7 – Pharmacodynamics Flashcards
Pharmacodynamics
- What the drug does to the body
Receptors
- Strictly defined as proteins that normally serves as receptors of ENDOGENOUS LIGANDS
- For this course: any cellular constituent (ex. enzymes, cell membranes, DNA)
Agonists
- 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)
Antagonists
- Drugs that bind to receptors and produce NO response
- Competitive or non-competitive
Partial agonists
- Drugs that bind receptors and produce LESSER effect than endogenous ligand
Classical receptor theory
- 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
Dose-response relationships: 2 main types
- Graded
- Quantal
- *all plots of dose (x-axis, independent) vs response (y-axis, dependent)
Graded dose-response relationships
- Show responses of INDIVIDUALS
- Continuous responses
- Y-axis: ‘percent response’ (0-100%)
Graded dose-response provides info about
- Intensity of response over a dose range
Quantal dose-response relationship
- Show POPULATION responses
- ‘all or none’ responses
- Y-axis: ‘percent of individuals responding’ (0-100%)
Quantal dose-response provides info about
- Number of patients exhibiting a specified effect over a dose range
Graded response curve
- Used mainly to compare potency and efficacy
Quantal response curve
- Used mainly to determine drug safety
- Important to see where the dose is on an average distribution curve
Relative potency
- More potent if it takes LESS of a dose to get a desired response
*further left=more potent (horizontal)
Relative efficacy
- More efficacious if at its max it can get 90% maximal effect
*further up=more efficacious (vertical)
EC50 or ED50
- Concentration or dose causing 50% maximal response
- Used to characterize drugs and compare potencies
Dose response curves can be used to
- Determine any effective dose (ED) (Ex. ED1, ED10)
- Determine toxic doses (TD) or lethal doses (LD)
What are the 2 main measures to measure drug safety?
- Therapeutic index
- Margin of safety
Therapeutic index
- Difference in dose need to get a response and dose that is toxic/kills the animal
- Want it to be very big
Therapeutic index equation
- =TD50/ED50
Margin of safety
- 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
Margin of safety equation
- =TD1/ED99
Dynamic nature of receptors: desensitized
- 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
Dynamic nature of receptors: sensitization
- UPREGULATION
- Due to increased receptor concentration
- Ex. some auto-immune diseases
- Rare
Significance of receptor subtypes
- Tissue specificity and selectivity
- Allows same endogenous signaling agent to act in different tissues
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
Signal transduction pathways: 2 main things they do
- Involved in phosphorylation of proteins
- Influence gene expression
Main signals/molecules in the brain
- Glutamate: excitatory
- GABA: inhibitory
