lecture 3

Question 1

define drug

Answer 1

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

Question 2

4 types of protein drug target sites

Answer 2

receptors, ion channels, transport systems, enzymes

Question 3

receptor location

Answer 3

normally within membrane (steroid is IC)

Question 4

normal receptor activation

Answer 4

neurotransmitter or hormone

Question 5

how many types of receptor

Answer 5

4

Question 6

what are receptors defined by

Answer 6

seeing how they respond to agonists and antagonists

Question 7

example of receptor agonist

Answer 7

acetylcholine

Question 8

example of receptor antagonist

Answer 8

atropine (antagonist of muscarinic acetylcholine receptors)

Question 9

2 types of ion channels with examples

Answer 9

voltage-sensitive (VSCC - Ca2+ channel), receptor-linked (nAChR - nicotinic acetylcholine receptor)

Question 10

feature of ion channel and examples of drugs

Answer 10

selective pores in membranes to allow ions to diffuse down electrochemical gradient; LAs (local anaethetics preventing Na+ into cell to prevent action potentials), calcium channel blockers (all end in -pine)

Question 11

feature and examples of transport systems

Answer 11

transport specific substances against concentration gradient, e.g. Na+/K+-ATPase, noradrenaline “uptake 1” (presynsaptic nerve terminals)

Question 12

examples of transport system drugs

Answer 12

tricyclic anti-depressants (TCAs): lipid soluble so diffuse through BBB, binding to UT1 so NA spends more time in synaptic cleft -> CNS euphoric effects (analagous effect on 5HT serotonin receptors), cardiac glycosides (increase in IC Ca2+ by interfering with Na+/K+-ATPase pump to treat cardiac failure by increasing contractility)

Question 13

3 drug interactions of enzymes

Answer 13

inhibitors (e.g. anticholinesterases like neostigmine), false substrates (e.g. methyldopa - false substrate for DOPA in biosynthesis of NA, producing false transmitter methylNA, which has less effect on a1 adrenoceptors), prodrugs (e.g. chloral hydrate to treat insomnia converted to trichloroethanol in liver to be effective); can mediate unwanted effects such as toxicity e.g. paracetamol - oversaturates normal metabolism enzymes so metabolised by others which cause unwanted effects; can give drugs to boost glutathione system to mop up toxic by-products to prevent kidney damage

Question 14

non-specific drug action: physiochemical properties

Answer 14

antacids (adds base to acid environment to reduce symptoms of dyspepsia), osmotic purgatives (orally to draw water into gut and soften stools); plasma protein binding (reservoir of inactive drug by binding to drug - not drug target site so pharmacokinetics as doesn’t mediate response)

Question 15

what does drug potency depend on

Answer 15

affinity (strength of binding - avidity of drug to receptor), efficacy (instrinsic activity causing conformational change of receptor)

Question 16

types of agonist

Answer 16

selective - when increase in dose some overlap with other targets: full (produce maximal response) or partial (less than maximal response; agonists, but in presence of full agonst has degree of antagonist activity)

Question 17

agonist vs antagonist

Answer 17

ligands which are stimulatory vs ligands which have no effect or block

Question 18

structure-activity relationship

Answer 18

small changes in structure can change activity: lock and key; agonists can generate antagonists; changes pharmacokinetics (e.g. duration of action)

Question 19

pathway from agonist and receptor to response

Answer 19

agonist bind to receptor, forming complex; binds to transducer (e.g. binding to enzyme or opening up ion channel) to form agonist/receptor/transducer complex

Question 20

what is affinity in pathway

Answer 20

affinity of agonist to receptor using intermolecular forces

Question 21

what is intrinsic efficacy in pathway

Answer 21

affinity of agonist/receptor complex to transducer

Question 22

dose-response curve: full agonist vs partial agonist

Answer 22

rectangular hyperobola but partial agonist have lower maximum (so reduced efficacy)

Question 23

log dose-response curve: full agonist vs full agonist with lower affinity vs partial agonist

Answer 23

sigmoid curves; full agonist further left than full agonist with lower affinity (both have same maximum and gradient); partial agonist furthest right with lower maximum, and shallower gradient

Question 24

key property of antagonists

Answer 24

has affinity but no efficacy

Question 25

2 types of receptor antagonist

Answer 25

competitive and irreversible

Question 26

features of competitive receptor antagonist

Answer 26

bind to same site as agonist so are surmountable (increase [agonist], can overcome antagonist effect), shifts dose-response curve right (same maximum and gradient)

Question 27

examples of competitive receptor antagonist

Answer 27

atropine, propranolol (wide therapeutic antagonst on B1 and B2 adrenoceptors - non-selective B-blocker e.g. migraines, heart problems)

Question 28

features of irreversible receptor antagonists

Answer 28

binds tightly or at different site so are insurmountable; further right than agonist or competitive antagonist, with smaller maximum and shallower gradient; longer duration of action

Question 29

example of irreversible receptor antagonists

Answer 29

hexamethonium (blocks nicotinic acetylcholine receptor ion channel)

Question 30

pharmacokinetics

Answer 30

effect of body on drug (absorption, excretion, metabolism)

Question 31

pharmacodynamics

Answer 31

effect of drug on body (mechanisms of action)