Pharmacodynamics

Question 1

Does an Agonist, antagonist, both or neither;

1. Binds to receptor
2. Does not bind to receptor
3. Receptor binding causes secondary effect to take place
4. Receptor binding prevents action of agonist
5. Receptor binding enhances action of agonist
6. Has affinity for receptor
7. Does not have affinity for the receptor
8. Has efficacy
9. Does not have efficacy

Answer 1

1. Both
2. Neither
3. Agonist
4. Antagonist
5. Neither
6. Both
7. Neither
8. Agonist
9. Antagonist

Question 2

Explain these terms:
Affinity
Efficacy
Potency

Answer 2

Affinity → The attraction a drug has for a receptor
Efficacy → A measure of the effectiveness of a drug at producing a maximum response
Potency → A measure of the drug dosage or concentration needed to produce a defined effect

Question 3

How does high and low affinity relate to binding? (talk about binding and displacement)

Answer 3

High affinity → binds tightly and difficult to displace
Low affinity → does not bind tightly and easy to displace

Question 4

Do the following have hight, low, negative or no efficacy;

Full agonists
Partial agonists
inverse agonists
Antagonists

Answer 4

Full agonists → high efficacy,
Partial agonists → lower efficacy,
Inverse agonists → negative efficacy,
Antagonists → no efficacy

Question 5

How is potency related to ED50?

Answer 5

High potency → Low ED50,
Low potency → High ED50

Question 6

Define EC50 (ED50)

Answer 6

The dose that produces a half maximum effect

Question 7

What are the main features of competitive antagonism?

Answer 7

• Agonists and antagonists compete for the same receptor sites
• Surmountable
• Can dissociate from the receptor
• Maximal effect is unchanged
• Parallel shift to the right

Question 8

What are the main features of non-competitive antagonism?

Answer 8

• irreversible binding
• Can cause conformational change (the equivalent of removing a number of receptors in the system)
• Maximum effect no longer produced (with the exception of spare receptors)
• Decrease slope

Question 9

What are spare receptors, what is their effect in non-competitive antagonism, Kd and curves?

Answer 9

• receptors are receptors that exist in excess of those required to produce a full effect
• Act as receptor reserve in non-competitive antagonism, allows max response to be reached
• Because of their existence ED50 may not equal Kd (the binding affinity measurement)
• shifts dose-response curve to the left of the Kd

Question 10

What is physiological antagonism, provide 2 examples.

Answer 10

• Functional (not true) antagonism
• When 2 agonists act on different receptors to produce opposite effects
• Drugs have posting mechanisms of action
• Eg. Bronchoconstriction due to histamine which can be treated with adrenaline which acts as a vasodilator
• Eg. Alcohols and Cafine

Question 11

What is a partial agonist?
What kind of response does it give?
How does it effect max response and the response dose curve?

Answer 11

• Less efficacious
• max never reached
• it also acts as an antagonist
• when combined with a full agonist, parallel shift right

Question 12

What are inverse agonists, and why do we have them?
How do they affect efficacy?
What is their mechanism/ how do they increase the proportion of inactive receptors?

Answer 12

• Restores the receptor to its inactive state since some receptors are constitutively active even without an agonist.
• produce negative efficacy
• involved the destabilisation of g-protein receptor coupling

Question 13

What is the potentiation of agonists?
How is Ach and Noaraadrenaline increased?

Answer 13

The effect of increasing the potency or effectiveness of a drug or other treatment.

Anticholinesterases (neostigmine, physostigmine) inhibit cholinesterase enzymes (catalyze the hydrolysis of the neurotransmitter acetylcholine) therefore allowing ACh to accumulate.

Up-take blockers (like cocaine, and tricyclic anti-depressants) allow noradrenaline to accumulate in the synaptic cleft.

Question 14

Whare are allosteric modulators? What is their effect?

Answer 14

a third less common class of drugs. bind to allosteric sites, different from where agonists bind and therefore are not competitive.

can either increase of decrease the response to an endogenous agonist.

Question 15

What are quantitative and quantal response/ curves?

Answer 15

Quantitative response: measured in gradual steps. eg fall in blood pressure
Quantal response: all or nothing

This curve shows the potential for variability. The close ED50 and LD50 are the less safe.

Question 16

What is the therapeutic and toxic ratio? What problems do they have?

Answer 16

Therapeutic = LD50/ED50

• ethical dilemma as the end point is death
• it is only a measure of mortality and not sub-lethal toxicity
• animal data is not always tightly correlated to human data. A drug can have varying levels of toxicity in different species.

Toxic = TD50/ED50

• The end point is not very well defined.
• Drugs can produce an array of toxic effects and this measure will produce differing results dependent on what toxic effect is being measured

Question 17

Explain the difference between a selective and non-selective drug.

Answer 17

Non-selective drugs bind to more than one available receptor subtype.
Selective drugs bind preferentially to one particular receptor subtype.

Question 18

Explain the difference between specificity and selectivity.

Answer 18

Specificity: the extent to which the receptor recognises and responds to only one ligand or agonist.
Selectivity: when a drug acts preferentially with only one receptor subtype.

Question 19

Describe four ways tolerance can occur.

Answer 19

1. Change in receptor conformation (phosphorylation)
2. Down-regulation of receptors (internalisation/reduced expression)
3. Depletion of mediators
4. Increased metabolic breakdown