Principles Of Drug Therapy 1

Question 1

What are pharmacodynamics and pharmacokinetics?

Answer 1

What the drug does to the body

What the body does to the drug

Question 2

Tylenol names?

Answer 2

N 4 hydroxyl phenyl acetamide

Acetaminophen

Question 3

How does a drug exert its effects?

Answer 3

Via a receptor

Question 4

How does epi affect BP?

Answer 4

Binds to a receptor
2nd mssgrs pass on and amplify the message
Inactive G binds, becomes active which leads to: Vasoconstriction, ⬆️HR and B
Via smooth m or heart cell

Question 5

What does [G-active] depend on?

Answer 5

Rate of activation

Question 6

How does a full agonist work, specifically?

Answer 6

It binds a receptor which causes a conf change which A+ the receptor

G protein linked receptors transduce the signal by A+ GTP binding proteins

Activated G proteins then A+ or I- other enz

End result: phys or pharm change (ex: HR, BP)

Question 7

How does a partial agonist differ from a full agonist?

Answer 7

When bound to receptor it’s less effective, A+ G pro slower

Question 8

How are the terms “full” and “partial” used?

Answer 8

Comparing different agonists at a given receptor. Not absolute quantities

Question 9

How does an antagonist work?

Answer 9

It’s a molecule similar to agonist

Binds recep, but no conf change/no receptor activation

Has no effect by itself

Blocks action of agonist (endo or drug)

May cause neg effect if agonist is present

Question 10

What is efficacy?

Answer 10

Relative term, compares effect of 2 or more drugs, no units

Full ago, eff = 1, partial < 1, anta = 0

Question 11

What determines response to a drug?

Answer 11

Efficacy, potency, aff and dose

Question 12

What does aff measure and what determines potency?

Answer 12

How long a drug binds to its receptor

Question 13

If a drug is only bound for a short time how can we increase the reponse to the drug?

Answer 13

Increase chances of rebinding

Question 14

How do you increase chances of rebinding?

Answer 14

Increasing the concentration

Question 15

What does the activity of a receptor depend on?

Answer 15

How tight and how long the drug binds

Question 16

What does Rmax depend on?

Answer 16

Drug efficiency

Question 17

What does max rate represent?

Answer 17

The activity of the receptor when occupied by the agonist all the time

Question 18

An increase in EC50?

Answer 18

Decrease in potency

Question 19

What is EC50?

Answer 19

Dose that produces half the max effect

Question 20

Features of drugs that bind less tightly?

Answer 20

Use higher dose for same effect on receptor
Have higher EC50 value
Less potent
If full ago, at high dose, Rmax will be same for each drug

Question 21

With Rmax, what’s the deal with EC50?

Answer 21

It’s independent of efficacy

Question 22

With partial ago, what happens when you increase the conc?

Answer 22

The effect will increase but the max effect will be less than with full ago

Question 23

The effect at each conc depends on?

Answer 23

Efficacy and potency

Question 24

If an antagonist binds tightly?

Answer 24

Low EC50, 0 efficacy

Question 25

What happens if comp anta is in presence of ago?

Answer 25

Higher conc of ago is needed for response | EC50 is increased

Question 26

What happens if you increase the anta conc?

Answer 26

Ago dose response curve shifts right, higher dose of anta (fixed for each curve), further shift More anta, more ago needed for same effect

Question 27

When does anta have an effect?

Answer 27

Only in presence of ago

Question 28

What is the EC50 of the anta dependent on? Why?

Answer 28

The ago conc | Because they compete

Question 29

In the absence of full ago, partial ago does what?

Answer 29

Stimulates the process by activating the receptor with lower efficacy

Question 30

In the presence of full ago, partial does....?

Answer 30

Displaces/antagonizes full ago and since it has lower efficacy, the net effect can be diminished

Question 31

Re: eff, partial ago acts like?

Answer 31

Like a partial anta | Efficacy between 0 and 1

Question 32

What does increasing the # of receptors do?

Answer 32

Increase the response But no changes in eff, potency or drug dose

Question 33

What happens with irr anta?

Answer 33

Prob that ago binds to any one receptor is unchanged of receptors decreases Prob that ago will dissc is unchanged Can allow 100% inhibition Response to ago only after new receptors are made

Question 34

Does an irr anta stay bound?

Answer 34

Yes even after free drug is out of system Never leaves binding site So ago and anta don't compete

Question 35

When do anta and ago not compete?

Answer 35

When there's no free anta In this case the % occupancy of free receptors is not affected by loss of receptors

Question 36

Adding more anta leads to?

Answer 36

Blockade of all receptors

Question 37

What's the effect of an irr non comp anta on response to ago?

Answer 37

The potency (E50) of ago is unaffected because of no competition for binding Response to ago is lessened at all doses of ago so Rmax is decreased which looks like decrease in efficacy

Question 38

What are some features of receptor #s?

Answer 38

Variation in response with time Tolerance Tachyphylaxis (appearance of a decrease in response after repetitive administration) Variation in response w/ diff ppl

Question 39

Response w/ lots of receptors?

Answer 39

Will increase with more receptors until a ceiling is hit and no extra effect

Question 40

Consequences of limiting receptors?

Answer 40

Max response b4 all receptors are filled (w/ decrease in EC50) Low doses of irr anta may not decrease Rmax Due to spare receptors

Question 41

How is # of receptors regulated?

Answer 41

Persistent A+ of receptors may lead to down reg Short term phosphorylation of receptors Decrease in #s over longer term

Question 42

Prolonged blockade of receptors can lead to?

Answer 42

Increase in receptor # Stimulation of adverse effects with abrupt withdrawal Tolerance???

Question 43

Examples of pharmacodynamic tolerance w/ opioids and benzodiazepines?

Answer 43

Opioids: tolerance for all actions except miosis and constipation, DR curve to right with large shift, increase dose to maintain analgesia Benzo: tolerance to antiepileptic effect

Question 44

What does potency relate to?

Answer 44

Dose required to get a given effect More potent drug has lower EC50

Question 45

Effects of antas?

Answer 45

Comp anta: DR curve for ago R Ago acts as if less potent but raising dose can restore effect No change in Rmax ``` Irr non comp anta: Decrease max effect of drug Drug acts like less efficacious No R shift Potency unaffected ```

Question 46

Ppl drug diff?

Answer 46

Diff responses, diff EC50s Measured response = quantal

Question 47

What's ED50?

Answer 47

Dose at which 50% of population has defined response

Question 48

Features of sigmoidal quantal DR curve?

Answer 48

Reflects variation in response in pop, so can have diff slopes Steeper slope Non log plot also sigmoidal Steepness different for each drug effect examined

Question 49

EC50 differs due to?

Answer 49

Receptor density Diff isoforms of expressed receptors

Question 50

DR curve features?

Answer 50

Each drug has one Each might have diff ED50 for each effect Can define therapeutic range/window

Question 51

TD50 and LD50?

Answer 51

TD50 = toxic effect LD = lethal effect

Question 52

Therapeutic Index (TI)?

Answer 52

LD50/ED50 (Ratios may be diff for 20 or 80) Ratio of lowest TD50 and ED50 for desired effect Higher the TI, lower risk of seeing toxic effect Alone not a good predictor of drug safety, need more info on slope of curve