Lecture 4

Question 1

Define a Full Agonist

Answer 1

Agonist whose maximal response is the largest that tissue is able to give

-only few receptors occupied for maximal response

Question 2

Define Partial Agonist

Answer 2

Agonist whose maximal response is less than full response - aways below Emax

• limiter to system
• all receptors are occupied, maximal response not reached

Question 3

What is the Efficacy of an antagonist?

Answer 3

• efficacy = 0
• it is a blocker that inhibits the system in th presence of an agonist, so if there is no agonist the antagonist does nothing to slow the system down
• i.e. no wffect on its own

Question 4

Define Affinity

Answer 4

the ability of a ligand to bind to a receptor.

• applies to both agonists and antagonists and is measured by the equinlibrium dissociation constant Kd

Question 5

Define Occpancy and how it is calculated

Answer 5

The proportion of receptors occupied by ligand

p = N / Ntot

N - occupied receptors

Ntot - total nomber of receptors for an agonist in a tissue

Question 6

Describe a Dose - Binding Curve and its shape on a logarithmic graph

Answer 6

• [dose] compared to % of receptors bound (100% occupancy)
• sigmoid curve
• Bmax
• Kd

Question 7

Define Bmax on a dose - binding curve

Answer 7

= the maximum number of ligands bound to receptors

No. on y axis

Question 8

Define Kd

Answer 8

the concentration of a drug that results in thr binding of 50% of the receptors

Question 9

What re Spare Receptors?

Answer 9

receptors that do not need to bind to drug in order to produce maximum biological effect to be produced (Emax)

Therefore at Emax not all receptors bound to get Emax

Question 10

What are the 5 types of antagonism?

Answer 10

1. Competitive (reversible / irreversible)
2. Non-competitive
3. Chemical
4. Pharmacokinetic
5. Physiological

Question 11

Describe COMPETITIVE ANTAGONISM

Answer 11

The ability of an antagonist to compete and displace an agonist/ligand from it’s receptor binding site thus decreasing the agonist. The mc forms are:

1. Reversible competitive antagonism - if agonist on site can reverse process by increased [agonist] i.e. antagonist can be removed from binding site
   E.g. NALOXONE is used to reverse opiod overdose (heroin/morphine)
2. Irreversible competitive antagonism - antagonist won’t come off binding site no matter how much [agonist] is incresed NALOXAZONE

Question 12

Describe NON-COMPETITIVE antagonism

Answer 12

Antagonist blocks system at some point in the chain of events that leads to agonist response - not blocked at site

E.g. VERAPAMIL & NIFEDIPINE prevent theinflux of Ca ions specifically blocking the contraction of smooth muscle produced by other drugs

Question 13

Descibe CHEMICAL antagonism

Answer 13

2 substances combine in solution and the effect of the active drug is lost

E.g. the chelating agent DIMERCAPROL binds tightly to heavy metal ions (lead, cadmium) forming an inactive (less toxic) complex

Question 14

Define PHARMACOKINETIC antagonism

Answer 14

antagonist reduces the [agonist] at the site of access to the system

• this may be due to increase in metabolism or renal excretion of the agonist or decreased adsorbtion of the drug from the GI tract

E.g. PHENOBARBITONE reduces the anticoagulant effect of WARFARIN by accelerting its hepatic metabolism

Question 15

Define a PHYSIOLOGICAL antagonist

Answer 15

describes the interction of 2 drugs who are acring on two opposing physiological functions of the body and thus cancelling each other out

E.g. NORADRENALINE raised arterial BP while HISTAMINE lovers arterial BP by causing vasodilation