Drug-Receptor Interaction & Dose-Response Graph Flashcards
Substance that binds to receptors
Ligand
Ability of a ligand to bind to a receptor
Affinity
Ability of a ligand to activate the receptors
Intrinsic activity
Types of Ligands (3)
- Agonist
- Antagonist
- Inverse Agonist
Types of Ligands
Affinity + Intrinsic Activity (IA)
Agonist
Types of Ligands
Affinity only
Antagonist
Types of Ligands
▪️Affinity + ↓IA
▪️Decrease IA
Inverse Agonist
Types of Agonist (3)
- Full Agonist
- Partial Agonist
- Inverse Agonist
What Type of Agonist is:
▪️ Produces all the effects of the receptor
▪️100% effect
▪️IA=1
▪️Ex. Morphine-mu receptor
Full Agonist
What Type of Agonist is:
▪️Produces some of the effects of the receptor
▪️Has a mixed agonist and antagonist action
▪️IA>0 but <1
▪️Ex. Nalbuphine, Tamoxifen
Partial Agonist
What Type of Agonist is:
▪️Favors the inactive form of the receptor
▪️ Ligand which produces an effect opposite to that of an agonist occupying the same receptor
▪️IA<0
▪️Ex. All antihistamine
Inverse Agonist
Morphine is a full agonist to mu receptor while Nalbuphine is a partial agonist for the same receptor. When taken together, the result is(?)
Reduction of Analgesia
Types of Antagonist Based on Mechanism (3)
- Functional/Physiologic Action
- Pharmacologic/Receptor Antagonism
- Chemical Antagonism
What Type of Antagonist Based on Mechanism
▪️Produces OPPOSITE EFFECTS by binding to DIFFERENT receptors
▪️2 ligands acting on different receptors, producing opposite effects
▪️Ex. Epinephrine in the management of anaphylaxis
Functional or Physiological Antagonism
What Type of Antagonist Based on Mechanism
▪️Produces OPPOSITE EFFECTS by binding to SAME or similar receptors
Pharmacologic or Receptor Antagonism
Type of Antagonists Based on Interaction (2)
- Reversible Antagonism
- Irreversible Antagonism
What Type of Antagonists Based on Interaction is:
▪️Mabilis : safer
▪️Temporary (DOI:<24hrs)
▪️Weak forces (non-covalent) VDW, H-bond
Reversible Antagonism
What Type of Antagonists Based on Interaction is:
▪️Matagal : toxic
▪️Permanent (DOI: days to weeks)
▪️Covalent bond
▪️As long as the receptor is viable, effect still present
Irreversible Antagonism
Type of Antagonists Based on Surmountability (2)
- Competitive/Surmountable
- Non-competitive/Non-surmountable
What Type of Antagonists Based on Surmountability is:
▪️ Completely overcome the effect of the antagonist by increasing the dose of the agonist
▪️Quantity based (kung sino mas marami siya ang magbibind sa receptor)
▪️ Inhibitor binds to the active site
Competitive/Surmountable
What Type of Antagonists Based on Surmountability is:
▪️Kahit gaano mo damihan ang dose ng ligand, hindi na niya maka-counteract yung effect ng isa pang ligand
▪️Inhibitor bind to allosteric site
Non-competitive/Non-surmountable
What type of antagonism exhibited by the two agents?
Ex:
1. Morphine + Naloxone
2. BZD + Flumazenil
3. ACh + Atropine
Pharmacologic/Receptor Antagonism
What type of antagonism exhibited by the two agents?
Ex:
1. ACh + NE
2. Histamine + Epi
Functional/Physiologic Antagonism
What type of antagonism exhibited by the two agents?
Ex:
1. Heparin + Protamine
2. Heavy Metals + Chelating Agent
Chemical/Inactivation Antagonism
What type of antagonism exhibited by the two agents?
Ex:
1. Activated Charcoal
2. Ipecac Syrup
Dispositional/Mechanical Antagonism
▪️ Shows the relationship between the degree of response with dose
▪️Plot: Degree of Response VS Dose or Log Dose
▪️Log dose (sigmoidal) dose (hyperbolic)
Graded Dose-Response Curve/Graph
Maximum achievable response
Efficacy (E)
Dose required to achieved 50% of efficacy
Potency
Smallest dose that produces the maximum effect
Efficacy 100%
Ceiling Dose
Degree of change in response with a change in the dose
Slope
What type of graph antagonism is
▪️ shifts to the right with the same height for efficacy
Competitive antagonist
What type of graph antagonism is
▪️ rightward shift; lower height
▪️ increases amount of agonist and non-competitive antagonist, but never reaching max efficacy
Non-competitive Antagonist
▪️ Shows how a population responds to a given dose
▪️Plot: Cumulative number of Px (Y-axis) VS Log Dose (X-axis)
Quantal Dose Response Graph/Curve
▪️ Median Effective Dose
▪️Effective Dose in 50% of the give of the given population
ED50
▪️Median Toxic Dose
▪️Toxic Dose in 50% of the given population
TD50
▪️Measure of relative safety
▪️Wider/Higher TI=SAFER Drug
▪️TITE
Therapeutic Index
