pharmacodynamics

Question 1

what are the 3 different types of naming for drugs?

Answer 1

chemical
generic
trade

Question 2

drugs can be…

Answer 2

naturally occurring or synthetic

Question 3

how do drugs work generally?

Answer 3

mimic or block the action of our own signalling molecules

Question 4

what are the targets of drug action?

Answer 4

proteins - enzymes, transporters, ion channels and receptors
DNA

Question 5

what are the receptor families?

Answer 5

ligand-gated ion channels
G protein coupled receptors (metabotropic)
kinase-linked receptors
nuclear receptors

Question 6

how do kinase linked receptors work?

Answer 6

receptor > protein phosphorylation > gene transcription > protein synthesis > cellular effects

Question 7

how do nuclear receptors work?

Answer 7

receptor in nucleus > binds to receptor > gene transcription > protein synthesis > cellular effects

Question 8

specificity

Answer 8

drugs bind selectively to particular receptor types

no drug is 100% specific, only selective and bind to one receptor preferentially over another

Question 9

What do agonist drugs do?

Answer 9

activate receptors

Question 10

what do antagonist drugs do?

Answer 10

block receptors, often inhibit endogenous agonist action

Question 11

how do agonist drugs work?

Answer 11

2 phases

Question 12

what are the phases of agonist drugs

Answer 12

1. drug binding/ affinity

2. receptor activation/ efficacy

Question 13

Drug binding/ affinity

Answer 13

agonist/ drug binds to receptor forming a drug- receptor complex

Question 14

receptor activation/ efficacy

Answer 14

activated D-R complex causes the biological effect

e.g. opens channel

Question 15

what are the different agonist types?

Answer 15

full
partial
super
inverse

Question 16

full agonists

Answer 16

cause 100% effect of the endogenous agonist

Question 17

partial agonists

Answer 17

cause less than 100% of endogenous effect

Question 18

super agonists

Answer 18

rarer

cause more than 100% of the endogenous effect

Question 19

inverse agonists

Answer 19

reduce the basal receptor activity, by causing them to be inactive and so they cannot elicit a response

Question 20

drug effect

Answer 20

is proportional to drug concentration

both agonists and antagonists elicit effects

Question 21

agonist drug potency

Answer 21

involves affinity and efficacy

Question 22

What is EC50

Answer 22

the concentration required to bring about a 50% response

Question 23

potency curve

Answer 23

further to the left on a % effect vs log[drug] conc. = more potent

Question 24

what is the target for botox?

Answer 24

glycoprotein, at presynaptic vesicle release of ACh

Question 25

how does Galpha q work?

Answer 25

activates Phospolipase C which produces DAG and IP3, activates Calcium release and Protein kinase C > vasoconstriction and smooth muscle contraction

Question 26

how do antagonist drugs work?

Answer 26

bind to receptor and form drug-receptor complex which makes the receptor inactive and prevents endogenous agonist binding causing the biological effect

Question 27

antagonist potency

Answer 27

only involves affinity not efficacy, as it blocks the receptor

Question 28

different types of antagonist

Answer 28

reversible/ irreversible competitive non-competitive uncompetitive

Question 29

are competitive antagonists reversible or irreversible?

Answer 29

reversible

Question 30

what are uncompetitive antagonists?

Answer 30

requires agonist binding before it can bind to allosteric site of receptor/ enzyme. It then lessens the effect elicited by the substrate

Question 31

what are the non-receptor antagonists?

Answer 31

chemical antagonists physiological antagonists pharmacokinetic - influence the 4 processes

Question 32

what are chemical antagonists?

Answer 32

reduce concentration of agonist by binding

Question 33

occupancy and response

Answer 33

often not all receptors need to be occupied for maximum effect to be achieved - spare/ reserve receptors. Therefore a partial agonist may be sufficient over a full one

Question 34

tolerance

Answer 34

decrease in a drug's effectiveness over days/ weeks

Question 35

resistance

Answer 35

adaptive changes making a drug less effective

Question 36

what causes changes in drug effectiveness?

Answer 36

desensitisation tolerance resistance

Question 37

how does resistance occur?

Answer 37

``` change in receptors loss of receptors loss of mediators enhanced drug metabolism increased removal from site of action§ ```

Question 38

pharmacogenomics

Answer 38

genetic variability in the way drugs behave in the body PK = enzyme polymorphism PD = receptor variants

Question 39

what factors are used to guid drug administration?

Answer 39

drug factors and patient factors

Question 40

what patient factors affect drug administration?

Answer 40

age weight gender disease

Question 41

what drug factors affect drug administration?

Answer 41

pharmacokinetic and pharmacodynamics

Question 42

inpredictability

Answer 42

there is always unpredictability in PK and PD responses even if adjustments are made

Question 43

why might the outcome of drugs not be easily measured?

Answer 43

long delay in seeing result | multi-factorial condition

Question 44

Kd

Answer 44

relationship between the ability of a drug to bind and to dissociate concentration required to occupy 50% of receptors

Question 45

when does EC50 = Kd

Answer 45

when all the receptors need binding to cause maximal response

Question 46

when there are spare receptors

Answer 46

the EC50 is much less than the Kd, provides degree of tolerance to things going wrong

Question 47

what happens when a competitive inhibitor and an agonist are used where there are spare receptors

Answer 47

more receptors need to be bound to elicit the 50% response but it can be done . Shifts EC50 to right

Question 48

what happens when a irreversible inhibitor and an agonist are used where there are spare receptors

Answer 48

shift in EC50 to right and loss of maximal response as receptor reserve is lost and receptors are no longer available so complex formation is reduced.