November 29, 2022

Hello and welcome to the 79 news where the stories shine like gold that’s right folks buckle up because today you’re in for a ride welcome everyone i’m your host helia newton and i’m john dalton boy do we have some stories for you that’s right john today’s headliners are a doozy mice have infested the world’s largest cherry an eight-year-old kid broke the world

Record for solving three rubik’s cubes with both his hands and his feet and lastly a mother-daughter duo were arrested in pensacola florida after hacking into the school’s computer system and flooding the ballots for homecoming queen with votes for the daughter now healy can you believe that i really can’t john you know funny enough that’s how i won my homecoming

Oh is it now it is i looked so snazzy in my little joke okay well i moving on from that um before we get into those stories we will be starting off today with an interview with two students from moravian college who are here to answer some questions and tell us all about a drug called um metropolitan that’s right helia metroprolol is a very common drug and we here

At 79 news think that it’s important to stay informed and so we figured we would use our platform to try and tell you guys about a drug that either you might be taking or a loved one might be taking and so i think it’s nice to you know stay in the know that’s right john so um i believe we should have them here live or are they going to show up on the monitor oh

Okay we got it now can you guys hear us okay yeah we can hear you great john perfect why don’t you guys introduce yourselves and tell us a little about why you’re here hi i’m rachel my name is elliot and we are junior biochemistry majors at moravian college and we are currently taking a bio-organic and medicinal chemistry class yes and we are here because we have

Been doing a lot of research about a drug called metoprolol and we wanted to tell you a little bit about it and answer any questions you might that’s fantastic now rachel and elliot i am quite possibly the furthest thing from a doctor you got that right and i have no idea what metropole is other than that my father takes it and helia does when i raise her blood

Pressure so what exactly is it what is it used for and where did it come from great question so metoprolol is a drug used to treat high blood pressure prevent angina and improve survival after a heart attack it is a beta blocker which functions to slow heart rate and relax blood vessels in order to improve blood flow and lower blood pressure so it was first made

In 1969 it was patented in 1970 and it was approved for use in 1982. so the idea of beta blockers being used as drugs started with a man named sir james black who wanted to stop the expression of adrenaline in the heart which he hypothesized would decrease chest pain in patients with heart problems and this all started because his dad died of a heart attack and

So that’s where he started to get these ideas from and so that idea then led to him developing the drug propranolol which then won no won him a nobel prize and he did that at the company ici pharmaceuticals and then this created a whole new class of drugs called beta blockers oh wow that’s so interesting it’s so crazy to think that a drug that was developed not

That long ago is now so widely used in having such an impact i totally agree now i have another question i took a chem class or two back in my day but that by no means makes me an expert but would you be able to talk about how the drug is made no problem john so the synthesis of metoprol can be carried out by reacting 4-2 methoxyesylphenol with epichlorohydride

In the presence of a base the product of this reaction will be 1-2 epoxy 3 4-prime 2-methoxyethylphenoxypropane this is then reacted further with isopropyl amine and through an epoxide ring opening you generate metoprolol um and this is found as a racemic mixture in its drug form you know what’s funny rachel that is exactly what i was telling john earlier when he

Asked me the same question as we were getting ready for today yeah it’s true she just didn’t explain it as well as you guys did so i was a little fused so rachel and elliot how exactly does metoprolol work in the body and what are the toprolol is what is known as a beta blocker it is lipophilic cardioselective and it exhibits selectivity towards beta 1 adrenergic

Receptors which is a type of receptor that predominates in the cardiac muscle beta 1 adrenergic receptors are gpcr receptors that trigger the activation of pka in the heart so metoprolol works by inhibiting the pka signaling pathway the blocking of the beta-1 adrenergic receptor in heart muscle cells reduces sodium ion uptake and slows potassium ion release it also

Suppresses atrial fibrillation by suppressing the norepinephrine induced increase in calcium ion leak in the sarcoplasmic reticulum and the spontaneous calcium ion released from the sarcoplasmic reticulum the side effects include dizziness depression nausea dry mouth stomach pain vomiting gas or bloating so it says here that pharmacodynamics and pharmacokinetics

Are i don’t know something important is there any chance you could tell us about that absolutely so pharmacokinetics is the study of what our body does to the drug and pharmacodynamics is the study of what the drug does to our body so metoprolol is metabolized by cytochrome liver enzymes and undergoes o demethylation and alpha hydroxylation metoprolol causes a

Reduce a reduction in heart rate and cardiac output based on the prescribed dose so metoprolol can be administered in two forms metoprolol tartrate is an immediate release formulation and metoprolol succinate is an extended release formulation it is administered orally both of them are and the bioavailability of metoprolol tartrate is 50 which is normally taken

With food and then the bioavailability of metoprolol succinate is 40 percent metoprol is able to cross the blood-brain barrier and has a value of distribution of 4.2 kilogram liters per kilogram while some does bind to serum albumin in the blood only about 11 percent of administered drug is found to bind to this protein and metoprol is eliminated fairly effectively

Since less than 5 percent is recovered unchanged the dose of the drug ranges from 25 to 100 milligrams once a day for about two weeks or on an as needed basis determined by your doctor very cool now i have one more question so it says here that from 2008 to 2018 there were over 71 million prescriptions for metoprolol in the united states and with the average total

Drug cost around 28 dollars that means that the drug netted almost 2 billion dollars within those 10 years i think it’s safe to say that it’s a pretty successful drug it has even been deemed one of the most essential drugs by the world health organization but do you think the drug could be improved upon in any way and if so how so one problem with metoprol is

That has been chosen to raise blood sugar and so that presents a problem in diabetic patients and so a common substitute for metoprolol is the drug carbidolol so while metal parallel performs just as well as carbidolol it has been shown that carvitalol at times is preferred over metoprolol when a patient has diabetes or congestive heart failure so one possible

Modification to metoprolol could be to try and make it look a little bit more like carbidolol so we would suggest that if you change the two methyl groups on metoprolol to hydroxyl groups this would increase the hydrophilicity of the overall molecule which would possibly also increase the bioavailability in the bloodstream with the overall goal of trying to make

The drug a more efficient binder to the receptor wow that sounds like you guys really know what you’re talking about um thank you both so much for being here today it has been an absolute pleasure getting to talk well we wanted to thank you both so much for this opportunity and we hope that you were able to take something away from this thank you guys so much

Absolutely well that puts us at time for this interview so stay tuned for when we come back because i really want to know how in the world these people got caught rigging the homecoming queen ballot elliot guy was kind of cute you

Transcribed from video
Metoprolol Talk By Andrew Barr