7 – Pharmacodynamics Flashcards
1
Q
Pharmacodynamics
A
- What the drug does to the body
2
Q
Receptors
A
- Strictly defined as proteins that normally serves as receptors of ENDOGENOUS LIGANDS
- For this course: any cellular constituent (ex. enzymes, cell membranes, DNA)
3
Q
Agonists
A
- Drugs that bind to receptors and mimic the effect of ENDOGENOUS LIGAND
- High affinity and highly lipophilic (to only have to take once a day)
4
Q
Antagonists
A
- Drugs that bind to receptors and produce NO response
- Competitive or non-competitive
5
Q
Partial agonists
A
- Drugs that bind receptors and produce LESSER effect than endogenous ligand
6
Q
Classical receptor theory
A
- Reversible interaction between drug and receptor follows the law of mass action
- [D]+[R] <-> [DR] -> EFFECT
- DR=activated drug-receptor effect
- *amount of drug and amount of receptor determine DR which determines the effect
7
Q
Dose-response relationships: 2 main types
A
- Graded
- Quantal
- *all plots of dose (x-axis, independent) vs response (y-axis, dependent)
8
Q
Graded dose-response relationships
A
- Show responses of INDIVIDUALS
- Continuous responses
- Y-axis: ‘percent response’ (0-100%)
9
Q
Graded dose-response provides info about
A
- Intensity of response over a dose range
10
Q
Quantal dose-response relationship
A
- Show POPULATION responses
- ‘all or none’ responses
- Y-axis: ‘percent of individuals responding’ (0-100%)
11
Q
Quantal dose-response provides info about
A
- Number of patients exhibiting a specified effect over a dose range
12
Q
Graded response curve
A
- Used mainly to compare potency and efficacy
13
Q
Quantal response curve
A
- Used mainly to determine drug safety
- Important to see where the dose is on an average distribution curve
14
Q
Relative potency
A
- More potent if it takes LESS of a dose to get a desired response
*further left=more potent (horizontal)
15
Q
Relative efficacy
A
- More efficacious if at its max it can get 90% maximal effect
*further up=more efficacious (vertical)
16
Q
EC50 or ED50
A
- Concentration or dose causing 50% maximal response
- Used to characterize drugs and compare potencies
17
Q
Dose response curves can be used to
A
- Determine any effective dose (ED) (Ex. ED1, ED10)
- Determine toxic doses (TD) or lethal doses (LD)
18
Q
What are the 2 main measures to measure drug safety?
A
- Therapeutic index
- Margin of safety
19
Q
Therapeutic index
A
- Difference in dose need to get a response and dose that is toxic/kills the animal
- Want it to be very big
20
Q
Therapeutic index equation
A
- =TD50/ED50
21
Q
Margin of safety
A
- Conservative measure of drug safety
- Ratio of drug dose that causes toxicity/death in 1% of population to the drug dose that causes desired therapeutic effect in 99% of the population
22
Q
Margin of safety equation
A
- =TD1/ED99
23
Q
Dynamic nature of receptors: desensitized
A
- Can happen upon continuous exposure to drug
- One reason for drug tolerance and need for ‘drug holidays’
- Ex. desensitization of beta-adrenergic receptors due to DOWNREGULATION
24
Q
Dynamic nature of receptors: sensitization
A
- UPREGULATION
- Due to increased receptor concentration
- Ex. some auto-immune diseases
- Rare
25
Significance of receptor subtypes
* Tissue specificity and selectivity
* Allows same endogenous signaling agent to act in different tissues
26
Orphan receptors
* Receptor with no know endogenous ligand
* Classic example: opioid receptors IDed using morphine as agonist
* New example: cannabinoid receptors IDed using THC as agonist
27
Signal transduction pathways: 2 main things they do
1. Involved in phosphorylation of proteins
2. Influence gene expression
28
Main signals/molecules in the brain
* Glutamate: excitatory
* GABA: inhibitory
