Unit 1- Pharmacodynamics Flashcards
Pharmacodynamics
Relationship between drug concentration and intensity of action at the receptor level
Types of Drug Targets
Enzyme, carrier, ion channel, receptor
Receptor Usage
When the interaction triggers a cascade of events for signal transmission
Binding Site
Drug molecule must bind with target and result in a response
Drug
Molecule that interacts with molecular components of an organism to produce biochemical and physiological changes, exogenous ligands
Enzymes
Enzymes as targets are inhibited
Cyclooxygenase Enzymes
Targeted by NSAIDs to suppress proinflammatory prostaglandins
Acetylcholinesterase Enzyme
Cholinesterase inhibitors prevent metabolism of acetylcholine
Antibiotics
May inhibit enzymes in cell wall biosynthesis, nucleic acid metabolism and repair, or protein synthesis
Carriers
Membrane transport proteins targeted by drugs
Na+/K+/2Cl- Carrier
Targeted by diuretics in the nephron
Sodium Pump Carriers
Targeted by digitalis
K+/H+ Carrier
Targeted by proton pump inhibitors in the gastric parietal cells
Ion Channels
Voltage gated calcium channels targeted by calcium channel blockers
Receptors
Regulatory proteins that play a roll in cell communication
GPCRs
Largest family of receptors involved in almost all physiological processes, most drugs act on GPCRs
Beta 2 Adrenergic Receptor
Albuterol binding activates adenylate cyclase forming cAMP and causing smooth muscle cell relaxation in the airways
Ligands
The exogenous compounds that bind receptors
Endogenous Ligands
Endogenous transmitters
Occupancy Theory
Drug response is a linear function of drug occupancy at the receptor level, drug has to occupy all receptors to achieve a maximal effect
Unliganded Receptor in Occupancy Theory
Is silent with no basal activity
Concept of Efficacy
The more receptors occupied by a drug the greater the response
Antagonist in Occupancy Theory
A drug with null efficacy but that blocks access of the receptor to other ligands
Two-State Model
Receptor exists in active and inactive form in dynamic equilibrium, ligand binding can shift equilibrium
Agonist in Two-State Model
A drug with a higher affinity for the active state will drive equilibrium to active and activate the receptor
Full Agonist in Two-State Model
A drug that highly favors the active state and drives the receptor all the way to active to get a maximal response
Partial Agonist in Two-State Model
A drug only has moderately higher affinity for the active state and has lower effect than a full agonist
Inverse Agonist in Two-State Model
A drug has higher affinity for the inactive state and drives equilibrium to inactive
Neutral Agonist in Two-State Model
Antagonist, binds the active and inactive states in equal affinity and will not alter equilibrium, but acts as a competitive antagonist
Antagonist vs Neutral Agonist
Antagonist has no intrinsic activity, a neutral agonist binds equally to both states of receptors
Primary Agonist
Binds to the same site as endogenous ligands
Allosteric Agonist
Drug that binds to a different region of the receptor than endogenous ligands
Receptor Antagonists
Prevent the action of natural agonists
Drug Affinity
The ability of a drug to bind to a receptor
Constant of Affinity
Numerical representation of drug affinity
Drug Receptor Complexes
Binding of drugs to receptors that is responsible for drug action
Drug Efficacy
Drug ability to initiate changes that lead to the production of responses
Level of Maximal Response
Highest response an agonist can achieve, characterized by efficacy
Drug Potency
Concentration of a drug required to achieve a given effect, expressed by EC50
EC50
Concentration of agonist that produces 50% of its maximal response
Potency and EC50
Potency varies inversely with EC50, higher potency requires lower EC50
Requiring Potent Drugs
Spot on treatments, eyedrops, and intra-articular administration
Potency of Antagonist
Effect of inhibition, determined by IC50
IC50
Concentration of antagonist that reduces agonist response by 50%
Competitive Antagonism
Antagonists act on the same receptor as the agonist
Reversible Competitive Antagonism
Antagonism can be reversed when agonist concentration is increased
Irreversible Competitive Antagonism
Displacement of antagonist from its binding site cannot be achieved by increasing agonist concentration
How to investigate receptor function?
Use irreversible competitive antagonists as experimental probes
Dose Response Curve and Competitive Antagonism
Agonist curve is shifted to the right: potency decreases because it depends on dosage but efficacy remains the same
Noncompetitive Antagonism
The drug blocks the agonist response at a downstream point in the cascade of events
Dose Response Curve and Noncompetitive Antagonism
Maximal efficacy of the agonist is reduced
Drug Specificity
Most drugs can be agonist or antagonist and do not have specificity to one type of receptor
Submaximal Drug Response
Increase dose of the drug to increase therapeutic effect
Clinical Efficacy
Therapeutic effectiveness of a drug in patients
Intrinsic Efficacy
Capacity of agonists to activate a receptor
Antagonist Efficacy
No intrinsic efficacy (no receptor activation) but clinical efficacy (therapeutic effect)
Quantal Dose Response Relationships
Relationship between dose of a drug and proportion of a population of patients that respond to it, used to determine the dose at which most of the population responds
ED50
Median effective dose, dose at which 50% of subjects exhibit a therapeutic response to a drug
TD50
Median toxic dose, dose at which 50% of subjects experience a toxic effect
LD50
Median lethal dose, dose at which 50% of subjects die
Therapeutic Index
Ratio of TD50 to ED50, used as a measure of drug safety
Certain Safety Factor
CSF should be >1, a dose effective in 99% of the population is less than what would be lethal in 1% of the population
Therapeutic Window
Range of drug doses that provides therapeutic efficacy with minimal toxicity, range between ED50 and the start of the toxicity curve
