Pharmacodynamics

Question 1

Efficacy

Answer 1

Ability of drug to drive a reactions response to full effect. Measured by Emax.

Question 2

Potency

Answer 2

EC50 - concentration of drug required to produce a response

Question 3

Affinity

Answer 3

Kd - strength of drug binding to receptor (action is longer plus higher chance of binding)

Question 4

Orthosteric site

Answer 4

Where agonist binds

Question 5

Endogenous ligand

Answer 5

what the ligand normally binds to

Question 6

Agonist

Answer 6

has affinity and efficacy. Drug binds to receptor and produces a response (like endogenous ligand)

Question 7

Partial agonist

Answer 7

binds (has affinity) but doesn’t fully activate to maximal efficacy, even at 100% occupancy (acts as antagonist)

Question 8

Full agonist

Answer 8

Will produce full effect (at lower capacity)

Question 9

Receptor reserve

Answer 9

irreversible antagonist act as a reversible due to not 100% binding having 100% efficacy

Question 10

Inverse agonist

Answer 10

has negative efficacy, reduces basal activity “turns receptor off”

Question 11

Constitutive activity

Answer 11

basal activity

Question 12

Antagonist

Answer 12

binds to ligand but has no effect (efficacy)

Question 13

Competitive orthosteric antagonist

Answer 13

binds reversible to orthosteric site but has no efficacy

Question 14

Irreversible antagonist

Answer 14

reduces the maximal response of agonist by covalent bonds

Question 15

Allosteric modulator

Answer 15

binds to a different place on receptor to the endogenous ligand and modifies response to orthosteric ligand (affinity or efficacy)

Question 16

Allosteric vs orthosteric

Answer 16

selective, natural signalling pattern, no ceiling effect

Question 17

Surmountable

Answer 17

action of agonist can be restored

Question 18

Two state model

Answer 18

RR, agonist (towards R), inverse (towards R), antagonist (no change)

Question 19

Therapeutic index

Answer 19

lethal dose 50/ED50

Question 20

cAMP

Answer 20

PKA, ATP->ADP, Ca2+, fat and glycogen metabolism, release energy, lipolysis, decrease synthesis

Question 21

G protein receptor kinase (GPRK) -> phosphorylation

Answer 21

= desensitisation, Arestin - binds to c terminal, blocks binding lead to invagination = tolerance

Question 22

Nerve terminal drug targets (10)

Answer 22

Precursor transporter, neurotransmitter formation enzyme, vesicle storage, Na+ (action potential) ion channel, Ca2+ ion channel, vesicular fusion (enzymes), post synaptic receptor, pre synaptic receptor, off signal enzyme, neurotransmitter uptake transporter

Question 23

Ion channel

Answer 23

protein creates pore across cell membrane. Can be blocked or modulated.

Question 24

Ligand gated ion channel

Answer 24

receptor/protein that drug binds to. Receptor pore increases permeability.

Question 25

Voltage gated ion channel

Answer 25

response to change in membrane potential

Question 26

Carrier molecules/transporters

Answer 26

move ions/molecules across membranes. Can be normal transport, inhibited, false substrate.

Question 27

Enzymes

Answer 27

biological catalysts. inhibitor, false substrate or prodrug. (non-competitive/competitive)

Question 28

GPCR

Answer 28

G protein coupled receptors. (guanine nucleotide binding protein). 7 transmembrane domains, single polypeptide. intracellular c terminal. alpha, beta and gamma. binding -> GTP (alpha) -> dissociates

Question 29

Family A GPCR

Answer 29

ligand binds in transmembrane bundle (small molecule/peptide)

Question 30

Family B GPCR

Answer 30

binding in exterior N terminal (peptide hormones)

Question 31

Family C GPCR

Answer 31

large N terminals, folding pocket

Question 32

Adhesion family GPCR

Answer 32

chops off N terminal and binds ligand

Question 33

Frizzled family GPCR

Answer 33

extracellular N terminal, intracellular C terminal

Question 34

Gs

Answer 34

activates adenylate cyclase, increase cAMP

Question 35

Gi

Answer 35

inhibits adenylate cyclase, decreases cAMP

Question 36

Gq

Answer 36

activates PLC -> PIP2 -> DAG (->PKC) and IP3 (->Ca2+)

Question 37

Kinase linked/cytokine receptor

Answer 37

extracellular domain, intracellular transmembrane domain, tyrosine kinase domain. dimerisation -> autophosphorylation -> phosphorylate SH2 domains -> signalling cascade (growth hormones, cytokines, hormones)

Question 38

Kinase linked categories

Answer 38

tyrosine kinase, serine/threonine, cytokine

Question 39

Nuclear/steroid hormone receptor

Answer 39

N terminal, AF1, DNA BD, HR, LBD, C terminal, AF2. regulate CYP.

Question 40

Type one nuclear receptor

Answer 40

Steroid nuclear receptor. cytoplasm, homodimers, endocrine. Binding -> conformation change -> nucleus.

Question 41

Type two nuclear receptor

Answer 41

metabolite receptor. nucleus, heterodimers, lipids. nucleus -> binding ->conformation -> gene transcription

Question 42

Allosteric binding example

Answer 42

Benzodiazepine binding to GABAa to increase efficacy (Cl transport)

Question 43

Antagonists example

Answer 43

Propranolol (beta blocker), antihistamine

Question 44

Irreversible antagonist example

Answer 44

Novichok (Poison) - irreversible AChE inhibitor, parasympathetic then sympathetic

Question 45

Partial agonist example

Answer 45

Buprenorphine, replacement therapy for opioids

Question 46

Na+ channel inhibitor example

Answer 46

Lignocaine = local anaesthetic

Question 47

Nicotinic ion channel antagonist

Answer 47

Nicotine, pancuronium - muscle relaxant

Question 48

Prodrug

Answer 48

L-dopa - prodrug for dopamine = alzheimers (+carbidopa to inhibit metabolism in body)

Question 49

False substrate example

Answer 49

Methyl dopa - creates methyl noradrenaline a2 agonist

Question 50

Inhibits p-gp (p-glycoprotein)

Answer 50

Verapamil = increase bioavailability of drug/xenobiotics

Question 51

activates insulin receptor orthosteric site as Kinase linked receptor drug

Answer 51

Insulin

Question 52

RTK inhibition of multiple kinase linked receptors

Answer 52

Lapatinib

Question 53

Class one nuclear receptor drugs

Answer 53

Cortisol (glucocorticoid receptor), estrogen

Question 54

Class two nuclear receptor drugs

Answer 54

PPAR, cholesterol