Lecture 2 Flashcards
(21 cards)
What is an Antagonist?
-Binds the receptor and blocks the effect
What would happen if Morphine is administered with an antagonist?
The curve will shift to the right -> indicating that a higher dose is needed to achieve 100% efficacy
-the more of the antagonist is added the higher dose of morphine is needed to achieve 100% (more shifted to the right)
How can morphine overcome the effects of a competitive antagonist?
-By increasing the dose of morphine to swap out the antagonist (Naloxone) -> morphine and naloxone compete for the same receptor!
Why can drugs be swapped out of its receptor?
Because certain drugs bind to their receptor through weak bonds
Do Antagonist have any effect when given alone?
No
What is the function of alpha-adrenergic drugs?
increase blood pressure
-> Phenylephrine (OTC decongestant, also raises BP)
What would happen if an alpha adrenic drug is administered with a non-competitive antagonist?
Phenylephrine with Phenoxybenzamine
-there will be a shift to the right -> more dose is needed to reach 100% efficacy
-as we increase the dose of the antagonist there will be a shift to the right + decrease in efficacy
-non-competitive antagonists bind covalently to the receptor (until the receptor is degraded) -> it cant be outcompeted by an increase of the drug dose
What are spare receptors?
-indicates that not all receptors are needed to reach 100% efficacy
-some organ systems have more, and some have fewer space receptors
-f.e. in Parkinsons disease, no evidence is seen until 70% of receptors are destroyed
What are uncompetitive Antagonists?
-something away from the receptor has to happen before the receptor works
-f.e. Mg needs to bind to an ion channel before the channel opens, blocking the Mg binding site will prevent the drug from working -> ALLOSTERIC effect
What do partial agonists and non-competitive Antagonists have in common?
They reduce efficacy+ of a drug
When should drugs against withdrawal symptoms be administered?
-when they are experiencing withdrawal symptoms, rather than when they are high (it will reduce the highness)
An example where partial agonists are used?
Treat withdrawal symptoms (vomiting, nausea, pain)
-the efficacy is reduced compared to the addictive drug -> but still high enough to treat the symptoms
Example: Morphine + Diprenorphine (partial Agonist)
Phenylephrine + Phenoxybenzamine (non-competitive Antagonist)?
What happens if Diprenophine (partial agonist) + Naloxone are given sublingually and Naloxone is swallowed?
Naloxone is supposed to counteract Diprenorphine, but is less lipid soluble -> it won’t get absorbed so much sublingually and is getting swallowed and undergoes first-pass metabolism -> so it won’t work against morphine
What happens if Naloxone (Antagonist) + Diprenorphine (partial agonist - makes high) are taken intravenously (drug abuse)?
No effect because Naloxone will block the receptors as an Antagonist
Why does Suboxone have Naloxone in it?
What is a biased agonist?
It will activate either the ß-arrestin or the cyclic AMP pathway
Examples of receptors that work with cyclic AMP
-opioid receptor: deactivating effect
-ß-receptor: stimulating effect
Why is a higher dose of opioids needed for the same effect, after several times of use?
The cell gets desensitized -> ß-arrestin downregulates the sensitivity of the G-proteins and the receptor population
How is the structure of an Agonist and Antagonist different?
-Agonist: it has a binding domain and an agonist domain
-partial agonist: has a binding domain and a shorter agonist domain; can only partially bind to the binding pocket of the receptor
-a non-competitive agonist binds covalently
-Antagonist: only has the binding domain, so it binds without causing an effect
What is a neutral Antagonist?
What is an inverse Agonist?
Neutral Antagonist: just blocks no effect ???
inverse Agonist: Counteracts (agonists act as the drug, this one counteracts)
What is the constitutive activity?
-Always ON at a low background level
-constant background noise at point 0
-f.e. the opposite would be Inductive (enzyme activity for drug metabolism): turned ON, will be above the background
(at the constitutive level there would be a low enzyme metabolism activity level)
