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ICPP Flashcards

1
Q

What is the difference between homeostasis and heterostasis?

A

Homeostasis-the extracellular environment can be maintained so that there is a constant internal environment
Heterostasis-the intracellular environment is constantly changing in order for the cell to carry out specific functions

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2
Q

What is the difference error signal?

A

Set point- optimal set point for a physiological parameter
System output-sensor detects a physiological parameter and produced this signal related to the parameter
The system set point comparator produces a negative feedback signal proportional to set point - system output.

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3
Q

After what temperatures can the temperature control system no longer regulate itself by negative feedback so positive feedback occurs?

A

Above 40 and below 30

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4
Q

What is the difference between endogenous and exogenous signalling molecules?

A

Endogenous signalling molecules are signalling molecules in our body whereas exogenous molecules are drugs that aim to mimic or affect endogenous signalling molecules

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5
Q

What the three different types of endocrine signalling molecules?

A

Catecholamines, peptides to proteins, steroids

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6
Q

Order the 3 endocrine signalling molecules from fastest course of action and plasma half life to slowest

A

Catecholamines: Plasma half life-seconds, course of action-milliseconds to seconds
Peptides/proteins: Plasma half life-minutes, course of action-minutes to hours
Steroids: Plasma half life-hours, course of action- hours to days

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7
Q

What main processes are controlled by the endocrine system? (3)

A

Growth and development
Digestion
Sexual and stress behaviour

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8
Q

What are the 2 major types of paracrine signalling molecules?

A

Neurotransmitters

Local chemical mediators

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9
Q

What are the main types of neurotransmitters?

A

Amino acids (glutamate, glycine), monoamines (eg. Adrenaline, dopamine, seratonin), peptides, acetylcholine

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10
Q

What are the main types of local chemical mediators (2)

A

Cytokines

Eicosanoids

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11
Q

What happens when a signalling molecule binds to its receptor?

A

This causes a functional change that transduces the chemical signal into an alternative signal or performs a signal dependent task eg. Transport/synthesis

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12
Q

What are the signalling molecule targets?

A

Receptors- protein molecules whose function is to recognise and respond to endogenous signalling molecules
Kinase-linked receptors eg. Cytokine receptor
Ionotropic receptors (LGIC’s) eg. Nicotinic acetylcholine receptor
Nuclear receptors eg. Oestrogen receptor
G-protein coupled receptors: Gi, Gs, Gq

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13
Q

How do kinase-linked receptors work?

A

A ligand binds to the receptor and this stimulates a protein-kinase enzyme to phosphorylate certain groups. This causes increased or decreased transcription and protein production and can lead to growth, cell differentiation.

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14
Q

How many transmembrane domains to GPCR’s have and where is the N-terminal and C-terminal?

A

7 transmembrane domains

N-terminal outside cell and C-terminal inside cell

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15
Q

What is the essential property of all ligands that bind to nuclear receptors?

A

Lipid soluble

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16
Q

What is the intracellular effect of ligands binding to ionotropic receptors?

A

Depolarisation or hyperpolarisation

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17
Q

How is calcium involved in regulating metabolism?

A

Lipolysis
Glycogenolysis
Regulation of many metabolic enzymes eg. Krebs cycle
Bone metabolism

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18
Q

How is calcium involved in membrane-linked functions?

A

Excitation contraction coupling
Excitation secretion coupling eg. Release of neurotransmitters
Plasma membrane-vesicle fusion

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19
Q

What is basal intracellular calcium concentratio in nM?

A

1x10-7M
1x10-4mM
0.1microM
100nM

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20
Q

What is basal extracellular calcium in moles?

A

1x10-3 M

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21
Q

What is basal concentration of calcium in intracellular stores of SER/SR?

A

3x10-4M to 1x10-3M

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22
Q

How does Ca2+ leave across the plasma membrane?

A

PMCA- plasma membrane calcium ATPase

NCX- 3Na+ enters for 1 Ca2+ to leave by indirect active transport (antiport transporter)

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23
Q

How does Ca2+ enter across the plasma membrane?

A

NCX- 3Na+ leaves for 1Ca2+ to enter when cell membrane is depolarised
VOCC-activated by depolarisation
LGIC-activated by excitatory neurotransmitters binding
SOCC-activated when sensor protein detects low ca2+ reserves in SER/SR

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24
Q

How does Ca2+ enter SER/ER?

A

SERCA- SER Ca2+ ATPase, ca2+ enters by active transport

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25
Q

How does Ca2+ leave the SER/SR?

A
  • Calcium induced calcium release stimulating RyR

- Gq activation stimulating ip3 receptor

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26
Q

If Ca2+ concentrations are high, which organelle other than the SER can take up Ca2+ and how?

A

Mitochondria through Ca2+ uniporter

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27
Q

What is the role of calcium buffers?

A

They bind to Ca2+ preventing rapid entry of Ca2+ into the cell and its compartments.

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28
Q

What is the role of Ca2+ sensors? Give an example.

A

Ca2+ causes a conformational change in these proteins so they can transduce Ca2+ signals to other proteins as Ca2+ would not be able to interact with these proteins alone. Eg. Calmodulin increases activity of PMCA

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29
Q

What is signal transduction?

A

Initial binding of a ligand to a receptor stimulates a cascade of reactions involving intracellular molecules to carry out a specific cellular response.

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30
Q

What does signal transduction allow?

A

Amplification. A small change in extracellular molecule can elicit a large change in intracellular molecules to create a response.

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31
Q

Explain three ways in which GPCR’s allow amplification.

A
  1. One activated receptor can change GDP to GTP on many G proteins.
  2. One activated G-protein can stimulate/inhibit many effectors.
  3. Effectors work in a catalytic manner. Each enzyme can catalyse the formation of many secondary messengers. Each open ion channel can allow many molecules inside.
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32
Q

What determines how long a G-proteins activity on the effector lasts for?

A

The intrinsic GTPase activity of the alpha subunit. This can be affected by proteins inside the cell that regulate its activity. It can also be affected by intracellular substrates required for its activity.

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33
Q

How does cholera occur?

A

CTx toxin systematically changes the Gs alpha subunit so that the GTP cannot be hydrolysed to GDP so they remain active. This allows the Gs alpha subunit to continuously stimulate adenlyl cyclase to form CAMP and hence PKA. PKA phosphorylates ion channels which remain open. Cl- floods out of gut epithelial cells and water follows.

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34
Q

How does the pertussis toxin work?

A

PTx systematically changes Gi alpha subunits by preventing GDP from being converted to GDP. The G protein remains in its heterotrimeric inactive form and adenlyl cyclase is not inhibited

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35
Q

How can ionotropy in the heart be increased?

A

Sympathetically released adrenaline
B1 adrenoreceptors in heart.
Adenylyl cyclase stimulated
PKA phosphorylates VOCC’s opening them. The alpha s-GTP subunit can directly interact with VOCC’s opening them so Ca2+ enters.

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36
Q

How can chronotropy of the heart be decreased?

A

Parasympathetically released Ach
M2 muscarinic receptors in heart
Adenlyl cyclase inhibited
Less VOCC’s phosphorylated. Gi alpha-GTP subunit directly binds to K+ ion channels so more K+ enters causing hyperpolarisation

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37
Q

How can bronchoconstriction occur

A

Acetylcholine
Binds to M3 receptors
Stimulated phospholipase C
Ip3 causes release of Ca2+ from SER and DAG stimulates phospholipase C that phosphorylates VOCC’s causing further increase in cytosol Ca2+

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38
Q

What regulates the amplification that GPCR’s cause?

A

Once a ligand has bound to its receptor and GDP has changed to GTP on a G protein, its bond with the ligand weakens
Once a G protein has had its GDP changed to GTP, protein kinases are likely to phosphorylate the GPCR so no more G proteins can bind
The GTPase activity of the alpha subunit is stimulated by substrates and proteins in the cytosol
The secondary messenger is metabolised by proteins to maintain basal levels

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39
Q

What is the permeability coefficient?

A

It tells you the speed at which a substance diffuses across a lipid bilayer. The greater the permeability, the higher the permeability coefficient.

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40
Q

Why is the speed at which water crosses lipid bilayers much higher than other polar molecules?

A

Water is a small polar molecule that exists as a gas so can pass between the phospholipids in the membranes.

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41
Q

What is passive diffusion directly proportional to?

A

Temperature and concentration gradient

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42
Q

What are the different types of proteins involved in facilitated diffusion?

A 
Ping pong proteins (carriers) =change in conformation when ligand binds so it is released on to the other side
Protein channels (pores) =certain stimuli causes the channel to remain open/closed eg. LGIC, VGIC, gap junction
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43
Q

What is an electrochemical gradient?

A

For an ion, there is a concentration gradient and a difference in charge across a membrane. If there are unequal concentrations, the ion moves from a region of higher concentration to a region of lower concentration. If there is unequal distribution of charge across a membrane, the electrical potential generates a force that drives ion diffusion until the charges are balanced.

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44
Q

What are the different types of transporters in a membrane?

A 
Uniport= A solute molecule is transported from one side of the membrane to another
Co-transport = A solute molecule is transported simultaneously with another molecule. Can be symport (transported in the same direction) or antiport (transported in opposite directions)
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45
Q

What is secondary active transport?

A

The transport of a substance depends on an electrochemical gradient of another substance via a co-transporter. The electrochemical gradient of this substance had been set up by active transport.

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46
Q

If the free energy change of the transport of a substance across a membrane is negative, will the process by which it is transported be active or passive?

A

Passive diffusion

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47
Q

If the free energy change for the movement of a substance across a membrane is positive, will the process by which it moves be passive or active?

A

Active transport

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48
Q

Which primary active transporters can be called pumps?

A

Those in the plasma membrane, in the membrane of organelles they are not called pumps

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49
Q

What is ischaemia?

A

Inadequate blood supply to part of the body. Tissues deprived of oxygen and nutrients.

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50
Q

Why does intracellular calcium increase during ischaemia?

A

Cells deprived of oxygen. Less ATP produced. Na+/K+ ATPase does not work.
Intracellular Na+ increases. NCX reverses. 3 Na+ is pumped out for 1 Ca2+ pumped in.

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51
Q

What is intracellular/extracellular Na+ and K+ concentrations?

A

Na+ i= 12mM o=155mM

K+ i=145mM o=4mM

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52
Q

Describe the structure of the sodium potassium pump.

A

Beta subunit anchors pump into plasma membrane

Alpha subunit is where Na+ K+, ATP and ouabain bind

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53
Q

List some functions of the Na+/K+ pump (6)

A

Creates a concentration gradient for Na+/K+
Drives secondary active transport processes for:
Ca2+ regulation
pH regulation
Cell volume regulation
Nutrient uptake

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54
Q

Which transporter is mainly responsible for removing Ca2+ from the cell

A

NCX

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55
Q

Why is high intracellular Ca2+ toxic?

A

Calcium phosphate forms causing ossification

Stimulates caspases involved in apoptosis

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56
Q

How do we stop acidification of cells?

A

Hydrogen ion extrusion by
NHE - Na+/H+ exchanger
Hydrogen ion extrusion and bicarbonate intrusion by
NBC - Na+/H+ HCO3-/CL- cotransporter
Bicarbonate intrusion by
3HCO3-/Na+ symporter
These are all secondary active transporters driven by the Na+ gradient set up by the Na+/K+ pump

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57
Q

How do we stop alkalisation of cells

A

Extrusion of bicarbonate

AE= HCO3-/Cl- exchanger

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58
Q

How do we stop cells from shrinking or bursting?

A

Opposing shrinking = Na+/K+/Cl- enter and 6 water molecules follow each
Opposing bursting = Na+/K+/Cl- leave and 6 water molecules follow each

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59
Q

How can we treat hypertension?

A

By blocking the protein transporters in the kidney that transport Na+ from the lumen of the tubules into the epithelial cells and thereafter the capillaries. This prevents water from following and re-entering the capillaries, decreasing blood pressure

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60
Q

In which area of the kidney is bicarbonate reabsorbed and why is bicarbonate reabsorption important?

A

The proximal tubule. Bicarbonate is the main buffer in the blood.

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61
Q

In which areas of the kidney is Na+ reabsorbed?

A

In the nephron
Thick ascending limb
Distal convoluted tubule
Cortical collecting duct

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62
Q

What is a membrane potential and what is it measured in?

A

Membrane potential is the magnitude of electrical charge across a plasma membrane and is always expressed relative to the extracellular solution. It is measured in millivolts.

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63
Q

How can membrane potential be measured?

A

Using a microelectrode. Voltmeter connected to 2 electrodes. One electrode in a beaker with solution. The other electrode is a fine glass pipette less than 1 micrometer which can penetrate the cell membrane without killing the cell. It is filled with a conducting solution of KCl.

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64
Q

What is the membrane potential of an erythrocyte and why is it this?

A

-9mV, virtually no selective permeability for K+ so Ek is close to 0

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65
Q

What is the membrane potential of skeletal muscle and why?

A

Around -90mV, very selectively permeable to K+ so very close to Ek.

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66
Q

What is membrane potential established by?

A

Asymmetrical distribution of ions across a plasma membrane

Selective ion channels in the membrane, especially K+, Na+ and Cl-

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67
Q

Why is resting potential negative?

A

High concentration of anions, negatively charged proteins and amino acids inside of the cell.
Most cells are very selectively permeable to K+ so membrane potential is close to Ek (the equillibrium potential when the electrical force and chemical force is balanced so there is no net movement across the membrane).
Membranes are not perfectly selectively permeable to K+ so other ion channels increase or decrease the size of the membrane potential.

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68
Q

If a membrane is very selectively permeable to K+, will this cause the membrane potential to become more negative or positive?

A

Negative

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69
Q

If a membrane is very selectively permeable to Na+, will this cause the membrane potential to become more negative or positive?

A

Positive

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70
Q

If a membrane is very selectively permeable to Cl-, will this cause the membrane potential to become more negative or positive?

A

Negative

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71
Q

Which equation allows you to work out the equilibrium potential of an ion?

A

The nernst equation

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72
Q

Which equation allows you to work out the membrane potential relative to permeabilities of different ions?

A

Goldman -Hodgkin-Katz equation

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73
Q

Why do ion channels contribute to establishing the membrane potential but transporters for ions do not?

A

Ion channels allow the rapid movement of ions down an electrochemical gradient in either direction. They are selective and open in response to certain stimuli.
Transporters allow very small movement of ions in one direction so do not contribute to membrane permeability.

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74
Q

What is the equillibrium potential of an ion measured in?

A

mV

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75
Q

Why does caffeine increase the efficacy of drugs?

A

Caffeine stimulates the RyR receptor on the SER of cardiomyocytes and smooth muscle cells so more Ca2+ enters by CICR. Therefore, there is increased force of contraction and stroke volume is increased. Vasoconstriction occurs and this causes hypertension. The increase in blood pressure means the blood flows faster and the drug is transported around the body faster. More of the drug reaches the target cells, increasing its efficacy.

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76
Q

When is the resting membrane potential changed? (3)

A

To generate an action potential in nerve and muscle cells
When converting a chemical signal in sensory cells to electrical signals
For the release of neurotransmitters or hormones

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77
Q

What are changes in membrane potential caused by?

A

Changes in ion channel activity and hence differential ion distribution across a membrane
Changes in the activity of electrogenic pumps

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78
Q

What are the different ways in which an ion channel can be controlled to change membrane potential?

A

LGIC
VOCC
Mechanical ion channels

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79
Q

Which types of ion channels are present in the hair cells of the inner ear that respond to sound?

A

Mechanical ion channels
Ca2+ open
K+ close

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80
Q

Give an example of an ion channel that is not perfectly selective for one type of ion.

A

Nicotinic acetyl choline receptor which is selective for Na+ and K+. Therefore when ACh binds a membrane potential intermediate to Ek and ENa is achieved.

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81
Q

How does the Na/K+ pump contribute to membrane potential?

A

It contributes a few mV to directly making the membrane potential negative as one positive charge is extruded from the cell.
However, it mainly contributes indirectly by maintaining the concentration gradient for K+ and Na+ by the active transport of these ions. These ionic gradients are responsible for resting membrane potential.

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82
Q

What is depolarisation? How are ions responsible for depolarisation?

A

Making membrane potential more positive so a decrease in size of membrane potential.
Na+ and Ca2+ channels open and enter the cell causing membrane potential to move towards ENa and ECa, making it more positive.

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83
Q

What is hyperpolarisation? How are ions responsible for this?

A

Hyperpolarisation is making the membrane potential more negative so an increase in the size of membrane potential.
K+ and Cl- ion channels open so K+ leaves the cell and Cl- enters the cell.

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84
Q

What occurs during synaptic transmission?

A

A neurotransmitter is released from the pre synaptic neurone and binds to a receptor on the post synaptic neurone. This causes ions to enter via an ion channel causing either hyperpolarisation or depolarisation.

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85
Q

What is involved in all fast synaptic transmission and give an example of one.

A

LGICS

Nicotinic ACh

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86
Q

What is summation?

A

Inhibitory synapses and excitatory synapses are present and the balance between the EPSP and IPSP determines whether an action potential is generated in the post synaptic neurone

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87
Q

What are the different methods of slow synaptic transmission?

A

Direct G protein gating

G protein gating via an intracellular messenger

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88
Q

What are the main differences between the two types of slow synaptic transmission?

A

Direct GPCR gating is localised in the plasma membrane and relatively quicker
Indirect GPCR gating via an intracellular messenger can be more widespread in the cell and is relatively slower

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89
Q

How do erythrocytes show that the Na+/K+ ATPase pump is not responsible for maintaining resting potential?

A

They have a resting membrane potential of -9mV.
If this was responsible it would be -90mV.
Erythrocytes have virtually no selective permeability for K+ channels demonstrating this is more important in maintains the resting potential.

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90
Q

How is membrane potential in the release of insulin from the beta cells of the islet of Langerhans?

A

Glucose enters
ATP conc increases
Binds to ATP-sensitive K+ channels which close
Membrane potential increases
VOCC’s open, Ca2+ enters
Exocytosis of insulin and vesicles fuse with membrane

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91
Q

How can membrane potential be exploited to treat type II diabetics?

A

Constantly depolarise the membrane so that VOCC’s are always open and insulin is continuously secreted by beta cells of islet of langerhans
Sulphonylurea activates K+ channels by binding to sulphonylurea receptors physically linked to them

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92
Q

What properties of cardiac ion channels enable the heart to be myogenic?

A

Selectivity-very specific to certain ions
VOCC- sensitive to small changes in membrane potential
Time dependent- close and open very quickly

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93
Q

Why do membrane potentials not equal to Ek?

A

They are not perfectly selective for K+. There are other ion channels present in the membrane.

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94
Q

What is the equillibrium potential of an ion?

A

The membrane potential when there is no net flow of ions.

Electrical gradient = concentration gradient

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95
Q

What are the properties of an action potential?

A

Change in membrane potential
Depends on ionic gradients and relative permeability
Depolarisation which must reach threshold at axon hillock
All or nothing
Propagated without loss of amplitude

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96
Q

What proves that Na+ is responsible for the rapid depolarisation that occurs during an action potential.

A

When we decrease Na+ extracellular conc, ENa decreases and becomes less positive.
When we decrease Na+ extracellular conc, the membrane potential at the peak of the action potential decreases in a manner proportional to the decrease in ENa.

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97
Q

How can we measure the flow of Na+ and K+ currents at a set membrane potential?

A

Voltage-clamp

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98
Q

How does a voltage clamp prove that Na+ channel inactivation occurs?

A

When a membrane potential is set to be depolarised, Na+ flows into the cell demonstration the voltage gated channels were open. However, this stops after a certain point, even if the membrane is continuously depolarised, demonstrating inactivation occurs.

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99
Q

What is conductance?

A

The number of channels for an ion that are open in a membrane

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100
Q

What happens when the conductance to a particular ion is increased?

A

The membrane potential moves towards the equillibrium potential of that ion

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101
Q

What is a major difference between the voltage gated sodium and potassium ions involved in an action potential?

A

Voltage gated sodium ions open rapidly and become inactivated when depolarisation is maintained
Voltage gated potassium ions open much more slowly but once opened, they stay open for the duration of depolarisation. Once resting membrane potential is established, they close slowly.

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102
Q

What proves that the sodium potassium pump is not important in repolarisation during an action potential?

A

There is only a small change in the intracellular concentration of Na+ during depolarisation, 40mM

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103
Q

What is responsible for the upstroke during an action potential?

A

Rapid opening of Na+ voltage gated channels

Na+ influx

104
Q

What is responsible for the downstroke of an action potential?

A

Inactivation of Na+ voltage gated channels
Slow opening of K+ voltage gated channels
K+ outflux

105
Q

What is responsible for the dip in membrane potential below resting membrane potential after repolarisation?

A

Slow closing of K+ channels while Na+ channels are closed .
There are more K+ channels open than there are at resting potential
K+ outflux

106
Q

Is there are large or small influx/ efflux of ions during an action potential?

A

Small

107
Q

What is the absolute refractory period?

A

The period during which no action potential can be produced. Most of the Na+ voltage gated channels are inactivated. Many K+ voltage channels are open.

108
Q

What is the relative refractory period?

A

The period during which an action potential can be generated if there is a large enough stimulus. Na+ voltage gated channels are recovering from inactivation and K+ voltage gated channels are closing slowly.

109
Q

Which voltage gated ion channels have a similar structure and what are the similarities

A

Na+ and Ca2+
Made up of one polypeptide
Can undergo inactivation if blocked by an inactivation particle when open

110
Q

How many homologous repeats are present in Na+ Ca2+ and K+ ion channels?

A

Four

111
Q

How many transmembrane domains are present in the homologous repeats of K+ Ca2+ and Na+ ion channels?

A

6

112
Q

In addition to the selective pore, what can affect the selectivity and fine tune the properties of Na+ and Ca2+ channels?

A

Glycocylation and phosphorylation

113
Q

Can K+ voltage gated channels be inactivated?

A

No

114
Q

How do local anaesthetics work?

A

Local anaesthetics block Na+ voltage gated channels in the axon when they are open. They have a high affinity for the channels when depolarisation is maintained and they are inactivated. This prevents Na+ from entering and local depolarisationn does not occur.

115
Q

In which locations and in what order do local anaesthetics block the voltage gated ion channels?

A

Small myelinated axons
Un-myelinated axons
Large myelinated axons

116
Q

What is conduction velocity?

A

The speed at which an action potential travels along an axon

117
Q

How can conduction velocity be measured?

A

Measure the distance between the stimulating electrode and recording electrode
Measure the time gap between the stimulus and the action potential being registered by the recording electrode

118
Q

What is an axon?

A

A nerve fibre is composed of many axons of varying diameter and conduction velocity

119
Q

Explain the local circuit theory of propagation

A

Localised depolarisation causes immediate depolarisation of adjacent sections of the membrane.

120
Q

What makes conduction velocity faster?

A

Increased resistance of axonal membrane =less ion channels
Decreased capacitance of axonal membrane=reduced ability to hold charge
Decreased cytoplasmic resistance=increased axon diameter

121
Q

Why does a large axonal diameter increase conduction velocity?

A

Less ions come into contact with the membrane so there is reduced cytoplasmic resistance and the current flows faster.

122
Q

What effect does myelination have?

A

Increases conduction velocity as it increases axonal membrane resistance because the myelin covering has no ion channels and decreases axonal membrane capacitance because it is a good insulator

123
Q

What is saltatory conduction?

A

Impulse jumps from node to node

124
Q

Why is demyelination a problem?

A

Resistive and capacitive shunting occurs. Depolarisation may not reach threshold because ions and the speed of conduction is reduced as there is no saltatory conduction.

125
Q

Which disease involves autoimmune destruction of myelin sheath?

A

Multiple sclerosis

126
Q

How can you increase the strength of a response caused by an action potential?

A

Quick successive action potentials

127
Q

Which isoform of Ca2+ is a target for most drugs and give an example of a clinical condition where this is targeted?

A

L-type

Hypertension, less Ca2+ entry into smooth muscle of arteries

128
Q

What are the differences between the properties of voltage gated Ca2+ and Na+ channels?

A

Ca2+ channels deactivate slower than Na+ channels

A high concentration of Ca2+ can lead to more inactivation

129
Q

What is synaptotagmin?

A

Ca2+ binds to this in the post-synaptic neurone and this brings the vesicle containing ACh to move closer to the membrane

130
Q

What is a snare complex?

A

A complex formed between a vesicle containing ACh, synaptotagmin and the pre-synaptic membrane to form a fusion pore.

131
Q

Why does Na+ movement predominate in activated nicotinic ACh receptors?

A

Resting membrane potential is closer to Ek than ENa so the driving force to reach ENa is stronger

132
Q

What prevents the build up of acetyl choline in the synaptic cleft?

A

Acetyl cholinesterase

133
Q

What do competitive blockers of nicotinic acetylcholine receptors do?

A

Bind to the receptor but do not cause a conformational change so aqueous ion pore does not open. Prevents acetyl choline from binding.

134
Q

Can competitive blockers or depolarising blockers of nicotinic acetylcholine receptors be overcome by increasing the concentration of acetylcholine?

A

Competitive blockers

135
Q

What do depolarising blockers of nicotinic acetylcholine receptors do?

A

They bind to nicotinic acetylcholine receptors and cause the aqueous ion pore to open so Na+ continuously enters causing maintained depolarisation of the membrane. This inactivates voltage gated ion channels and prevents further action potentials from being generated.

136
Q

In a clinical context, when are depolarising blockers of nicotinic acetylcholine receptors used?

A

In conjunction with the general anaesthetic to stop pain

137
Q

What is myasthenia graves?

A

An autoimmune disease in which antibodies attack nicotinic acetyl choline receptors. This either causes complement activated apoptosis of the cell or degeneration of these receptors.

138
Q

What is the effect of myasthenia graves?

A

Less functioning acetyl choline receptors on the skeletal muscle post-synaptic plate so endplate potentials are reduced in amplitude leading to muscle weakness and fatigue.

139
Q

In hyperkalaemic patients, what are the changes in the action potentials produced compared to normal action potentials?

A

Higher extracellular K+ increases resting membrane potential and allows less Na+ channels to be functional.
Therefore, a higher proportion of Na+ channels need to be activated. This requires a greater depolarisation so threshold is increased.
The amplitude of the action potential is decreased because less Na+ enters during depolarisation due to less functional Na+ channels

140
Q

What four steps are involved in the generation of an action potential?

A

Depolarisation
Repolarisation
Hyperpolarisation
Resting potential

141
Q

What does capacitance mean?

A

The ability of a membrane to hold a charge

142
Q

What does resistance mean?

A

The greater the number of ion channels in a membrane, the greater the resistance

143
Q

What unit is used to measure the concentration of drugs?

A

Moles M

144
Q

How can you calculate molarity from:
Molecular weight
G/L

A

G/L divided by molecular weight

145
Q

What is an agonist?

A

An agonist binds to a receptor (affinity), activates the receptor by changing its conformation (intrinsic efficacy) and generates a measurable response (efficacy)

146
Q

What is an antagonist?

A

An antagonist binds to a receptor (affinity) and prevents an antagonist from binding.

147
Q

What relationship will a graph of proportion of bound receptors against drug concentration show?

A

Rectangular hyperbola if drug conc is measured linearly

Sigmoidal if drug conc is measured logarithmically

148
Q

What is Bmax?

A

The maximum proportion of bound drugs

149
Q

What is Kd?

A

The concentration of drug required for 50% of receptors to be occupied

150
Q

What Emax?

A

Maximal response

151
Q

What is EC50?

A

A measure of potency. Concentration drug required for 50% of maximal response.

152
Q

What if functional antagonism?

A

An antagonist binds to a completely different receptor to the endogenous agonist and produces a response which is functionally the opposite of the agonist

153
Q

How are functional antagonists used in the treatment of asthma?

A

Stimulation of B2 adrenoreceptors in the bronchioles by a functional antagonist.
Gs protein binds to activated receptor and adenlyl cyclase is stimulates
ATP —> CAMP —> PKA
PKA causes relaxation of the bronchioles

154
Q

How can we achieve high selectivity/specificity for a specific receptor?

A

Selective affinity for the receptor or

Selective efficacy for the receptor

155
Q

For a drug, Kd concentration is required for maximal response. Why is binding to only 50% of the receptors only required for the maximal response?

A

Spare receptors increase sensitivity so they allow responses at low concentrations of agonist. If there were no spare receptors and 100% binding was required for full response then > or equal to Kd concentration of drug is required for full response.

156
Q

When patients are given opioids for pain relief such as morphine over long periods of time, greater concentrations are required for the same effect. After longer periods, the effect is no longer of the same amplitude. Why?

A

Down-regulation. The cells detect that there is high activity of m-opioid receptors so decrease the receptor number on their surface. Therefore, a greater concentration drug is required as their is reduced sensitivity. If the receptor decreases below the number of receptors required to be bound to for the maximal response, then it is no longer possible to achieve the maximal response.

157
Q

What is the difference between a full and partial agonist?

A

Full agonists are able to achieve maximal response because they have higher intrinsic efficacy and greater intrinsic activity.
Partial agonists are not able to achieve maximal response because they have lower intrinsic efficacy and lower intrinsic activity.

158
Q

How can partial agonists act as antagonists for full agonists?

A

If they have a higher affinity than the full agonist, they will bind to a receptor and produce a smaller response than the maximal response because they have a lower intrinsic efficacy.

159
Q

How can you change a partial agonist to a full agonist?

A

Increase the number of receptors so that efficacy increases.

160
Q

Two drugs have the same drug concentration against response curve. How can you tell which has the better efficacy?

A

Compare to drug concentration against binding curve. The drug which has a greater response with less binding has a higher efficacy.

161
Q

What is reversible competitive antagonism?

A

An antagonist binds to a receptor and blocks an agonist from binding. This relies on the dynamic equilibrium of ligand binding to receptor and can be overcome by increasing agonist concentration.

162
Q

What is irreversible competitive antagonism?

A

An antagonist binds to a receptor permanently and prevents an agonist from binding. This cannot be overcome by increasing agonist concentration. If it binds to enough receptors then the maximal response of the agonist is decreased.

163
Q

Which of the following is the maximal response that an agonist is able to achieve decreased by
A) reversible competitive antagonism
B) non-reversible competitive antagonism
C) non-competitive antagonism

A

B

C

164
Q

What is non-competitive antagonism?

A

The antagonist binds to an allosteric site on the receptor where the endogenous ligand does not bind. This changes the conformation of the receptor so the endogenous ligand has a reduced affinity for the receptor.

165
Q

What is intrinsic efficacy?

A

The ability of a ligand to activate a receptor by changing its conformation

166
Q

What are the four main processes in drug therapy?

A

Absorption
Distribution
Metabolism
Excretion

167
Q

What are the different types of drug administration?

A

Enteral - via GI tract: oral, sublingual, rectal

Parenteral- not via GI tract: subcutaneous, intravenous, intramuscular

168
Q

For drugs administered via the enteral route, where are they absorbed?

A

In the small intestine because:

large surface area, large conc gradient (well vascularised and motility)

169
Q

A drug that is a weak acid is administered enterally. How is it absorbed in the small intestine?

A

There is an equilibrium between the ionised and ionised form of the drug. The pH in the small intestine is about 6. The drug is acidic so its pKa value is low. Therefore there are few hydrogen ions so equilibrium shifts to increase the proportion of the drug in ionised form. The ionised drug is transported either by facilitated diffusion or secondary active transport via OAT’s.

170
Q

By which methods are drugs absorbed from the small intestine?

A

Passive diffusion
Facilitated diffusion
Secondary active transport
Endocytosis

171
Q

What factors affect drug absorption? (5)

A 
Drug properties- lipophilic or hydrophilic. Weak acid or base. 
Lumen pH
Density of SLC's in small intestine
Intestinal motility
Blood flow to intestine
172
Q

Where does first pass metabolism occur?

A

Intestines and liver

173
Q

What is bioavailability?

A

The relative amount of drug that reaches the systemic circulation once the drug molecules have gone through their first hepatic circulation. Depends on absorption and first pass metabolism.

174
Q

What is the initial phase of drug therapy for a drug that is administered intravenously?

A

Distribution

175
Q

What influences the rate of drug distribution to a specific tissue?

A

Density of capillary supply

Permeability of capillaries

176
Q

What influences how much drug leaves the plasma and enters interstitial fluid/intracellular fluid?

A

Lipophilicity
Density of SLC’s on cells
The degree to which it binds to plasma proteins
The degree to which it binds to tissue proteins

177
Q

What is Vd and what is it measured in?

A

Apparent volume of distribution.
It is the amount of drug that ultimately reaches systemic circulation by plasma concentration of the drug at time 0.
L or kg

178
Q

Vd of insulin = 3 litres

What does this tell you?

A

There is a high concentration of insulin in the plasma.

This could be because it is not lipid soluble or it is highly bound to plasma proteins.

179
Q

What do large Vd values tell you?

A

There is a high concentration of drug in the extracellular fluid/intracellular fluid.The drug is very lipophilic or highly bound to tissue proteins.

180
Q

How are drugs metabolised by the body?

A

Phase I enzymes- cytochrome P450 increases the ionic charge of drugs by hydroxylation/dealkylation
Phase II enzymes-conjugating enzymes further increase the ionic charge of drugs by addition of glucoronate, methyl, acetyl, sulphur, amino acids.
This enhances renal elimination.

181
Q

What is CYP450 induction?

A

Concurrent administration of drugs can activate CYP450 so there is increased transcription, translation or decreased degradation. Therefore, any other drugs administrated will be metabolised and excreted faster. Bioavailability decreases.

182
Q

What is CP450 inhibition?

A

Concurrent administration of drugs van lead to CYP450 inhibition. This is by competitive or non-competitive inhibition. If another drug is administered, it will be metabolised and excreted more slowly so bioavailability increases.

183
Q

What is the main route of drug excretion?

A

Renal excretion

184
Q

How does renal excretion occur?

A

80% of the plasma enters the peritubular capillaries
There are many OATs and OCTs in the kidney tubules so ionised drugs are transported into the tubules by facilitated diffusion or secondary active transport.
Lipophilic drugs diffuse back into the peritubular capillaries because there is a high concentration of solutes in the tubules.

185
Q

What is clearance?

A

The rate of elimination from the body (ml/min)

186
Q

What is drug half life a balance between?

A

The greater the volume of distribution, the greater the half life.
The greater the clearance, the lower the half life.

187
Q

What are the units of clearance?

A

Ml/min

188
Q

What is the relationship between plasma concentration and time?

A

As time increases, plasma concentration decreases proportionally.
First order kinetics/ linear elimination kinetics.

189
Q

Why does plasma concentration and time show linear elimination kinetics?

A

As plasma concentration increases, the rate of elimination and clearance increases proportionately.

190
Q

In a saturated system, some drugs show 0 order kinetics. Why?
Why is this dangerous?

A

As plasma concentration increases, the rate of metabolism and elimination stays the same. Enzymes are a limiting factor.
The therapeutic window is more narrow so high doses can lead to poisoning.

191
Q

What increases renal elimination?

A

Ionisation of drugs by phase I (CP450 catalyses hydroxylation) and phase II (conjugates glucaratonate) enzymes

192
Q

Describe in simple terms by which heritable changes in gene expression occur without entailing changes in DNA sequence.

A

Uniparental disomy most commonly caused by trisomy rescue.
Imprinted chromosomes show differential expression of specific genes depending on the parental origin of the chromosome. If two imprinted chromosomes are inherited from one parent, there will be differential gene expression.

193
Q

What is the difference between nerves in the autonomic and somatic nervous system?

A

Somatic-single myelinated neurone to skeletal muscle

Autonomic-pre-ganglion myelinated neurone, ganglion (cholinergic synapse nACh ), post-ganglion unmyelinated neurone

194
Q

What is the difference between nerves in the sympathetic nervous system and the parasympathetic nervous system?

A

Sympathetic- short myelinated pre-ganglion neurone, long unmyelinated post-ganglion neurone
Originate in thoracic and lumbar regions
Ganglia in paravertebral column
Parasympathetic-long myelinated pre-ganglion neurone, short unmyelinated post-ganglion neurone
Originate in medullary and sacral regions
Ganglia in innervated tissue

195
Q

What main processes does the sympathetic nervous system aim to do to the cardiovascular system?

A

Increased heart rate and force of contraction

Increased blood pressure

196
Q

What is the function of the parasympathetic nervous system?

A

Maintains basal rate

197
Q

What nerve is important in the regulation of the heart?

A

Vagus nerve

198
Q

How is acetylcholine, noradrenaline and adrenaline synthesised?

A

AcetylcoA + choline —> acetylcholine
Catalysed by choline acetyltransferase (CAT)

Tyrosine ---> DOPA
Tyrosine hydroxylase
DOPA ---> Dopamine
DOPA decarboxylase
Dopamine--->noradrenaline
Dopamine B-hydroxylase
199
Q

How is acetylcholine and noradrenaline stored?

A

Stored in vesicles in the pre-ganglionic neurone and post-ganglionic neurone for ACh
Stored in vesicles within the varicosities of the post-ganglion neurone for noradrenaline

200
Q

What is different about the structure of a post-ganglionic sympathetic neurone and post-ganglionic parasympathetic neurone?

A

Post-ganglionic sympathetic neurones generally possess a highly branching axonal network with numerous varicosities, each of which is a specialised site for Ca2+ dependent noradrenaline release. This allows the smooth muscle/cardiac muscle to contract synchronously.

201
Q

How is action terminated at cholinergic and adrenergic synapses?

A

Acetylcholine is broken down by acetylcholine esterase in the synaptic cleft. Activity of this enzyme is higher at fast cholinergic synapses
Acetylcholine —> acetate + choline

Noradrenaline is rapidly removed from the synaptic cleft by noradrenaline transporter proteins so have a very limited time to influence pre and post synaptic adrenoreceptors.
Uptake 1 - NA actions are terminated by re-uptake into the pre-synaptic terminal by Na+-dependent, high affinity transporter
Uptake 2 - NA not taken up by uptake 1 is taken up by a lower affinity non-neuronal mechanism

202
Q

What happens to the adrenaline that is not taken back up by vesicles in the pre-synaptic neurone after re-uptake?

A

Susceptible to metabolism by:

  • monoamine oxidase
  • catechol-O-methyltransferase (COMT)
203
Q

What is the difference between cholinergic transmission at between the

1) pre-ganglionic neurones and post-ganglionic neurones
2) post-ganglionic neurones and the effector?

A

1) muscarinic ACh receptors on post ganglion neurone (GPCRs)

2) nicotinic ACh receptors on post ganglion neurone (LGIC)

204
Q

What are the neurotransmitters found in the post-ganglionic neurones in the sympathetic nervous system?

A

Noradrenaline (most common)
Sometimes acetylcholine
Others (NANC)
ATP, NO, neuropeptides

205
Q

What are the equivalent of sympathetic post ganglionic neurones in the adrenal glands?

A

Chromaffin cells which are epithelioid cells that release adrenaline

206
Q

What is the role of receptors in the pre-synaptic neurone and post-synaptic neurone?

A

Pre-synaptic neurone
Regulate processes eg. Neurotransmitter release

Post-synaptic neurone
Open channels so cations/anions can enter to trigger depolarisation/hyperpolarisation

207
Q

What does parasympathetic release of ACh cause to regulate the heart?

A

Bradycardia - SA node in atria
Reduced conduction velocity - AV node
Via m2 Muscarinic cholinoreceptors

208
Q

What does parasympathetic release of ACh cause in the lungs and intestines?

A

Lungs- bronchiolar/ bronchial contraction
Intestines-increased intestinal mobility/secretion
Via m3 receptors

209
Q

What is the effect of sympathetically released NA on the heart?

A

Tachycardia - SA node
Positive ionotropy - ventricles
Via b1 adrenoreceptor

210
Q

What is the effect of sympathetically released noradrenaline on the smooth muscle?

A

Arteriolar contraction/venous contraction a1

Arteriolar relaxation in heart, brain, skeletal muscle) b2

211
Q

What does sympathetic release of noradrenaline do the kidneys?

A

Renin release

212
Q

What does sympathetic release of noradrenaline do to the intestines and lungs?

A

Relaxation

Via b2 adrenorecepors

213
Q

Outline the various mechanisms by which drugs can influence neurotransmission and the major drug classes used to manipulate autonomic function. (4)

A

Degradation of neurotransmitter before release
Interaction with post-synaptic receptors
Inactivation of neurotransmitter in synaptic cleft
Re-uptake of neurotransmitter

214
Q

What is an important property that drugs interfering with the post-synaptic receptors require to prevent them having unwanted side effects?

A

Be specific to a sub-type of receptors

215
Q

Give examples of unwanted side effects that limit the usage of non-selective muscarinic ACh receptor agonists.

A

Decrease heart rate, decrease cardiac output
Increased bronchoconstriction
Increased sweating/salivation

216
Q

What indicated increased parasympathetic activity?

A

Stimulation salivary glands
Stimulation of lacrimal glands
Smooth muscle tone changes causing GI problems diarrhoea and vomiting
SLUDGE

217
Q

Give an example of how drugs can increase the activity of the parasympathetic nervous system?

A

Drugs can covalently modify acetylcholine esterase to irreversibly deactivate the enzyme and raise acetylcholine receptors

218
Q

Give a treatment for asthma.

A

B2 adrenoreceptor selective functional antagonists eg. Salbutamol, salmeterol

219
Q

Give a treatment for hypertension?

A

a1 b1 adrenoreceptor antagonists

220
Q

Is major innervation of the human airways sympathetic or parasympathetic?

A

Parasympathetic m3 Muscarinic cholino receptors

221
Q

Although there is very little sympathetic innervation of the human airways there is a large population of (non- innervated) adrenoceptors in the airway – what subtype of adrenoceptor are these, and where in the bronchial tree are they predominantly situated?

A

B2 adrenoreceptors

Density of receptors increases as airways get narrower

222
Q

What are the consequences of stimulating airways adrenoceptors? When might this occur in normal physiology?

A

Stimulation of airway beta causes airway smooth muscle to relax = bronchodilation
Although there is little direct sympathetic innervation of the airways, beta adrenoceptors will be activated by the circulating adrenaline and noradrenaline in the blood
This adrenaline and noradrenaline are released by the adrenal medulla, for instance during sympathetic nervous system activation during the “fight or flight” response, or during exercise

223
Q

Why does increased adenlyl cyclase activity cause smooth muscle relaxation?

A

Phosphorylation causes:
reduced Ca2+ intake by sarcolemma
Increases ca2+ uptake by SER
Decreases actin myosin interactions-muscle contraction

224
Q

What are the main categories of drugs that are used to treat asthma?

A

Bronchodilators- relievers
1. B2 adrenoreceptor functional antagonists
2. M3 cholinergic antagonists
3. Xantines
Preventers-anti inflammatory drugs
1. Glucocorticoids
Down regulate the genes involved in mediating an inflammatory response and suppressing the immune system
2. Sodium cromoglicate
reduces release of histamine from mast cells

225
Q

Compared to muscarinic cholinergic antagonists, adrenoreceptor agonists have a greater therapeutic benefit to asthmatic patients. What advantage does adrenoreceptor agonist therapy confer over the use of muscarinic cholinergic antagonists?

A

Adrenoreceptor agonists cause bronchodilation irrespective of the reason behind the bronchoconstriction
In contrast, muscarinic receptor antagonists only inhibit the action of the parasympathetic nervous system- not usually the cause of an asthma attack, so less useful clinically.

226
Q

Blood pressure is regulated by…

A
  • Sympathetic nervous system

* Renin angiotensin aldosterone system RAAS

227
Q

How does the sympathetic nervous system act to increase BP?

A

Arterioles in the peripheral vasculature – increases peripheral resistance
Heart – increases cardiac output
Kidney – to reduce Na/water loss

228
Q

Briefly explain what hypertension is.

A

Hypertension 140/90 mmHg

229
Q

What target sites for drug action can you define to control abnormally elevated BP?

A
  1. B1 adrenoreceptors- beta blockers
    (Antagonist- reduce heart rate and inotropy)
    (Antagonist- reduces renin production and hence reduces reabsorption of water and NaCl into capillaries)
  2. A1 adrenoreceptors- alpha blockers
    (Antagonist-reduces vasoconstriction)
  3. ACE inhibitors
    (Reduces the amount of angiotensin I converted to angiotensin II)
  4. Angiotensin II inhibitors
    Inhibits the release of aldosterone from the adrenal glands
    Inhibits vasoconstriction
  5. Calcium channel blockers
    Inhibits smooth muscle contraction
  6. Diuretics
    Blocks channels in kidneys so less water/ ions are reabsorbed into the capillaries
230
Q

What are the major population of adrenoceptors that mediate vasoconstriction of the vasculature?

A

Alpha1 adrenoreceptors

231
Q

Describe the role of the thyroid gland.

A

Produces hormones that regulate our metabolic rate
– Triiodothyronine (T3) – active hormone, increases basal metabolic rate
– Thyroxine (T4) – relatively inactive, reduces levels of T3
• Responds to ‘Thyroid stimulating hormone’ (TSH) released from the
anterior pituitary

232
Q

What is thyrotoxicosis?

A

refers to the clinical
symptoms due to high levels of thyroid
hormone in the bloodstream

233
Q

Explain how renin production increases blood pressure.

A

Activation of beta 1 adrenoreceptors stimulates renin production by the kidneys.
Renin converts angiotensin produced by the liver into angiotensin I
ACE produced by the lungs converts angiotensin I into angiotensin II
Angiotensin II stimulates vasoconstriction directly and stimulates the adrenal glands to produce aldesterone
Aldersterone stimulates the reabsorption of NaCl and water into the capillaries

234
Q

What are the main unwanted side effects of using alpha 1 adrenoreceptor antagonists to reduce blood pressure?

A

Diarrhoea ( increased intestinal motility due to GI tract contraction)
Arrhythmia
Postural hypotension
Impotence

235
Q

What are the unwanted side effects of beta adrenoreceptor antagonists (beta blockers) used to treat hypotension?

A

Bronchoconstriction
Decreased ionotropy and chronotropy leading to cardiac failure in in patients with pre-existing heart disease as they may rely on their sympathetic system for increased cardiac output.
Physical fatigue
Hypoglycaemia- beta blockers reduce the ability to sense hypoglycaemia

236
Q

What is the difference between the symptoms of anxiety and thyrotoxicosis?

A

Some symptoms are quite similar
– Palpitations
– Restlessness
– Increased bowel movements
– Tremor
Some differences…
– No goitre/proptosis
– May not have increased appetite and weight loss
– Thyrotoxicosis you see vasodilation (warm and sweaty)
- Anxiety you see vasoconstriction (cold and
clammy)

237
Q

How are symptoms of thyrotoxicotis caused by changes in the autonomic nervous system?

A

Thyroid hormones upregulate the number of adrenoceptors in the body
For example…
Increased beta-adrenergic receptors in the heart results in tachycardia and can result in hypertension

238
Q

What treatments are used for thyrotoxicotis?

A

Non-selective beta adrenoreceptor antagonists
Eg. Propanolol

Iodide- reduces the amount of T4 converted to T3
Long term treatment- may require thyroidectomy

239
Q

Where do loop diuretics work?

A

In the thick ascending limb of the loop of Henle.

240
Q

Where does thiazide and amiloride work? What are they?

A

Thiazides block a symport Na+/Cl- channel in the distal convoluted tubule.
Amiloride blocks an Na+ channel in the distal convoluted tubule and cortical collecting duct

Therefore on the side of the cell opening to the capillary less Na+ is transported via NCX and Na+/K+ ATPase

241
Q

Where is ADH produced and secreted? What is its function?

A

Anti-diuretic hormone-more water reabsorbed into the kidneys

ADH is produced in the hypothalamus and secreted into the capillaries of the pituitary gland by neurocrine communication. It then travels in the blood to the kidneys where it increases transcription of the gene for aquaporins in the cortical collecting duct.

242
Q

What is aldosterone? Where does it work? What are its receptors called?

A

Anti-diuretic. Increases the reabsorption of water and Na+ in the cortical collecting duct via mineralocorticoid receptors.

243
Q

Which drug can oppose the effects of aldosterone and why?

A

Spironolactone because it binds to mineralocorticoid receptors

244
Q

Where are aquaporins present and why?

A

Cortical collecting duct of kidney nephron. To allow reabsorption of water into the capillaries to increase BP.

Transcription of gene that makes aquaporins is increased by ADH hormone secreted by posterior pituitary and produced by the hypothalamus.

245
Q

What is the difference between osmolality and osmolarity. Which is more useful clinically?

A

Osmolality- mOsmol/kg
Osmolarity-mOsmol/L
Osmolality is more useful because volume changes with temperature whereas mass does not.

246
Q

What is the difference between molarity and molality?

A

Molarity= moles/L

Molality=moles/kg

247
Q

Suggest why 5% dextrose becomes hypotonic once in the body?

A

The glucose is quickly absorbed and metabolised by cells. The resulting solution is water which is hypotonic.

248
Q

When is 5% dextrose used instead of normal saline?

A

Normal saline is used to rehydrate healthy patients who cannot take fluids by mouth because it is isotonic and does not cause any osmotic changes.
5% dextrose is used when the individual is dehydrated and needs water to go into their cells. The glucose is quickly metabolised by cells and the solution becomes hypotonic so that water flows into cells rehydrating the patient

249
Q

When repairing double stranded breaks, what can single stranded annealing cause in the repaired DNA molecule that doesn’t occur in synthesis dependent strand annealing?

A

Deletions

250
Q

Which types of receptors affect the rate of protein synthesis?

A

Kinase-linked receptors - phosphorylate a protein which can then inhibits/stimulates gene transcription
Nuclear receptors- signalling molecule-nuclear complex migrates to nucleus and binds to gene transcription factor to inactivate/activate genes

251
Q

What do myasthenia graves and multiple sclerosis have in common?

A

They’re both autoimmune diseases affecting the nervous system.

252
Q

At a receptor site there is 0.2 mM of drug. Its molecular weight is 135. How many of the grams are there per litre of fluid?

A

0.0002 mol/kg x 135 g/mol = 0.027 g/L

253
Q

What is the equation for working out molarity? What are the units?

A

Molarity (mol/kg) x Mr (g/mol) = Concentration (g/L)

254
Q

What is Avogadro’s constant? What does this tell you?

A

6x10^23

How many molecules are in 1 mole of substance

255
Q

100 mg/L of insulin and acetylcholine
Mr insulin = 5808
Mr acetylcholine = 146.21
How many molecules are there per litre of substance of acetylcholine and insulin?

A

C = 0.1 g/L
M = 0.1 / 5808
Molecules of insulin = 0.1/5808 x6.8x10^23 = 1.17x10^19
Molecules of aCh = 4.08x10^20

256
Q

How can analgesics or opioids exert their effects via GPCR’s?

A

G protein-coupled receptors located pre-synaptically can influence the release of neurotransmitters at the synapse. For example, pre-synaptic μ-opioid receptors can be stimulated, either by endogenous opioids, or by analgesics such as morphine, to couple to Gαi proteins. The Gβγ subunits liberated from the Gαi-βγ heterotrimer interact with voltage-operated Ca2+ channels (VOCCs) to reduce the entry of Ca2+ through these channels. This decrease in Ca2+ influx inhibits the release of neurotransmitter from the pre-synaptic terminal, since neurotransmitter release is a Ca2+-dependent process.

257
Q

What are the different types of protein kinases?

A 
PKA (cAMP) dependent)
PKG (cGMP dependent) 
CaM-kinase (Ca2+ calmodulin dependent)
PKC (diacylglycerol dependent) 
Phosphorylate serine or threonine residues

zesa1 (5 decks)

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