ICS- Pharmacology

Question 1

what is pharmacodynamics?

Answer 1

the study of the biochemical, physiologiv and molecular effects of drugs on the body, the mechanisms of their actions and the relationship between drug concentration and effect.

Question 2

what is the the dose-response relationship?

Answer 2

the relationship between the dose of a drug and the magnitude of its effect (e.g. theraputing and toxic effects)

Question 3

what is the theraputic window?

Answer 3

the margin between a drug’s effective dose and its toxic dose

Question 4

what does an agonist do?

Answer 4

binds to a receptor and activates it but produces the maximal possible effect

Question 5

what does a partial agonist do?

Answer 5

binds to a receptor and activates it but produces a submaximal effect, even at full receptor occupancy

Question 6

what does an antagonist do?

Answer 6

binds to a receptor but doesnt activate it, blocking the action of agonists or endogenous ligands

Question 7

what do competitive antagonists do?

Answer 7

compete with agonists for the same receptor site, their effects can be overcome by increasing agonist concentration

Question 8

what do non-competitive antagonists do?

Answer 8

bind irreversibly or at a different site on the receptor, reducing the maximal effect of agonist regardless of agonist concentration

Question 9

what does an inverse agonist do?

Answer 9

binds to an agonistic receptor and reduces its baseline (constitutive) activity, producing an effect opposite to that of an agonist

Question 10

what is selectivity of a drug?

Answer 10

selectivity emphasises the drug;s preference for a particular receptor or target compared to others

Question 11

what is specificity of a drug?

Answer 11

specificity is the extent to which a drug produces only the desired theraputic effect without causing any other physiological changes (a drug with a higher specificity is less likely to produce unwanted effects)

Question 12

give examples of cell membrane receptors.
how do drugs interact with them?
*

Answer 12

example: GPCRs, ion channels
drugs bind to extracellular domains of transmembrane receptors and initiate rapid, short-term effects like ion flux changes or second messenger cascades.

Question 13

give examples of cytoplasmic receptors.
how do drugs interact with them?

Answer 13

example: Glucocorticoid receptors
Lipophilic drugs cross the membrane and bind to cytoplasmic receptors. receptor drug complexes migrate to the nucleus, affecting transcription factors and cellular function

Question 14

give an example of nuclear receptors.
how do they function in drug interactions?

Answer 14

example: oestrogen receptors
lipophilic drugs diffuse into the cell and bind directly to nuclear receptors. they modulate gene transcription, leading to long-term cellular effects.

Question 15

what is the difference between cytoplasmic and nuclear receptors?

Answer 15

cytoplasmic receptors migrate to the nucleus after drug binding. nuclear receptors are already present in the nucleus.

Question 16

what is affinity Kd and how does it relate to drug binding?

Answer 16

• measures drug-receptor binding strength
• inversley related to the dissociation constant (Kd)
• lower Kd = Higher affinity

Question 17

what is efficacy in drug-receptor interactions?

Answer 17

• describes the ability of a drug-receptor complex to produce a response
• agonists- have both affinity and efficacy
• antagonists- have affinity but zero efficacy

Question 18

what is potency and how is it measured?

Answer 18

• measures the intensity of the effect produced for a given drug dose
• EC50: the concentration of a drug needed to produce 50% of its maximal effect
• influenced by both affinity and efficacy; commonly used to assess potency

Question 19

what is a receptor reserve?

Answer 19

a concept where not all the receptors need to be occupied by the drug to acheive a maximal response, observed with highly efficacious drugs.

Question 20

what does a large receptor reserve mean?

Answer 20

the drug is highly efficacious so only a few receptors are occupied.

Question 21

do partial agonists have a receptor reserve?

Answer 21

they do not, even with 100% occupancy a maximal response is not seen

Question 22

list the types of drug targets

Answer 22

receptors
enzymes
ion channels
transport proteins (carrier proteins)

Question 23

list the types of receptors targeted by drugs

Answer 23

ligand gated ion channels
G-protein coupled receptor
enzyme-linked receptor
cytosolic/ nuclear receptor

Question 24

describe ligand gated ion channels in terms of being a drug target

give an example of one.

Answer 24

• fit under both receptors and ion channels
• activated by specific ligands (e.g. neurotransmitter or drug)
• in nicotinic ACh example, ACh binds to the receptor which opens the channel and allows Na+ to flow in causing depolarisation

e.g. Nicotinic ACh receptor

Question 25

describe G protein couple receptor in terms of being a drug target Give an example

Answer 25

G coupled receptors are transmembrane proteins which span the cell membranes 7 times

Question 26

what happens when a ligand binds to a GPCR?

Answer 26

the GPCR undergoes a conformational change

Question 27

how does a GPCR activate a G-protein?

Answer 27

* it promotes the exchange of GDP for GTP on the alpha subunit * the G-protein then dissociates into a GTP-bound alpha subunit and a beta-gamma dimer

Question 28

what happens after the G-protein is activated?

Answer 28

the GTP-bound alpha subunit and beta-gamma dimer trigger intracellular signalling cascades.

Question 29

what are the major intracellular signalling pathways activated by GPCRs?

Answer 29

* adenylyl cyclase- increases or decreases cyclic AMP (cAMP) levels. * phospholipase C (PLC)- produces second messengers liek IP3 and DAG * Ion channels- regulate ion flow across the membrane

Question 30

how is GPCR signalling terminated?

Answer 30

* the alpha subunit has intrinsic GTPase activity that hydrolyses GTP back to GDP, inactivating the G-protein * the alpha subunit re-associates with the Beta-gamma dimer, returning the system to its resting state.

Question 31

what cellular responses can GPCR activation lead to?

Answer 31

* muscle contraction * enzyme activation * gene expression

Question 32

what are enzyme linked receptors?

Answer 32

receptors for growth factors that are most often kinase-linked they are transmembrane proteins with an extracellular ligand-binding doman and an intracellular enzymatic (kinase) domain.

Question 33

what happens in the resting state of enzyme-linked receptors?

Answer 33

the receptor remains inactive, spanning the membrane with separate extracellular and intracellular domains

Question 34

how are enzyme-linked receptors activated?

Answer 34

a signalling molecule (e.g. growth factors like EGF or insulin) binds to the extracellular domain

Question 35

what happens after ligand binding in enzyme linked receptors?

Answer 35

the receptor's kindase activity is triggered, leading to activation

Question 36

what is autophosphorylation in enzyme linked receptors?

Answer 36

the receptor phosphorylates specific tyrosine residues on its intracellular domain, creating docking sites for downstram signalling proteins

Question 37

how does signal transduction occur after receptor activation in enzyme linked receptors?

Answer 37

proteins bind to the phosphorylated tyrosines and activate intracellular signalling pathways

Question 38

how is enzyme-linked receptor signalling terminated?

Answer 38

* dephosphorylation of the receptor or downstream molecules by phosphatases * endocytosis of the receptor-ligand complex may also terminate signalling.

Question 39

where are cytosolic and nuclear receptors located?

Answer 39

* in the cytoplasm or nucleus in their inactive form * unlike other receptors they are not found on the cell surface

Question 40

what keeps these cytosolic receptors inactive in their resting state?

Answer 40

they are often bound to inhibitory proteins (e.g. heat shock proteins- HSPs) which prevent activation

Question 41

how are cytosolic and nuclear receptors activated?

Answer 41

a lipophilic ligand (e.g. steroids like testosterone or oestrogen) crosses the cell membrane and binds to the receptor

Question 42

what happens after ligand binding in cytosolic receptors?

Answer 42

the receptor undergoes a conformational change leading to: * release of inhibitory proteins (HSPs) * exposure of a DNA-binding domain and a nuclear localisation signal (if the receptor is cytoplasmic)

Question 43

how do cytosolic receptors reach the nucleus?

Answer 43

* after ligand binding, cytosolic receptors translocate to the nucleus * nuclear receptors are already inside the nucleus and do not need to move.

Question 44

how do cytosolic nuclear receptors regulate gene transcription?

Answer 44

* the receptor-ligand complex binds to specific DNA sequences called hormone response elements (HREs) in the promoter regions of target genenes * this recruits coactivators or corepressors to regulate gene transcription.

Question 45

how is cytosolic/nuclear receptor signalling terminated?

Answer 45

* the response ends when the ligand dissociates. * the receptor may be degraded or recycled to stop the signal. * post-translational modifications (e.g. phosphorylation) can also regulate receptor activity.

Question 46

what is the type 1 nuclear receptor also known as?

Answer 46

a cytoplasmic receptor

Question 47

what is an enzyme inhibitor?

Answer 47

a molecule that binds to an enzyme and (normally) decreases its activity. it prevents the substrate from entering the enzyme's active site and prevents it from catalysing its reaction.

Question 48

what are the two types of enzyme inhibitors?

Answer 48

reversible inhibtors and irreversible inhibitors

Question 49

what are reversible enzyme inhibitors?

Answer 49

they bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme, the enzyme-substrate complex, or both.

Question 50

what are irreversible enzyme inhibitors?

Answer 50

usually react with the enzyme and change it chemically (e.g. via covalent bond formation)

Question 51

give an example of irreversible enzyme inhibitors

Answer 51

* organophosphates- irreversible inhibitors of acetylcholinesterase * insecticides and nerve gases * they cause 200,000 deaths worldwide per year * muscarinic- salivation, defaecation, urination, bradycardia, hypotension * nicotinic- twitching, severe weakness paralysis, diaphragm * CNS- confusion, loss of reflexes, convulsions, coma.