Mechanisms of drug action

Question 1

What is a good definition of a drug?

Answer 1

A chemical substance that interacts with a biological system to produce a physiological effect

Question 2

What are the 4 type of proteins drugs target?

Answer 2

Receptors, Ion channels, transport systems and enzymes

Question 3

Define agonist, Full agonist, Partial agonist

Answer 3

Agonist-bind to receptors and activate them (eg: nicotine on ACh receptors
Full agonist: Drug can general maxiumum tissue response
Partial Agonist: drug that can NEVER generate the maximum tissue response (partially antagonist)

Question 4

Define antagonist, Selectivity

Answer 4

Bind a receptor but does not activate-reduces activity eg; Atropine
Selectivity-ability to only bind the right receptor (depends on the dose as well)

Question 5

What defines the theoretical potency of a drug targetting a receptor

Answer 5

AFFINITY of the drug for the receptor and EFFICACY of what it does to receptor (intrinsic activity)

Question 6

Define the shape of a dose-response curve for an agonist

Answer 6

Tissue response should increase in a logarithmic fashion to the agonist concentration
Full agonists reach higher maximums than partials

Graphing a Log-dose-response curve allows to achieve a sigmoid curve-the maximum is easier to observe

Lower affinities would lead to “movement to the right”-need higher concentration of drug to achieve same effect

Question 7

What are the 2 types of antagonists?

Answer 7

Competitive and irreversible

Question 8

Define Competitive antagonists

Answer 8

largest group of drugs-bind the same site as the ligand/agonist. Can be surmounted-if you increase agonist you can overide the block
shifts the dose response curve to the right (need more agonist dose)
eg: atropine-competitive Nicotinic, propanolol-B blocker

Question 9

Define irreversible antagonists

Answer 9

Binds very tightly or at a different site

Most importantly-insurmountable-changes DR curve down AND right

Question 10

What is drug antagonisms and what are the 4 ways they can work

Answer 10

Drug antagonism-if drugs are administered at the same time, they can interact with one another and reduce/improve the effect
Can be-receptor blockade, Physiological Antagonism, Chemical antagonism and Pharmacokinetic antagonism

Question 11

Explain Receptor blockade as a mechanism of drug antagomism

Answer 11

Competitive and irreversible antagonists can interfere with agonists-therefore antagonistic drugs and agonist drugs if they target the same receptor will interact (competitive increases needed dose, etc)
Irreversible creates Use-dependency for local anaethetic-exemple-the more the tissue is used the faster the ion channel blockers work (need to get in channel to work)

Question 12

Explain physilogical antagonism as a mechanism of drug antagomism

Answer 12

different Drugs can interact with different receptors-and in different tissues can cause the opposite effects
eg Noradrenaline and histamine have opposite effects on blood vessels

Question 13

Explain chemical antagonism as a mechanism of drug antagomism

Answer 13

Rarer-but the drugs interact in solution and change each others properties
eg: Dimercaprol-chelating agents can act on other

Question 14

Explain Pharmacokinetic antagonism as a mechanism of drug antagomism

Answer 14

One drug can reduce the concentration of another at the side-by reducing absorbtion, increasing metabolism or excertion of the other drug
eg: Barbituates (epilepsy-on a long term “upgrades” barbituates enzymes-and barbituate like drugs lose effect (eg Warfarin))-clinically important

Question 15

Define drug tolerance and list the 5 main mechanism

Answer 15

Gradual reduction of responsiveness to repeated administration (not all drugs do this tho)
Pharmacokinetic factors
Loss of Receptors
change in receptors 
Exhaustion of mediator stores
physiological adaptiation

Question 16

Explain how pharmacokinetic factors can lead to drug tolerance

Answer 16

Can be due to Pharmacokinetic factors (as given, lead to increased enzyme activity to clear the drug (eg Barbituates, alcohol as well)

Question 17

Explain how Loss of Receptors can lead to drug tolerance

Answer 17

Usually caused by membrane endocytosis-down regulation in response of constant activation
B-receptors are prone to this

(just to mention-upregulation is also a thing)

Question 18

Explain how change in receptors stores can lead to drug tolerance

Answer 18

change in receptors -as the receptors keep being stimulated they change conformation to not react as much/at all
ech nictonic receptor at NMJ

Question 19

Explain how exhaustion of mediator can lead to drug tolerance. exemple!

Answer 19

Amphetamines-gets acess through blood very fast, and binds vesicules that contain NA-and releases it
Causes euphoria and excitement-if repeats fast tho, reponse is lowered because the NA stores are lowered and cannot be re-made that fast
Can happen with drugs
exemple!

Question 20

Explain how physiolgical adaptiation can lead to drug tolerance

Answer 20

Not well understood, but homeostatis can change the response to the drugs-and can lose effects (like antihypertensive-can lead to increase of BP)
But can also reduce the bad side effects of some drugs

Question 21

What are the 4 main types of receptor families?

Answer 21

Type 1- Ion channels
Type 2- GCPR
Type 3-Kinase Linked
Type 4-intracellular steroid receptors