drug mechanisms and receptor interactions

Question 1

what is tolerance?

Answer 1

• measured effect of repeated administration

Question 2

state the 4 main target sites for drugs

Answer 2

• receptors
• ion channels
• transport systems
• enzymes

Question 3

describe receptors

Answer 3

• proteins within cell membranes
• activated by NT or hormones
• agonist or antagonist actions
• 4 types of receptors: 1,2,3,4

Question 4

give an example of an agonist and an antagonist

Answer 4

agonist - ACh

antagonist - Atropine

Question 5

describe ion channels

Answer 5

• selective pores

- allow transport down electrochemical gradient

Question 6

what are the 2 types of ion channels?

Answer 6

• voltage-gated e.g. VGCC

- receptor linked e.g. nAChR

Question 7

describe transport systems

Answer 7

• transport against the concentration gradient

- specificity for certain species

Question 8

give examples of transport systems and drugs

Answer 8

e.g. Na/K-ATPase, Na Uptake 1

Examples of drugs: TCAs, cardiac glycosides

Question 9

describe enzymes

Answer 9

catalytic proteins that inc. rate of reaction

Question 10

name the 3 drug interactions

Answer 10

• enzymes inhibitors (anticholinesterases)
• false substrates (methyldopa)
• prodrugs (choral hydrate –> trichloroethanol)

Question 11

give an example of an enzyme drug that can have unwanted effect

Answer 11

• paracetamol
• system becomes satured
• switches to a new enzyme to break down drug
• creates toxic-by products

Question 12

why can warfarin be dangerous?

Answer 12

it is a drug that binds very strongly to plasma proteins and so can provide a dangerous and untapped reservoir of the drug

Question 13

what is the MoA of ant acids?

Answer 13

simple addition of a base to acidic environment which evens acid-base balance

Question 14

describe the MoA of osmotic purgatives (laxatives)

Answer 14

draws water into gut to dec. viscosity

Question 15

how can drugs be described

Answer 15

• agonists/ stimulatory
• antagonists/ mimic and block
• full or partial agonistic effects

Question 16

what does the potency of a drug depend on?

Answer 16

• affinity

- efficacy

Question 17

what is affinity?

Answer 17

strength of binding of the drug to the receptor

Question 18

what is efficacy?

Answer 18

biological effect of drug

Question 19

what are antagonists?

Answer 19

have affinity but no efficacy

Question 20

what are the 2 types of receptor antagonism?

Answer 20

• competitive

- irreversible/non-competitive

Question 21

describe competitive antagonists

Answer 21

e.g. Atropine
same site as agonist
surmountable
shifts dose-response relationship to R

Question 22

describe non-competitive antagnonists

Answer 22

e.g. Hexamethonium
- bind to active site irreversibly
- changes conformation
insurmountable

Question 23

what are the 4 types of drug antagonism

Answer 23

• receptor blockade
• physiological antagonism
• chemical antagonism
• pharmacokinetic antagonism

Question 24

describe receptor blockade

Answer 24

• competitive and irreversile

- display use dependency

Question 25

what is use dependency?

Answer 25

more the cell is active, the faster the block is absorbed and blocks the ion channels

Question 26

describe physiological antagonism

Answer 26

drug that counters the effect of another substance by acting on different receptors

Question 27

give an example of physiological antagonism

Answer 27

if the body has too much NA so too much vasoconstriction, histamine can be delivered to counter vasoconstriction
act on H1 receptors instead of adrenergic receptors

Question 28

describe chemical antagonism

Answer 28

drugs that interact in solution to antagonise a reaction

Question 29

give an example of chemical antagonism

Answer 29

if people have heavy metal poisoning, you give dimercaprol to bind the heavy metal and form non-toxic clumps which can be excreted

Question 30

describe pharmacokinetic antagonism

Answer 30

drugs that are administered, are antagonised by body itself that reduces the conc

• reduced absorption
• blocked distribution
• inc. metabolism
• inc. excretion

Question 31

what are the 5 reasons for drug tolerance?

Answer 31

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

Question 32

describe pharmacokinetic factors

Answer 32

due to inc. rate of metabolism e.g. alcohol

Question 33

describe loss of receptors

Answer 33

due to membrane endocytosis of receptors e.g. beta adrenoreceptors

Question 34

describe change in receptors

Answer 34

• conformational change in receptors
• may reduce affinity
• e.g. beta adrenoreceptors

Question 35

describe the exhaustion of mediator stores

Answer 35

physiological mediators become exhausted e.g. amphetamine - stores of NA that are usually released become exhausted

Question 36

describe physiological adaption

Answer 36

body physiologically adapts to administration of drug over time

Question 37

what are the 4 different receptor families?

Answer 37

1. ion-channel linked receptors (5 binding domains in subunit, milliseconds)
2. GPCR (7-TM structure, seconds)
3. Kinase-linked receptor (only one subunit (alpha helix), minutes)
4. intracellulae steroid type receptor (intracellular, zinc fingers, houes)