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ESA2 - Amy's Cards > MR > Flashcards

MR Flashcards

1
Q

What percentage of a biological membrane is lipid, carbohydrate and proteins?

A

40% lipid, 60% protein, 10% carbohydrate

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2
Q

What accounts for 20% of the total weight of a biological membrane?

A

Water to maintain the hydrophilic interactions that create the bilayer

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3
Q

Name the 3 types of lipid that are involved in membrane formation.

A

Phospholipids, sphingomyelin, glycolipids

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4
Q

Describe the structure of a phospholipid.

A

Central glycerol backbone, two fatty acids attached. Phosphate group attached to 3rd carbon of the backbone which is attached to a polar head group.

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5
Q

What 4 molecule types can the polar head group of a phospholipid be?

A

Amine, amino acid, choline or sugars

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6
Q

How long are the fatty acid chains of a phospholipid?

A

14-24 carbons (16 and 18 most common)

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7
Q

What is the difference between a phospholipid and sphingomyelin?

A

Sphyngomyelin lacks the glycerol backbone

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8
Q

What is the structure of a glycolipid?

A

Similar to sphingomyelin but the phospho-head group moiety is replaced with a sugar

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9
Q

What is the difference between a cerebroside and ganglioside?

A 
Cerebroside = a glycolipid with a single sugar residue (a monomer)
Ganglioside = a glycolipid to multiple sugar residues (a polymer)
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10
Q

What type of bond is formed between the hydrophobic tails of lipids in a bilayer?

A

Van Der Waals

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11
Q

What are the 4 modes of movement of a phospholipid in a bilayer?

A

Flexion (fatty acid tails move side to side).
Rotation (phospholipid turns round on the spot).
Lateral diffusion (phospholipids move along their lamellae swapping with their neighbours).
Flip flop (change from one Lamellae to another).

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12
Q

Why is flip flop of phospholipids rare?

A

Because the polar head group has to pass across the hydrophobic core of the membrane

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13
Q

What maintains fluidity of the membrane?

A

One of the fatty acid chains of the phospholipids contains a cis double bond. Causes a kink in the chain and pushes neighbouring phospholipid away allowing more movement of phospholipids.

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14
Q

45% of the total membrane lipid is what?

A

Cholesterol

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15
Q

How and when does cholesterol decrease fluidity?

A

Decreases fluidity at high temperatures.
Uses its polar OH head group to form hydrogen bones with C=O groups of phospholipid molecules. This places the rigid central ring structure of cholelsterol next to the fatty acid tails of the phospholipid to limit their movement.

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16
Q

What reduces the ability of heat to increase membrane fluidity?

A

Cholesterol

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17
Q

When ones cholesterol increase membrane fluidity and how?

A

Increases fluidity at low temperatures.

Does this by spacing out phospholipids in the bilayer so they cannot pack tightly together.

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18
Q

What is the functional evidence of the presence of membrane proteins?

A

Facilitated diffusion, ion gradients and cell responses occurring at membranes

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19
Q

How does membrane fractionation give evidence of proteins in a membrane?

A

Spinning of a cell in a centrifuge forms a white pellet of only membrane which can be run on a gel electrophoresis to separate out the proteins.

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20
Q

Explain the freeze fracture technique of membranes and what it is used for.

A

Cell is frozen and broken up using a knife to separate the two Lamellae of the membrane. Transmembranous proteins remain with one lamellae only and this surface can be visualised under the electron microscope.
Evidence of protein presence in membranes.

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21
Q

How are peripheral proteins attached to membranes? And therefore what can cause their removal?

A

Bound with electrostatic or hydrogen bonds.

PH and ionic strength can cause their dissociation.

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22
Q

How do integral proteins interact with the lipid bilayer?

How are they removed?

A

With the hydrophobic domains of the bilayer.

Removed with detergent or organic solvents only.

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23
Q

Ionic strength and pH manipulation of a membrane will remove which type of protein?

A

Peripheral only (not integral)

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24
Q

Which amino acids are you likely to find in the hydrophobic domain of a transmembrane protein?

A

Glycine (small), alanine, cysteine (hydrophobic), histidine (polar uncharged)

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25
Q

What is a hydropathy plot used for?

A

Screening of proteins for clusters of hydrophobic amino acids to determine whether they are transmembrane proteins and how many times they cross the membrane.

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26
Q

Other than having a hydrophobic region, how else might an integral protein be anchored to the membrane

A

Post-translational modification by the addition of a lipid molecule

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27
Q

What modes of action can proteins do?

A

Conformations change, lateral diffusion, rotation

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28
Q

Why can membrane proteins not perform flip flop?

A

Membrane proteins getting across the hydrophobic core is not energetically favourable

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29
Q

How can protein movement in a membrane be restricted?

A

Proteins form aggregates that bind to one another, they can tether to the basement membrane extracellularly or to the cytoskeleton intracellularly, they can form interactions with proteins on other cells.

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30
Q

What are the 5 functions of a biological membrane?

A
  • Selectively permeable barrier
  • Create an enclosed, controlled chemical environment
  • Communicate with outside of cell or organelle
  • Recognise signalling molecules, adhesion proteins and immune molecules
  • Signal generation
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31
Q

What is spectrin?

A

A cytoskeletal protein that lines the intracellular side of the plasma membrane.

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32
Q

What are the names of the 2 integral proteins of the membrane that form interactions with the cytoskeleton?

A

Band 3 and Glycophorin A

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33
Q

What 2 peripheral, intracellular proteins do band 3 and glycophorin integral proteins bind to anchor the cytoskeletal spectrin to the membrane?

A

Band 3 binds Band 4.9

Glycophorin binds Band 4.1

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34
Q

Describe how the cytoskeleton is grafted onto the membrane.

A

Spectrin cage binds intracellular proteins band 4.1, adducin and actin. Band 4.1 and ankyrin (band 4.9) act as peripheral proteins and bind integral proteins glycophorin A and band 3 respectively.

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35
Q

Describe how membrane protein mutations can cause haemolytic anaemias.

A

Mutations in spectrin and other proteins that anchor the cytoskeleton to the plasma membrane can cause abnormally shaped erythrocytes that are prone to lysis

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36
Q

How are membrane proteins being translated in the cytosol first recognised?

A

Membrane proteins contain a hydrophobic signal sequence that is recognised by a signal recognition particle in the cytoplasm.

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37
Q

What is the role of signal recognition particle in membrane protein translation?

A

Binds to the hydrophobic signal sequence in the cytosol to prevent further translation, targets the ribosome and protein to the ER by binding a docking protein. SRP is then released so that translation can continue.

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38
Q

Is the membrane protein hydrophobic signalling sequence N or C terminal? And is it cleaved or not within the ER lumen?

A

N terminal

Cleaved

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39
Q

How do membrane proteins become anchored in the ER membrane?

A

They contain an 18-22 hydrophobic amino acid sequence directly followed by charged amino acids. This sequence acts a stop transfer sequence during translation as it is more energetically favourable for it to remain within the membrane.

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40
Q

Where is translation completed in translation of membrane proteins?

A

In the cytosol after the stop transfer sequence has been reached and the ribosome detaches from the ER.

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41
Q

What orientation are membrane proteins in?

A

C terminal in cytosol.
N terminal extracellularly.
(Same orientation as in ER membrane during translation)

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42
Q

Why can oxygen, CO2, nitrogen and benzene cross a lipid bilayer?

A

Because they are hydrophobic molecules

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43
Q

Explain why water, urea and glycerol can cross a pure lipid bilayer but glucose cannot?

A

Water, urea and glycerol are small uncharged polar molecules, whereas glucose is much larger and would require a much larger free energy change.

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44
Q

Give an example of a ligand-gated ion channels that closes on ligand binding.

A

ATP-sensitive K+ channel in beta cells of pancreas

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45
Q

How do voltage gated ion channels work?

A

When the electrical potential across a membrane changes, it changes the charges on the amino acids of the protein. This causes conformational change in the protein and channel opening (or closing).

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46
Q

What causes gap junction / connexins to close?

A

Intracellular calcium concentration of more than 10uM or acidic intracellular solution

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47
Q

What is the mechanism employed by membrane transport proteins?

A

Ping-pong transport - binding of a substrate on one membrane surface, conformational change to release the substrate on the other side of the membrane.

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48
Q

Why can flip flop and rotating carrier not be mechanisms for membrane transport proteins?

A

Thermodynamically unlikely for proteins to cross hydrophobic core of membrane.

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49
Q

What are the intra and extracellular concentrations of sodium?

A 
Intracellular = 12 mM
Extracellular = 145 mM
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50
Q

What are the intracellular and extracellular concentrations of potassium?

A 
Intracellular = 155 mM
Extracellular = 4 mM
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51
Q

What are the intracellular and extracellular concentrations of calcium?

A 
Intra = 10^-4 mM
Extra = 1.5 mM
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52
Q

What are the intra and extracellular concentrations of chloride ions?

A 
Intra = 4 mM
Extra = 123 mM
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53
Q

Is the concentration of other anions (A-) higher intracellularly or extracellularly?

A

Intracellularly

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54
Q

What ‘other anions’ are present in addition to chloride?

A

Bicarbonate, phosphate, amino acids

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55
Q

What is the gradient of calcium ions across the cell membrane?

A

20,000 fold

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56
Q

Define passive diffusion.

A

The ability of a molecule to diffuse across a phospholipid bilayer with no energy requirement. Dependent on permeability and concentration gradient.

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57
Q

Define active transport.

A

Transport of ions or molecules across a membrane using proteins against unfavourable concentration and/or electrical gradients. Requires energy from ATP either directly or indirectly.

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58
Q

What is the difference between primary and secondary active transport?

A

Primary active transport directly couples ATP hydrolysis to a movement of ions or molecules across a membrane against an unfavourable electrochemical gradient.

Secondary active transport is where the transport of one substance against an unfavourable electrochemical gradient is coupled to the free energy release of moving another molecule down its electrochemical gradient.

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59
Q

What type of graph will facilitated diffusion have with substrate concentration and why?

A

Michalis menten curve as eventually all proteins will become saturated with substrate.

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60
Q

What is co-transport?

A

More than one molecule or ion is transported by a membrane transporter across a membrane in one reaction cycle.

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61
Q

Symport is..

A

2 or more ions or molecules are transported across a lipid bilayer in the same direction using a membrane transport protein.

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62
Q

How many sodium and potassium molecules are moved by the sodium pump?

A

3 Na+ out of cell

2 K+ into cell

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63
Q

How many mV of the resting membrane potential are contributed to by the sodium pump?

A

5mV only

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64
Q

What is the most crucial role of the sodium pump?

A

Formation of sodium and potassium gradients (important for secondary active transport and membrane excitability)

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65
Q

What is 25% of the BMR used by?

A

The sodium pump

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66
Q

What is meant by the sodium pump being a ‘P-type ATPase’?

A

ATP hydrolysis transfers a phosphate directly to the protein on an aspartate residue to cause a conformational change.

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67
Q

What is the structure of the sodium pump?

A

Alpha and beta subunits. Alpha is the active part (binds Na+, K+ and ATP and carries out transport). Beta just directs to membrane after synthesis.

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68
Q

Name a molecule that inhibits the sodium pump.

A

Ouabain

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69
Q

What is the PMCA?

A

The plasma membrane calcium ATPase.

Couples the hydrolysis of ATP to the outward movement of one calcium ion.

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70
Q

PMCA has a *** affinity but ** capacity for calcium.

A

High affinity but low capacity - good for getting last few calcium ions when levels are near to resting

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71
Q

What is the NCX?

A

Sodium-calcium exchanger.
Couples the movement of 3 sodium ions down their electrochemical gradient to the outward movement of a single calcium ion.

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72
Q

Why is the NCX thought to have a role in ischaemia and reperfusion injury?

A

When the cell becomes depolarised the NCX switches direction. During ischaemia there is no ATP and the sodium gradient is not maintained (by sodium pump), depolarisation occurs and the pump reverses. Pumping calcium into the cell can cause a high intracellular calcium level which is toxic.

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73
Q

NCX has a *** affinity but ** capacity for calcium.

A

Low affinity but high capacity - good for clearing out calcium levels when high

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74
Q

Explain why NCX is important n the cardiac action potential.

A

As it reverses its mode of direction on depolarisation, it is important for the calcium influx in cardiac action potentials.

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75
Q

What is SERCA?

A

Sarco(endo)plasmic reticulum calcium ATPase.
Couples the hydrolysis of ATP to the inward movement of calcium into the ER with the outward movement of a single proton.

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76
Q

SERCA has a **** affinity but ***** capacity for calcium.

A

High affinity but low capacity - same as PMCA. Clears remaining calcium after NCX.

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77
Q

What is NHE?

A

Sodium-hydrogen exchanger.
Couples the movement of a single sodium ion down its electrochemical gradient to the outward movement of a single proton.

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78
Q

Is NHE electrogenic?

A

No - moves a single positive charge in and out

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79
Q

What is the importance of NHE being activated by growth factors?

A

Growth factors simultaneously activate metabolism which causes a rise in H+. Activation of NHE at the same time to remove it.

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80
Q

What is the AE cotransporter?

A

Anion Exchanger - couples outward movement of HCO3- to the inward movement of Cl- down it electrochemical gradient.

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81
Q

Does AE acidify or alkalify the cell?

A

Acidifies as removing bicarbonate ions

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82
Q

Name 3 cellular processes for which calcium signalling is required.

A

Fertilisation, contraction, secretion

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83
Q

Name the 5 transporters involved in intracellular calcium regulation.

A
  1. NCX
  2. PMCA
  3. Sodium Pump
  4. SERCA
  5. Calcium uniporters (in mitochondria)
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84
Q

Which transporter clears most of the calcium out of a cell after calcium influx?

A

NCX - low affinity, high capacity

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85
Q

What is the role of calcium uniporters in intracellular calcium exchange?

A

Found in the mitochondria and transport calcium into mitochondria down its electrochemical gradient when intracellular levels are near pathological.

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86
Q

Name the 2 transporters activated in an acidic cell and a third that is also crucial to the process.

A

NHE - sodium hydrogen exchanger
NBC - sodium bicarbonate co-transporter
Sodium pump - to establish sodium gradient.

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87
Q

What is NBC and when is it activated?

A

Sodium bicarbonate co-transporter. Couples inward movement of a single sodium ion down its concentration gradient with inward movement of 3 bicarbonate ions.
Activated in an alkaline cell.

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88
Q

Name the one transporter activated in a basic cell.

A

AE - anion exchanger. Couples the inward movement of chloride ion down its electrochemical gradient with the outward movement of a bicarbonate ion = eliminating base.

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89
Q

In general terms, in order to resist cell swelling, what must the cell do?

A

Extrude ions so that water follows

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90
Q

In general terms, in order to resist cell shrinkage, what must the cell do?

A

Influx ions

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91
Q

Describe mechanisms employed to resist cell swelling.

A

Efflux of chloride and potassium ions through open channels.
Efflux of amino acids.
Co-transport of chloride and potassium ions out of the cell.
Influx of H+ coupled to efflux of K+ & AE Co-transporter. H+ and HCO3- can join to form CO2 and water and diffuse out.

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92
Q

Describe mechanisms employed to resist cell shrinkage.

A

Influx of sodium and calcium ions through opened channels.
Influx of sodium and chloride co-transport
Inward flow of sodium with organic osmolytes co-transport
NHE & AE due to breakdown of H2CO3 from CO2 and water.
Sodium pump to maintain sodium concentration.

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93
Q

Where is bicarbonate normally reabsorbed in the kidney and how much?

A

In the proximal tubule - usually all bicarbonate ions

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94
Q

Describe renal bicarbonate absorption.

A

NaHCO3 in the tubule lumen. Breaks down into Na and HCO3-.
Na taken up by NHE.
H+ and HCO3- in lumen join to form CO2 and H2O by carbonic anhydrase.
Diffuse across and reform inside cell (into H+ and HCO3-).
HCO3- expelled on basal cell surface via AE.
H+ re-expelled by NHE on apical surface.
Sodium pump required on basal surface to maintain sodium gradient.

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95
Q

What is the name of the enzyme that converts H2CO3 to H2O and CO2 and visa Versa?

A

Carbonic Anhydrase

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96
Q

What is the first line treatment for mild hypertension?

A

Diuretics - prevent renal sodium reuptake to reduce water reabsorption and blood volume.

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97
Q

When using diuretics, will urine be hypo or hyper osmotic?

A

Hyper osmotic as sodium reabsorption is reduced so more in the urine

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98
Q

Describe the process of sodium handling by the thick ascending limb of the kidney (5 crucial ion transporters).

A
  1. NKCC2 –> co-transport of 1 Na+, 1 K+ and 2 Cl- into the cell.
  2. ROMK –> potassium leak channels in apical membrane.
  3. Sodium pump –> in basal membrane to maintain sodium gradient.
  4. Chloride channels –> in basal membrane to remove chlorine ions.
  5. KClCT –> potassium-chloride co-transporter on basal membrane.
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99
Q

In renal sodium handling, what happens to the sodium ions?

A

They are reuptaken

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100
Q

Which part of the kidney do loop diuretics target and which channel in particular?

A 
Thick ascending limb of proximal tubule.
Inhibit NKCC2 (sodium reuptake)
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101
Q

Which part of the kidney do thiazides target and which channel in particular?

A

Distal convoluted tubule.

Inhibit sodium-chloride co-transporter (sodium reuptake)

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102
Q

Which parts of the kidney do amiloride diuretics target and which channel?

A

Distal convoluted tubule and cortical collecting duct.

Target/inhibit ENaC channel - epithelial sodium channel in apical membrane.

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103
Q

Which part of the kidney is targeted by spironolactone and how?

A

Targets the cortical collecting duct indirectly by acting as an aldosterone receptor antagonist. Aldosterone would normally act to up regular ENaC expression.

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104
Q

What diameter does a micro electrode have?

A
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105
Q

How is a membrane potential measured?

A

using a micro-electrode to penetrate the cell membrane and a second electrode on the cell surface. Electrodes filled with conducting solution and voltmeter measures the potential differences between the two electrodes.

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106
Q

Resting membrane potentials varying from ** to ** depending on **.

A

Form - 20mV to -90mV depending on cell type.

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107
Q

What is the equilibrium potential for an ion?

A

The membrane potential at which the electrical and chemical gradient for an ion is balanced across the membrane so that there is no net flow of ion across that membrane.

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108
Q

What is the Nernst equation?

A

Used to calculate the equilibrium potential for an ion.

= 61/z X log10([conc]o/[conc]i)

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109
Q

What is the approximate equilibrium potential for potassium?

A

-95mV

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110
Q

What is the equilibrium potential for chloride?

A

-96mV

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111
Q

What is the equilibrium potential for sodium?

A

+70mV

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112
Q

What is the equilibrium potential or calcium?

A

+122mV

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113
Q

Why is the resting membrane potential not at the equilibrium potential for potassium?

A

Because the membrane is no solely permeable to potassium ions - occasionally a sodium or calcium ion will leak moving the membrane potential towards their equilibrium potential (I.e. More positive)

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114
Q

What is the normal resting membrane potential for the following tissues: cardiac muscle, nerve cells, smooth muscle cells, skeletal muscle

A

Cardiac muscle = -80mV
Nerve cells = -70mV
Smooth muscle cells = -50mV
Skeletal muscle cells = -90mV

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115
Q

What is the resting membrane dependent on?

A

The membrane permeability to different individual ions and their equilibrium potentials.

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116
Q

What equation takes into account the different permeabilities of the membrane to ions?

A

Goldman-Hodgkin-Katz equation

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117
Q

What is the definition of depolarisation?

A

A decrease in the size of the membrane potential from its normal value - meaning that the cell interior becomes less negative.

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118
Q

What is the definition of hyperpolarisation?

A

An increase in the size of the membrane potential from its normal value, meaning that the cell interior becomes more negative.

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119
Q

In what 3 ways can ion channel activity be controlled?

A

Ligand gated, voltage gated, mechanically gated

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120
Q

What triggers mechanical gating of an ion channel?

A

Membrane deformation - e.g. Stretch receptors

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121
Q

As well as membrane permeability to ions, what two factors can influence membrane potential?

A
  1. Ion concentration on either side of the membrane

2. Electrogenic pumps (e.g. Sodium pump)

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122
Q

Synaptic transmission can be broken down into…

A

Fast and Slow

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123
Q

What is fast synaptic transmission?

A

Where the receptor at the post-synaptic membrane is also an ion channel where binding of the ligand to receptor causes channel opening

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124
Q

What does ‘EPSP’ and what causes them?

A

An excitatory post-synaptic potential caused by opening of cation ligand gated channels that cause depolarisation.

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125
Q

What is the difference between ESPCs and action potentials?

A

ESPCs are depolarisation at the post-synaptic membrane that have a much greater time course that action potentials and are graded with the amount of transmitter.

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126
Q

What is an IPSP and what causes it?

A

An inhibitory post synaptic potential caused by opening of ligand gated ion channels at the post-synaptic membrane that cause hyperpolarisation of the cell.

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127
Q

Give 2 examples of neurotransmitters that cause inhibitory post synaptic potentials.

A

Glycine and GABA

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128
Q

What is slow synaptic transmission?

A

The receptor on the post-synaptic membrane and the ion channels that cause the changes in membrane potential are separate proteins That must communicate directly or through a second messenger.

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129
Q

The neuromuscular junction is an example of fast or slow synaptic transmission?

A

Fast

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130
Q

Why does the membrane potential become more positive in the neuromuscular junction despite nicotinic ion channels allowing both K+ and Na+ ions through.

A

The permeability to both ions is increased and so the membrane potential moves towards 0mV - between the sodium and potassium equilibrium potentials.

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131
Q

How do we know that neurotransmitter release is calcium dependent?

A

Hypocalcaemia (decreased external calcium & reduced gradient across the membrane) result in a decreased amplitude of end plate potential

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132
Q

What is the cause of miniature end plate potentials (MEPPs)?

A

Spontaneous release of individual neurotransmitter vesicles at a synapse. (

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133
Q

What is Myasthenia Gravis?

A

An autoimmune disease that targets nicotinic ACh receptors via complement mediated lysis and receptor degredation. Results in muscle weakness due to reduced amplitude of end plate potentials.

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134
Q

What is the pore-forming subunit of sodium and calcium channels?

A

The alpha subunit

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135
Q

How many subunits do calcium channels have?

A

5 - 2 alpha, 1 beta, 1 gamma and 1 delta

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136
Q

How do different calcium channels vary?

A

In location and inhibitors

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137
Q

Where are L type calcium channels found?

A

Muscle, nerves and lungs.

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138
Q

What are L type calcium channels blocked by? What are these used to treat?

A

Dihydropyridines. Used to treat hypertension.

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139
Q

Describe neurotransmitter release from a neurone.

A
  1. Calcium enters through calcium channels following depolarisation
  2. Calcium binds to synaptotagmin on neurotransmitter vesicles.
  3. Brings vesicle close to the membrane where they bind SNARE complexes.
  4. SNARE complexes make a fusion pore allowing the inside of the vesicle to become continuous with the extracellular space.
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140
Q

How many ACh binding sites does each nicotinic receptor have?

A

2

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141
Q

Each fusion pore than a SNARE complex makes releases how much neurotransmitter?

A

300nm

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142
Q

To what membrane potential does the membrane depolarise at a neuromuscular junction during an end plate potential?

A

-10mV

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143
Q

What is the structure of a nicotinic receptor?

A

2 alpha, beta, 1 gamma and 1 delta subunit

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144
Q

What does tubocararine inhibit? Explain how it works.

A

Inhibits nicotinic ACh receptors. A competitive blocker with a similar structure to ACh. Binds without causing a conformational change in the protein. Since ACh can no longer bind, the channel cannot be opened and paralysis occurs.

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145
Q

Explain how succinylcholine acts as a nicotinic receptor blocker.

A

A depolarising blocker - binds and opens the channel but binds with such high affinity that the channel remains open. Causes inactivation of sodium channels adjacent to end plate and receptor desensitisation. Results in paralysis.

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146
Q

In what 5 ways is the low resting calcium concentration maintained?

A
  1. Relative impermeabililty of the membrane to calcium
  2. Calcium expulsion by PMCA and NCX
  3. Calcium buffers
  4. Trigger proteins
  5. Intracellular calcium stores
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147
Q

Name 3 calcium buffers and explain how they work.

A

ATP, calsequestrin and calbindin.

Bind to intracellular calcium and limit its diffusion.

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148
Q

What are trigger proteins?

Give 3 examples.

A

Proteins that bind to free calcium ions in the cell, and in response alter their function.
Synaptotagmin, calmodulin & troponin

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149
Q

By what 3 channel types is the membrane permeability to calcium increased during calcium influx?

A
  1. Voltage gated ion channels (VOCCs) - open due to membrane depolarisation.
  2. Receptor operated ion channels (ROCCs) - ligand gated (e.g. Glutamate or nicotinic).
  3. NCX reversing its mode of action due to a local increase in sodium concentration
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150
Q

In addition to increased membrane permeability, how else can calcium influx occur?

A

Release from rapidly releasable intracellular stores

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151
Q

Which protein increases the capacity of the ER to store calcium?

A

Calsequestrin

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152
Q

Calsequestrin has a ** affinity but *** capacity for calcium.

A

Low affinity but high capacity

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153
Q

Where are calcium release channels found and what stimulates them to open?

A

In the ER membrane - opened by IP3 causing a conformational change.

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154
Q

What is meant by ‘calcium induced calcium release’?

A

Calcium influx through VOCCs or intracellular stores. Calcium itself binds to ryanodine receptors in the ER membrane causing a conformational change in receptor and opening of aqueous pore. Further release of calcium.

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155
Q

What other molecule than calcium is thought to be able to open ryanodine receptors in cardiac muscle?

A

CADP ribose.

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156
Q

How is release of calcium from intracellular stores triggered in skeletal muscle?

A

Through mechanical coupling of VOCCs to ryanodine receptors in the ER - conformational change in VOCCs is passed along.

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157
Q

How much of the calcium in muscle contraction comes from intracellular stores and how much from the extracellular fluid?

A

85% from intracellular stores and 15% from extracellular fluid

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158
Q

What is meant by a ‘microdomain’ in calcium regulation? What is their function?

A

An area of intracellular calcium concentration that are in excess of that measured globally. E.g. Around an open channel.
Allows some calcium-dependent processes to occur that require a very high calcium concentration without causing toxicity.

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159
Q

Where are non-rapidly releasable stores of calcium found?

How do they take up calcium?

A

In the mitochondria = calcium uniporters that only work at extremely high calcium concentrations.
Use the enters from the respiratory chain proton production to uptake calcium.

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160
Q

In what cell type are non-rapidly releasable stores of calcium in the mitochondria particularly important?

A

Neurones

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161
Q

What 2 factors allow for prolonged depolarisation in cardiomyocytes?

A

The fact that calcium channels become inactivated much more slowly that sodium. And there is a low potassium conductance.

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162
Q

What is the equation for converting between molarity (molar concentration), g/L and molecular weight.

A

Molarity (M) = g/L / MWt

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163
Q

Why do drug concentrations always need to be in molar concentration?

A

Molar concentration refers to the number of particles in 1L.

Whereas the number of grams in a L cannot be compared between drugs because drugs weigh different amounts.

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164
Q

Define drug affinity.

A

The ability to bind and the strength of association between drug and receptor.

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165
Q

What is the intrinsic efficacy of a drug?

A

How well an agonist generates the active conformation of the receptor.

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166
Q

Define ‘efficacy’ of a drug.

A

The ability of a drug, and how good it is, at generating a response.

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167
Q

What 2 things is the efficacy of a drug dependent on?

A

Dependent on intrinsic efficacy and cell dependent factors.

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168
Q

Define agonist.

A

A drug that interacts with an mimics the effects of the endogenous ligand.

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169
Q

Define an antagonist.

A

A drug that interacts with a receptor and blocks the effects of the endogenous ligand.

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170
Q

Out of affinity, intrinsic efficacy and efficacy, which does an antagonist have?

A

Affinity only

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171
Q

What is Kd?

A

The dissociation constant. A measure of affinity - the concentration of drug that occupies 50% of receptors.

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172
Q

If the concentration of drug A is its Kd and there are 60 receptors, how many will be occupied? What about if there are 500 receptors?

A

30 receptors occupied if 60 present.

250 receptors occupied if 500 present.

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173
Q

What is the shape of the graph if a [drug]-response graph is a normal scale?

A

Hyperbola

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174
Q

What is the shape of the graph if a [drug]-response graph is a log scale?

A

Sigmoidal

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175
Q

On a log scale, how much is the Y axis increasing by with every value?

A

10 fold.
E.g. 10-9 = 1nm
10-8 = 10nm

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176
Q

What is the difference between a concentration-response and dose-response graph?

A

Concentration-response graph refers to an individual cell so that the concentration of drug at the target site is known. A dose-response graph refers to the response of the animal or tissue as a whole so that the concentration at the target site is not known.

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177
Q 
Log(a)X = *****
A^B = ******
A 
Log(a)X = B
A^B = X
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178
Q

What is the definition of EC50? What is it a measure of?

A

The effective concentration giving 50% of maximal response.

A measure of potency.

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179
Q

Define potency.

A

The amount of drug required to give a given response.

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180
Q

What makes EC50 different to Kd?

A

It is influenced by the number of available receptors.

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181
Q

On a concentration-response graph of 2 drugs, which has the greatest efficacy?

A

The one with the greatest Emax value.

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182
Q

On a concentration-response graph, which has the greatest potency?

A

The one with the greatest EC50 - usually the one furthest to the left.

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183
Q

Define IC50.

A

The inhibitory concentration giving 50% of maximal inhibition.

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184
Q

If 3 agonists have the same Emax values on a graph, which has the greatest efficacy?

A

The one furthest to the left (also the one with the greatest potency)

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185
Q

What is the specificity of a drug?

A

Whether the drug has one effect at one receptor site.

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186
Q

What is selectivity of a drug?

A

The concentration range at which a drug acts on a single receptor site only

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187
Q

What 3 things is selectivity dependent on?

A

Affinity of drug for receptor type, efficacy of the drug at a specific receptor and route of administration

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188
Q

Why is Salbutamol used despite being poorly B2 selective?

A

Selectivity enhanced by route of administration and B2 selective efficacy

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189
Q

If there are spare receptors will EC50 be more or less than Kd? What does this mean in terms of response and binding?

A

EC50&raquo_space; binding.

190
Q

Define ‘spare receptors’.

A

When response is limited by other cellular factors other than the amount of drug bound.

191
Q

In terms of spare receptors, what would you see on a graph of binding and response?

A

Response curve would be to the left of binding curve? (EC50

192
Q

What percentage of M3 receptors in the lung are required to give maximal contraction?
Therefore, what percentage are spare receptors?

A

Only 10% binding required.

Therefore 90% spare receptors.

193
Q

What is the sensitivity of a tissue?

A

The proportion of receptors that must be occupied in order to generate a response.

194
Q

What increases the sensitivity of a tissue?

A

Having spare receptors. So that only a small percentage need to be occupied in order to generate maximal response.

195
Q

When will receptor number be increased and why?

A

If there is low activity of the tissue - to increase tissue sensitivity.

196
Q

Define a partial agonist.

A

A drug that cannot produce maximal effect even when all receptors are occupied.

197
Q

Why are partial agonists unable to produce maximal effect?

A

Have insufficient intrinsic efficacy for maximal response.

198
Q

Can partial agonists be more potent than full agonists?

A

Yes because EC50 is a measure of an individual drugs maximal response.

199
Q

Give 2 examples of when partial agonists can be used advantageously.

A
  1. If full response has some unwanted side effects - e.g. Buprenorphine rather than morphine for less respiratory depression.
  2. Act as an antagonist in high levels of agonist - withdrawal from heroin using buprenorphine as occupies opioids receptors.
200
Q

How can a partial agonist be a full agonist in some tissues?

A

If there are more receptors to contribute to the overall response

201
Q

Name the 3 types of antagonist.

A
  1. Reversible competitive
  2. Irreversible competitive
  3. Non-competitive
202
Q

Which site on the receptor do reversible competitive antagonists bind?

A

Orthosteric site

203
Q

What effect does addition of a reversible competitive antagonist have on an [Agonist]-response curve?

A

Shifts the curve to the right so that more agonist is required to produce a given effect.

204
Q

What is the drug nalaxone used for and why?

A

Used to treat opioid overdose as a reversible competitive antagonist of u-opioid receptors.

205
Q

Describe irreversible competitive antagonism.

A

Drug binds to orthosteric site but dissociates very slowly or not at all so that its effects are not surmountable by addition of agonist.

206
Q

Describe the effects on an agonist-response graph of an irreversible competitive antagonist.

A

Shifts the graph to the right until a point where there is a decrease in maximal response as there are no longer enough receptors free for agonist to bind to produce maximal response.

207
Q

What is the drug phenoxybenzamine used for and why?

A

Used as a irreversible competitive antagonist of adrenaline in pheochromocytoma hypertension. Binds to alpha1 adrenoceptors.

208
Q

Describe non-competitive antagonist.

A

Binds to an allosteric site on the receptor to alter affinity or intrinsic efficacy of the orthosteric site for agonist.

209
Q

Why are non-competitive antagonists thought to be good drugs in the future?

A

Receptors that bind the same ligand, and therefore have similar orthosteric sites, may have different allosteric sites which may allow for more specific drug targeting of receptor subtypes.

210
Q

What type of antagonist are benzodiazapines and barbiturates and at what receptor?

A

Non-competitive at the GABA-a receptor.

211
Q

What type of antagonist is ketamine and at what receptor?

A

Non-competitive at the NMDA receptor (cation channel).

212
Q

How does the drug Cinacalet work in hyperparathyroidism?

A

An allosteric modulator of the calcium sensing receptor to stimulate calcitonin release from the thyroid.

213
Q

Define desensitisation.

A

A loss of functional response of receptors when exposed to continuous agonist stimulation.

214
Q

What is the difference between homologous and heterozygous desensitisation?

A

Homologous desensitisation is loss of response to agonist at a particular receptor subtype only.

Heterozygous desensitisation is a generalised loss of responsiveness to a particular agonist.

215
Q

Describe 2 mechanisms of homologous desensitisation.

A
  1. Phosphorylation of the GPCR by GRK interferes with the ability of the G-protein to interact.
  2. Internalisation of the receptor by endocytosis targeted by phosphorylation and Beta-arrestin binding
216
Q

How does heterozygous desensitisation occur?

A

Phosphorylation of the receptors by non-specific kinases which cause inactivation / impaired coupling to G-protein.

217
Q

Define tolerance.

A

A decreased response to repeated dose of a drug where increasing doses are required to maintain a constant response.

218
Q

How is an action potential conducted along an axon?

A

Local current flow of sodium ions to adjacent bits of the axon causing immediate depolarisation. If this depolarisation reaches threshold, voltage gated sodium channels will open and an action potential will be fired.

219
Q

In terms of local current, how is conduction velocity of an axon increased.

A

The further the spread of local current, the faster the conduction velocity. This is increased by high membrane resistance and low capacitance.

220
Q

What is meant by an action potential being all or nothing?

A

If the depolarisation threshold is reached, an action potential will fire. If it is not, then an action potential will not fire. There is no change in amplitude according to initial signal size.

221
Q

What membrane potential is reached during depolarisation of an action potential in an axon?

A

+30mV

222
Q

Which tissue type has the shortest action potential and what membrane potential does it reach during depolarisation?

A

Skeletal muscle - +40mV

223
Q

What is voltage clamping and what is it used for?

A

A method of controlling the membrane potential of a cell so that ionic currents can be measured at a set membrane potential.

224
Q

What is the sodium hypothesis of the action potential?

A

Refers to the hypothesis that sodium is the main ion responsible for depolarisation of an action potential.

225
Q

If you reduce extracellular sodium, what will happen to the action potential?

A

Depolarisation will become less positive and action potential amplitude reduced.

226
Q

By what percentage does the intracellular sodium concentration need to increase in order for an action potential to occur?

A

0.4% (0.04mM increase onto 10mM)

227
Q

The opening of voltage-gated sodium channels in response to a small depolarisation by sodium is an example of what type of feedback?

A

Positive feedback loop

228
Q

Do potassium open and close faster or slower that sodium channels?

A

Both open and close more slowly

229
Q

Do potassium channels inactivate?

A

No

230
Q

What 2 processes contribute to repolarisation?

A

Opening of potassium channels and potassium ion efflux.

Inactivation of sodium channels which do not pass current.

231
Q

What causes the initial depolarisations that may or may not reach threshold?

A

The excitatory post-synaptic potentials (EPSPs)

232
Q

Why does refractoriness occur?

A

After an action potential, the membrane potential is in a hyperpolarised state reducing the excitability of the membrane

233
Q

What is the ‘absolute refactory period’?

A

The period during an action potential where the membrane excitability is 0. Nearly all sodium channels are inactivated and potassium channels are open.

234
Q

What is the relative refactory period?

A

The period occurring immediately after an action potential has occurred. Membrane excitability is reduced because sodium channels are still recovering from inactivation while the membrane is hyperpolarised And some potassium channels are still open.

235
Q

Is the threshold higher or lower during the relative refactory period? Therefore the stimulus must be….. For an action potential to occur.

A

Higher. Therefore the stimulus must be larger.

236
Q

What is accommodation?

A

The longer or larger intensity stimulus, the larger the depolarisation required to initiate an action potential (threshold becomes more positive).

237
Q

Explain the basis of accommodation.

A

A small EPSP will open some voltage gated sodium channels, even if not enough to cause an action potential. This causes inactivation of these sodium channels and reduces the number available to open on a second EPSP so that a larger stimulus will be required in order to cause the same level of depolarisation.

238
Q

The main potre-forming subunit (alpha subunit) of calcium and sodium channels is formed from how many peptides? How many repeats?

A

One peptide formed of 4 repeats.

239
Q

How many transmembrane domains does a sodium or calcium channel alpha subunit have in total? How are they grouped?

A

24 in total grouped into 4 repeats of 6

240
Q

Which transmembrane domain of each repeat in a sodium or calcium channel is responsible for membrane potential sensitivity? How do they work?

A

4th. Contain positively charged amino acids that will undergo conformational change on a change in membrane potential.

241
Q

How many transmembrane domains does a potassium channel have in total?

A

6

242
Q

How many peptides make up a functional potassium channel? (How many alpha subunits)

A

4.

243
Q

How do local anasthetics work?

A

Block sodium channels so that depolarisation and action potentials cannot be fired

244
Q

Name a local anasthetic.

A

Procaine.

245
Q

Are local anasthetics more effective when sodium channels are closed or open? What does this mean?

A

Open - therefore area must be stimulated to open sodium channels. Have a higher affinity for inactivated state.

246
Q

In what order do local anasthetics block nerve axons?

A

Small myelinated first (pain fibres), then un-myelinated, finally large myelinated (motor nerves)

247
Q

What is the difference between diphasic and monophasic recording of an action potential?

A

Diphasic measures the difference in extracellular potential at 2 points along an axon.
Monophasic measures at one point - a damaged point.

248
Q

Will a cathode stimulate or reduce membrane excitability?

A

Cathode = negatively charged - stimulates membrane excitability

249
Q

In what 3 ways is conduction velocity increased?

A

High membrane resistance.
Low membrane capacitance.
Large axon diameter.

250
Q

Why does an action potential not pass backward in the local current theory?

A

Because the sodium ions in the previous portion of axon are inactivated (in the refactory period)

251
Q

What is the length constant of an axon?

A

The distance an action potential will spread in either direction (the distance it takes for the change in potential to fall to 37% of original value)

252
Q

What is capacitance?

A

The ability of the lipid bilayer to store charge

253
Q

What is meant by membrane resistance?

A

The number of ion channels open - more channels open = lower resistance as there is leak across the membrane

254
Q

What is the cable theory of action potentials?

A

Spread of local current depends on membrane resistance and capacitance. An action potential will spread further with a high membrane resistance but a low capacitance.

255
Q

What effect does axon diameter have on conduction velocity?

A

Larger diameter = faster conduction velocity

256
Q

How does myelination increase the length constant/conduction velocity?

A

Myelin sheath insulates the membrane to increase membrane resistance - prevents any leakage of ions in the insulated regions. Also decreases membrane capacitance at the nodes.

257
Q

Where are the ion channels found on a myelinated axon?

A

At the nodes of ranvier (10,000 per node)

258
Q

How are the ion channels distributed in an unmyelinated axon?

A

Along the length of the axon.

259
Q

What is saltatory conduction?

A

Due to the increased membrane resistance and low capacitance at the nodes, the length constant in myelinated axons is massively increased. This means that depolarisation is able to spread a long distance to the next node to raise it above threshold and initiate an action potential. Action potential jumps from node to node with a much faster conduction velocity.

260
Q

In myelinated axons… The conduction velocity is proportional to what? What type of graph is seen?

A

Directly proportional to diameter. Linear graph.

261
Q

In unmyelinated axons, the conduction velocity is proportional to what? What type of graph is seen?

A

The square root of diameter. Hyperbola graph.

262
Q

Prolonged depolarisation or slowly developing depolarisation will cause what?

A

Accommodation

263
Q

How many alpha subunits are required to make a functional sodium channel?

A

1

264
Q

Give 3 features of a sodium channel alpha subunit.

A
  • 1 peptide with 4 repeats
  • 4th transmembrane domain has positive amino acids for membrane potential sensitivity
  • Has an inactivation particle
265
Q

Hat forms do sodium channels need to be in to be blocked by local anasthetics?

A

Open or inactivated

266
Q

What is the relationship between length constant and conduction velocity?

A

The longer the length constant, the faster the conduction velocity

267
Q

What is the difference in ion channel distribution between myelinated and unmyelinated axons?

A

In myelinated axons, the ion channels are concentrated at the nodes of Ranvier, whereas in unmyelinated axons, they are equally distributed along the length of the axon.

268
Q

What is the approximate maximum velocity of a myelinated neurone?

A

120 m/s

269
Q

What is the maximum velocity of an unmyelinated neurone?

A

20 m/s

270
Q

Why at very small diameters do unmyelinated neurones have a faster conduction velocity than myelinated?

A

In smaller myelinated neurones, the myelin takes up a greater proportion of the total diameter so that below a certain total diameter, the diameter of the axon alone becomes increasingly small and becomes the limiting factor on conduction velocity.

271
Q

Name 2 demyelinating diseases of the CNS.

A

Multiple sclerosis and Devices disease.

272
Q

Name 2 demyelinating diseases of the PNS.

A

Landry-Guillain-Barre Syndrome

Charcot-Marie-Tooth Disease

273
Q

Explain the overall effect of demyelination on the properties of a nerve fibre (in terms of length constant).

A

Decreased membrane resistance = more current leak.
Increases membrane capacitance.
= reduced length constant and conduction velocity.

274
Q

Immediately after loss of the myelin sheath, what happens to conduction of nerve impulses?

A

Conduction block as due to decreased resistance and increased capacitance, the length constant is reduced and the depolarisation is unable to reach the next Node of Ranvier during saltatory conduction.

275
Q

What happens to the conduction of nerve impulses in a demyelinated nerve fibre after a period of recovery?

A

Redistribution of ion channels occurs along the entire length of the axon restores current. However, the action potential must now be propagated along the axon by local circuit theory rather than saltatory conduction which significantly decreases conduction velocity.

276
Q

Define a receptor.

A

A molecule that specifically recognises another molecule, or family of molecules, which in response to this ligand binding brings about regulation of cellular processes.

277
Q

Define a ligand.

A

Any molecule that binds specifically to a receptor site.

278
Q

Define an agonist.

A

A ligand that on binding receptor, activates it.

279
Q

Define an antagonist.

A

A ligand that binds to a receptor without causing activation.

280
Q

Define an acceptor. How is this different to a receptor?

A

A molecule that binds to ligand, and in response has its activity modulated. However, the acceptor itself operates in the absence of ligand.

281
Q

Give an example of an acceptor and its ligand.

A

Voltage gated sodium channels - operate in the absence of ligand but can have their activity modified by local anaesthetics.

282
Q

Does a receptor have a higher or lower affinity for its ligand than an enzyme for its substrate?

A

Higher - Kd in nanomolar or micro molar range whereas Km in micro-molar to milli-molar range.

283
Q

What is meant by paracrine signalling?

A

A local mediator is secreted into the interstital space to target adjacent cells.

284
Q

Other than by secreted molecules, by what other mechanism can cells communicate intercellularly?

A

By cell to cell interaction with membrane bound molecules

285
Q

Give examples of 2 molecules that have intracellular receptors.

A

Thyroid and steroid hormones

286
Q

How are receptors generally sub-divided into super families? Give an example.

A

Classified according to their specific endogenous signalling molecule / agonist. E.g. Cholinergic receptors bind acetylcholine

287
Q

After being divided into super families, how might receptors be further sub-divided? Give an example.

A

They might be classified on their ability to be selectively activated by different exogenous agonists. E.g. Muscarinic cholinergic receptors are activated by muscarine whereas nicotinic cholinergic receptors are activated by nicotine.

288
Q

Once being sub-classified into super-families, and sub-divided according to endogenous ligand, how might you further subdivide a receptor? Give an example.

A

According to their affinity for antagonist. E.g. M1, M2 and M3 are all cholinergic receptors activated by endogenous agonist muscarine, but all bind to different antagonists with varying affinities.

289
Q

What are the 4 major classes of receptor?

A
  1. Membrane bound receptors with an integral ion channel.
  2. Membrane bound receptors with integral enzyme activity.
  3. Membrane bound receptors that couple to effectors via transducing proteins.
  4. Intracellular receptors.
290
Q

What is the general mechanism by which membrane bound receptors with an integral ion channel work?

A

Ligand binds to cause a conformational change in the receptor which opens at gated ion channel. Ions flow through the channel down their electrochemical gradient to cause a change in membrane potential which transduced the signal into an electrical event.

291
Q

Give 5 examples of ‘classical’ membrane bound receptors with an integral ion channel.

A
  1. Nicotinic acetylcholine receptor
  2. GABA receptor
  3. Glycine receptor
  4. Glutamate receptor
  5. IP3 receptor in ER
292
Q

Describe the structure of a classical ligand-gated ion channel.

A

Pentameric structure (5 subunits) - 2 of which are alpha subunits that bind the ligand. Each subunit has 4 transmembrane domains, with TM2 forming the lining of the channel pore.

293
Q

What is the difference between classical and non-classical ligand-gated ion channels?

A

They are structurally distinct - the non-classical do not have the same common structure as the classical

294
Q

Give 2 examples of ‘non-classical’ membrane bound receptors with an integral ion channel / ligand-gated ion channels.

A
  1. ATP-sensitive potassium channel

2. Ryanodine receptor in cardiac muscle

295
Q

Explain the general mechanism of membrane bound receptors with integral enzyme activity.

A
  1. Ligand binding causes a conformation change resulting in dimerisation and activation of catalytic domains on cytoplasmic domains.
  2. Autophosphorylation on tyrosine residues (Transfer from ATP).
  3. Phosphates act as binding sites for transducers or enzymes which themselves become Phosphorylated.
296
Q

Give 2 examples of membrane bound receptors with integral enzyme activity.

A
  1. ANP receptor

2. Growth factor receptors (insulin, PDGF and EGF)

297
Q

Describe the structure of the insulin receptor.

A

2 alpha and 2 beta subunits. Insulin binds to alpha subunits which the beta subunits form the cytoplasmic region which becomes Phosphorylated. The 4 subunits are held together by disulphide bonds.

298
Q

How many transmembrane domains do GPCRs have?

A

7

299
Q

Which region of a GPCR (C or N) forms the G-protein coupled region?

A

The C terminus

300
Q

Where can the ligand bind to a GPCR?

A
  1. At the N terminal

2. In the transmembrane region

301
Q

Describe the structure of a G protein.

A

3 subunits - alpha, beta and gamma with the alpha subunit bound to a GDP molecule.

302
Q

What is the advantage of having several steps in GPCR signalling?

A

Allows amplification of the initial signal

303
Q

Describe the general structure of intracellular receptors.

A

Usually monomeric and held in inactivated state by binding of an inhibitory protein complex.

304
Q

Give 2 examples of proteins that can act as inhibitory binding complexes for intracellular receptors.

A

Heat shock proteins

Chaperone proteins

305
Q

Describe intracellular receptor signalling.

A

Ligand binds to ligand binding site. Induces conformational change to release inhibitor protein complex. DNA binding site exposed. Receptor-ligand complex transported to the nucleus. Binds to DNA and modulates gene transcription of specific genes.

306
Q

Which terminus is the ligand binding domain of an intracellular receptor usually located?

A

C terminus

307
Q

What is meant by ‘zinc fingers’ in terms of intracellular receptors?

A

DNA binding domain in the centre of the receptor

308
Q

Where can intracellular receptors be located?

A

IN the nucleus or the cytoplasm

309
Q

Which terminus is the ligand binding domain of an intracellular receptor usually located?

A

C terminus

310
Q

What is meant by ‘zinc fingers’ in terms of intracellular receptors?

A

DNA binding domain in the centre of the receptor

311
Q

Where can intracellular receptors be located?

A

IN the nucleus or the cytoplasm

312
Q

Name the 2 broad subdivisions of endocytosis.

A

Phagocytosis & Pinocytosis

313
Q

Describe phagocytosis.

A

The cell ingests large objects - e.g. Apoptosed cells or bacteria - as the membrane folds around the object via pseudopods sealing it off into large vesicles called phagosomes.
Occurs in specialised cells.

314
Q

Define Pinocytosis.

A

The membrane uptakes fluids and solutes by invagination of the membrane into a small lipid vesicle.

315
Q

Receptor mediated endocytosis falls into which type of endocytosis?

A

Pinocytosis

316
Q

What is receptor mediated endocytosis?

A

Molecules bind to receptors on the the cell surface and the plasma membrane folds inwards to form coated pits. Inward budding vesicles form cytoplasmic vesicles.

317
Q

How are receptors to be internalised concentrated over clathrin coated pits?

A

Integrins proteins bind the clathrin and the receptor

318
Q

What percentage of the cell surface is covered by clathrin coated pits?

A

About 2%

319
Q

Coated pit formation is energy independent or dependent?

A

Spontaneous - energy independent

320
Q

Uncoating of clathrin coated pits is energy dependent or independent?

A

Dependent - requires ATP

321
Q

Clathrin coating puts are formed from ***** of clathrin and light chains.

A

Triskelions

322
Q

The clathrin pit is on the **** of the plasma membrane and the ** of the vesicle.

A

Inside of the plasma membrane but outside of the vesicle

323
Q

What type of coated pit is found at the plasma membrane, ER and Golgi?

A 
PM = clathrin
ER = COP-I
Golgi = COP-II
324
Q

Give 2 examples of how receptor-mediated endocytosis contributes to the uptake of metabolites.

A
  • Uptake of cholesterol via LDL particles

- Uptake of ferric ions (Fe3+) via transferrin

325
Q

What receptor do cholesterol-requiring cells express at clathrin coated pits?

A

Apoprotein B receptor

326
Q

Describe the general common pathway of receptor mediated endocytosis.

A
  1. Ligand to be internalised binds receptor localised to clathrin coated pit.
  2. Internalisation to form a coated vesicle
  3. Uncoating of vesicle in energy dependent process
  4. Uncoated vesicle fuses with larger endosome
327
Q

What is the pH of the endosome and why?

A

About 5.5 to 6 due to an ATP-dependent proton pump

328
Q

Why is the endosome known as ‘CURL’? What does this stand for?

A

In most cases, the acidic pH of the endosome changes the affinity of receptor for ligand so that dissociation occurs here.
CURL = Compartment for the Uncoupling of Receptor and Ligand.

329
Q

Once fused with an endosome, what happens to internalised LDL-receptor complexes?

A

At the acidic pH, the LDL receptor has a low affinity for the LDL particle and so the two dissociate.

330
Q

In LDL-receptor internalisation, what is the fate of the receptor and what is the fate of the LDL?

A

The receptor is sequestered to a domain within the endosome which buds off and is recycled to the plasma membrane (receptor recycled)
The endosome remaining containing the LDL fuses with the lysosome so that cholesterol is hydrolysed from the esters and released into the cell. (Ligand degraded)

331
Q

In what 3 ways can LDL receptors be dysfunctional to cause hypercholesterolaemia?

A
  1. Receptor deficiency
  2. Non-functional receptor that cannot bind LDL but has normal internalisation
  3. Receptor binding normal receptor = has an abnormal interaction with the clathrin coated pit so that receptors are evenly distributed across the whole cell and so the receptor is unable to internalise.
332
Q

How are ferric ions transported in the circulation?

A

2 ferric ions bind to receptor apotransferrin to form transferrin

333
Q

What receptor does transferrin bind?

A

Transferrin receptor

334
Q

What happens to the transferrin-receptor complex after internalisation and fusion with the endosome?

A

At the lower pH, the transferrin has lower affinity for the ferric ions so the two dissociate, however the apotransferrin remains bound to the receptor = free ferric ions and apotransferrin-receptor complex.

335
Q

What is the fate of the following in uptake of ferric ions: transferrin receptor, apotransferrin, ferric ions?

A

Tranferrin receptor and apotransferrin remain bound in the endosome and are recycled back to the plasma membrane where as neutral pH they dissociate.
Ferric ions dissociate in the endosome
= receptor recycled (transferrin receptor), ligand recycled (apotransferrin / transferrin)

336
Q

Give an example of a large molecule that receptor mediated endocytosis allows the passage of across a cell.

A

IgA

337
Q

What is the fate of the ligand and the receptor in IgA transport across the cell?

A

The IgA remains bound to its receptor at the endosome and is transported across the cell. The receptor is proteolytically cleaved during transport so that secreted IgA is bound to a ‘secretory component’ that is derived from the receptor.

338
Q

Give 2 situations where IgA might be transported across a cell.

A

From the circulation into the liver bile.

From the maternal placenta to the foetus (IgG).

339
Q

When do insulin receptors become concentrated at clathrin coated pits? Why?

A

Only when the receptor binds to ligand (insulin binds) as a conformational change occurs that allows the receptor to be recognised by the coated pit.

340
Q

What is the fate of insulin and the insulin receptor after receptor mediated endocytosis?

A

In the acidic endosome, the insulin remains bound to its receptor and both are targeted to the lysosome for degredation. (Ligand degraded, receptor degraded).

341
Q

How does receptor mediated endocytosis control the number of insulin receptors at the cell surface?

A

As when insulin binds its receptors, both are internalised and degraded at the lysosome this means that circulating insulin leads to a down-regulation of insulin receptors. The higher the circulating insulin, the greater number of receptors will be occupied, internalised and degraded. This means cells become desensitised to high circulating insulin levels.

342
Q

Name 2 other molecules, other than insulin, that receptor mediated endocytosis of the receptor-ligand complex leads to down-regulation of the receptor.

A

Epithelial growth factor (EGF) and immune complexes

343
Q

Explain how receptor mediated endocytosis plays a role in entry of membrane-enveloped viruses.

A

Virus or toxin binds receptors on plasma membrane. Endocytosis by clathrin coated pits. Once fused with the acidic endosome, membrane fusion proteins become unfolded and exposed so that viral membrane can fuse with the endosomal membrane releasing the viral RNA into the cell.

344
Q

Name 2 viruses that rely on receptor mediated endocytosis for entry into the cell.

A

Cholera and diphtheria.

345
Q

How many polypeptide chains form one GPCR and how many amino acids?

A

1 polypeptide chains of 300-1200 amino acids

346
Q

How many GPCRs are coded by the human genome?

A

> 800

347
Q

Describe the 4 stages of GPCR activation.

A
  1. Ligand binding causes interaction of GPCR with G protein
  2. Interaction activates G protein and GDP on alpha subunit is exchanged for GTP
  3. Alpha-beta-gamma complex dissociates into alpha-GTP and beta-gamma as GTP binding reduces their affinity for one another
  4. Both part interact with downstream effector proteins
348
Q

Where is the guanine-nucleotide binding site of a G protein found?

A

On the alpha subunit

349
Q

What determines the length of G protein activity?

A

The alpha subunit possesses GTPase activity so that after dissociation the GTP is hydrolysed to GDP, which terminates the effector interaction and increases the affinity of the alpha-GDP complex for the beta-gamma complex and the two rejoin to form a heterotrimer. Length of time taken to hydrolyse will determine the length of G protein activity.

350
Q

How does cholera toxin effect G-protein activity?

A

Covalently modifies G-alphaS subunit to inhibit GTPase activity so that there is constitutive activation of the pathway. The continuously raised cAMP levels in the cell opens water channels.

351
Q

How does Pertussis Toxin affect G-protein activity?

A

Covalently modifies Galpha-I subunit preventing GDP to GTP exchange and receptor-G protein association. Results in irreversible inactivation of the pathway.

352
Q

What disease does Pertussis Toxin cause?

A

Whooping cough

353
Q

In what 3 ways is the initial GPCR signal amplified?

A
  1. The activated GPCR causes GDP to GTP exchange on multiple G proteins
  2. The activated alpha-GTP and beta-gamma subunits activate multiple effector molecules.
  3. The catalytic activity of effector molecules converts 1000s of molecules
354
Q

Give 5 mechanisms by which deactivation of a GPCR signal is terminated.

A
  1. Binding of agonist to GPCR is weakened once G-protein interaction occurs.
  2. Activated receptor susceptible to protein kinases which phosphorylate and prevent further G-protein activation
  3. Cellular factor stimulate GTPase activity of Galpha
  4. Cell has high levels of enzymes that metabolise second messengers
  5. Enzyme cascades are opposed by activities to reverse the second messenger effect.
355
Q

Name 2 types of receptors that are coupled to Gs G-proteins.

A

Beta-adrenoceptors.

D1 dopamine receptors.

356
Q

What is the effector molecule of Gs G-proteins?

A

Adenylyl Cyclase

357
Q

Describe the pathway from Gs G-protein activation to substrate activation.

A

Galpha-S activates adenylyl cyclase, which is an enzyme that catalyses conversion of ATP to cAMP. As cAMP levels in the cell rise, protein kinase A becomes activated which can phosphorylate downstream targets.

358
Q

Name 4 receptors linked to Gi G-proteins.

A

Alpha2-adrenoceptors.
D2 dopamine receptors.
M2 cholinergic receptors.
U-opioid receptors.

359
Q

What is the downstream outcome of Gi G-protein activation?

A

Inhibition of effector molecule adenylyl cyclase. Causes a decrease in cellular cAMP levels.

360
Q

Name 5 receptors linked to Gq G-proteins.

A

5HT2 serotonin receptor.
Alpha1-adrenoceptors.
M1 and M3 cholinergic receptors.
H1 histamine receptor.

361
Q

WHat is the effector protein of Gq G-proteins?

A

Phospholipase C

362
Q

What are the 2 second messengers produced in the Gq pathway and what is their function?

A

IP3 binds to IP3 receptors on the ER leading to increases calcium entry into the cell.
DAG activates PKA.

363
Q

Name one receptor that is coupled to Gt G-proteins and the ligand that activates it.

A

Rhodopsin receptor activated by light

364
Q

What is the effector molecule of Gt G-proteins?

A

cGMP phosphodiesterase

365
Q

What is the outcome of activation of Rhodopsin receptors?

A

Levels of cGMP decrease in the cell and calcium/sodium channels are inhibited leading to membrane hyperpolarisation.

366
Q

Give 3 places that beta2 receptors are found.

A

Blood vessels (vasdilation), bronchioles (relaxation), glucagon-mediated effects

367
Q

Name an antagonist of muscarinic acetylcholine receptors and what effect this will have on the heart.

A

Atropine - will increase HR

368
Q

How/where do U-opioid receptors usually work?

A

At pre-synaptic membrane to reduce calcium influx and decrease neurotransmitter release.

369
Q

What is the drug pilocarpine used for and why?

A

Used to treat glaucoma to reduce intraocular pressure by pupil constriction. Inhibits M3 receptors.

370
Q

In addition to vascular smooth muscle, give 2 other places with alpha1 adrenoceptors are found.

A

Pupils (dilation), localised sweating (palms)

371
Q

What is the action of the drug prazosin and what is it used to treat?

A

Antagonist of alpha1-adrenoceptors. Used to treat hypertension.

372
Q

What is retinitis pigmentosa?

A

A loss of function mutation in the rhodopsin receptor.

373
Q

What is meant by pharmacokinetics?

A

What the body does to a drug.

374
Q

What are the 4 questions to be asked when prescribing a drug?

A
  1. Is the drug getting into the patient? (Pharmaceutical process)
  2. Is the drug getting to the site of action? (Pharmacokinetic process)
  3. Is the drug producing the desired effect? (Pharmacodynamic process)?
  4. Is this translated into a therapeutic effect? (Therapeutic process)
375
Q

What is parenteral administration of a drug? Give 3 examples.

A

Any method than is non-oral.

E.g. Sub-cutaneous, intravenous and intramuscular

376
Q

How could you speed up the pharmaceutical process (the rate the drug gets into the body)?

A

Use a soluble form of the drug.

Use a drug with a simple regimen so that patients are more likely to be compliant.

377
Q

Define the ‘oral bioavailability’ of a drug.

A

The proportion of drug given orally that reaches the circulation unchanged.

378
Q

In what two ways can oral bioavailability of a drug be measured?

A

By the AMOUNT of drug that reaches the circulation unchanged.
By the RATE the drug reaches the circulation unchanged.

379
Q

Give 2 examples of factors that oral bioavailability is dependent on.

A
  1. First pass metabolism

2. Gut absorption

380
Q

Give 3 examples of enteral drug administration methods.

A

Sublinguinal, oral, rectal

381
Q

How would you calculate oral bioavailability if you were trying to find out the AMOUNT of drug that reaches the circulation in an unchanged form?

A

Draw a graph of blood drug level against time and find the area of the curve.
Do this for both intravenous and oral administration and the oral bioavailability would be – ((AUC Oral) / (AUC Injected)) X 100

382
Q

How would you calculate oral bioavailability if you were trying to find the rate it reached the systemic circulation unchanged?

A

The slope of a plasma concentration - time graph.

383
Q

Define the ‘therapeutic ratio’ for a drug.

A

The LD50 / EC50.

= maximum tolerated dose / minimum effective dose.

384
Q

Which type of drugs are affected by first pass metabolism?

A

Oral drugs

385
Q

What is ‘first pass metabolism’?

A

Blood from the gut (into which oral drugs are absorbed) is taken to the liver by the portal system. This means the liver could metabolise the drug before it ever reaches the systemic circulation.

386
Q

Give 4 examples of drugs that undergo first pass metabolism.

A

Opiates, propranolol, glyceryl nitrate, lignocaine

387
Q

How can first pass metabolism of an oral drug be avoided?

A

Parenteral routes, sublinguinal route or rectal route of administration

388
Q

What is meant by ‘volume of distribution’ in reference to a drug?

A

The theoretical volume into which a drug has distributed assuming this occurred instantaneously.

= amount of drug given / plasma concentration at time 0

389
Q

What type of drug tends to have a higher volume of distribution (Vd)?

A

Lipid soluble

390
Q

Explain how protein binding interactions can occur.

A

If an object drug is given at a dose much lower than the number of albumin binding sites, but then a precipitant drug is given at a dose much greater than the number of albumin binding sites, the precipitant drug can displace the object drug leading to a sudden increase in free plasma concentration of object drug.

391
Q

Why are protein binding interactions relevant?

A

When a patient is taking an object drug, and is given a precipitant drug, this will lead to temporarily higher plasma levels of the object drug. This increases risk of toxicity - especially if has a low therapeutic index.

392
Q

Give an example of an object drug that has protein binding interactions with a precipitant drug.

A

Object drug = warfarin

Precipitant drug = aspirin & sulphonamides

393
Q

What is meant by ‘first order kinetics’ of drug metabolism?

A

Drug metabolism is proportional to drug concentration = the rate of decline in plasma drug level is proportional to drug level.

394
Q

On a linear scale of time against plasma concentration, what shaped graph would a drug obeying first order kinetics have?

A

A curved graph - (L shaped curve - as elimination slows at lower plasma concentrations)

395
Q

On a log-scale graph, what shape would a drug obeying first order kinetics have?

A

A linear graph

396
Q

What is meant by zero order kinetics?

A

When the decline in plasma drug level is constant as all metabolism enzymes are saturated.

397
Q

When would a drug obey first order kinetics?

A

When it is used at a concentration lower than its Km

398
Q

When would a drug obey zero order kinetics?

A

When the drug is used at a concentration much greater than its Km.

399
Q

For what type of drug can half life be defined? What is half life?

A

Drugs obeying first order kinetics only.

= the time taken for 50% of the drug to be eliminated / concentration to fall to half its initial value

400
Q

Following drug administration, when will a steady state (steady plasma concentration) be reached?

A

Within 5 half lives of that drug

401
Q

What is meant by a drug being in ‘steady state’?

A

Overall intake of a drug is in dynamic equilibrium with its elimination at therapeutic level

402
Q

If you require an immediate effect of a drug (I.e. Cannot wait 5 half lives), what must you do?

A

Use a loading dose (one large dose to reach therapeutic level)

403
Q

Give an example of a drug that obeys zero order kinetics.

A

Alcohol

404
Q

What 2 processes can a drug undergo to be eliminated?

A

Metabolism by the liver or excretion by the kidneys

405
Q

Describe the 2 phases of liver drug metabolism.

A

Phase 1 = oxidation, reduction and hydrolysis (to activate, inactivate or unchange).

Phase 2 = conjugation to make inactive

406
Q

What type of enzymes carries out phase I of liver metabolism of drugs?

A

Oxidase enzymes

407
Q

How can the liver metabolism of a drug be a point of drug interaction?

A

Because the oxidase enzymes that metabolise drugs are inducible and inhibitable by other drugs.

408
Q

Give an example a drug (drug A) that induces the liver enzymes responsible for metabolism of drug B.
What effect will this have on drug B?

A

Drug A = Phenobarbitone (barbiturates)
Drug B = Warfarin

Will reduce levels of warfarin / drug B as it is metabolised more readily. This can reduce its therapeutic effects.

409
Q

Give an example a drug (drug A) that inhibits the liver enzymes responsible for metabolism of drug B.
What effect will this have on drug B?

A

Drug A = Cimetidine
Drug B = Warfarin

This will raise plasma blood levels of warfarin / drug B as its metabolism is reduced. Could exceed therapeutic index levels.

410
Q

Give 3 reasons why Warfarin is prone to drug interactions.

A
  1. Normally highly bound to albumin in the plasma (prone to protein binding interactions).
  2. Has a small volume of distribution so that large amounts of dose remain in the plasma.
  3. Has a low therapeutic index (if metabolism is inhibited, could easily exceed the maximum tolerated dose).
411
Q

What form must drugs be in to be filtered b the glomerular tuft of the kidneys?

A

In the free, unbound form

412
Q

What determines how much of a drug is excreted in the urine?

A

The pH of the urine and the acid / base properties of the drug

413
Q

Aspirin is a weak acid, what happens to aspirin if the urine is alkaline?

A

Alkaline urine = drug dissociates into ionised form = less reabsorption across tubule = greater excretion of urine.

414
Q

Amphetamine is a weak base, what happens to amphetamine if the urine is acid?

A

Acid urine = greater dissociation of base into ionised form = less reabsorption across the tubule = greater excretion of amphetamine

415
Q

What will happen to elimination of a weak acid drug if the urine is acidic?

A

There will be increased reabsorption (as less weak acid in its ionised form) meaning reduced elimination

416
Q

As we know that aspirin is a weak acid, how might you treat aspirin overdose?

A

By forcing alkaline diuresis (alkaline urine) to increase aspirin excretion in the urine.

417
Q

If a drug is mainly eliminated by kidney excretion, what will happen in renal disease?

A

The half life of the drug will be prolonged = maintenance dose needs to be reduced.
Loading dose unaltered.
Protein binding properties may be altered - if protein being lost in urine.

418
Q

Give an example of a autonomic controlled action where sympathetic and parasympathetic pathways do not another.

A

In salivary secretion - requiring regulation from both pathways

419
Q

Where are the cell bodies of sympathetic pre-ganglionic neurones located?

A

In the lateral horn of the grey matter.

420
Q

All pre-ganglionic neurones of the ANS are….

A

Cholinergic

421
Q

Give 2 examples in the sympathetic nervous system where post-ganglionic neurones are cholinergic.

A

Sweat glands and pilorector muscles

422
Q

What is a NANC transmitter?

A

Non-adrenergic, non-cholinergic transmitter usually co-released with ACh or NA from ANS

423
Q

Give 6 examples of NANCs.

A

ATP, serotonin, nitric oxide & neuropeptides (substance P, neuropeptides Y and vasoactive peptide)

424
Q

How is acetylcholine synthesised in ANS neurone terminals?

A

By the enzyme choline acetyl-transferase. From choline from diet and Acetyl CoA metabolism intermediate.

425
Q

What is the fate of newly synthesised acetylcholine?

A

Can be packaged into vesicles by active transport or degraded by cytoplasmic cholinesterase.

426
Q

How is acetylcholine degraded in the synaptic cleft?

A

By acetylcholinesterase to acetate and choline

427
Q

What is the fate of acetate and choline broken down from acetylcholine in the synaptic cleft?

A

Most of the choline is reuptaken and recycled by the pre synaptic nerve terminal using a choline carrier protein. The acetate diffuses away and is metabolised.

428
Q

What is the half life of acetylcholine in the synaptic cleft?

A

A few milliseconds only

429
Q

Name a nicotinic cholinergic receptor antagonist that binds preferentially to receptors in the ANS ganglions.

A

Trimethaphan

430
Q

Why is Trimethaphan not commonly used as an ANS inhibiting drug?

A

Acts non-specifically within the ganglions of both sympathetic and parasympathetic nervous systems - inhibiting all of their actions.

431
Q

Name a nicotinic cholinergic receptor antagonist that is used clinically and explain how it is used.

A

Tubocararine. Used as a neuromuscular blocker to cause muscle paralysis during anaesthesia.

432
Q

Why are muscarinic receptor agonists or antagonists used less preferentially to adrenoceptors drugs?

A

Muscarinic agonists and antagonists show very little subtype selectivity

433
Q

Name a muscarinic agonist that is used clinically and explain how it is used.

A

Pilocarpine. Used to treat glaucoma / raised intraocular pressure. Also sometimes used for increasing GI activity, stimulation of bladder emptying and suppression of atrial tachycardia.

434
Q

What class of drug is Hyoscine and what is it used for?

A

A muscarinic receptor antagonist used for anaesthetic premedication - decreases bronchial and salivary secretions, reduced bradycardia and prevents bronchioconstriction.

435
Q

What class of drug is ipratropium bromide and what is it used for?

A

Muscarinic receptor antagonist. Used to treat bronchioconstriction in asthmatics caused by increased parasympathetic discharge.

436
Q

Name a drug and its class used for ophthalmoscopic examination and why.

A

Homatropine. Muscarinic receptor antagonist. Causes pupil dilitation.

437
Q

What 3 things are cholinesterase inhibitors used for clinically?

A
  1. To reverse effects of non-depolarising neuromuscular blockers in anaesthesia.
  2. Treatment of glaucoma.
  3. Treatment of myasthenia gravis.
438
Q

Name a drug and its class that is now used in the treatment of Alzheimer’s disease.

A

Tacrine. Acetylcholinesterase inhibitor.

439
Q

Noradrenaline and dopamine are synthesised from which amino acid?

A

Tyrosine

440
Q

The rate limiting enzyme in adrenergic synthesis is…

A

Tyrosine hydroxylase

441
Q

Give the pathway of adrenergic synthesis.

A

Tyrosine – DOPA – Dopamine – Noradrenaline – Adrenaline

442
Q

Which enzyme do the chromaffin cells have that adrenergic neurones don’t?

A

Phenylethanolamine-N-methyl transferase. Converts noradrenaline to adrenaline.

443
Q

Where within the nerve terminal is the enzyme dopamine-beta-hydroxylase located?

A

Within the synaptic vesicles - meaning dopamine is transported into vesicles prior to conversion to noradrenaline.

444
Q

How is noradrenaline packaged into vesicles despite the intra-vesicle concentration being so high compared to the cytoplasmic concentration?

A

Uses a hydrogen gradient formed between the cytoplasm and vesicle by a hydrogen ATPase to couple noradrenaline uptake to hydrogen movement.

445
Q

What enzyme breaks down cytoplasmic noradrenaline?

A

Monoamine oxidase

446
Q

How is the opportunity for released noradrenaline to react with receptors limited?

A

Uptake 1 – high affinity reuptake system removes noradrenaline from synaptic cleft

447
Q

What is the fate of any noradrenaline escaping the synaptic cleft?

A

Uptake 2 - low affinity, widespread uptake

448
Q

What are the possible fates of noradrenaline reuptaken into synaptic cleft?

A
  1. Re-vesiculated

2. Metabolism by monoamine oxidase

449
Q

What is alpha-methyl tyrosine and what is its clinical use?

A

Inhibits tyrosine hydroxylase to inhibit de-novo synthesis of noradrenaline. Used in pheochromocytoma (noradrenaline secreting tumours)

450
Q

Describe the mechanism of action of alpha-methyl-DOPA in treatment of hypertension.

A

Taken up by adrenergic neurones and undergoes same processing pathway as noradrenaline to create false transmitter alpha-methyl-noradrenaline. This is poorly metabolised so accumulates in the synaptic vesicles. On release by exocytosis, it preferentially activates pre-synaptic alpha2-adrenoceptors resulting in a negative feedback response and reduced transmitter release.

451
Q

What is the action of carbiDopa? What is it used for clinically?

A

Inhibits synthesis of dopamine from Tyrosine and DOPA in the periphery. Used in treatment of Parkinson’s disease.

452
Q

How do adrenergic blocking drugs like guanethidine work?

A

Undergo uptake 1 in to nerve terminal. Can reduce impulse conduction and calcium dependent exocytosis of noradrenaline vesicles, partially block reuptake of noradrenaline transmitter and deplete noradrenaline from synaptic vesicles.

453
Q

What is an IASA and how do they work?

A

Indirectly acting sympathomimetic agent. Structurally related to noradrenaline but only a weak agonist at adrenergic receptors. Uptaken by uptake 1. Cause noradrenaline leak from the vesicle and into the synaptic cleft.

454
Q

What class of drug are uptake 1 inhibitors?

A

Tricyclic anti-depressants

455
Q

Name an uptake 1 inhibitor. What is the downside to using these drugs clinically?

A

Amitriptyline. Want to exert central effects for use as antidepressants but also have peripheral side effects such as tachycardia.

456
Q

Name a selective beta1 adrenoceptor agonist.

A

Dobutamine

457
Q

What might you use a beta1-agonist for? What are the downsides?

A

In shock to increase inotropy and chronotropy. However, cause arrhythmias.

458
Q

Salbutamol is what kind of agonist?

A

Selective beta2 adrenoceptor agonist. Used for reversing bronchioconstriction in asthmatics.

459
Q

Give 2 clinical uses of alpha1 adrenoceptor agonists.

A

Nasal de-congestion.

Vasoconstriction along with local anaesthetics to prevent dissipation.

460
Q

Name an alpha1 adrenoceptor agonist.

A

Phenylephrine

461
Q

What are selective alpha2 adrenoceptor agonists used to treat and why?

A

Hypertension. Act pre-syntactically to inhibit noradrenaline release and through a centrally mediated action.

462
Q

What are non-selective alpha-adrenoceptor antagonists used to treat?

A

Peripheral vascular disease - cause peripheral vasodilatation

463
Q

Why are non-selective alpha adrenoceptor antagonists not used to treat hypertension?

A

Because they cause postural hypotension and reflex tachycardia

464
Q

Name a non-selective alpha adrenoceptor antagonist.

A

Phentolamine

465
Q

Name a selective alpha1-adrenoceptor antagonist and state what it’s used for clinically.

A

Prazosin. Used to treat hypertension.

466
Q

Name 4 conditions that beta blockers are used to treat.

A

Hypertension, cardiac dysarrhytmias, angina and myocardial infarction.

467
Q

Name a non-specific beta blocker.

A

Propranolol

468
Q

Name a specific beta1-adrenoceptor antagonist.

A

Atenolol

469
Q

Give some side effects of using beta blockers.

A

Bronchoconstriction, bradycardia, cold extremities, insomnia and depression

470
Q

What is an alternative to using beta adrenoceptor antagonists if you want to reduce the effects of the sympathetic nervous system?

A

Could use a partial agonist such as alprenolol to cause low tonic stimulation whilst blocking full agonist (noradrenaline) binding.

471
Q

Are post-ganglionic neurones of the ANS myelinated or unmyelinated?

A

UnMyelinated

ESA2 - Amy's Cards (3 decks)

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