spread in oral direction, inhibitory in aboral
- Afferent fibres are all over the wall
- As food is detected by the afferent fibres, the intestinal muscles (controlled segmentally) contract to push food forward while below food the wall relaxes to allow pushing of food in aboral direction
- As food passes, inhibitory neurones release NTs (e.g. NO) that lead to muscle relaxation so muscles ahead of food relax and allow movement of food through lumen
- Efferent and afferents work in short reflex arcs = the intramural (enteric) nervous system
83
Describe the structure and action of the intramural ganglia
- Tightly packed nerve cell bodies and glial cells
- 2 main types of neurons
- Type 1: many club shaped processes plus a single, long slender process
- Type 2: multipolar, many long smooth processes
- Glial cells: outnumber neurons, modulate inflammatory responses in the intestine
- Innervation travels through mesentery
84
What are the 2 plexuses found in the enteric nervous system?
- Submucosal (Meissner's)
| - Myenteric (Auerbach)
85
Describe the location and function of the submucosal (Meissner's) nerve plexus
- Found in lamina of the submucosa
- Best developed in small intestine
- Important in secretory control
- Also has some control of submucosal blood vessels, muscularis mucosae
86
Describe the location and function of the myenteric (Auerbach) nerve plexus
- Between the 2 main muscle layers
- Extends entire length of the gut
- Primarily provides motor innervation to 2 muscle layers and secretomotor innervation of the mucosa
- Also projections to gall bladder, pancreas, sympathetic ganglia
87
Describe the autonomic innervation of the intestine
- Afferent fibres have visceral sensibility
- Efferent fibres can be PSNS or SNS
- PSNS increases gut motility and digestion
- SNS decreased motility, targets preganglionic nerves
- There are interactions between the CNS and ENS
- The motor input (PSNS and SNS) is from CNS
- Sensory output to the CNS (primary afferent neurons)
88
Outline the importance of the enteric nervous system in the development of intestinal problems/disease
- Over or underactive gut
- If autonomic system is damaged then underactive (equine dysautonomia)
- If sympathetic system damaged then overactive (diarrhoea?)
89
Describe the organisation of the spinal cord pathways in tracts
- Similar fibres run together in tracts
- Afferent and efferent regions
- Fibres run in white matter
- Spatial orientation from receptor sites is retained within fibre orientation within tracts
- Cuneate, gracile and spinocerebellar tracts important
- Rarely run in grey matter for more than one segment (cuneat and gracile never run in grey matter)
- Some sensory have transmission in grey matter
- Synapse at least once in each tract
90
What are the areas of the grey matter in the spinal cord and what are their roles?
- Dorsal horn: sensory
- Ventra horn: motor
- Lateral horn: mixture
91
What areas do the cuneate, gracile and spinocerebellar tracts innervate, what do they pass through and what is their end point?
- Cuneate: forelimb, dorsal funiculus, somesthetic cortex
- Gracile: hindlimb, dorsal funiculus, somesthetic cortex
- Spinocerebellar: hindlimbs/trunk = dorsal/ventral spinocerebellar, via lateral funiculus, into cerebellum
92
Describe polysynaptic motor tracts.
- e.g. pyramidal system
- All follow similar pathways
- Either pyramidal or extra-pyramidal system
- Fibres pass via corona radiata, internal capsule to pyramidal tract
- Decussate caudal to the obex of the medulla
- Run within lateral corticospinal tract
- Project onto alpha motor neurones in grey matter of ventral horn
93
Describe the pyramidal system
- Region at the base of the brainstem
- 2 bulges
- gets to level of medulla, decussates then runs down corticospinal tract in lateral funiculus then synapses onto alpha motor neurone
- May have an interneurone but is usually direct to the motor neuron
94
Outline decussation and its importance in identifying what side a lesion is on.
- Tracts passing into the cortex decussate (switch sides) to project contralaterally
- Tracts passing into the cerebellum project ipselaterally
- If paralysos os present on the left side of teh body then there is either problem on left side of spinal cord or in the right side of the brain
- Vestibular region sits within brainste,, component also in overlying cerebellum
- If damage to brainstem, head tilt towards same side, if damage to cerebellum then tilt towards the other side
95
Describe and explain some species differences in relation to the pyramidal system
- In dog makes up 10% of white matter
- In sheep does not project beyong C4 segment
- In horses stops at C1 - do not have a corticospinal tract
- Pyramidal tract mainly for fine motor control, not needed by the horse
- The rest of the motor system is extrapyramidal
96
Describe the extrapyramidal system
- Respondible for locomotion and posture
- Starts at motor cortex (may involve cerebellum but does not start here)
- All pathways polysynaptic
- Run in specific tracts
- Decussate
- Run in white matter
- Most project onto gamma motor neuron
- Vestibular spinal tract is exception: does not decussae, projects mainly to alpha motor neurons, strongly facilitatory
97
Describe the spinothalamic tract
- Bilateral projection in domestic species
- Primary sensory fibres synapse in multiple segments
- Small fibres
- Advantageous as give collateral supply, difficult to lose all pain sensation
98
Describe the difference between upper and lower motor neurons.
UMNs: input from the motor centre in the brain (cortex to SC)
LMNs: carry out the motor function (ventral horn to effector muscle cell)
99
What clinical signs would be consistent with an UMN lesion?
- Increased reflexes
- Rigid paralysis
- Normal muscle size/slow muscle wastage
- Absence of fasciculations (muscle twitch)
100
What clinical signs would be consistent with a LMN lesion?
- Hypo/areflexia
- Flaccid paralysis
- Atrophy of muscle/fast muscle wastage
- Presence of fasciculations (muscle twitch)
