Pharmacodynamics

Question 1

what determines drug half-life?

Answer 1

Vd and clearance of drug

Question 2

how do you determine the halflife? (what is the equation?)

Answer 2

T1/2= (0.7*Vd/Cl)

Question 3

what is accumulation factor?

Answer 3

when drug is given repeatedly and cumulate to reach a steady state level, must be considered in calculating loading and maintenance dose

Question 4

when is 95% of drug cleared?

Answer 4

4.3 half-lives

Question 5

why is it important to consider potency when dosing a drug?

Answer 5

high potency drugs (ACE inhibitors) will will have a very high effect in the body even after multiple half lives, when dosing you need to know that happens to the effect as the half lives pass (think if the ACE example, 87.5% of drug was gone but it still had 75% effect)

Question 6

how does half life length impact pharmacodynamic effect?

Answer 6

it doesn’t. they are separate principals

Question 7

what is an acute effect on drug action?

Answer 7

drug effect occurs within minutes to hours (effect is proportional to concentration)

Question 8

what is important to consider with delayed effect drugs?

Answer 8

effect takes days or weeks

Question 9

what might cause a delay in drug action?

Answer 9

delay in distribution, turnover of the enzyme/receptors or accumulation factor needed to reach steady state

Question 10

what are cumulative effects?

Answer 10

irreversible effects that produce higher drug peak and saturate uptake mechanism (example chemo drugs on DNA biding results in cytotoxic effect)

Question 11

how does tolerance shift the effect curve?

Answer 11

to the right (sensitivity shifts to the left)

Question 12

what are steady stat plasma concentrations used for?

Answer 12

calculating loading and maintenance doses

Question 13

what is the therapeutic window?

Answer 13

plasma concertation between MEC desired and adverse

Question 14

is the pharmacodynamic effect lost after concentration falls below MEC desired?

Answer 14

not necessarily but it is no longer in the therapeutic window

Question 15

how do you calculate the loading dose?

Answer 15

Vd*TC/bioavailability

(tc is target concentration)

Question 16

what kind of drugs can you give once a day therapeutic window wise?

Answer 16

large therapeutic window

Question 17

what is different about the plasma concentration graph for IV vs oral?

Answer 17

both average to the same but oral has high peaks and low troughs and IV is constant (if you did 3x a day dose might be better but you have to be realistic about what a pt will actually maintain which is why most are one a day when can be)

Question 18

how do you calculate the dosing rate?

Answer 18

CL*TC/bioavailability

Question 19

what is an agonist drug?

Answer 19

a chemical that upon binding triggers a response
(endogenous example: hormone, neurotransmitter, cytokines)
(drug ex LDOPA, morphine)

Question 20

what type of effect is seen by signaling?

Answer 20

short or long term

Question 21

what is the speed of extracellular signaling?

Answer 21

faster than ones that go into the nucleus to do protein syn

Question 22

what does receptor occupancy indicate?

Answer 22

magnitude of the effect depends of affinity and intrinsic activity of the drug

Question 23

what must occur for the effect size to increase?

Answer 23

the numbers of receptors bound with drug must increase or the intrinsic activity must increase

Question 24

what kind of drugs are full or strong agonists?

Answer 24

those with high biding affinity

Question 25

what is EC50?

Answer 25

need 50% of concentration to get 50% effect

Question 26

what is Kd?

Answer 26

where 50% of the binding sites are occupied by the drug

Question 27

what effect does high Kd have on affinity?

Answer 27

low affinity (low Kd=high affinity)

Question 28

a drug at E max is a _____

Answer 28

full agonist

Question 29

what do graded response curves show?

Answer 29

differences in potency and efficacy of different drugs

Question 30

what does a shift to the left on a graded response curve indicate?

Answer 30

higher potency (Kd is less)

Question 31

on the graded response curve what shows the efficacy?

Answer 31

the highest point on the curve (on slide 66 both have same efficacy in pic 1 but in 2 X is the highest Z is lowest)

Question 32

higher intrinsic activity means higher ____

Answer 32

efficacy

Question 33

what are non competitive antagonists?

Answer 33

irreversible antagonists that decrease both efficacy and potency (shift curve down and right)

Question 34

what do competitive antagonists do?

Answer 34

reversible, shift curve to right, efficacy can be the same if you get enough of the agonist to override the competitive, but does not effect the efficacy of the agonist

Question 35

what type of antagonist is more common?

Answer 35

competitive (most drugs are comp) because reversibility is so important for safety

Question 36

what are inverse agonists?

Answer 36

negative intrinsic capability, induces increases in something other than the what is more commonly targeted by agonists

Question 37

go over slide70 with the allosteric activators and inhibitors graphs

Answer 37

!!!

Question 38

what is the therapeutic index?

Answer 38

ratio of Lethal dose to effective dose for a given measure of drug safety

Question 39

what kind of therapeutic index does a safe drug have?

Answer 39

high (unsafe drugs very low)

Question 40

how is the effective dose determined?

Answer 40

median effective dose is where 50% of individuals have a therapeutic effect

Question 41

how is EC50 determined?

Answer 41

drug concentration that produces 50% of max response

Question 42

How should drugs be dosed?

Answer 42

lowest dose possible to produce acceptable benefit

Question 43

what are adjunctive drugs?

Answer 43

drugs acting through a different receptor mechanism may allow clinician to lower the initial dose, imp if toxicity of the drug is high (ex use of immunosuppressive agents with glucocorticoid to treat inflammatory disorder)

Question 44

what is selectivity of drugs?

Answer 44

drug action may increase by manipulating concentration of receptors available in different parts of the buy (taking the drug from a different method)

Question 45

a quantal dose curve plots :

Answer 45

outcome occurrence in population against he drug dose

Question 46

how do lipophilic agonists activate responses?

Answer 46

pass through the membrane and bind to nuclear receptors allowing for intracellular signaling and gene transcription

Question 47

what are ionotropic receptors?

Answer 47

slow ions to traverse the membrane depolarize/hyperpolarize membranes

Question 48

describe the second messenger system that works through PLC? which G protein is it?

Answer 48

gaq protein, PLC, PIP2, DAG + IP3 DAG: PK-C IP3: Ca efflux (go signal smooth muscle reaction VASOCONSTRICTION)

Question 49

describe the second messenger system that works through adenylate cyclase? which G protein is it?

Answer 49

Gas, AC, cAMP, gAMP (VASODILATION)

Question 50

what is physiological antagonism?

Answer 50

when you have a drug like a glucocorticoid, raising blood sugar but the body reacts by secreting insulin to stop or reduce those effects

Question 51

what is pharmacological antagonism?

Answer 51

when you have a drug that blocks another drug

Question 52

what is buprenorphine?

Answer 52

partial agonist that helps with the withdrawal, gives some euphoria and helps to prevent the pt from using harder drugs because it does not allow them to have the full effect of the drug

Question 53

what should you consider when considering drug selection?

Answer 53

1. is the drug clinically indicated for a particular use. need to provide reason to provide the drug (some use off label if a drug has a desired anterior effect) 2. mechanism of action 3. adverse effects 4. contradictions (review this slide again for details 85)