Drug Receptors Flashcards
What does an agonist do?
Produces/promotes a similar response to the intended chemical
(acts like the ligand on the target receptor)
What does an antagonist do?
Blocks the effect of the ligand on the target receptor
How can two different drugs have the same result for a patient? Example: pt with COPD and pt with Asthma, both have constricted bronchioles but two different drugs could treat them.
One drug (sympathetic beta2 activation) causes bronchial dilation and one drug (parasympathetic m3 antagonism) blocks constriction….both lead to the same end result of opening bronchioles
What does pharmacology study?
At the receptor level, what is the mechanism of action?
Ex: Beta 2 agonist, M3 antagonist
What does pharmacodynamics (PD) study?
What is the physiological effect of the drug on the body?
Ex: dilates bronchial tubes, increases HR
What does pharmacokinetics (PK) study?
What does the body do to the drug?
ADME
What does pharmacotherapy study?
Choosing which drug is best for the pt
What does a modulator drug do?
Has both agonist and antagonist effects
What channels have quick acting effects?
Ligand-gated ion channels and G protein-coupled receptors
5 protein subunits form the _____ of a ion channel
Pore
T/F a specific ion channel let ions flow in and out of a cell
False. Ion channels either allow ions into a cell OR out of a cell (one way flow)
How are voltage gated ion channels activated?
By a charge, activation of one leads to activation of the next one and so on
T/F Voltage gated ion channels are specific for one ion
True
Voltage gated ion channels do not require a _____
Ligand
Where are voltage-gated ion channels found?
On nerves
What is an example of a drug that uses a voltage-gated channel?
Lidocaine (antagonist) it blocks voltage-gated Na+ receptors which blocks Na+ permeability
How do ligand gated ion channels work?
A endogenous ligand binds to a subunit of the pore which causes the permeability of the channel and allows ions to flow through it
What is an example of a ligand gated ion channel?
Nicotinic Acetylcholine Receptor. At rest, the channel is closed and no ions flow through. Acetylcholine binds to 2 of the subunits (alpha) which opens the channel and Na+ flows through (intracellularly which is down the concentration gradient) and finally initiates a muscle contraction.
Why do people respond to drugs in different ways?
We all have the same subunits that make up the pores of ion channels, but there are different subtypes of the subunits which we all differ in.
Short answer: we have different receptor subtypes
What is Dr. Stremski’s favorite ion channel?
GABA-A (binds to subunit which allows Cl- influx)
What does the 5HT3 Ligand-gated channel responsible for?
When serotonin binds to the 5HT3 receptor, the channel opens leading to an influx of Na and K into neurons –> this causes you to puke.
*5HT-3 Anti-emetic drugs are antagonist, they bind to the receptor and block serotonin from binding = no more puking!
What is the structure of a G-Protein Coupled Receptor? (GCPR)
- One long peptide chain
- Wraps in and out of the membrane 7 times
- Amino Terminal = extracellular
- Carboxyl Terminal = intracellular
Where does a ligand bind in a G-protein coupled receptor?
Active site in the transmembrane region
What do G-proteins interact with?
Cytoplasmic region
What is an example of a GCPR?
All sympathetic NS receptors are GPCR (classified as Alpha and Beta)
Do GPCR require a ligand to be activated?
Yes
What are the three components to G-protein coupled receptors?
- Ligand binds to receptor
- Receptor triggers the activation of a G-protein
- G-protein changes the activity of an effector element (usually an enzyme or ion channel)
What is the role of adenyl cyclase?
Catalyzes the reaction of ATP –> cAMP
(less adenyl cyclase, less cAMP)
Migraine example (migraines occur because of vasodilation, so to reverse a migraine, you want vasoconstriction)
5HT-1B and 5HT-1D receptors are found in CNS and on blood vessels. Coupled to inhibitory Gi, the 5HT-1 receptors have an inhibitory effect on adenyl cyclase and reduce intra-cellular cAMP. cAMP mediates smooth muscle relaxation of large cerebral arteries –> inhibition of cAMP leads to vasoconstriction = no more migraine!
(in short: 5HT-1B/1D inhibit adenyl cyclase, which causes a decrease in cAMP which then causes vasoconstriction of cerebral blood vessels which gets rid of a migraine)
Which receptor is ionotropic and which is metabotropic?
Ion channels = ionotropic
G-coupled protein channels = metabotropic (indirectly linked to ion channels through signal transduction pathways)
Ionotropic Receptors: 5 units form a _____ which alters ______
Pore, Permeability
Metabotropic Receptors: combined to ______ which cause synthesis of ______
G-proteins, activators
What is the structure of Tyrosine Kinase Receptor (TKR)?
- Extracellular hormone binding site
- Cytoplasmic enzyme domaine that has multiple tyrosine AA
Explain how a TKR is activated and the cellular response
- Two inactive monomers that contain multiple tyrosine AA’s
- A ligand binds to the signal-binding site (extracellular) and the two monomers form a dimer (it is not activated)
- ATP donates a phosphate to each tyrosine
- The phosphorylated tyrosines activate kinases which causes a cellular response (DNA Transcription)
In what ways can a Tyrosine Kinase Receptor’s activity be inhibited?
- Something can bind in place of the ligand
- Something can alter the effects of the kinase
How do TKRs play a roll in cancer?
- EGF ligand enhances cell growth and division
- We stop cancer by blocking cell growth and division
- Drug is an antagonist to EGF - the drug binds on the receptor so EGF cannot
A ligand has to be _____-soluble to act on an intracellular receptor
Lipid
Where specifically are intracellular receptors found?
Cytoplasm
Is the effect of intracellular receptors immediate or delayed?
Delayed because time is required to copy DNA and make new proteins
How long can the effects of intracellular receptors last?
Hours to days (even after the drug is all gone because new proteins are active for days after synthesis and slow turnover of enzymes and proteins)
What are examples of biological lipid-soluble ligands?
-Steroids (corticosteroids, sex steroids, vitamin D) and thyroid hormone
What happens when a intracellular receptor is activated?
Transcription and translation
Overview of all four receptors
What do glucocorticoids do?
They suppress the inflammatory response (antagonist?)
Occurs via DNA transcription
- Decrease transcription of lipid soluble and protein based inflammatory mediators
- Are cytotoxic to lymphocytes (B and T)
- Inhibit function of tissue macrophage in antigen processing
