Drug action

Question 1

what is a drug?

Answer 1

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

Question 2

what are the four drug target sites?

Answer 2

1) receptors
2) ion channels
3) transport systems
4) enzymes

Question 3

how are receptors defined?

Answer 3

usually within the cell membrane
by there agonist and antagonist actions

activated by NT or hormones

Question 4

examples of an agonist and antagonist

Answer 4

agonist- ACh

antagonist- Atropine

Question 5

what are the two types of ion channels?

Answer 5

voltage sensitive/gated channels e.g. VGCC

receptor linked e.g. nAChR

Question 6

examples of drugs that target ion channels?

Answer 6

Local anaesthetics (sodium channels) 
calcium channel blockers

Question 7

examples of transport systems that can be targeted

Answer 7

Na+/K+ ATPase (by cardiac glycosides e.g. digoxin)

NA re-uptake (e.g TCAs) monoamines in general

Question 8

examples of drugs that target transport systems

Answer 8

tricyclic anti-depressants (TCAs)

cardiac glycosides e.g digoxin

Question 9

what are the types of drug interactions with enzymes?

Answer 9

enzyme inhibitors e.g. anticholinesterases

false substrates e.g. methyldopa

prodrugs e.g. choral hydrate–> trichloroethanol

Question 10

give an example of a drug with non-specific action

Answer 10

drugs that aren’t specific to receptors like paracetamol can have unwanted effects

Question 11

what is the danger with some non specific drugs?

Answer 11

they bind tightly to plasma proteins and therefore create a dangerous untapped reservoir of the drug e.g. warfarin

Question 12

examples of non specific drugs

Answer 12

antacids

osmotic purgatives

Question 13

what is an agonist drug?

Answer 13

it is stimulatory and has an effect

Question 14

what is an antagonist drug?

Answer 14

it mimics and blocks but does not have an effect

Question 15

the 2 types of agonist drugs

Answer 15

full agonists

partial agonists- do not produce the full response and can therefore have some antagonist activity

Question 16

what does potency of a drug depend on?

Answer 16

potency- amount of drug needed to produce a given effect

affinity- strength of the binding between drug and receptor
efficacy- the biological effect of the drug in that it causes a conformational change in the receptor

Question 17

why is selectivity not specificity?

Answer 17

drugs may not be specific to the same receptors at a higher concentration

Question 18

what are the 2 types of antagonist?

Answer 18

competitive

irreversible

Question 19

what are competitive antagonists?

Answer 19

they bind to the same site as the agonists co-administered
they are surmountable
they shift the D-R curve to the right

e. g. atropine
e. g. propranolol

Question 20

what are irreversible antagonists?

Answer 20

the bind tightly to the active site or they bind elsewhere
they are insurmountable
e.g. hexamethonium

Question 21

what are the 4 types of antagonism?

Answer 21

• receptor blockade
• physiological
• chemical
• pharmokinetic (drug met by enzymes)

Question 22

what is the receptor blockade and what activity does it show?

Answer 22

competitive and irreversible antagonist action

displays user-dependency

e.g. local anaesthetics

Question 23

what is user-dependency?

Answer 23

the more active/often used tissue is, the faster the block is absorbed and becomes effective as there is a higher chance of it entering

e.g. LAs

Question 24

what is physiological antagonism?

Answer 24

drugs that bind to two or more different receptors to counter the effects of another substance producing different effects on the same tissue

e.g. histamine (dilator) and NA (constrictor) on blood pressure

Question 25

what is chemical antagonism ?

Answer 25

interaction in solution to negate the effects of another substance not bound to receptors e.g. the use of dimercaprol in heavy metal poisoning to clump them together into non-toxic lumps for excretion chelating agents anti-venom

Question 26

what is pharmacokinetic antagonism ?

Answer 26

the clinically important form where the antagonist decreases the concentration of the active drug at the site of action the body itself antagonises the agonists administered e.g. barbiturates and their effects of reduced absorption , increased metabolism and increased excretion

Question 27

what are the 5 types of drug tolerance?

Answer 27

- pharmacokinetic factors - loss of receptors - change in receptors - exhaustion of mediator stores - physiological adaption

Question 28

what are the pharmacokinetic factors leading to drug tolerance?

Answer 28

due to increase rate of metabolism unregulated enzymes so metabolism is quicker e.g. barbiturates and alcohol

Question 29

what are the reasons for a loss of receptors leading to drug tolerance ?

Answer 29

this is due to membrane endocytosis of receptors (down regulation) there can also be upregulation (e.g. denervation super sensitivity) e.g. beta adrenoreceptors

Question 30

what sort of change can occur in receptors leading to drug tolerance?

Answer 30

conformational change in receptors (may reduce affinity) e.g. nAChR at the NMJ

Question 31

what drug causes an exhaustion of mediator stores lead to drug tolerance?

Answer 31

e.g. amphetamine where the stores of NA that are usually released become exhausted

Question 32

what is physiological adaption ?

Answer 32

the body adapts physiologically to the administration of drugs over time e.g. a drug causes BP to fall can cause RAS to activate in response to raise BP

Question 33

what is drug tolerance?

Answer 33

the gradual decrease in responsiveness to repeated administration

Question 34

what are the four receptor families and what are they based on?

Answer 34

type 1- ion channel linked R type 2- GP linked R type 3- kinase linked R these are all embedded in membrane type 4- intracellular steroid type R based on molecular structure and/or the signal transduction system

Question 35

type 1 receptors (ICLR)

Answer 35

e.g. nAChR, GABAa 4 or 5 binding domains in the subunit acts in milliseconds

Question 36

type 2 receptors (GPLR)

Answer 36

e.g. beta-1-adrenoreceptors (cardiac), mAChR most receptors of the body are this type 7-TM structure acts in seconds

Question 37

type 3 receptors (KLR)

Answer 37

e.g. insulin type growth factor receptor only one alpha helix subunit acts in minutes

Question 38

type 4 receptor (ISTR)

Answer 38

e.g. oestrogen receptor, thryoid located intracellularly unlike the other 3 types no alpha helix subunit uses zinc fingers affects DNA transcription acts in hours

Question 39

what is the difference between an agonist and antagonist?

Answer 39

both have high affinities but antagonists have no efficacy i.e. no biological effect

Question 40

what is the role of excipients?

Answer 40

added to drug formulations to improve - chemical and biological stability - increased acceptability: improved appearance, flavour, fragrance

Question 41

what are some formulations for drugs?

Answer 41

- aerosols - capsule - cream - liquid - syrup - powder - soluble tablet some use the same administrative route e.g. capsule and syrup use oral route