Lecture 2- PD and drug-receptor interactions Flashcards
Pharmacodynamics (PD)
The effect of the drug on the body
Pharmacokinetics (PK)
Effect of the body on the drug (ADME)
- absorption
- distribution
- metabolism
- excretion
Is a target receptor necessary?
A few clinically useful drugs do not require a target receptor to evoke biological response (osmotic diuretics i.e. mannitol, antidotes for heavy metal poisoning
How do drug receptors function?
Most drugs have a specific structural interaction with specific cellular target molecules (receptors)
Who pioneered the concept of receptor?
Langley and Ehrlich in early twentieth century
Where is a receptor located pharmacologically?
Mostly on the cell membrane, but also within the cytoplasm or cell nucleus that binds to a specific molecule such as a neurotransmitter, hormone, metabolite, or a drug molecule and thereby initiating cellular response
What is the result of drug-induced changes in the biochemical and biophysical properties of the receptor?
physiological changes that constitute the biological actions of the drugs
What does a receptor’s affinity for binding a drug determine?
The concentration of drug required to form a significant number of drug-receptor complexes
What might the total number of receptors limit?
the maximal effect a drug may produce
Ensemble
Multiple chemical interactions (ie van der Waals, covalent..)
What does ensemble provide?
Specificity of the overall drug-receptor interaction
What is affinity (KD value)?
A measure of the favorability of a drug-receptor interaction
What contributes to the overall potency, efficacy, and duration of drug action?
Minor variation in the functionalities of the drug molecules can significantly alter the binding interactions
Bond Types
Covalent Bond
Non-covalent bonds
- ionic
- dipole
- hydrogen bonds (specialized dipole dipole)
- van der waals
- hydrophobic
- chelation and complexation
- charge transfer interactions
Covalent Interaction examples
alkylation and acylation
Receptor Classes
Protein and Non-protein
Types of protein drug receptors
Enzymes
Ionotropic
metabotropic
kinase
nuclear
cytoskeletal or structural
transporters or carrier
Types of non-protein receptors
nucleic acids (dna, rna), membranes, and fluid compartments
Enzyme example
dihydrofolate reductase, the receptor for the antineoplastic drug methotrexate
ionotropic receptors or ion channels
ligand gated channels and voltage gated channels
metabotropic receptors
G-protein coupled receptors that bind to endogenously produced hormones, neurotransmitter, etc.
nuclear receptors
receptors for thyroid hormone, some fat-soluble vitamins and steroids
kinase linked and related receptors
receptors for various growth factors and thus for some anticancer drugs
cytoskeletal and structural proteins
ie tubulin, the receptor for colchicine, an anti-inflammatory agent