Receptors Flashcards
What is the difference between Pharmacodynamics and Pharmacokinetics?
Pharmacodynamics: Biochemical and physiologic effects of drugs
Pharmacokinetics: Refers to the movement of drug into, through and out of body
Define Receptor
The component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to the drug’s observed effects
What are Four Major Types of Receptors?
- Ion Channels (fast neurotransmitters e.g. ACh)
- G-Protein Coupled Receptor (slow neurotransmitters e.g. NA)
- Tyrosine Kinase Coupled Receptors (e.g. insulin)
- Intracellular Receptors (e.g. steroids)
Define Ligand
A substance that forms a complex with a biomolecule to serve a biological purpose
Define Agonist
A chemical that binds to a receptor and activates it to produce a biological response
Define Antagonist
A type of receptor, ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor, rather than activating it
What are Four Major Drug Targets?
- Receptors
- Ion Channels
- Enzymes
- Membrane Transporters
What are the types of forces that cause binding of drugs to their receptors?
- Van der Waals Forces (weakest non-covalent bonds)
- Hydrophobic (more of a characteristic of a compound)
- Hydrogen bonds
- Ionic bonds (strongest non-covalent bonds)
- Covalent bonds
What is the Law Mass of Action?
The rate of any reaction is proportional to the concentrations of the reacting substances
Are covalent bonds described as reversible or irreversible interactions?
Covalent bonds are described as irreversible under biological conditions because once the covalent bond is formed, the resulting structure is typically extremely stable
Define B
Drug Bound (fraction or percent of maximum)
Define Bmax
Maximal drug binding (100%)
Define Kd
Dissociation constant (concentration of drug required to saturate 50% of the receptors)
What are the Six Major Characteristics of Receptors?
- Recognition
- must exist in conformational state allowing for recognition and binding of a specific compound
- Saturability
- exist in finite numbers
- Reversibility
- binding must occur non-covalently
- Stereoselectivity
- should recognise only one naturally occurring optical isomers
- Agonist Specificity
- structurally related drugs should bind well, dissimilar compounds bind poorly
- Tissue Specificity
- binding should occur in tissues known to be sensitive to the endogenous ligand
- binding should occur at physiologically relevant concentrations
Why isn’t the ‘Lock and Key’ model not entirely correct?
Because it cannot explain the fact that some drugs bind to the receptor very efficiently but are still not able to activate it
Conformational Selection Model of Drug-Receptor Interaction Conditions
- Receptor is spontaneously changing between numerous conformations
- Each drug selects and stabilises one particular conformation
- If the drug selects and stabilises proper (active) conformation, such binding will result in biological activity [agonist of receptor]
- Stabilising active conformation initiates intracellular signalling events mediating drug biological activity
- If the drug binds and stabilises inactive conformation, it is an antagonist
- If the drug does not bind to receptor at all, it is inactive
Why is the amount of drug bound at any time determined by number of receptors?
- There are finite number of receptors
- When a sufficient number of receptors are bound on or in a cell, the cumulative effector of receptor may become apparent in that cell
Why is the amount of drug bound at any time determined by concentration of ligand?
- When ligand concentration increases, the concentration of bound receptors increases
- An increase in the effect of a drug can result from an increase in the concentration of either the ligand or receptor
Why is the amount of drug bound at any time determined by affinity of drug for its receptor?
- Measure of the tightness with which a drug binds to the receptor
- If Drug A has a low affinity for a receptor but drug B has a much higher affinity, Drug B will displace Drug A and bind to the receptor
What is the definition of Therapeutic Index?
A comparison of the average dose of a drug that causes the therapeutic effect to the average dose that causes toxicity
TI = TD50/ED50
TI = Max dose/Min dose
What is the difference between competitive antagonists and non-competitive antagonists?
Competitive Antagonists: Bind to receptors at the same active site as the endogenous ligand or agonist, but without activating the receptor
Non-Competitive Antagonists: Binds to a non-agonist site on the receptor to prevent activation of the receptor
