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LCRS 1 - Pharmacology > Drug-receptor interactions and mechanisms of drug action > Flashcards

Drug-receptor interactions and mechanisms of drug action Flashcards

1
Q

What is pharmacokinetics?

A

The effect of the body on the drug

E.g. ADME

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2
Q

What is pharmacodynamics?

A

The effect of the drug on the body (responses produced, mechanism of action)

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3
Q

What is a drug?

A

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

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4
Q

What are the 4 main drug target sites?

A

Receptors
Ion channels
Transport systems
Enzymes

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5
Q

What is a receptor?

A

Protein molecules whose function it is to recognise and respond to endogenous chemical signals

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6
Q

What is an ion channel?

A

Selective pore within membrane of lipid bilayer

Allows passage of ions depending on EC gradient

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7
Q

What are the 2 types of ion channel?

A

Voltage-sensitive

Receptor-linked

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8
Q

What are some drugs that interact with ion channels rather than with the receptors themselves?

A

Local anaesthetics - block VGSCs in sensory axons; fewer APs propagated; reduced perception of pain

Calcium channel blockers

  • Usually end in -dipine
  • Block VSCCs
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9
Q

What is a transport system?

A

System of carriers that transport substances against their CG, e.g. glucose, ions, NTs

Show specificity for certain species
E.g. Na/K pump, NA uptake 1

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10
Q

Why are transport systems not receptors?

A

Don’t mediate a response

Just allow NT to bind to protein and then move it somewhere else

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11
Q

What are the 3 ways in which drugs interact with enzymes?

A
  1. Enzyme inhibitors
  2. False substrates
  3. Prodrugs
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12
Q

What are the exceptions to the 4 target site rule?

A

Some drugs produce responses due to the physiochemical properties

  1. General anaesthetics dampen synaptic transmission but don’t interact with specific transport system or receptor
  2. Antacids - reduces acidity of stomach contents - basic
  3. Osmotic purgatives (laxatives) - stimulate voiding of gut contents - draw water into stomach contents - softens stool
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13
Q

What is an agonist?

A

A molecule that binds to a receptor and stimulates it to generate a response

E.g. nicotine

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14
Q

What is an antagonist?

A

A substance that interacts with and binds to a receptor but does NOT produce a response

Gets in the way of agonist

E.g. atropine

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15
Q

Define potency

A

How powerful a drug is

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16
Q

What does potency depend on?

A

Affinity

Efficacy

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17
Q

What is affinity?

A

How willingly a drug binds to its receptor

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18
Q

What is efficacy?

A

AKA intrinsic activity
Ability of a drug to generate a response once bound to receptor
Usually involves some sort of conformational change

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19
Q

What is a full agonist?

A

An agonist that generates the maximal response

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20
Q

What is a partial agonist?

A

An agonist that generates less than the maximal response

21
Q

What is selectivity?

A

When a drug prefers interacting with a particular receptor type

22
Q

Explain the log dose-response curve

A

Tissue response Y
Log [A] X

Full agonists with lower affinity with still generate a maximal response but needs much higher concentration

Partial agonist curve peaks before it gets anywhere near maximal tissue response

23
Q

Do antagonists have:

a) affinity?
b) efficacy?

A

Have affinity

No efficacy

24
Q

What are the 2 main types of antagonists?

A
  1. Competitive

2. Irreversible

25
Q

How does a competitive antagonist work?

A

Binds to same site as agonist on receptor

Need higher agonist conc to generate maximal response

26
Q

Why are the responses of competitive antagonists surmountable?

A

They bind to same site as agonist on R

By increasing agonist concentration, you can overcome the effect of competitive antagonist

27
Q

How do competitive antagonists affect the log dose-response curve?

A

Shifts it RIGHT

Need higher [A] for same tissue response

28
Q

How do irreversible antagonists work?

A

Bind to same site as agonist but more tightly with covalent forces - can’t be shifted

OR

Bind to different site –> insurmountable antagonism bc not competing

29
Q

What is receptor reserve? Advantages?

A

‘Spare receptors’
In some tissues, you don’t have to occupy 100% of Rs to generate maximal response
May be as low as 1%
Advantage = increased sensitivity of tissue to agonist and increased speed of response

30
Q

How do irreversible antagonists affect the log dose-response curve?

A

Curve falls away and won’t be able to generate maximal response regardless of [A]

31
Q

What are the 4 types of drug antagonism?

A

Receptor blockade
Physiological antagonism
Chemical antagonism
Pharmacokinetic antagonism

32
Q

Explain receptor blockade

A

Antagonist binds to receptor and prevents binding of agonist

33
Q

What is use dependency? Give an example

A
  • Refers to ion channel blockers
  • The more active the target tissue, the more effective the blocker
    E.g. normal neurones fire at a relatively low rate
    Put local anaesthetic on them –> relatively low blockage
    Nociceptor neurones fire rapidly and bc APs are generated rapidly, ion channels are open more often
    LAs work by binding to inside of ion channels after they open – channels open more often –> more chance for blockage
    Gives LAs a selective action on nociceptor neurones - act on pain conducting fibres more specifically than normal neurones
34
Q

Explain physiological antagonism and give an example

A

2 drugs act at different receptors to have opposite effects in same tissue
E.g. NA on vasculature binds to adrenoceptors –> vasoconstriction
Coadminister histamine - acts on different Rs to cause vasodilation

35
Q

Explain chemical antagonism and give an example

A

Interaction of drugs in solution
E.g. dimercaprol is a chelating agent - forms heavy metal complexes which are more rapidly excreted by kidneys - reverses lead poisoning

36
Q

Explain pharmacokinetic antagonsim and give an example

A

One drug reduces concentration of another drug at the site of its action
by reducing absorption, increasing metabolism or increasing excretion of the other drug
Must be aware of this so you don’t administer two drugs that interfere with each other

E.g. repeatedly administering barbiturates increases production of microsomal enzymes
Administering another drug metabolised by same enzymes –> metabolised more quickly –> reduced effect

37
Q

What is drug tolerance?

A

Gradual decrease in responsiveness to a drug with repeated administration

38
Q

What can cause drug tolerance?

A 
Pharmacokinetic factors
Loss of receptors
Change in receptors
Exhaustion of mediator stores
Physiological adaptation
39
Q

How can pharmacokinetic factors cause drug tolerance?

A

Metabolism of drug increases when given repeatedly over time

E.g. barbiturates and alcohol

40
Q

How can loss of receptors cause drug tolerance?

A

If cell is repeatedly stimulated by an agonist, cell will endocytose some receptors so there are fewer available on cell surface = receptor downregulation
Beta adrenoceptors are susceptible to this

41
Q

How can change in receptors cause drug tolerance?

A

No. of receptors on cell surface stays same but Rs themselves undergo desensitisation
Trigger = continued stimulation over long period of time
Involves conformational change
Proportion of Rs are no longer effective

42
Q

How can exhaustion of mediator stores cause drug tolerance?

A

Happens with amphetamines
Amphetamine = CNS stimulant - gets into BS, crosses BBB into brain and acts on noradrenergic neurones
Amphetamine binds to uptake 1 protein - taken into central NA synthesis system - replaces NA in vesicles - big increase in NA production
2nd dose - less severe response due to exhausted NA stores - no more NA unless de novo synthesis

43
Q

How can physiological adaptation cause drug tolerance?

A

Like a homeostatic response

Body attempts to maintain a stable internal environment

44
Q

What are the 4 receptor families?

A

Type 1 - ionotropic
Type 2 - G-protein coupled
Type 3 - tyrosine kinase-linked
Type 4 - intracellular steroid type

45
Q

Describe type 1 ionotropic receptors and give 2 examples

A

Ion channel linked
Mediate very fast responses - milliseconds
4 or 5 subunits
Defining feature: transmembrane alpha helices
External binding domain - stimulates and opens ion channel
E.g. nicotinic ACh R and GABA

46
Q

Describe type 2 G-protein coupled receptors and give an example

A 
Must first link to a G protein before it can mediate a response
Much slower - seconds
1 subunit
7 transmembrane alpha helices
E.g. b1 adrenoceptors in heart
47
Q

Describe type 3 tyrosine kinase linked receptors and give 2 examples

A 
Single protein
1 transmembrane domain
When agonist stimulates R, activates catalyst inside cell and stimulates kinase activity of R --> phosphorylation of IC proteins --> response
E.g. insulin receptor, GF receptor
Minutes
48
Q

Describe type 4 intracellular steroid type receptors

A

Activated by steroids and thyroid hormones
Regulate DNA transcription
Drug must pass through cell membrane and into nucleus before effect
R stimulates –> zinc fingers uncovered –> DNA binding –> increased transcription
Hours

49
Q

What is a drug target site?

A

Anything to which a drug is directed and/or binds, resulting in a change in its behaviour or function

LCRS 1 - Pharmacology (33 decks)

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