Lecture 4-5 Pharmacodynamics Flashcards
What is the component of a cell to which a drug binds to initiate the chain of events that leads to a biological response
Receptor
Most receptors are ___, some are ___
Proteins, nucleic acids
For most drugs the duration of action is directly related to the __ the drug is bound to the receptor
Time
As the drug is cleared from the blood stream its action will be ___
Terminated
What are some drugs that are exceptions to the relationship between time bound to receptor and action
Corticosteroids, MAO inhibitors, omperazole, aspirin, DFP
How do corticosteroids persist for several weeks after the drug has been cleared from the body
Act on nuclear receptors and alter the expression of genes
How does the effect of MAO inhibitors, omeprazole, aspirin and DFP persist for a long period of time even without lots of free drug in the plasma
Irreversibly bind to and inhibit enzymes and their effects
What are the 5 drug-receptor interactions
- Electrostatic interactions
- Hydrogen bonds
- Van der waals
- Hydrophobic interactions
- Covalent binding
Which drug-receptor interactions have low energy bonds and therefore break easily
Electrostatic interactions, hydrogen bonds, van der waals, hydrophobic interaction
Which drug-receptor interactions have high energy bonds and therefore are irreversible
Covalent binding
Why type of receptors regulate gene expression
Intracellular receptors
How do intracellular receptors work/interact with hormone or drug
Hormone or drug crosses the plasma membrane, stimulates intracellular receptor.
Then stimulates gene transcription
Effect on intracellular receptors occurs after ___ period and ____over time
Lag period and persists over time
What some examples of molecules/hormones that can act on intracellular recpetors
Corticosteroids, mineralcorticoids, sex steroids, Vitamin D, and thyroid hormone
Can steroid hormones that act on intracellular receptors be stored
No, except for thyroid hormone
Why can’t steroid hormones be stored
They must be very lipid soluble to cross plasma membrane and interact with intracellular receptor and considering storage vesicles are made of lipids they would just diffuse out
How do allosterically regulated transmembrane proteins work
Ligand binds causing receptors to associate, stimulating tyrosine kinase, phosphorylating receptors and other downstream proteins
What enzymes can be used in allosterically regulated trans membrane signaling
Tyrosine kinase, serine kinase, guanylyl cyclase
What are some molecules that can active protein tyrosine kinases
Insulin, epidermal growth factor and platelet derived growth factor
How do ligand gated ion channels work
Binding of neurotransmitter or drug opens the channel, causing influx of ions either depolarizing or hyperpolarizing the cell
Do nicotine acetylcholine receptors excite/depolarize or inhibit/hyperpolarize
Excite/depolarize
Do GABA-a receptors inhibit/hyperpolarize or excite/depolarize
Inhibit/hyperpolarize
What ion channel opens when ACh binds
Na+
What channel is always open at NMJ and why
K+ to establish membrane potential