cells to systems 4 Flashcards

(94 cards)

1
Q

two broad-types of smooth muscle, how contract and example of where present in the body

A

1) Multiunit - represents functionally independent smooth muscle cells which are often innervated by single nerve terminal and never contract spontaneously
Eg - smooth muscle in the walls of blood vessels
2) Visceral - represents bundles of smooth muscle cells connected by GAP junctions, which contract spontaneously if stretched beyond a certain limit
Eg - smooth muscle in the wall of intestine - peristalsis

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

what bands can you see under microscope in sarcomere and what shade

A

○ Can only really see A and I bands
○ A is the darker band (darker has A in it)
○ I is the lighter band (lighter has I in it)

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

What does the I, A, H band and Z and M line represent

A

I band - actin filaments
A band - myosin filaments that overlap with actin filaments
H band - zone of myosin filaments (where no overlap)
Z line - where actin filaments join and define boundary of the sarcomere
M line - band of connections between myosin filaments

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

what is a muscle tendon junction and neuromuscular junction

A

Muscle tendon junction
- Ends of skeletal muscle fibres are connected at muscle tendon junction
○ Linkage between sarcomeres inside muscle and collagen fibres that make up the tendon
Neuromuscular junction
- Way skeletal muscle fibre and nervous system communicate
- Essential to get skeletal muscle contraction

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

cardiac muscle what are the muscle cells called, what are the 2 types and list 3 special characteristics

A
cardiomyocytes 
Type 1 and Type 2 muscle cells 
1) muscle spindles 
2) intercalated disc
3) purkinje fibres
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the two types of cardiac muscle cells

A

Type 1
- Predominantly red muscle cells - large amounts of oxygen needed
- Comparatively thin (allow diffusion of oxygen) and contain large amounts of myoglobin and mitochondria
- Myosin with low ATPase activity - this is what creates larger amount of time between contractions
- Contractions are slow and sustained
Eg - in the control of posture
Type 11
- Predominately found in white muscle - not dependent on oxygen
- Thicker and contain less myoglobin - rely on glycolysis - anaerobic respiration
- ATPase activity of the myosin in white fibres is high and contraction fast
- Type IIA fibres (red). Type IIB/IIX fibres (white) contain only few mitochondria.

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

Muscle spindles, what contain, what surround and function

A
  • Sensory specialisation of muscular tissue
  • Contain small specialised intrafusal (within capsule) muscle fibres surrounded by
    A capsule of connective tissue
  • Detect stretch and prevent over stretching
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

intercalated disc what are the 3 parts and Purkinje fibres function

A

1) Fascia adherens - anchor actin to nearest sarcomere
2) Mascula adherens - desmosome, stop separation during contraction
3) Gap junctions - allow action potentials to spread between cells
Purkinje fibres
- Conduct stimuli faster than ordinary cardiac muscle
- Allow contraction to spread around the heart rapidly

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

what are the two major classes of cells in the nervous tissues

A

1) Neurons

2) Glia - or accessory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

neurons what does cytoplasm contain and size of cell

A
  • Cytoplasm contain aggregates of rough ER (nissl-bodies)
    ○ Prominent in motor neurons and grey matter in spinal cord
  • Size of cell depends on level of activity and length of process with neuron has to support
    ○ Generally longer axon/distance larger cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List the 4 main glia and their main function

A

1) astrocytes - star shaped, mechanical and metabolic support as well as scar forming cells
2) olgiodendrocytes - form myelin shealth around axons (may surround several axons)
3) microglia - derived from monocytes and become phagocytic with tissue damage
4) ependymal cells - line ventricles of brain and spinal cord often ciliated

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

what are the two main peripheral nervous systems

A

Efferent neurons - nerve fibres originate from neurons within CNS and pass out of CNS
Afferent neurons - nerve fibres originate from nerve cells outside the CNS but enter the CNS

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

what are the two main cells in the peripheral nervous system and their functions

A

1) Schwann cells
- Form a sheath around one axon and surrounds this axon with several double layers of cell membrane
- Insulates the axon and improves its ability to conduct
2) Ganglia
- Ganglia are aggregation of nerve cells outside the CNS
- Individual ganglion cells are surrounded by a layer of flattened satellite cells

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

what is the resting membrane potential and how is it maintained

A

= -70mV

  • More negative within the cell than outside the cell
  • Dependent on the K+ concentration maintained by the slightly leaky K+ channel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the 4 stages in a membrane potential

A

1) pre-threshold
2) threshold
3) post-threshold
4) repolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe pre-threshold phase of membrane potential

A

movement of Na+ into the site causes depolarisation and further movement of Na+ into the cell making the inside more positive until it reaches threshold
ways in which Na+ enters
1) Na+ leaking into the cell, via leaky channels
2) Na+ from an action potential further back that flow forward after entering the cell and depolarise the adjacent membrane further upstream of the AP
3) Mechanical disruption to the neuronal membrane to make it more leaky to Na+ etc

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

describe threshold phase of a membrane potential

A
  • -30mV
  • Stimulus must reach threshold in order for AP to occur
  • Once reach threshold AP is the same magnitude each time no matter the stimulus
    ○ Always reach +30mV membrane potential
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

describe the post-threshold and repolarisation phase of a membrane potential

A

3) Post-threshold
- Once threshold reach causes opening of voltage gated Na+ channels causing a rush of Na+ into the cells and rapid depolarisation
- When reach +30mV gates slowly close creating a small plateau
4) Repolarization
- At +30mV voltage gated ion open so K+ leaves the cell and makes the cell more negative so goes back to the resting membrane potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how does propagation of the action potential occur in only one direction

A
  • Na+ floods in and along the axon and depolarises adjacent part of the axon
    ○ Na+ is sent only forward as when the channels backward start to close they become less sensitive to a charge - (refractory period)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is the refractory period and name and describe the phases

A

Refractory period
Minimum time during which the neuron is unresponsive to further stimulation
1st phase - absolute refractory period
- Na+ channels have become inactivated are incapable of been opened
2nd phase - relative refractory period
- Some but not all Na+ channels are responsive to further stimulus and are capable of being opened

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

List 4 characteristics of a action potential

A

1) Unidirectional electrical flow (one way)
2) Constant stimulus strength (self-perpetuating) - strong AP at start and end of propagation
3) Signals can be passed on to other neurons and effector organs (muscles and glands)
4) Larger axons propagate action potentials at faster velocities - less resistant to flow so Na+ moves along the axon quicker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

myelinated nerves what feature present, what does it do and how achieve

A

Node of Ranvier - voltage gated ion channels are located at large concentrations
- Myelination increases the speed of action potential propagation
Unmyelinated axon - takes time for ions such as Na+ and K+ to flow in and out
Myelinated axon - action potential jump across myelin sheath so Na+ flow down to adjacent node of Ranvier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

List and describe one way that sensory information is converted to language that CNS can understand

A

Pecinian corpuscle - sensory unit in the skin
receives deep pressure and vibration
Unstimulated Pacinian receptor
The Na+ ion channels are closed
Stimulated Pacinian receptor
Compression stretch the membrane and opens the Na+ ion channels allowing Na+ to move through the membrane depolarising the cell
Signal intensity and AP frequency
More pressure more frequent the AP occur telling the brain that there is more pressure applied

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

describe the 6 steps that occur within a synapse

A

1) AP propagation in the presynaptic axon and the synaptic knob
2) AP causes the opening of Ca2+ channels allowing Ca2+ to flow into the cell
3) Ca2+ migration causes vesicles full of neurotransmitters which causes them to migrate and merge with the presynaptic membrane where the neurotransmitters are released
4) Neurotransmitters diffuse across the synaptic cleft and bind with receptors such as ligand gated channels and may allow Na+ to enter the postsynaptic neuron bringing it closer to threshold
- Can also cause Cl- to move into the cell which hyperpolarises the neuron as the negative charge pushes the cell further away from threshold
5) Acetylcholinesterase (enzymes) are within the synaptic cleft and degrade acetylcholine into acetic acid and choline.
6) The choline is recycled back into the presynaptic membrane via a channel protein preventing them from remaining in the synapse and continually activating the postsynaptic membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
function of neuropeptides and give some examples
modulate activity of neurotransmitters, can assist or inhibit substance P, cholecystokinin
26
post-synaptic potentials what occurs what type of potential is it called
- The Na+ concentration decreases as move down the cell body towards the axon hillock - Graded potential - If by the time it gets to the axon hillock (where all the voltage gates ion channels are) the Na+ concentration is at threshold an AP will occur
27
graded potentials how different from action potentials and how does this affect action potentials
- signal dissipates into the cytoplasm so signal becomes less and less until reach axon hillock -Usually takes multiple stimulus or different stimuli from different areas to generate an action potential at the action hillock therefore the graded potential is additive unlike an action potential ○ To add the two stimulus they must occur within a short time frame - Temporal summation - To add two stimulus together from different area/pre-synaptic neurons they need to occur within a short time frame from one another - Spatial summation
28
acetylcholine what are the receptors called, the two types and what they do in terms of threshold
A cholinergic synapse - Nicotinic ○ increases Na+ permeability, drives membrane closer to threshold - Muscarinic ○ M1 decreases K+ permeability, drives membrane closer to threshold (e.g. exocrine glands) ○ M2 increases K+ permeability, drives membrane further from threshold (e.g. Heart)
29
what is the mechanism of botulinus toxin
Cuts up snare complex which allows neurotransmitters to be released stopping the propagation of AP across the synaptic cleft As it is an enzyme it can cut up more than one snare complex and therefore move around the cell until it has cut up all the snare proteins only way to overcome is to produce more SNARE proteins
30
List 6 functions muscles are used for
1) Locomotion 2) Movement through hollow organ (peristalsis) 3) Emptying of contents to outside 4) Vocalisation 5) Generate heat through metabolism 6) Manipulation of external objects
31
list the 5 parts of the neuromuscular junction
1) Motor neuron 2) Motor end pate synapse 3) Synaptic cleft 4) Synaptic vesicles 5) Neurotransmitters
32
what is the number of skeletal muscle fibres associated with
Amount of fibres present depends on regulation If want fine control then smaller amount of fibres per motor unit Eg - around the eye
33
what is the stimulus for contraction of skeletal muscle
- Acetylcholine is the neurotransmitter used which bind onto receptors on the motor end plate on the post-synaptic muscle fibre ○ Need influx of Calcium to cause the vesicles to release the neurotransmitter into synaptic cleft This generates a muscle impulse that eventually reaches the sarcoplasmic reticulum and the cisterna
34
what are the 6 layers of structures within a muscle
1) Muscle organ 2) Fascicles - a handful of fibres 3) Muscle cells or fibres 4) Myofibrils - within each muscle fibre (proteins) 5) Thick and thin myofilaments - work together to get contractions 6) Actin and myosin protein - As well as titin - an elastic myofilament
35
list the 3 muscle covering layers and what they cover
1) Epimysium - around the whole muscle 2) Perimysium - around each fascicles 3) Endomysium - around each individual fibre
36
define the following sarcolemma, sarcoplasm, sarcoplasmic reticulum (SR), transverse tubule,
- Sarcolemma - muscle cell membrane - Sacroplasm - cytoplasm of skeletal muscle - Sarcoplasmic reticulum (SR) - specialised skeletal muscle endoplasmic reticulum which stores Ca2+ within the skeletal muscle - Transverse (‘T’) tubule - come from outside to the inside of the cell and comes into close contact with the sarcoplasmic reticulum providing communication from the outside
37
Myofilaments what are the two types, what composed of and function
1) Thick myofilaments - Composed of myosin protein - Form cross-bridge ○ Tube with head on an angle able to interact with thin myofilaments to cause contraction 2) Thin myofilaments - Composed of actin protein - Associated with troponin and tropomyosin proteins ○ Different types of troponin - troponin C - calcium binding
38
troponin function
- Has a calcium binding site and once calcium binds conformational change occurs which pulls tropomyosin away from actin and opens up myosin binding sites on the actin
39
List the 8 steps in excitation-contract coupling of skeletal muscle
1) Muscle impulses cause SR to release calcium ions into cytosol(sarcoplasm) via a voltage gated ion channel 2) Calcium binds to troponin to change its shape (troponin C) 3) The position of tropomyosin is altered and binding sites on actin are now exposed Cross bridge cycling 4) Myosin cross-bridge attaches to actin binding site 5) Energy stored in the head of the thick filament causes the thin filament to be pulled past the thick filament which results in ADP and phosphate being released from myosin head 6) New ATP binds to the myosin head causing the link between actin and myosin cross-bridge break 7) ATP splits so ADP and Pi are now bound to the myosin head releasing energy that is stored for the next movement and myosin is ready to contract again ○ This is done by ATPase in the myosin head 8) Myosin cross-bridge goes back to original position
40
what are the 3 roles of calcium in neuromusclar contraction
1) Calcium in the presynaptic membrane causes the release of acetylcholine into the synaptic cleft 2) Once calcium is released from the SR it binds to troponin and removes blocking action of tropomyosin to reveal the myosin binding site on actin 3) Ca2+ leaving the troponin restores the tropomyosin blocking action and Ca2+ is taken back up by the SR
41
what occurs in terms of the sarcromere with muscle contraction
- When sarcromeres shorten, thick and thin filaments slide past one another - H zones and I bands narrow - Z lines move closer together - as the sarcromeres become closer together
42
what are the steps in relaxation of the muscle
- Acetylcholinesterase – rapidly decomposes Ach remaining in the synapse - Muscle impulse stops - Stimulus to sarcolemma and muscle fiber membrane ceases - Calcium moves back into sarcoplasmic reticulum (SR) - Myosin and actin binding prevented due to the reduction of Ca2+ in the sarcoplasm and therefore reduction in Ca2+ binding - Muscle fiber relaxes
43
what are the stages in a muscle contraction and how do you record a muscular contraction
``` • Latent period • Period of contraction • Period of relaxation • Refractory period • All-or-none response - Muscle contraction can be observed by removing a single skeletal muscle fiber and connecting it to a device that senses and records changes in the overall length of the muscle fiber ○ Measure the amount of tension or force within that muscle - Each contraction is called a twitch ```
44
length-tension relationship what occurs when overly shortened and overly stretched
Overly shortened - when AP arrives the muscle is already contracted a little so actin and mysoin already overlapping so there isn't as many cross bridges available to bind to actin and therefore the force of contraction is reduced Overly stretched - when AP arrives the myosin and actin are quite far apart and the muscle needs to spend more time to overlap these two and therefore the force of contraction is reduced
45
what occurs with summation and tetanus in terms of contraction and relaxation of muscle
Don't let the muscle relax fully before hit with next AP - Get summation of the AP tetanus - not getting relaxation of the muscle at all - Get increase force of contraction as more AP arrive
46
what occurs with recruitment of motor units, what increases recruitment
- Recruitment - increase in the number of motor units activated - whole muscle composed of many motor units - More precise movements are produced with fewer muscle fibers within a motor unit - As intensity of stimulation increases, recruitment of motor units continues until all motor units are activated ○ This occurs because increases amount of cross bridging and therefore able to generate a larger tension - Produce smooth movements - Muscle tone – continuous state of partial contraction
47
what is the order of recruitment of motor units
1) Motor unit 1's - slow-oxidative fibres - smallest 2) Motor unit 2's - Fast-oxidative fibres - medium 3) Motor unit 3's - Fast-glycolytic fibres - largest (in size)
48
characteristics of slow-twitch fibres (type 1)
``` Always oxidative • Resistant to fatigue • Red fibers • Most myoglobin • Good blood supply ```
49
characteristics of fast-twitch fatigue resistant fibres (type 2 A)
* Intermediate fibers * Oxidative * Intermediate amount of myoglobin * Pink to red in color * Resistant to fatigue
50
characteristics of fast-twitch glycolytic fibres (type 2 B)
* White fibers (less myoglobin) * Poorer blood supply * Susceptible to fatigue
51
what are the similarities and differences between cardiac and skeletal muscle in terms of contraction
``` Similar to skeletal muscle - Contractile force generated by sarcomere - Role of calcium Differences - Not initiated by neuronal input - All cells are electrically coupled - (skeletal cells act independently) - Long action potential - Source of calcium ```
52
what are the 2 regions of an intercalated disc
1) Transverse portion, aligned with Z line, desmosomes, mechanical cohesion 2) Lateral portion, parallel to myofilaments/sarcromeres, rich in gap junctions, low resistance pathways
53
what are the 3 types of heart muscle cells
1) Cells of myocardium 2) Rhythmically active self excitary “pacemaker” cells 3) Purkinje fibres, specialised conducting pathways which enhance spread of localised excitation
54
what does cardiac muscle contraction dependent on
diffusion of extra-cellular calcium (also have some from the sarcoplasmic reticulum)
55
contractibility of cardiac muscle what influenced by
- Ca++ levels - Hormones (epinephrine) - Nervous (autonomic) - Extent of stretch ○ Cardiac muscle operates in a range of lengths shorter than optimal
56
smooth muscle how contraction mediated, does it have a sarcomere, how are cells bound and what does it lack
- Contraction mediated by actin and myosin cross-bridge cycling - Poorly defined sarcomere structure - Cells bound together by basement membrane and transmits force - Lack T-tubules ○ Small membrane invaginations called caveoli ○ SR if present is rudimentary
57
what are present in the smooth muscle contraction, what attached to
- Actin filaments attached to dense bodies - Dense bodies are attached to membrane - Linked by diagonal network of intermediate filaments (desmin)
58
what is different about smooth muscle contraction
- Thick and thin filaments present ○ NO Troponin - therefore no Ca2+ binding site - Myosin heads along entire length - no tail region like cardiac and skeletal muscle ○ Therefore cross-bridging binding modulated by Ca2+ dependent phosphorylation of myosin (chemical change) which then allows cross-bridges to be formed between myosin and actin § Ca2+ binds to calmodulin in cytosol and the Ca2+-calmodulin complex binds to myosin kinase that phosphorylates myosin etc. - also control of Ca2+ is different
59
what are the two types of smooth muscle units and characteristics, where present
Multi-unit Smooth Muscle - Individual cells - Discrete innervation ○ Individual activity ○ Not neuromuscular junction but neurotransmitters diffuse around the extracellular fluid - Few gap junctions - Poor response to stretch - Minimal response to hormones - Ciliary muscle of eye, large airways of lung Single-Unit Smooth Muscle - Visceral (function not anatomy) - Network of closely opposed cells acting as a single unit - Direct stimulation of only a few - Multiple adherence points (desmosomes) - Linked electrically by gap junctions respond to neural signs, hormones, mechanical stretch, local pacemarker potential - muscle of uterus, intestinal tract, bile duct
60
what are the 5 innervation of smooth muscle
1) Extrinsic: both sympathetic and parasympathetic 2) Intrinsic: short neurons forming plexuses (networks) within tissue 3) Afferent sensory: autonomic reflexes - detect stretch and induce contraction 4) non-neural activation - hormones can pen or close ion channels changing membrane potential - also release Ca2+ from SR 5) oxygen, pH, body temp
61
describe how afferent sensory reflexes innervate smooth muscle
- No neuromuscular junction - Branching of fibres with “varicosities” that contains vesicles with neurotransmitter (both acetylcholine and norepinephrine) - Transmitter released into interstitial fluid and then diffuses - Potential for both sympathetic and parasympathetic input Modulatory rather than inducing - doesn't need nerve to innervate it
62
how is Ca2+ controlled in smooth muscle
○ Extracellular - receptor mechanism and membrane-potential dependent channels ○ Intracellular - released from the sarcoplasmic reticulum upon receptor activation
63
what are the two organs tat provide motor control where present and what detects
``` proprioceptors in muscle - Golgi Tendon Organs ○ Present in tendons ○ Report muscle tension development - Muscle Spindles ○ Embedded within muscle ○ Report muscle position, “Stretch” ```
64
what is the two ways information from the muscle spindles and golgi tendon is used
1) Appraisal of motor areas of the brain about muscle length and tension. 2) Control of muscle length and tension in a negative-feedback fashion by means of local spinal reflexes - Don't need to have conscious thought at local level - just to the spinal cord and back An example is controlling posture
65
what are the 2 organisation of motor control
1) Local reflex circuitry | 2) Descending pathways from the brain stem and cerebral cortex
66
what are the 3 sources that afferent fibres carry information from
1) In skeletal muscles controlled by motor neurons 2) In other nearby muscles, especially antagonists - muscle working in opposite direction 3) In the tendons, joints, and skin of body parts affected by muscle action
67
what does muscle spindle detect and aid in
- rate of change at which the muscle fibers are stretched - changes in length of muscle fibers • aids in coordination and efficiency of muscle contraction
68
what are the two types of fibres within muscle spindles and what activated by
1) Nuclear bag fibres - Large number of nuclei packed into mid-portion - Sense onset of stretch 2) Nuclear chain fibres - Nuclei in longitudinal row - Sense sustained stretch Both are activated with rapid stretch - External force stretching the muscle also stretches the intrafusal fibres activating their receptors endings
69
what is the nerve supply to intrafusal and extrafusal fibres and what effects firing rate
gama motor neuron alpha motor neuron The more or the faster the muscle is stretched, the greater the rate of receptor firing
70
stretch reflex what receptor involved what used for
muscle spindle - stretch | basis for postural reflexes to maintain body position
71
golgi tendon organs where located, what protects, what detects what pathway involved in
located at junction of tendon and muscle, protects tendon and muscle from excessive tension, detects force of muscle contraction and tension applied to the tendon involved in the tendon reflex
72
myasthenia gravis what is it, what occurs, what does it lead to and what management in place
auto-immune disorder develop antibodies against own nicotinic receptors 1) local immune response damages post-synaptic membrane 2) antibodies bind and interact two receptors selecting them for internalisation 3) bind to nicotinic receptors and block signalling leads to progression of muscle weakness use anti-acetylcholinesterase drug to increase amount of ACh in cleft however only managing symptoms and get to a point where this no longer works
73
what do receptors do in terms of pharmacodynamics
1) regulate cellular signalling - many different duration of responses as well as availability of receptor 2) make drug powerful and potent - amplification 3) contribute to specificity of drug action
74
define affinity, efficacy, potency and what do antagonists have
Affinity - ability to bind Efficacy - ability to turn on a pathway - create a response Potency - how much drug needed to get a response Antagonists - have potency which is measured in how much drug is needed to block a response at the site
75
what does EC50 and Emax represent
EC50 - measure of the potency of a drug (how much drug?) | EMAX - measure of the efficacy of a drug (How much effect?)
76
what occurs with antagonist in terms of response curve
parallel shift to the right - potency of the antagonist is measured by ability to shift the graph no change in maximum
77
clinical efficacy of agonist and antagonists
○ Agonists mimic endogenous molecules ○ Antagonists inhibit endogenous molecules § Activity evident only when agonist is active
78
what does the therapeutic range represent and what is a safe drug
optimise benefit while minimising the risk by being between maximum tolerated by body and minimum effective larger the therapeutic range the safer the drug
79
what are the characteristics in pharmacodynamics and pharmacokinetics
``` Pharmacodynamics - Know where a drug acts ○ Predict response ○ Desired / undesired Pharmacokinetics - Know how much to give ○ How often to give? ○ Long term consequences? ```
80
what changes within individuals
- Cellular distribution - Tissue distribution - Organ distribution - Organ system response - Reflexes - Idiosyncrasy - Genetics
81
what are the 2 main ways of chemical signalling between cells and sub-types within
1) Release of molecules - Local mediators (shouting) - Neurotransmitters (wired networks) - Hormones (broadcast) 2) Membrane bound molecules - Immune system (cellular neighbours)
82
anatomy of the peripheral nervous system
1) Somatic - Motor - single peripheral nerve spinal cord to skeletal muscle 2) Autonomic - 2 peripheral nerves - pre- and post-ganglionic Parasympathetic - craniosacral segments - ganglia close to target- Sympathetic - thoracolumbar segments - ganglia remote from target
83
what chemicals and receptors are involved with pheriphery nervous system for both preganglinic and postganglionic nerves
Somatic = acetylcholine + nicotinic (ligand gated receptor) Autonomic preganglionic Parasympathetic and Sympathetic = acetylcholine + nicotinic Autonomic Postganglionic Parasympathetic = acetylcholine + muscarinic Sympathetic = noradrenaline + alpha and beta-receptors (Ach at sweat glands with nicotinic)
84
what is the rate limiting step in the production of noradrenalin and what is an important drug in that pathway
Tyrosine hydroxylase - rate limiting enzyme - can be a drug target L-DOPA - precursor of dopamine - used for Parinson's disease as able to cross blood brain barrier due to the role of dopamine in motor control in the CNS
85
why don't you see an increase in heart rate with noradreanline and why do you see increase with adrenalin
- Only see vasoconstriction as if increase blood pressure too much autoregulation occurs with homeostasis and therefore body decreases blood pressure by decreasing heart rate which involves increasing parasympathetic effect and decreasing sympathetic - Adrenaline doesn't give the large increase in blood pressure so homeostatic mechanisms are not put in place
86
what drug inhibits the alpha-adrenoreceptor and what inhibits the beta-adrenoreceptors
alpha - phentolamine | beta - propranolol
87
What are some ways you can pharmacological modulate a synapse
1) control AP - via sodium channel blockers or potassium 2) synthesis of neurotransmitter - could block, inhibit, provide more substrate 3) storage of neurotransmitters - modulate storage either displace or inhibit uptake into these sites 4) metabolic enzymes that degrade neurotransmitter that is leaked from storage - inhibits to enhance levels of neurotransmitters 5) vesicular exocytosis - can target that process and prevent or enhance 6) termination of neurotransmitter via uptake 7) enzymes that degrade the released neurotransmitter - acetylcholinesterase inhibition or stimulation 8) receptors that neurotransmitters act upon - agonist or antagonist drug also pre-junctional receptors - regulate further release of neurotransmitter
88
nicotinic receptor what activates it, how fast response and what does activation cause
Binding of ACh causes a conformational change Ligand-gated ion channel receptor - allowing influx of Na+ which causes depolarisation - Very fast response (ms) - Causes ○ Skeletal muscle contraction at NMJ (Neural Nicotinic receptor Nn) ○ Action potential initiation at Ganglia (Muscle Nicotinic receptor Nm)
89
how many different types of muscarinic receptors are there, what type of receptors are they and what are the two main ones, where are they found and what do they do
5 different types of MuscR identified - all GPCRs M3 - Smooth muscle/glandular - Stimulatory - generates IP3 M2 - Cardiac - Inhibitory - inhibition of cAMP production - Increase K+ channel opening
90
what does the activation of muscarinic receptors cause
``` SLUD - Salivation - Lacrimation - Urination - Defecation Due to contraction of various smooth muscle (bladder and colon) - Sweating - Slowing of heart rate - Bronchoconstriction - Vasodilation (non-neural effect) ```
91
list an antagonist of muscarinic receptor, what it is used for and how it is reversed
d-tubocurarine pre-operative muscle relaxation - less anethertic needed so better recovery block reversed with neostigmine (anticholesterase drug so overcome with more ACh)
92
anticholinesterase drugs what do they act like, when do they have their effects, what is variable about them and give some examples
- Acts like an agonist as enhance levels of acetylcholine in synaptic cleft - However effects are more pronouced when ACh is being activity released - Therefore more selective effect as will only have effect on nerves that are already being activated as need to release of ACh into the synaptic cleft to occur first variable with access to CNS and duration of action organophosphates are irreversible neostigmine - more active at NMJ, used to reverse neuromuscular blockers (d-tubocurarine) and used to treat myasthenia gravis
93
differences between noradrenaline and adrenalin in terms of potency at receptors between each other and themselves
``` ○ NA > Adr at α ○ Adr > NA at β Noradrenaline: α1 > β1 ~ α2 >> β2 - mainly homeostatic adrenaline β2 ~ β1 ~ α1 > α2 - emergency hormone - fight or flight response ```
94
for smooth muscle relaxation and heart rate potency of drugs
Isoprenaline > Adr ≥ NA >> Phenylephrine