Week 11 - Therapeutic Response

Question 1

What is the difference between quantal (all-or-none) and graded (continuous) responses

Answer 1

Quantal (all-or-none) response:
- means absent or present e.g. pain or no pain
- provides info. on the probability that an effect will occur at or below at specific conc.

Graded (continuous) response:
- response (effect) varies continuously with the conc.
- non-linear system = non-linear plot produced
- drug effect can be excitatory or inhibitory
- assess response using eqation:
Eobs = E0 + Edrug + (Eplacebo)
- Eobs = observed effect
- E0 = effect with no drug
- Edrug = effect with drug
- Eplacebo = effect with placebo

Have to use unbound plasa conc. (as only unbound drug is the actual conc. of drug available)

Question 2

What does potency and efficacy mean

Answer 2

Potency - conc. required to produce 50% of the maximum response
- C50 = conc. required 50% of max. response
- lower C50 = more potent drug

Efficacy - maximum effect capable of being produced by the drug (Emax)
- drugs that prodcue Emax are called full agonisits or antagonists

Use both factors when deciding between 2 drugs which may have same general effect e.g. both analgesics but might need higher efficacy

Question 3

What does non-linear system mean

Answer 3

Means the effect isn’t changing linearly with the conc.
- i.e. the conc-effect plot line isnt increasing expotentially
- on conc-effect plot effect begins to level off (despite conc. increase) near the end as the system is saturable

Question 4

Why do responses decline linearly with time when the response is between the region of 20-80% of its maximum value

Answer 4

If data is above 20% or 0.2 (of the maximum effect) linear model won’t be able to describe it (as it has not been observed)

Decline linearly due to using log-linear model:
- the conc vs time plot is decreasing linearly / the same as the effect vs time plot during 20-80%
- the conc. is changing linearly on the log scale
- Use log-linear to describe data between 20-80%
- log-linear cant describe data <20% and >80% as not enough data has been collected
- linear model cant describe data >20%

Question 5

How do you detect time effects by plotting response against drug conc.

I.e. time delays

Answer 5

May have delays in drug conc. as it moves from plasma to effect site
- e.g. drug plasma conc. is reaching max. whilst the maximum effect is delayed / still rising
- when plasma conc. is decreasing the effect is still increasing = hysteresis loop

indirect response is when drug acts directly on another factor which then acts on the effect (it does NOT act on the effect directly)

Question 6

What are the 2 basic elements of a model combining pharmacokinetic and pharmacodynamic data

Answer 6

1. Linear model
   
   • Use linear model to describe data from 20% and below
2. Log-linear Model
   
   • Use log-linear to describe data between 20-80% (log-linear cant describe data <20% and >80%)
   • WON’T be able to describe whats going on above this point (20% or 0.2) as it hasn’t been observed

BOTH linear models cant be used for extrapolation only explain whats within the range of conc. its looking at

3. Power model
   
   • γ (gamma) parameter causes plot to become sigmoid (S shape, instead of hyperbola), it increases or reduces the power of the conc.
   • use this model if the gamma is not 1