Introduction to pharmacology Flashcards
What is pharmacology ? (1)
Pharmacology is the study of the **interactions **between a living organism and chemicals that affect normal or abnormal cell (biochemical) functioning - and the **mechanisms **by which the interactions occur.
What is pharmacology ? (2)
If substances have positive (medicinal) effects they are considered pharmaceuticals ( drugs - FDA approved). If the effects are mostly detrimental, it is generally in the realm fo toxicology. Interface chemical and biology.
The essence of pharmacology
Drugs responsibilities
- Drug must reach their target
- Drugs must interact with existing targets
Pharmacology nad medicinal chemistry are inter-related
Pharmacology is best understood as
communication within & with the body
- High fidelity of message: accomplish what is
intended (the therapeutic effect) with the least
misunderstanding (off-target effects) - Lowest dose: least need for ‘yelling’
- Use the body’s ‘words’ (e.g., NTs) and ‘ears’
(e.g., ‘receptors’) - Understand the body’s communication
system …
Communication systems
Sympathetic and parasympathetic divisions
Chemical communication
What are the molecules in the communication ?
- 1st - Drug
- 2nd - receptor
Receptor
- the molecule of the cell with which the drug molecule binds and produces it effect(s)
- they will stimulate the secondary dimension
- the drug molecule HAS TO MATCH the receptor
Receptor and signal transduction
Monitors outside environment - to respond or not ?
* Detects the signal
* Distinguishes the signals
* Determines the response for a given signal (intracellular sequences)
Signal transduction and 2nd messengers
Ligand-gated ion channel receptor (ionotropic)
- First one to develop
- Responds to ions
- Influx or efflux of the ions
What are the kinds of ligands for ionotropic receptors ?
Signal transduction and 2nd messengers
Tyrosine kinase (trk) recptor
- Ligand binds outside and regulates the enzymes inside
*
Signal transduction and 2nd messengers
G Protein-coupled (GPCR) Receptor (metabotropic)
- Metabotropic
- Large molecule of recptor
- Specific ligands can initiate specific intracellular events by activating specific the pathways involving the 2nd messengers
Biased ligand ?
Signal transduction and 2nd messengers
Nuclear receptors
- Relatively long-lasting effects
- Protein synthesis is the normal effects of these kind of receptors
- May not correspond well with the blood levels
- Eg : Hormones
- Fat-solubility is an important factor to consinder decades after the drug has been taken in
Eg : PPAR-Y is a nuclear recptor
Signal transduction and 2nd messengers
‘Chaperone’ Receptors
- Proteins (including receptors) need to fold into
the correct conformations for functionality - Pre- or post-translational mis-folding results in
reduced or lost functionality - Misfolded proteins can aggregate, leading to
numerous diverse diseases - ‘Chaperone’ proteins bind to misfolded
proteins, allowing correction of the misfolding - They also protect proteins from degradation
and ‘chaperone’ the proteins to their correct
destinations - Some chaperones are sensitive to modulation
by ligands. Hence are** ‘receptors’ (binding and
function).**
