Pharmacodynamics

Question 1

PK vs PD

Answer 1

PK - absorption, bioavailability, distribution, metabolism, excretion
PD - what does the drug do to the body - drug concentration and the target

Question 2

Drug targets

Answer 2

ion channels, enzymes, transporters, receptors

Question 3

Neurotransmission

Answer 3

action potential -> electrochemical message -> ion channels open -> release neurotransmitter -> next cell may be activated

Question 4

Serotonin drug targets

Answer 4

inhibit enzymes that convert tryptophan to 5HT
inhibit ion channels = no neurotransmission
inhibit transporters - SERT reuptake more 5HT in synapse or tryptophan transporter no synthesis of 5HT
inhibit vesicle = messy and uncontrolled serotonin release

Question 5

LGICs

Answer 5

Integral membrane proteins with pore to allow flow of select ions. Neurotransmisser gates the pore, binding = conformational change

Question 6

5-HT3

Answer 6

5 subunits around pore -> K+, Ca2+, Na+

Large EC domains for binding (one in each subunit)

Question 7

5-HT1b

Answer 7

GPCR, binding in TM domains

Question 8

G protein families

Answer 8

i = ion channels, inhibit cAMP, phospholipase
s = induce cAMP
q = decrease DAG and IP3
12 = Rho/Roc

Question 9

Gi presynapse

Answer 9

inhibit calcium channels via beta-gamma subunit = no release of 5-HT (negative feedback loop). alpha -> adenylate cyclase and cAMP

Question 10

Receptors

Answer 10

recognition molecules often found on the cell surface that detect a chemical message

Question 11

occupancy

Answer 11

affinity at a concentration of ligand

Question 12

activation

Answer 12

efficacy

Question 13

why use log scale

Answer 13

better visualisation, can see up to 100 fold concentration change
also easier to find EC50

Question 14

EC50

Answer 14

concentration of drug producing 50% of the maximum effect

Question 15

efficacy vs potency

Answer 15

efficacy determines if something might be useful clinically but potency determines if its useful enough

Question 16

potency vs affinity

Answer 16

full agonist can have a 100% response even if not all receptors are occupied

Question 17

GPCR life cycle

Answer 17

phosphorylated -> b arresting -> can’t signal -> recruit AP2 -> internalisation
recycling or degraded
may cause drug tolerance or regulate receptor expression

Question 18

intercellular GPCR signalling

Answer 18

in the vesicles
may target using conformation bias
eg kinase pathways

Question 19

ion channel life cycle

Answer 19

closed and desensitised and internalised

Question 20

competitive reversible antagonist

Answer 20

binds to same site as agonist, preventing binging
affinity but no efficacy
surmountable - agonist can overcome
eg naloxone, haloperidol, clozapine

Question 21

partial agonist

Answer 21

doesn’t reach 100% response
may be used as an antagonist - lower concentration has some effect but higher concentration of ligand = competing
eg treat opioid addiction

Question 22

irreversible competitive antagonist

Answer 22

covalent bond = permanent
orthosteric site
takes high dose due to receptor reserve

Question 23

inverse agonist

Answer 23

remove constitutive/basal activity
affinity and negative efficacy
may cause toxicity
mutated receptor = more likely to be turned on in absence of agonist
(antagonists may actually be inverse agonists)

Question 24

allosteric modulator

Answer 24

different binding site than ligand
no response on its own
PAMs and NAMs

Question 25

allosteric modulator pros

Answer 25

ceiling effect = once occupied doesn't do anything more with an increase in conc more selective = more diverse maintain temporal signalling = enhance normal signalling pathways

Question 26

probe dependance

Answer 26

depends on ligand/agonist present and the conformation doesn't get the associated toxicity receptor responds differently depending on which ligand is bound as well as the PAM/NAM

Question 27

orthosteric-allosteric ligands

Answer 27

two binding sites for one ligand | eg cinacalcet