Neurology Phisyology Flashcards
(180 cards)
1
Q
What are the 3 functions of the nervous system? How are these functions achieved?
A
Sensation - Receptors detect changes in the environment and provide information to the CNS Integration - Input from environment is processed and integrated by the CNS. Decisions are made and responses formulated Activation - Response forwarded to the appropriate muscles and glands
2
Q
What is the function of the nervous system dependent on?
A
Anatomical relationships between neurons (Axon length, type of neuron, amount of neurons in circuit) Interactions between neurons (Mode of communication, receptor density, number of transmitters)
3
Q
Give 5 reasons why there may be dysfunction of the nervous system
A
Damage by trauma or disease Neurons loose the ability to produce transmitters Neurons over or under produce transmitters Neurons fail to recognise transmitters Effector organs fail to respond
4
Q
How can dysfunction of the nervous system manifest in a patient?
A
Loss of sensation or function Gain of a new feature Change in behaviour, personality or perception
5
Q
What are the two main cell types in the nervous system?
A
Neurons Glia
6
Q
Give two examples of neurons
A
Principle cells Inter-neurons
7
Q
Give 5 examples of Glia
A
Astrocytes Ependymal cells Microglia Oliodendroglia Schwann cells
8
Q
Which cell type in the nervous system commonly malfunctions and forms tumours?
A
Glia cells
9
Q
What are the three main groups of neurons, and why are they classified in this way?
A
Multipolar Bipolar Unipolar Classified according to the number of processes in and out of the neuron
10
Q
What is the function of a dendrite?
A
Receptive field of the neurons. Sensitive to neurotransmitter input
11
Q
What is the Soma of a neuron?
A
The metabolic and integrating centre. Also may be called the cell body
12
Q
What is the function of an axon?
A
Rapid one way communication between the cell body and the axon terminals
13
Q
What is the function of synaptic terminals?
A
Releases transmitters and communicates with other cells in a pathway or circuit
14
Q
Name 4 common features of all neurons?
A
Dendrites, Soma, Axon, Synaptic terminals
15
Q
What are the functions and features of an Astrocyte?
A
Form a bridge between the neuron and blood vessels. Structure, homeostasis and neuro-vascular communication. Large star shaped cell with multiple dendritic processes.
16
Q
What are the functions and features of an Ependymal cell?
A
Form the lining of the ventricular system. Production and movement of CSF. Simple ciliated cuboidal epithelial cells.
17
Q
What are the functions and features of Microglia?
A
Immune response (WBC’s of the CNS). Activated on trauma. Small glial cells with multiple processes. Over activation can cause problems in the CNS.
18
Q
What are the functions and features of Oligodendroglia?
A
Myelin producing cells found in the CNS. Myelination and insulation of the axons. Large with broad processes.
19
Q
What are the functions and features of Schwann cells?
A
Mylein producing cells in the PNS. Myelination and insulation of the axons. Large with broad processes.
20
Q
What is the resting membrane potential in a neuron?
A
-70mV
21
Q
What is the threshold potential in a neuron and what happens at this point?
A
-55mV All sodium channels open and there is a surge of sodium into the cell
22
Q
The balance of what ions cause a action potential to fire in a neuron. How does this differ to a cardiac or a muscle cell?
A
Sodium and Potassium In a muscle or Cardiac cell there is also Calcium involved
23
Q
Name the 6 phases in action potential firing
A
Rest Depolarisation AP firing Repolarisation Refractory period After-hyperpolarisation
24
Q
What is Saltatory conduction?
A
The propagation of an action potential along a mylenated axon, from one node of Ranvier to another. This allows for faster transmission of the action potential, and therefore speeds up communication.
25
Name two Myelination disorders and what causes them
Multiple Sclerosis - Dysfunction in Oligodendrocytes in the CNS Guillian Barre - Dysfunction in Schwann cells in the PNS
26
What age is Myelination completed in the spinal cord and what is this important for?
Completed at 18 months. Essential in the spinal cord for control of motor function
27
What are the two types of synaptic transmission?
Chemical Electrical
28
How do chemical synapses work?
Action potential reaches the axon terminal and depolarises the membrane causing voltage gaited sodium channels to open Sodium ions enter the cell, causing the pre-synaptic membrane to further depolarise This causes voltage gaited calcium channels to open and calcium to enter the cell This initiates a signalling sequence that causes the vesicle and pre-synaptic membrane to fuse Neurotransmitters released across the synaptic junction Neurotransmitters act on receptors in the postsynaptic terminal MAJOR DRUG TARGET
29
How do electrical synapses work?
Pre-synaptic and Post-synaptic terminal join via channel proteins to form gap junction, resulting in a narrow gap between the membranes Allows currents to pass directly through the synapse and also allows molecules carrying the current through Can be bi-directional
30
How do chemical and electrical synapses differ in transmission times?
Chemical = Fast transmission, slower cell to cell transmission but can cope with a higher frequency of activity Electrical = Slower transmission, faster cell to cell contact, but more effective at lower frequencies
31
How is communication achieved between the nervous system and muscles?
Communication is achieved via the neuromuscular junction. Propergation of an action potential triggers exocyosis of Ach from the synaptic terminal Ach crosses the cleft and acts on cholinergic receptors in the motor end plate This initiates muscle contraction Impulse is carried through the muscle via T-tubules and sarcoplasmic reticulium
32
What is the cause of Myaesthenia Gravis? How is it investigated?
Autoimmune disease that affects the neuromuscular junction Circulating anti-bodies block Ach receptors, causing them to not work properly; thereby stopping communication Slows muscle activity and reduces tone investigated using nerve conduction tests and electromyography
33
What are the two main chemical transmitters used in the CNS? Are they excitatory or inhibitory?
Glutamate = Major excitatory trasmitter GABA = Major inhibitory transmitter
34
Why is inhibition essential in communication of the nervous system? Name the 3 types of inhibition in the CNS
Key for coding of signal and activity in order to get a pattern Direct inhibition Lateral inhibition Dis-inhibition
35
What factors does communication of the nervous system rely on? How do these factors help communication?
Inhibition = coding Synchrony = co-ordinates activity Plasticity = changes the strength of the signal
36
How does direct inhibition aid in communication in the CNS? Give a example of a drug that can alter this
Excitatory neurons have regular firing in the absence of inhibition Inhibition produces patterns of activity (coding) Coding carries the information and can be read by the brain LSD increases firing of excitatory neurons, making it a good drug for depression Drugs that increase firing can lead to loss of coding and therefore can decrease the effectiveness of the brain and lead to psychological side effects
37
How does lateral inhibition aid in communication in the CNS? What pathways is this type of inhibition normally found in?
Activation of excitatory cells also activates associated inhibitory cells Inhibition acts on neighbouring cells to reduce activity This strengthens the response of the cell directly stimulated Lateral inhibition can be seen in sensory pathways: Vision Touch Olfaction
38
How does Dis-inhibition aid in communication in the CNS? Where is this process key in the CNS?
Activation of a inhibitory circuit leads to excitation Inhibition of a inhibitory cell results in excitation of the excitatory cell (2 negatives make a positive) This types of inhibition plays a vital role in the basal ganglia, as it shapes motor function
39
How does synchrony modify communication in the CNS?
It changes strength at a network level This occurs cell to cell via gap junctions
40
How is synchrony investigated?
Using a Electroencephalography (EEG)
41
How does plasticity modify communication in the CNS?
Plasticity changes strength at a neuronal level It is the up or down regulation of synaptic strength, thereby making neurons change their behaviour
42
What is the benefit of plasticity occurring at the level of a synapse? Name 3 ways this can occur
When changes occurring at the level of the synapse in order to regulate synaptic strength, this allows east reactivation of a circuit should a event ever happen again Changes in size (no of neurotransmitters receptors/vesicles etc) Changes in perforation (increase in receptor recycling/transmission) Change in independent synaptic release sites
43
What is the difference between Neurotransmitters and Neuromodulators?
Neurotransmitters act directly to alter neuronal activity Neuromodultors act on receptors or membranes to indirectly alter neuronal activity
44
Describe the role and function of neurotransmitters in cell to cell communication. Indicate the difference between inhibitory and excitatory propagation
Neurotransmitters are used by neurons for rapid cell to cell communication. They are stored in the vesicles in the presynaptic terminal Nerve impulse arrives and calcium channels open Terminal is depolarised Calcium binds to the synaptic vesicle Synaptic vesicle fuses with pre-synaptic membrane Neurotransmitter is released into the synaptic cleft Neurotransmitter binds to receptors on the ligand-gaited channel on the post-synaptic terminal Sodium enters the channel Action potential is generated Excitatory neurons propagate the signal onward, whereas inhibitory neurons block onwards propagation
45
How do neuromodulators alter neuronal activity? What do neuromodulators act on?
Neuromodulators are co-localised with neurotransmitters. Found in vesicles. They act on receptors or membranes to indirectly alter neuronal activity by changing the sensitivity or kinetics of a neurotransmitter receptor Neuromodulators can also act on glial cells
46
Name 2 excitatory neurotransmitters
Glutamate Aspartate
47
Name 2 inhibitory neurotransmitters
GABA Glycine
48
What is the main role of Adrenaline and Nora-adrenaline?
Stress and arousal
49
What is the main role of dopamine?
Motivation/motor function
50
Give 2 examples of neuromodulators and their roles
Vasopressin = osmoregualtion Somatostatin = Growth
51
Give 3 examples of modulatory transmitters
NO CO ATP
52
What are most neurological disorders linked to?
A change transmitter efficacy. Some can result for a single transmitter alteration, however in the majority of cases multiple pathways will be affected
53
Name 3 disorders associated with 5HT
Migraine Fibromyaligia Depression
54
What disease is associated with GABA?
Huntington's
55
What neurotransmitter is associated with Alzheimer's?
Acetylcholine
56
Name 2 disorders associated with Dopamine
Parkinson's Schizophrenia
57
If activation of one class of neuron can have knock on effects on other pathways, explain how Noradrenaline levels can indirectly affect GABA activity
Noradrenaline alters 5HT activity 5HT levels alter Dopamine activity Dopamine levels alter Acetlycholine activity Acetylcholine levels alter GABA activity
58
Name 2 types of general receptors in the nervous system
Ionotropic G-protein linked receptors
59
What are the roles of specialised receptors in the nervous system?
General and sensory sensation Responsive to particular stimuli Transduce physical to electrical energy
60
Give 4 types of specialised receptors in the nervous system and their functions.
Mechanoreceptors = tactile sensation Thermoreceptors = temperature changes Nociceptors = painful/noxious stimuli Proprioceptors = detect changes in head and boy position
61
What is a channelopathy?
Mutations in channel sub-units that cause a change in kinetics or sensitivity
62
Give an example of a disorder caused by channelopathies, and a disorder that can cause channelopathies.
Developmental forms of epilepsy are caused Autoimmune disorders can cause
63
How many types of subtype receptor is a drug normally targeted at?
One
64
What is a polyvalent drug? Name a benefit of them
A non-selective drug, that can have effects on multiple sub-type receptors Have fewer side effects in the CNS
65
What mechanisms are involved in pathogenesis of neuronal and psychological disorders?
Altered neuronal activity Altered synchrony Cellular changes Subcellular changes Genetic/Epigenetic changes
66
What is the aim when treating neuronal and psychological disorders?
To restore balance leading to a good quality of life
67
What is neuroendocrinology?
A branch of life sciences dealing with neurosecretion and the physiological interaction between the CNS and endocrine system
68
What are the basic components of the neuroendocrine system?
Parvocellular neurones and Magnocellular neurones in the hypothalamus act on the anterior and posterior pituitary in the pituitary gland, which act on target tissue, adrenal glands, thyroid gland and the gonads.
69
What is the function of the hypothalamus in neuroendocrinology?
To integrate autonomic responses and endocrine function with behaviour
70
Give 3 ways the hypothalamus controls homeostasis
Behaviour concerned with everyday homeostatic requirements of life Neuronal control through the autonomic nervous system Hormonal control through hormone release from the pituitary gland
71
What are the six homeostatic functions controlled by the hypothalamus and how is this achieved?
1) Blood pressure and electrolyte composition 2) Body temperature 3) Energy metabolism 4) Reproduction 5) Stress response 6) Growth 1) Control of drinking salt appetite and control of blood osmolarity and vasomotor tone 2) Metabolic thermoregulation and behaviours like seeing an appropriate environment 3) Feeding, digestion and metabolic rate 4) Hormonal control of mating, pregnancy, lactation 5) Adrenal stress hormones 6) Growth hormone
72
Which hypothalamic nuclei is responsible for: Stress Energy balance Osmoregulation Maternal Control Blood pressure
Paraventricular nucleus
73
Which hypothalamic nuclei is responsible for: Osmoregulation Maternal control
Supraoptic nucleus
74
Which hypothalamic nuclei is responsible for: Reproduction Growth Lactation
Arcuate nucleus
75
What is associated with a loss of Hypothalamic Orexin Neurones?
Narcolepsy
76
Where is the pituitary gland located?
In a bony cavity at the base of the brain called the Sella Turcica
77
How is the pituitary gland connected to the hypothalamus?
Via the pituitary stalk
78
Respectively, where do the anterior and posterior pituitary glands develop from?
A = Pharyngeal Epithelium P = Neuronal
79
Respectively, what cells do the anterior and posterior pituitary glands contain?
A = Glandular cells P = Axon terminals
80
Respectively, which neurons act on the anterior and posterior pituitary glands?
A = Parvocellular neurons P = Magnocellular neurons
81
Respectively, what is the neuroendocrinological action of the anterior and posterior pituitary gland?
A = Releasing/inhibiting factors via hypophysial portal system P = Hormones directly released from magnocellular axons
82
Which hormone is responsible for long bone growth?
Growth hormone
83
Which hormone is responsible for Thyroid stimulation and regulation? (T3 and T4 release)
Thyroid stimulating hormone
84
Which hormone is responsible for stimulation of the adrenal cortex? What is released on stimulation?
ACTH Corticosteroids
85
Which hormones are responsible for stimulation of the ovaries and testies? What is released on stimulation?
FSH and LH Oestrogen and progesterone are released by the ovaries Testosterone is released by the testis
86
What hormone is responsible for milk production in lactating women?
Prolactin
87
What does the hormone oxytocin do? Where is it released from?
Milk letdown in lactating women and uterine contractions in pregnant women Released from the posterior pituitary gland
88
What does the hormone ADH do? Where is it released from?
Kidney water retention Posterior pituitary gland
89
What is the feedback mechanism of prolactin?
Prolactin secretion causes the Parvocellular neurons in the anterior pituitary gland to reduce dopamine secretion, which in turn causes increased prolactin secretion and therfore more milk production Dopamine secretion and therefore milk production can also be regulated by a suckling stimulus
90
Describe the HPT axis (Hypothalamic-pituitary-thyroid axis) feedback loop What type of feedback loop is this?
Hypothalamus senses low levels of T3/T4 and responds by releasing TRH (thyrotropin-releasing hormone). TRH stimulates the anterior pituitary to produce TSH which in turn stimulates the thyroid to produce thyroid hormone until blood levels return to normal. This is a negative feedback look
91
Describe the HPA axis (Hypothalmic-pituitary- adrenal axis) feedback loop
HPA axis is responsible for the stress response. Hypothalamus releases CRH (corticotropin-releasing factor) which binds to receptors on the anterior pituitary gland causing CTH to be released. ACTH binds to receptors on the adrenal cortex and stimulates the release of cortisol. At a certain blood level of cortisol , the cortisol exerts negative feedback on to the release of CRH and ACTH
92
What are the 3 major neuroendocrine systems through whch the hypothalamus and anterior pituitary gland direct neuroendocrine function?
HPT axis HPA axis HPG axis
93
Describe the HPG axis (Hypothalmic-pituitary-gonadal axis) feedback loop
94
Describe the feedback loop in which vasopressin is released as a result of low blood pressure
Major restriction in blood volume is detected by baroreceptors
CN IX and CN X carry this information to the NTS in the brainstem
This either stimulates or inhibits the release of Vasporessin from the hypothalamus
Vasopressin acts of the V1 receptors on blood vessels, causing vasoconstriction and therefore an increase in blood pressure
95
What is schizophrenia and how is it charecterized?
A psychotic disorder that at a miniumum consitists of dellusions and hallucinations
Charecterised by distortions of thinking and perception. It affects the emotionial response to stimuli/situations, becoming inapproprite or blunted
96
What are the 5 diensions of symptoms shown by Schizophrenic sufferers?
Posititve symptoms
Negitive symptoms
Cognitive symptoms
Agressive symptoms
Depression and anxiety
97
What is required for a diagnosis of Schizophrenia to be reached?
Disturbance lasting for 6 months or longer with at least one of the classical symptoms, delusions, hallucinations, disorganised or catatonic behavior or negitive symptoms
98
Name 5 classical symptoms of Schizophrenia
Thought echo/instertion/withdrawal
Delusional perception and control
Hallucinatory voices that comment or discuss the patient in the third person
Though disorders
Influence or passivity
99
Give 4 'negitive' symptoms of Schozophrenia
Affective blunting = reduced emotional reactivity
Ahedonia = loss of enjoyment or intrest in previously enjoyed activites
Alogia = Loss of the ability to speak
Apathy = Absence or supression of emotion feeling, concern or passion
100
Give 5 positive symptoms of Schizophrenia
Delusions
Hallucinations
Agitation
Exaggerated/disorganised speech
Exaggerated/disorganised bizzare behavior
101
What anatomical alreations can be see in Schizophrenia?
Imbalance in transmitter levels are thought to underpin schizophrena (dopamine)
Degeneration occurs within the grey matter - particularly within the medial temporal lobes
Enlarged ventricles and sulci are apparent on scanning as a result
Cerebral blood flow is reduced in the basal ganglia and frontal lobes
102
What is the target for antipsycotics?
Dopamine receptors
Dopamine antagonists have been proven to calm Schizophrenic patients
103
What is the major problem with antipsychotics?
Less effect on negitive symptoms
60% of patients still suffer these even when the negitive symptoms are under control
104
What are the two groups of antipsychotics?
First generation - Classical
Second generation - Atypical
105
What receptors do first generation antipsychotics act on?
Primarily potent antagonists at the D2 receptor
Also act on Muscaranic, Histamine, and Adrengic receptors
Low efficacy and 30% of patients are non-responders
106
What are the 4 main groups of first generation antipsychotics?
Phenothiazines
Butyrophenones
Thioxanthines
Dibenzoiazenes
107
Second generation antipsychotics were initially delveloped to around 5HT and dopamine antagonism, however they have been found to act on other receptors. What are these receptors?
Multiple receptor subtypes of 5HT and Dopamine
Muscarinic, histminergic and aderenergic receptors
May also inhibit reuptake mechanisms
108
What is the gold standard second generation Antipsychotic?
Clozapine
High efficancy but has the most associated side effects (cardiovascular)
Also causes Agranulocytosis
Generally only used after at least 2 second generation antipsychotics have been shown to be ineffective
109
Which two second generation antipsychotic drugs are the most effective at tacking negitive symptoms?
Risperidone and Olanzapine
110
Risaperidone can be classed as both a first and second generation antipsychotic. Why is this?
What other uses/benfits does this drug have?
Shows biphasic activity. Atypical at low doses and more conventional at higher doses.
Used to treat dementia
Can be used in children and adolescents
111
Name first (2), second (3) and third generation (1) antipsychotics
1st = Chlorpromazine, Haloperidol
2nd = Amisulpride, Risperidone, Clozapine
3rd = Aripiprazole
112
What are the majority of side effects seen with antipsychotics called?
What are they a result of?
Extrapyramidal symptoms
As a result of altering activity within the nigrostrital pathway
113
Give examples of 3 extrapyramidal symptoms caused as a side effect of antipsychotics
Dystonias
Akathisia
Parkinsonisms
114
What are the side effects of antipsychotics?
Extrapyramidal symptoms
Sedation
Seizures
Hypotension
Hypothermia
Hypersensitvity
Weight gain
115
Why are second generation antipsychotics associated with seeing reduced side effects?
2nd generation antipsychotics have a higher affinity for the mesolimbic and cortical pathways than the nigrostriatal dopaminergic pathways.
116
What is neuroleptic malignant syndrome?
Describes the side effects associated with the use of antipsychotics in patients with a genetic polymorphism of the D2 receptor
High fever, autonomic problems, and altered consciousness
117
Where a patient presents with neuroleptic malignant syndrome, how can the side effects caused by the use of antipsychotics be treated?
Dopamine agonists and benzodiazepines can be used following immedate withdrawal of the antipsychotic
118
What is Tardive dyskinesia?
Disabling invoulentary movements of the face and limbs: tounge protruding, grimacing and twisting of the face and limbs
Only side effect that is irrevesible - spontanelously remitts in 30% of presentations
119
What causes Tardive dyskinesia?
A result of oxidative neurodegneration caused by increased glutamatergic transmission wich results from a down-regulation of the dopamine system
Caused by prolonged use of classical antipsychotics
120
What would be the action you would take on presentation of Tardive dyskinesia?
Withdraw the classical antipsychotic
Switch to a atypical antipsychotic
Immediately stop any anticholinergics being used
121
What dopamine pathway is involved in the pathogenesis of schizophrenia?
Mesolimbic and Mesocortical
122
Which of the dopamine pathways are used in parkinsonism?
Striatongral
123
What substances can induce iatrogenic parkinsonism?
Antiemetics
Antiepileptics
Cardiovascular agents
Vestibular Seditives
124
What are the three main effects of anaesthetic drugs?
Unconsciousness
(action on the reticular dormationa nd ARAS)
Loss of reflex's
(Affects the sensory input to the reflex arc)
Analgesia
(reduced transmission of conscious sensation)
125
What are the two main groups of anaesthetics, and how do they differ in administration?
General
(Intravenous eg. propofol)
(Inhilation eg. isofluorane)
Local
(same as general but administered in low doses to affect small localised regions)
126
How are local anaesthetics grouped?
Split into 2 groups according to structure (normally have a 'caine ending)
Amino-esters = metabolised in the plasma
Amino-amides = metabolised in the liver
127
What is the mechanism of local anaesthetics?
Via sodium channel block which dampens down neuronal activity and reduces sensory transmission to the cortex
**2 ways:**
Directly entering the channel when its open (more channels open the bigger the effect = use dependence)
Accessing channel by crossing the axonal membrane and binding from the inside
128
Give a clinical example of when local anaesthetics wouldnt work and why.
When the tissue is inflamed.
Local anaesthetics ability to work is pH-dependent - inflammatory soup in damaged tissue tends to be acidic
Local anaesthetics ionise in acidic pH = reduces their ability to cross the neuronal membrane and attach to the sodium channel
129
How is sensation affected by administration of local anaesthetics?
Local anaesthetics work more easily on smaller or un-myelinated nociceptive sensory fibres (A-delta and C-fibres) and unmyelinated autonomic fibers.
This is because the access to the sodium channels via the membrane is easier than across the larger and highly myelinated proprioceptive fibres
130
What 3 factors need to be taken into consideraton when selecting a local anaesthetic?
Needs to be:
Agent with low irritant effect and toxicity
Rapid onset of action
Half-life to allow adequate time to do a procedure
131
Name 3 commonly used local anaesthetics and their uses and half lives
Lidocane (amide) = 1-2 hours
(Local infiltratioin, nerve block, dental and topical)
Bupivacaine (amide) = 1-3 hours
(Local infiltration, peripheral nerve block, epidural, and sympathetic nerve block)
Benzocaine (ester) = \<1 minuite
(Throat lozenges)
132
What are the main side effects of local anaesthetics?
Local irritation and inflammation occuring at the site of administration
Can be exasberated by the use of local vasoconstrictors or trauma to tissue on administration
133
Rarely there can be systemic side effects on the use of local anaesthetics.
What causes this and what are the systemic side effects?
Caused by overadministration of of the agent, leading to increased plasma levels of the drug
Cardiovasuclar changes
(Caused by local vasodialation or cardiotoxicity through binding in the heart)
CNS chnages
(Light-headedness, sedation, loss of consciousness)
Anaphylaxis
(Rare and only found with ester drugs)
134
What do general anaesthetics do?
Induce a loss of sensation, altered state of consciousness and a loss of memory for what happens under its influence
135
Name and explain the 6 steps in the process of anaesthesia
**Premedicaion**
Benzodiazepine to reduce anxiety and help with memory loss
**Induction**
Inhalation of IV administration of the anaesthetic
**Muscle relaxation and intubation**
Uses a neuromuscular blocking agent to relax the muscles during long surgical procedures
**Maintenance**
Inhilation or IV administration
**Analgesia**
Administration of agents to reduce pain on recovery from surgery
**Reversal**
Of both neuromuscular blocking agent and anaesthetic
Results in return of consciousness
136
What are some benifits of Inhilation anaesthetics?
Very potent and readily mixed with oxygen for administation (25% to prevent hypoxia)
Low blood solubility = rapid induction and recovery with fewer lingering effects
The speed of effect means anaesthetic levels can be quickly adjusted
137
Nitrous oxide (simple gas) can be used in combination with volitile liquids when administering inhilation anaesthetics.
Give an example of a volitile liquid and explain why NO is used.
Isoflurane
NO is not very potent but can be used in combiation with other inhilarion agents.
It provides some analgesia, so when used in combination it can mean reductions in the required doses of other drugs
138
What are the 4 factors that depth and speed of recovery from inhilation anaesthetics are linked to?
**Rate of alveolar absorption**
(depends on depth of inspiration and the concentration of the concentration of the agent administered)
**Speed of equilibration**
(balance of anaesthetic concentration in the air, blood and fats, which depends on solubility of the agent)
**The relative concentations at equlibrium**
**Cardiac output**
(controls delivery of drug o the brain)
139
Regarding inhilation anaesthetics, what is the activity of the agent linked to?
**The blood:gas partition coefficent**
Indicates solubility
**The oil:gas partition coefficent**
Indicates the relationship between concentration of inhaled ages and that in the fat (brain/lipid membranes)
140
What is the potency of an inhilation anaesthetic calculated as?
Minimum alveolar concentration (MAC) required to immoilise 50% of patients during noxious stimulation
141
What is the Meyer-Overton theory based on?
The correlation between lipid solubility of inhaled anaesthetics and minimum alvelolar concentration.
States that anaesthesia occured when a sufficent number of inhilational anaesthetic molecules had accumulated in the lipid cell membrane, regardless of the drug type
142
What are the main side effects of inhilation anaesthetic agents?
Reduce activity throughout the body, via depression of cardiac output and blood pressure
Cause respiritory depression through an action on teh brainstem respiritory centres
Cause irritation of the respiritory tract, resuting in bronchospasm and laryngospasm
143
Why are IV anaesthetics not used alone for long term anaesthesia?
IV is used to induce anaesthesia and maintainace is provided by inhilation or a combination of inhilation and IV
This is due to accumulation affects and slow redistribution
144
What are the 5 most commonly used IV anaesthetics?
Thiopental
Propofol
Etomidate
Ketamine (slower acting)
Midazolam (slower acting)
There is not just one mechanism of action for all the drugs
145
In general, how do IV anaesthetics work?
Supress consciousness through a reduction of activity within the CNS with agents acting on both the inhibitory and excitatory pathways
Thiopental and Midazolam increase activity at the GABA receptor (inhibitory)
Ketamine blocks glutamatergic NMDA receptors (excitatory)
146
What are the side effects of general anaesthetics?
Vary according to the concentration, duration and drug used
Decreased cardiac contractitlity
Respiritory depression (in overdose, leading to respiritory failure and death)
Decreased CNS fucntion
Reduced sympathetic activity
147
Why might opiods be given alongside anaesthetics?
When given at induction, opoids can provide analgesia and reduce the dose of antibiotic required to have a seditive effect
Their effect on the CV and respiritory system can also help counteract the effects of invasive treatments, reducing HR, BP and resp rate increases that are caused by the stress
148
Name 3 fast acting opiods used in combination with anaesthetics
Fentanyl
Alfentanil
Remifentanil
149
What are epidural anaesthetics used for?
Use general or local anaesthetics and sedatives to remove sensation
Use analgesics to block pain sensation specifically
150
Why does epidural anaesthetic have more of a effect on sensory rather than motor functions?
Sensory neurons are significantly more sensitive to the effects of local anaesthetics than motor neurons
Linked to the levels of myelination and the ease of entry of the anaesthetic
Epidurals do have an effect on the motor system but it is drug and concentration dependent
Midazolam = seditive and muscle relaxant effects
151
What sensation is removed during labour when a epidural is used?
Pain is removed, but pressure sensation is not
152
Whar are the most commonly used anaesthetics?
Bupivacaine and Lidocaine
153
Why may other agents be added to an epidural?
To prolong the duration of the block and decrease bleeding and toxicity
Adrenaine is the most commonly added
Opoids (fentanyl and morphine) can be added for muscle relaxing and analgesica properties
154
What is the Bromage scale?
A scale used to determine the level of epiduaral block.
Asseses and grades the patients ability to move their legs following induction - **4 levels:**
**1) Complete block**
Patient is unable to move the knees or feet
**2) Almost complete block**
Patient demonstrates an inability to flex the knees but has the ability to flex the feet
**3) Partial block**
Patient can partially flex the knees and resist gravity and has movemnt of the feet
**4) No block**
Patient can flex the knees and feet fully
155
What are the two groups of neuromuscular blockers?
Depolarising
Non-depolarising
Both groups are used to relax muscle by blocking the activity at the neuromuscular junction
156
What is the mechanism of depolarising neuromuscular blockers?
Non-competitive/agonist neuromuscular blockers
Also includes anticholinesterases
Depolarising NMB binds to the Ach receptor causing prolonged depolarisation (receptor closes and repolarises even though agonist is still bound) and the site to be blocked = prevents depolarisation and muscle contraction
Initial depolariation causes fasciculation of the muscles prior to relaxation occuring = increases likelihood of post-operative muscle pain
157
What is the most common neuromuscular blocker used?
Suxamethonium
Only administered IV
Rapid acting = muscle relaxation within 1 min
Rapidly metabolised by plasma cholinesterase (5-10 mins) so requires a constant infusion to maintain the blockade
158
What group of neuromuscular blockers do anticholinesterases fit into?
Give and example of one
Depolarising neuromuscular blockers
Neostigmine
159
How do anticholinesterases work when used as neuromuscular blockers?
(Acetylcholinesterase)
Work non-competitivly to increase the levels of Ach in the junctional cleft by blocking acetylcholinesterase breakdown of Ach
Cause muscle paralysis by overloading the system = activating all Ach receptors at maxiumum and leaving no room for additional movement
(similar to neuromuscular blockers)
160
What are the issuses associated with acetylcholinesterase inhibitors?
They increase activity in the PNS causing bradycardia, increased secretion and increased peristalsis
161
Give an example of a neurotoxin that works in a similar way to anticholinesterases
Botulinum toxin A ( botox)
Works to reduce muscle activity by blocking pre-synaptic release of Ach
Used clinicnally to treat muscle spazams and tic
Also known for its cosmetic uses
162
What is the mechanism of non-depolarising neuromuscular blockers?
Known as competitive or antagonist neuromuscular blockers
Compete with Ach to bind to the Ach receptors
Once bound they prevent depolarisation thereby blocking the effect of Ach
Also act pre-synaptically to reduce calcium entry = reduces the release of transmitter from presynaptic vesicles
Do not cross theh blood brain barrier = no effect on teh CNS
163
Name 2 common non-depolarising neuromuscular blockers
Atracurium
Vecuronium
164
Other than their direct mechanisms how do depolarising and non-depolarising neuromuscular blockers differ?
Non-depolarising have a slower onset time (2-5 mins) with a duration between 15-90 mins
Non-depolarising are also water soluble and show no accumulation with repeated doses = more suitible for long term use
165
What can happen is neuromuscular blockers and inhilation anaesthetics are taken together?
Inhilation anaesthetics can increase the effects of neuromuscular blockers
Must talior the cocentrations used by correlating teh effects of multiple drugs
Need a balanced level of anaesthesia, analgesia and muscle relaxation
166
Which group of neuromuscular blockers is always chemically reversed prior to recovery?
What are the drugs used to do this?
Non-depolarising
**Neostigmine (anticholinesterase)**
- Specific for a non-depolarising blockade
- Rapid (1 min)
- Effects last for 20-30 mins
**Sugammadex (Selective relaxant binding agent)**
167
Anticholinesterases work as a depolarising neuromuscular blocker (acetylcholineseterase inhibitors).
What other function can they have?
Also work to reverse the effects of some non-depolarising neuromuscular blockers eg. atracurium
But they can prolong the action of depolarising neuromuscular drugs eg. suxamethonium
168
In the event that anticholinesterases must be given, what else can be given to counteract the side effects?
Bradycardia and increased secretions as a result of the muscuranic effects on the PNS are the side effects
Give Glycopyrronium or Atropine prior to, or with a reversing agent
169
How do selective binding agents work to undo the blockade caused by neuromuscular blockers?
Give an example of one
Sugammadex
Selective relaxant binding agent used for raid reversal of NMB blockade and acts by forming a complex with the drug by encapsulating it to inactivate it
Well tollerated, no effect on the cholinergic nervous system, minimises the risk of residual paralysis and is rapidly cleared form the plasma and excreted within 24 hours
170
What is addiction defined as?
Relapsing remitting disorder comprising behaviors that are performed in a compulsive manner in spite of the potential for self harm
171
Define dependency
Comprised of two components
**Psychological dependence**
Describe the effects of the compulsive behaviors and is charecterised by emotional distress caused by withdrawal of the drug
**Physical dependence**
The functional effect of the drug on the body itself. It is charecterised by physical symptoms of withdrawal of the drug
172
What is required for a definate diagnosis of dependence?
Name the 6 boundaries used
Can only be made if 3 or more of the following have been present together at some point in the last year:
1) Stong desire or sense of compulsion to take the substance
2) Difficulties in controlling substance taking behavior (onset, termination, or amount)
3) A physiological withdrawal state (negitive behaviors associated with being unable to achive intoxication state)
4) Evidence of tolerance (the need to increase the amount of drug needed to achieve the same high/positive elements
5) Progressive neglect of alternative pleasure or increased intrest in the amount of time taking the drug or recovering from its effects
6) Persisting with substance abuse despite clear evidence of harmful consequences
173
What are the 3 general defining components for drug dependence?
Psychological tollerance
Physical dependence
Tolerance
174
What are the main pathways thought to be associated with controlling reward?
Mesolimbic and mesocortical dopamine pathways = changes in doperminergic activity
Drugs of abuse target many of the main transmitter systems also
175
What are the neuroreceptors targeted by the following drugs? What are the actions of these drugs?
1. Codeine/Heroin
2. MDMA/Ecstasy
3. Ketamine/PCP
4. Alcohol
5. Cocaine
6. Valium
7. Cannabis
1. Opiod receptor = Agonist
2. 5HT receptor = Increases release
3. Glutamate receptor = Antagonist
4. Potassium channel = Increases opening time
5. 5HT/DA/NA = inhibits reuptake
6. GABA receptor = co-agonist
7. Cannabinoid receptor = agonist
176
What are the 4 main dopamine containing pathways within the CNS?
Nigrostriatal
Mesocortical
Mesolimbic
Tuberoinfundibular
177
How does the Nigrostriatal dopamine pathway work?
Projections from the substantia nigra pars compacta (midbrain) release dopamine in the striatum (caudate and putamen), part of the basal ganglia, which modulates motor and impacts cognitive and function
178
How does the Mesocortical dopamine pathway work?
Projections from the ventral tegmental area (midbrain) release dopamine in the frontal cortex (particularly the pre-frontal cortex) to modulate reward, motivation and attention
179
How does the Mesolimbic dopamine pathway work?
Projections from the ventral tegmental area (midbrain) release dopamine into the limbic system structures and are involved in cognition, learning and memory
180
How does the Tuberoinfundibular dopamine pathway work?
Connects the hypothalamus to the median eminence. Dopamine released from these cells control prolactin secretions from the pituitary
