Define Efficacy

Define Affinity

Explain 'selectivity'

Drug Binding Equation

Define Kd

How do you can you calculate Kd using D and DR

What is Rt

What does P stand for? How do you calculate P?

What is the rearrangement of the fractional occupancy equation to give Kd?

Under which conditions is the receptor occupancy equation valid?

Why are semi-log plots more useful than linear?

Which 2 parameters does the ability of an agonist to produce a pharmacological response depend on?

a
(D) + (R) <> (DR) <> (DR*)
B
What determines how many bound receptors are in the activated state?

What does E stand for?

What is Furchgott's equation for response?

Define EC50

Why is the EC50 always lower than the KD?

What does Potency depend on? Why is potency useful?

In what three different scenarios can potency be used.

If testing a drug on 4 different tissues what information could you tell?

What does 'a' stand for?

Where will a partial agonist curve lie in compare to that of a full agonist in a concentration response curve?

When can a partial agonist elicit a full response?

What is the therapeutic value of a partial agonist? Give an example.

When might a full agonist not produce a full response?

How does receptor number affect a partial agonist in comparison to a full?

Name the four types of Antagonism.

Define Competitive antagonism.

Define Non-competitive antagonism.

Define Uncompetitive binding

Which type of antagonist can have efficacy?

What is the Gaddum-Schild Equation and what can it be used for?

How do you find Kb from the graph?

What is the equation for a Schild Plot.
What must the slope be?

What is pA2? What is it therefore equal to?

Worked example:

If a drug has a pA2 value of 9 what does this tell you about the drug?

For the next few flashcards describe the receptors that the drug acts on and the effect/use.

Propanalol

Haloperidol

Atropine

Ranitidine

D-tubocurarine

What is irreversible competitive antagonism? How does it look graphically?

How do non-competitive antagonists work? What is another term for non-competitive antagonists?

Explain physiological antagonism.

For the next few flash cards explain what the agonist does and how the physiological antagonist prevents this.

Noradrenaline/Acetylcholine

Endothlin/Nitrates

Histamine/Salbutamol

What is Constitutive Activity?

What can be used to reduce constitutive activity and how?

How does an inverse agonist curve compare to that of an agonist?

What causes a tissue to become desensitised?

Which type of desensitisation is recoverable?

What is drug Tolerance?

How can tolerance be used therapeutically?

List five properties of receptors.

Is selectivity greater for agonists or antagonist?

What is co-operativity in drug action?

How can you see co-operativity graphically?

What is the Hill equation?

What does 'n' stand for?

What do values of 'n' <1< signify?

What information do you plot a graph from a saturation binding experiment?

What are the 5 advantages of radioligand binding?

What is the half life (years) and specific activity (Ci/mA) of the following Isotopes?

3H

14C

35S

125 I

32P

What must be taken into consideration in radioligand binding experiments?

What are the 3 stages of radioligand binding?

What are the different methods for separating bound and free ligand for a) particulate fractions (cells,membranes) and b) Soluble receptors?

What is the simplest model/equation for receptor-ligand binding?

What would you plot to find Kd, Ro and Bmax?

What is the equation for Bmax?

How do you find non-specific binding of the radioligand?

What relationship does non-specific binding have with radioligand concentration?

What are the equations for non-specific binding and total binding?

What is the equation for a radioligand scatchard plot

How do you estimate non-specific binding?

Define IC50

Define Ki

What do you plot to find IC50 in a competition assay?

How do you find the IC50 graphically?

What equation can you use to find Ki in a competition binding assay?

What information do you get from a competition binding assay?

What are the advantages of a saturation assay?

(6)

What are the disadvantages of saturation binding assays?

INTRODUCTION TO ION CHANNEL PHARMACOLOGY LECTURE

What four states can a Voltage-Gated channel exist in?

Define the refractory period

What happens if you stimulate a cell during the refractory period?

If cations flow into a cell, what type of current will be observed?

Using physiological concentrations what types of current will Na+ and K+ always generate?

What could yo use to block sodium channels?

Why does current through a channel reduce despite a constant voltage?

How many subunits make up voltage-gated ion channels?

Why does K+ channels only require 1/4 of the DNA required for Na+ and Ca2+ channels?

What are the 5 states a ligand-gated channel can exist in?

Where do you find nicotinic acetylcholine receptors? What do they require to activate?

How many subunits does a nicotinic acetylcholine receptor have?

What are the subunits that make up a nicotinic acetylcholine receptor and how does this change at birth?

How many transmembrane segments does a glutamate receptor have?

How are voltage-gated channels classified?
(4)

How are ligand-gated channels classified?
(3)

What are the two roles of ion channels?

What 3 things can an increase in intracellular Ca2+ cause?

Define membrane potential

What is Ohm's law?

How do resistance (R) and conductance (G) relate to each other?

What drives ions through ion channels?

What are the standard physiological concentrations of Na+, K+, Ca2+ and Cl- inside and outside of cells? (mM)

What is the Nernst equation?

What constants can be used to replace RT/ZF?

How does Eion affect the direction that ion will move in?

What is the electrochemical gradient?

Define 'equilibrium potential'

On a current x voltage graph, how do you find the equilibrium potential of the ion?

When would a channel have an equilibrium potential that fitted no specific Eion?

Why is the equilibrium potential for nicotinic acetylcholine receptors slightly closer to the ENa+ than EK+?

Why is the delayed opening of potassium channel important during action potentials?

What does 'G' stand for?

What is 'G' the reciprocal of, and what is it represented by on which type of graph?

What unit is conductance measured in?

How does positive feedback affect both K+ and Na+ channels respond to positive feedback?

What causes EPSPs?

What causes IPSPs

Where do tetrododoxin (TTX), saxitoxin (STX) and Phenytonin act, and what are they used to treat?

Where do sulphonylureas (tolbutamide, glibencamide) act and what are they used to treat?

DRUG ACTION AT ION CHANNELS
Dr. M. Usowicz lectures

What are the 3 main benefits of the patch clamp technique?

What are the benefits of applying light suction to a patch clamp pipette?

What is the purpose of voltage clamping?

What are the three types of patch clamp configurations?

To get an perforate whole-cell configuration what must be applied?

What is the difference between how and outside-out and inside-out configuration are made?

Where is the external membrane face in an
a) outside-out configuration
b)inside-out configuration

Why does what you do to the patch of membrane have no effect on the rest of the cell in a whole-cell experiment?

What information do you learn from single channel currents? How quickly do they open/close?

How can you determine if a cell is voltage gated?

What determines the size and direction of a single channel current?

What is the equation for voltage gradient?

How do you identify the reversal potential? Why does this not mean that no channels are open?

If the voltage gradient is negative what will positive ions do? And if the voltage gradient is positive?

If the driving force/voltage gradient is negative what does this mean in terms of flow of ions and direction of current?

How would you determine the nature of a voltage gated channel?

Why might a an IV graph not be linear?

How can you determine if a channel is ligand gated?

TRUE/FALSE
For a ligand-gated ion channel voltage affects:
a) Probability of opening
b) Single channel current
c) Single channel conductance

What is the downfall of excised membrane patches?

Which antagonist might you use to block the effect of ACh?

Which antagonist could be used to block voltage gated sodium channels?

How might you tell that TTX isn't use dependent on a single channel current recording from a voltage gated channel?

What is QX-222?

PATCH CLAMP RECORDING LECTURES CONTINUED

What is the advantage of using a whole-cell recording?

What is the disadvantage of a whole cell recording?

What then is the advantage of a perforated-patch whole-cell recording?

Which antibiotics could you use to make a perforated-patch whole-cell configuration?
(3)

Why does the current decrease in a whole-cell recording from a ligand gated channel despite no change in voltage or ligand conc?

In which direction would chloride flow at 0V and what type of current would you have?

What two drugs could you use to block Ca2+ and K+ currents in order to observe just a Na+ current?

For the next 3 slides identify the voltage gated channels responsible for the current recorded and explain their inactivation time.

If a drug inhibits current through a voltage gated channel how would you tell if it was a voltage dependent drug or not? (2)

Why does the reversal potentials for current flowing through a Ca2+ channel occur at a more negative value than Eca?

Give an example of a voltage dependent drug. (Agonist at L-type channels)

What is the relationship between micro and macroscopic currents?

Describe graphically the relationship between ligand gated macro and micro currents.

Why are I/V graphs of single channel and whole cell recordings different for voltage gated channels?

Describe why a whole cell voltage gated channel recording is 'U' shaped.

VOLTAGE DEPENDENT CALCIUM CHANNELS
MARIA USOWICZ
19/10/15

What two roles do voltage-dependent CA channels have?

Which type of calcium channel is low-voltage activated and where is it found?
(Below ~-50mV)

Which types of Ca channels are high-voltage activated (Above ~-50mV), and where are the found?

What 3 classes of compounds act at L-type Ca channels?

Give an example of a phenylalkamine?

What concentration of verapamil is required for 100% block?

What are the clinical uses of Verapamil?
What is an adverse affect?

Give an example of an Benzothiazepine

How do DHP (1,4 - dihydropyridines) antagonists work on L-type channels?

Why would you expect a DHP antagonist to cause greater % inhibition when opened from -50mV than -100mV (to 0mV)
(2)

Why are DHP antagonists selective for vascular smooth muscle over cardiac?

Which DHP antagonist is selective for cerebral arteries?