Drug Receptor Concepts

Question 1

pharmacology

Answer 1

drug and human body
study of the ‘drug-body interaction’ called pharmacology.

Question 2

how do drugs act?

Answer 2

interact with biological systems in ways that mimic or affect the natural chemical messengers of the body.

Question 3

non-specific drug action vs specific drug action

Answer 3

non specific
some drugs act in a chemical or physical manner

lack any specific structure-activity relationship

requires large doses for effect.

specific
most drugs act this way
interact/bind to specific receptors.
shows structure-activity relationship
produces biological affects in very low doses.

Question 4

What is drug antagonism?

Answer 4

interaction between two drugs where the effect of one is diminished or completely abolished in the presence of the other.

Question 5

competitive antagonism

Answer 5

agonist and antagonist drug compete for the same receptor binding site. antagonist drug binding reduces chances of agonist binding and its effect. two types of competitive antagonism: reversible and irreversible.

Question 6

reversible competitive antagonism

Answer 6

agonist and antagonist bind reversibly to the receptor. fractions of receptors occupied depends on both drugs relative receptor affinities and concentrations. antagonism can be overcome by increasing concentration of agonist drug. two effects to the agonist log D-R curve: parallel shift to the right and no reduction in maximal response.

Question 7

irreversible competitive antagonism

Answer 7

antagonist drug bind irreversible to the receptor (due to high affinity or covelant bonding). fractions of receptors are unavaialble for the agonist drug binding. antagonism cannot by overcome by increasing concentration of agonist drug. lead to reduction in the slope of the D-R curve and a reduction in the maximal response.

Question 8

non competitive antagonism

Answer 8

antagonist drug doesnt compete with agonist drug for the same binding site. antagonist drug may bind to a different site on the receptor or may intefere with response coupling. antagonism cannot be overcome by increasing concentration of agonist drug. D-R curve: reduction in slope and reduction in maximal response.

Question 9

chemical antagonism

Answer 9

results from direct interaction between the antagonist and the agonist drug where they bind/combine together in solution. because of this, the active drug is rendered inactive or unavailable to interact with its target receptors. typical examples include: protamine vs heparine, dimercaprol vs heavy metals.

Question 10

pharmacokinetic antagonism

Answer 10

antagonist drug acts to reduce concentration of the agonist drug as its site of action.
possible mechanisms: reduced absorption from GIT- ferrous salts vs tetracycline antibiotics increases metabolic degradation - phenobarbital vs warfarin increased renal excretion - NaHCO3 vs aspirin.

Question 11

physiological/functional antagonism

Answer 11

interaction of two opposing agonist effects in a single biological system which results in them cancelling out eachothers effects. the two drugs elicit opposing responses by acting on different receptors. typical examples: acetylcholine vs noradrenaline (heart rate) glucocorticoids vs insulin (blood sugar levels)

Question 12

summation

Answer 12

combined effect of two drugs which elicit the same overt response, regardless of their mechanism of actions, is equal to the algebraic sum of their individual effects.

Question 13

additivity

Answer 13

combined effect of two drugs, which act by the same mechanism, is equal to the addition of their individual effects.

Question 14

synergism/potention

Answer 14

conjoint effect of two drugs greater than the algebraic sum of their individual effects. synergist may work to increase the concentration of the other drug at its receptor sites e.g. tyramine and MAO inhibitors; increase the responsiveness of the other drugs receptor-effector protein e.g. benzodiazepines and GABA (GABAa receptors)

Question 15

acquired tolerance

Answer 15

acquired state of progressivly decreasing responsiveness to a drug as a result of prior repeated exposure to the drug or another drug with a similar action

Question 16

Pharmacodynamic mechanism of acquired tolerance

Answer 16

-receptor ‘down regulation’. reduction in receptor density.
-receptor ‘uncoupling’ uncoupling of receptors from their effector systems.

Question 17

Metabolic mechanism of acquired tolerance

Answer 17

-enhanced metabolism of the drug -due to induction of metabolising enzymes

Question 18

exhaustion/depletion mechanism of acquired tolerance

Answer 18

-common with indirectly acting drugs - due to depletion of endogenous stores of mediators of the drugs action. e.g. amphetamine, nitrates. - physiological adaptation. evoked com

Question 19

physiological adaptation

Answer 19

evoked compensatory or homeostatic mechanism. -blunts/cancels drugs effects e.g. diuretics, nitrates.

Question 20

absolute vs relative selectivity

Answer 20

drugs produce spectrum of effects. hence relative not absolute selectivity of drug action.

Question 21

what is relative selectivity?

Answer 21

degree to which a drug acts upon a given site relative to all possible sites of interactions.

Question 22

therapeutic vs undesirable/side effects

Answer 22

drug effects split into therapeutic and undesirable. undesirable effects may be minor or serious.
how are undesirable effects produced? - both effects may be mediated via same receptor-effector mechanism/identical receptors located in different tissues/different types of receptors.

Question 23

therapeutic index

Answer 23

determined by the ratio of toxic to therapeutic dose therapeutic index = median toxic dose (TD50)/median effective doe (ED50) provides measure of: margin of safety of the drug, benefit to risk of ratio of the drug- e.g. penicillin vs warfarin.

Question 24

drug receptors

Answer 24

-protein/glycoprotein molecules
-most drug receptor are located on the cell membrane e.g. atenolol some located in the cell e.g. oestrogen, testosterone.

Question 25

types of drug targets/receptors

Answer 25

-classical receptors, regulatory protein/binding site from endogenous or natural chemical messengers, such as neurotransmitters and hormones.

-ion channels. e.g. lidocaine, diazepan.

-enzymes. Ace inhibitors, statins

-carrier/transport chains e.g. digoxin, SSRIS.

Question 26

types of drug-receptor interactions

Answer 26

basis of selectivity of drug: lock and key relationship

chemical selectivity
tissue selectivity.

Question 27

receptor occupancy theory

Answer 27

assumptions: drug effect is proportional to the fraction of receptors occupied. Emax=drug max effect when all receptors are binded.

Question 28

what is the fraction of receptors occupied by the drug a function of?

Answer 28

concentration of drug in biophase.
KD for drug receptor complex

Question 29

what happens when a drug binds to its receptor?

Answer 29

• drug may mimic natural. endogenous chemical messenger. same or natural chemical messenger (agonist)

-drug may block receptor, preventing natural chemical messenger from binding (antagonist). no effect.

-drug may bind to site near the binding site for natural, endogenous chemical messenger + influence its binding. can increase or decrease the effect of the effect of the natural chemical messenger (called allosteric modulator)

-drug may bind to normal site but produce an opposite effect to the natural chemical messenger (inverse agonist)

Question 30

drug agonism and antagonism

Answer 30

difference: agonist drug has efficacy, antagonist drugs have no efficacy.

similarity: both have affinity.

Question 31

affinity

Answer 31

the chances of the drug binding to its receptor.

Question 31

efficacy

Answer 31

measure of ability of drug receptor complex to couple/transduce the drug binding into a biological response.
efficacy can be low/ high or 0.

Question 31

agonist drug action

Answer 31

‘drug binds to receptor, activates it and elecits a biological response’

full agonist - elicits maximum response after binding

partial agonist - elicits less than the maximum response. e.g. salbutamol. intermediate efficacy, reduces response elicited by full agonist.

Question 32

antagonist drug

Answer 32

binds to receptor but fails to activate it so fails to elicit a response.
has efficacy of 0
competes with agonist drug to the binding site.
-biological effect results from preventing agonist drug/natural chemical messenger from binding to its receptor.

Question 33

spare receptor /receptor reserve concept.

Answer 33

-exception to the receptor occupancy theory.
-full agonists may ellicit maximum response without full receptor occupancy theory
-system is said to have spare receptor/receptor reserve.
this enable economy or hormone/transmitter secretion. allows allows low affinity drugs to to elicit maximum possible response.

Question 34

potency

Answer 34

measure of amount of drug needed to elicit a specific response.

Question 34

maximal efficacy

Answer 34

maximal response/effect produced by the drug.

Question 35

slope

Answer 35

reflects change in response per unit change of dose.

Question 36

biological availability

Answer 36

different responses to same drug in different individuals

different responses to same dose of drug in same individuals

sources of variation of drugs:
age
genes
gender
polypharmacy
pathological state.

Question 37

Answer 37

Question 38

Answer 38