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Flashcards in Receptor theory VI Deck (24)
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What are the 5 classes in which antagonists can be divided into?

1) Chemical
2) Pharmacokinetic
3) Physiological
4) Non-competitive
5) Competitive by receptor block


What is chemical antagonism?

- Drugs which bind up the agonist in a solution

- Chemically alter the agonist

- Effects of the active drugs are lost


What is an example of chemical antagonism?

Inactivation of heavy metals - toxicity reduced by the addition of a chelating agent

- Dimercaprol


What is pharmacokinetic antagonism and how do they work?

Drugs which reduce the concentration of the agonist by:

1) Affecting to absorption of the agonist

2) Increasing metabolism of the agonist - reducing the effects


What do you have to be careful with when treating patients with pharmacokinetic antagonists?

- May stimulate the metabolism of drugs that are treating the patient (eg. Warfarin)

- Reducing the effects


What is physiological antagonism?

Antagonist has opposing actions to the agonist

Eg. noradrenaline raises arterial blood pressure and histamine lowers ABP


What is non-competitive antagonism?

- Antagonist acts in some way to disrupt receptor signalling

- Blocks a step in the process between receptor activation and response

- Doesn't compete for the receptor site


What is competitive antagonism?

Competitive antagonist competes with the agonist for the occupancy of the receptor


What is reversible competitive antagonism?

If raise concentration of agonist high enough - increase in probability that the receptor will bind to the agonist instead of the antagonist


What is irreversible competitive antagonism?

Cannot overcome the antagonist binding with the receptor, even when increase the concentration very high


With reversible competitive antagonism, what happens when the concentration of the antagonist is increased?

- Parallel rightward shift of the agonist response curve

- Higher concentration of agonist is needed to achieve the same response

- Maximum stays the same


What is schild analysis used for?

Used to calculate the affinity of an ANTAGONIST using a conc-response curve


What is the dose ratio?

How much more times agonist is needed in the presence of an antagonist

[concentration in presence of antagonist] / [concentration in absence of antagonist]

- Using the EC50s


Describe a schild plot

- Linear plot (+ve direction)

- log10 (antagonist) on the X axis
- log (DR -1) on the Y axis

- PA2 is minus the x intercept

PA2 = -1 x log(Kd)


What is the schild equation?

DR = (concentration of antagonist/ Kd) + 1

DR - 1 = concentration of the antagonist/Kd


What is pA2?

- Constant which describes antagonist affinity

- Molar concentration of the antagonist which gives a dose ratio of 2 (requires DOUBLE the concentration of agonist to over come binding)

- Larger the pA2, the lower the Kd and the higher the affinity


Describe irreversible competitive antagonism

- Agonist reach the maximum response at the start of the experiment - due to binding with spare receptors

- Antagonist lowers the receptor reserve

- When there are no more spare receptors - maximum cannot be reaches

- Maximum response which can be achieved decreases with time

- Time dependant


What causes desensitisation?

Repeatedly adding and agonist, or treating with an agonist for a long time


What can limit desensitisation?

Treating with an antagonist


What are the consequences of desensitisation?

- Cell switches off signal
- Breaks down receptors
- Loss of receptor reserve
- Conc-response curve shift


How does a partial agonist act in the presence of a full agonist?

What happens when these drugs are given together?

As a competitive antagonist

When given together - effect is LOWER than if they were given on their own


If 2 full agonists are given together, what happens and why?

Below maximum concentrations - their response will act ADDITIVELY

As maximum response is governed by the downstream signalling and machinery of the cell - meaning that the agonists converge on the SAME downstream pathway


What is the maximum response of a agonist determined . by?

Downstream signalling and machinery of the cell


What happens when PA2 increase?

Kd decrease (inverse relationship - log??)
Antagonist affinity increase