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1. Foundations of Medicine PoNF > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Why must cells communicate

A

to coordinate complex activities

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2
Q

Explain specificity of intercellular signals

A

Chemical signals released from one cell produces a response only in those cells that express the right receptor. Different receptors for the same chemical signals can produce different responses in different cells - allows for specificity: the right response from the right cells

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3
Q

What can intercellular signalling molecule response include

A

Changes in:
* Secretory activity
* contractile activity
* metabolism
* membrane permenbility
* rate of proliferation or differentiation

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4
Q

What is the process of intercellular communication also called

A

signal transduction

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5
Q

What does the process of intercellular communication depent on

not sure if need to know

A

a range of receptors

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6
Q

Why are there 2 different types of receptor

A
  • Intracellular receptors - lipophilic molecules which can diffuse directly through lipid bilayer (e.g. hormones)
  • Cell surface receptors - hydrophilic signalling molecules, signal tranduced across membrane
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7
Q

Explain the action of lipidphilic (soluble) signalling molecules

A
  • Dissolve through lipid bilayer of plasma membrane
  • Bind to intacellular receptors in the cytosol (or nucleus)
  • Reponse is triggered
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8
Q

Give NO and steroid hormones as examples of lipophilic signalling molecules

A
  • NO (nitric oxide): binds to soluble guanylyl cyclase in the cytosol. Generates cGMP as a 2nd messenger that regulates cell activity
  • Steroid hormones: recepotr is often transcription factor that regulats transcription in the nucleus
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9
Q

What are examples of primary messengers (1st)

A

neurotransmitters and hormones

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10
Q

Where must hydrophilic signalling molecules bind and how many are there?

A

To receptors on the cell surface: 4

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11
Q

Name all 4 types of cell surface receptor

A
  1. Receptor-channels
  2. G protein-coupled receptors (GPCRs)
  3. Receptor-enzymes
  4. Integrin receptors

3/4 are both catalytic receptors

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12
Q

Explain each of the 4 types of cell surface receptor

A
  1. Receptor-channels - also called ionotropic receptors and ligand binding opens/closes channel e.g. nicotinic acetylcholine receptors
  2. G protein-coupled receptors (GPCRs) - aka metabotropic receptors and do all their work via a middle man (G protein) which regulates enzyme activity/opens ion channel when ligand binds
  3. Receptor-enzymes - receptors with intrinsic enzyme activity (insulin receptors) or which are bound to an enzyme (cytokine receptors) - ligand binding to receptor-enzyme activates an intracellular enzyme
  4. Integrin receptors - receptors that interact with the cytoskeleton - ligand binding alters enzymes or the cytoskeleton
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13
Q

What will different G-protein couple to in GPCRs

A

different 2nd messenger systems

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14
Q

What could a G protein couple to in GPCRs

3

A
  • Direct to ion channels: affects membrane potential and firing of action potentials (opens/closes ion channels)
  • Adenylyl cyclase: produces cAMP as 2nd messenger after breaking down ATP. Regulates protein kinase A activity ( which phosphorylates target protiens and changes their activity)
  • Phospholipase C: produce IP3 and DAG as 2nd messengers, releases Ca2+ and regulates protien kinase C activity. Phosphorylates target protiens and changes their activity
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15
Q

What does the phosphorylation of myosin by adenylyl cyclase pathway (GPCR) lead to?

A

smoother muscle contraction

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16
Q

Sources of Calcium

3

A
  1. Internal stores via IP3 - or Ca2+ - stimulated release Ca2+ from ER
  2. From outside the cell via voltage or ligand-gated Ca2+ channels - need neurotransmitter?
  3. Via inhibition of Ca2+ transport out of the cell
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17
Q

What G-protein messenger system release Ca2+

(and regulates protien kinase C activity)

A

Phospholipase C: produce IP3/DAG as 2nd messengers

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18
Q

What are the effects of Ca2+ in the cell

A
  • Directly affect target protein (e.g. PKC)
  • Bind to calmodulin which then activates target protein (e.g. Ca2+ - calmodulin dependent kinase - CamKinase)
  • Works via some other Ca2+ binding protien (e.g. troponin)
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19
Q

How is intercellular signalling achieved

A

chemical signalling molecules acting on specific receptors

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20
Q

What are receptors and their intracellular signalling pathways at the site of action of?

A

Drugs

21
Q

What can pharmacological agents be

A
  • Endogenous - made by body (e.g. neurotransmitters and hormones)
  • Exogenous - e.g. drugs
22
Q

Define drug and give examples of possible sources

A

Any chemical agent that affects a biological system
Sources inc: natural products (from plants), synthetic drugs, biotechnology useing living systems (insulin) to make therapeutic agents, gene therapy

23
Q

How do drugs act

A

by interacting with a binding receptor

24
Q

Give 6 examples of receptors

A
  • Cell surface receptors (B-adrenergic receptors)
  • Intracellular receptors (steroid receptors)
  • Ion channels (TTX blocks Na+ channels)
  • Carriers (ouabain inhibits na/k ATPase)
  • Enzymes (asprin/ibuprofen inhibit cyclooxygenase)
  • nucleic acids (tumor promoters bind to DNA)
25
Q

What happens greater the number of drug particles there are (whilst still less than total no. of receptors)

A

Size of response will inc, as more drugs bind to receptors which each produce an individual response

26
Q

What happens one there is more drug than receptors

A

Maximum (saturated) response is reached, where dose can’t inc any more

27
Q

Define EC50

A

Half maximal effective concentration is a measure of the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time. - dose required to give 50% of response

28
Q

How is (drug) affinity determined

A

by the strength of chemical attraction between drug and receptor

29
Q

What does a low EC50 indicate

A

a high affinity

30
Q

What does it mean if a lower [drug] is needed to intiate the same response (proportionally)

A

That drug has a higher affinity

31
Q

What graph can be used to determine drug affinity

A

Concentration response/dose curves

32
Q

Efficacy

A

How “good” a drug is at activating the receptor - the maximum response that can be achieved with a drug

33
Q

How do fully and partially activated receptors look on a conc response curve

A

see sheet: Efficay of partially activated receptor less so therefore, response (y-axis) not so great

34
Q

What does the size of a drug response depend on?

A
  • Drug affinity - does it bind?
  • Drug efficacy - does it activate receptor?

this determines the properties of the drug

35
Q

What do agonists and antagonists do?

A
  • Agonists: mimic normal effect of receptor
  • Antagonists: block normal action of receptor
36
Q

Give the affinity and efficay for:
* Full agonist
* partial agonist
* antagonist

A
  • Full agonist A=high E=high
  • Partial agonist A=high E=mid
  • Antagonist A=high E=low (blocks receptor)
37
Q

How are antagonists useful in terms of physiological responses

A

If don’t want response, anatagonists compete with endogenous agonists to bind with receptor. If greater [antagonist] then physiological response is blocked

38
Q

How can we overcome competitive agonists

A

Inc sub conc

39
Q

Which way is the agonist conc-response curve shifted in the prescence of a competitive antagonist

A

To the right - higher [agonist] required to overcome competitive antagonist inhibition

40
Q

non-competitive antagonist

A

stop receptor working by binding to a different site to the agonist - conc-response curve different

41
Q

What doesn’t EC50 explain

A

efficacy - only explains affinity

42
Q

What may one signalling molecule act on

A

several receptor subtypes

43
Q

Selective agonists

theraputic potential

A

drugs that activate only some of those receptors

e.g. salbutamol (B2 agonist)

44
Q

selective antagonist

theraputic potential

A

drugs that block only some of those receptors

propranolol (B1 and B2 antagonist)

45
Q

Explain how one signalling molecule can have multiple receptors

A

Shape of molecule means it can fit into multiple receptors (lock and key)

46
Q

How can some drugs be selective in binding to receptors

A

Can bind to, and activate only some receptors

or not activate in the case of selective antagonists

47
Q

in conclusion, what can the effect of drugs/endogenous signallingmolecules have on the body

A

neurotransmitter/hormone etc. can bind to different receptors in different parts of the body and** produce different responses**

48
Q

What are some common receptors (adrenaline/noradrenaline)

A

a1, a2, B1, B2 adrenergic recptors

49
Q

define receptor

A

molecules that recieves a stimulus

1. Foundations of Medicine PoNF (22 decks)

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