Principles Of Drug Therapy 1 Flashcards
What are pharmacodynamics and pharmacokinetics?
What the drug does to the body
What the body does to the drug
Tylenol names?
N 4 hydroxyl phenyl acetamide
Acetaminophen
How does a drug exert its effects?
Via a receptor
How does epi affect BP?
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
What does [G-active] depend on?
Rate of activation
How does a full agonist work, specifically?
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)
How does a partial agonist differ from a full agonist?
When bound to receptor it’s less effective, A+ G pro slower
How are the terms “full” and “partial” used?
Comparing different agonists at a given receptor. Not absolute quantities
How does an antagonist work?
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
What is efficacy?
Relative term, compares effect of 2 or more drugs, no units
Full ago, eff = 1, partial < 1, anta = 0
What determines response to a drug?
Efficacy, potency, aff and dose
What does aff measure and what determines potency?
How long a drug binds to its receptor
If a drug is only bound for a short time how can we increase the reponse to the drug?
Increase chances of rebinding
How do you increase chances of rebinding?
Increasing the concentration
What does the activity of a receptor depend on?
How tight and how long the drug binds
What does Rmax depend on?
Drug efficiency
What does max rate represent?
The activity of the receptor when occupied by the agonist all the time
An increase in EC50?
Decrease in potency
What is EC50?
Dose that produces half the max effect
Features of drugs that bind less tightly?
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
With Rmax, what’s the deal with EC50?
It’s independent of efficacy
With partial ago, what happens when you increase the conc?
The effect will increase but the max effect will be less than with full ago
The effect at each conc depends on?
Efficacy and potency
If an antagonist binds tightly?
Low EC50, 0 efficacy
What happens if comp anta is in presence of ago?
Higher conc of ago is needed for response
EC50 is increased
What happens if you increase the anta conc?
Ago dose response curve shifts right, higher dose of anta (fixed for each curve), further shift
More anta, more ago needed for same effect
When does anta have an effect?
Only in presence of ago
What is the EC50 of the anta dependent on? Why?
The ago conc
Because they compete
In the absence of full ago, partial ago does what?
Stimulates the process by activating the receptor with lower efficacy
In the presence of full ago, partial does….?
Displaces/antagonizes full ago and since it has lower efficacy, the net effect can be diminished
Re: eff, partial ago acts like?
Like a partial anta
Efficacy between 0 and 1
What does increasing the # of receptors do?
Increase the response
But no changes in eff, potency or drug dose
What happens with irr anta?
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
Does an irr anta stay bound?
Yes even after free drug is out of system
Never leaves binding site
So ago and anta don’t compete
When do anta and ago not compete?
When there’s no free anta
In this case the % occupancy of free receptors is not affected by loss of receptors
Adding more anta leads to?
Blockade of all receptors
What’s the effect of an irr non comp anta on response to ago?
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
What are some features of receptor #s?
Variation in response with time
Tolerance
Tachyphylaxis (appearance of a decrease in response after repetitive administration)
Variation in response w/ diff ppl
Response w/ lots of receptors?
Will increase with more receptors until a ceiling is hit and no extra effect
Consequences of limiting receptors?
Max response b4 all receptors are filled (w/ decrease in EC50)
Low doses of irr anta may not decrease Rmax
Due to spare receptors
How is # of receptors regulated?
Persistent A+ of receptors may lead to down reg
Short term phosphorylation of receptors
Decrease in #s over longer term
Prolonged blockade of receptors can lead to?
Increase in receptor #
Stimulation of adverse effects with abrupt withdrawal
Tolerance???
Examples of pharmacodynamic tolerance w/ opioids and benzodiazepines?
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
What does potency relate to?
Dose required to get a given effect
More potent drug has lower EC50
Effects of antas?
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
Ppl drug diff?
Diff responses, diff EC50s
Measured response = quantal
What’s ED50?
Dose at which 50% of population has defined response
Features of sigmoidal quantal DR curve?
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
EC50 differs due to?
Receptor density
Diff isoforms of expressed receptors
DR curve features?
Each drug has one
Each might have diff ED50 for each effect
Can define therapeutic range/window
TD50 and LD50?
TD50 = toxic effect LD = lethal effect
Therapeutic Index (TI)?
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
