In Episode 9 of Med School Question of the Week for USMLE, Leigh Finnegan answers the following: A 57-year-old man is brought to the neurologist by his wife. She says that over the past few months, the patient has been moving less. She says that he takes smaller steps and has developed a tremor. The patient has a past medical history significant for hypertension managed with lisinopril, and type II diabetes managed with metformin. On exam, he has masked facies, a shuffling gait, and a small-amplitude, high-frequency resting tremor. The neurologist recommends starting him on therapy with carbidopa-levodopa. What will be the effects of this drug on the man’s peripheral and central conversion of L-dopa into dopamine?
Hi my name is lee finnegan i am a fourth year medical student and i am a usmle tutor and content creator for med school coaches and here is this week’s question of the week a 57 year old man is brought to the neurologist by his wife he says that over the past few months she says that over the past few months the patient has been moving less she says that he
Takes smaller steps and has developed a tremor the patient has a past medical history significant for hypertension manage with lisinopril and type 2 diabetes managed with metformin on exam he has masked facies a shuffling gait and a small amplitude high frequency resting tremor the neurologist recommends starting him on therapy with carbidopa levodopa what will
The effects of this drug on the man what will be the effects of this drug on the man’s peripheral and central conversion of l-dopa into dopamine so this is a very difficult this is a very typical usmle step one question in that it gives you a lot of clinical information that isn’t actually necessary for answering the question itself because if you end it’s
An example of why it’s important to read the last line of the question before you before you start thinking about what the what the answer the question is going to be because if you start from the beginning and you’re reading through this man’s whole history you’re starting to think about what neurologic condition this man might have what you might know and
That’s an important thing to know that’s important general knowledge that you’ll need for answering another question but for this particular question we actually don’t need to know what condition this man has right because we’re told that he’s being started with this and we could answer this entire question if the only part of it was this last was these last
Two sentences right here because because all we need to know is that the man is on carbidopa levodopa sorry about that and that the and we need to know what the effect of the carbidopa carbidopa levodopa is on this man’s conversion in the peripheral and central conversion of l-dopa into dopamine so that said we can at least go through what this man has anyway
So what did it what condition does this man have based on his symptoms again it’s not it’s not actually relevant at all for answering the question but the hint we have here our man is moving less and has a tremor and smaller steps whoops and then on exam he has masked facies shuffling gait and a small amplitude high-frequency resting tremor all of those point
To one particular disease and that is parkinson’s so this man has parkinson’s disease this is an image that shows just some of the some of these symptoms of parkinson’s disease and the ones that that were mentioned here are the masked facial expression or the masked facies the shufflings short stepped gait with short there it’s very small very slow steps without
Really lifting the foot up very much off the ground and the tremor which is sort of the which is drawn here as trembling at the extremities but is typically described as a high frequency low amplitude pill rolling tremor that occurs at rest and extinguishes with um with movement no with activity so this man clearly has parkinson’s disease and another hint that
He has parkinson’s is that he’s being started on carbidopa levodopa therapy and we know that that is a treatment for parkinson’s disease because parkinson’s is a problem with decreased dopamine in the brain so now we need to talk about what carbidopa levodopa does and for that we have this map here which talks about the drugs that are used to treat parkinson’s
Disease so the drug that we’re giving here is written in here as carbidopa and levodopa levodopa is a synthetic l-dopa so we’re combining carbidopa and levodopa so let’s talk about what the mechanism of that is so we give the l-dopa which then can do two things so obviously we give it and it’s in the periphery we don’t deliver it directly to the central nervous
System right that would require intrathecal therapy which is not what we do here so this l-dopa can have two things that happen it can cross the blood-brain barrier and centrally it can be converted to dopamine dopamine is what we want right the problem is that there isn’t enough dopamine so if give l-dopa it crosses the blood-brain barrier and it gets turned
Into dopamine centrally but another thing happens today to that l-dopa as well which is that in the periphery or in the circulation ddc turns l-dopa into dopamine so we have dopamine being we have l-dopa being converted into dopamine both in the cns or centrally and in the circulation or peripherally now why would we maybe not want both of those things to happen
Which of those do we really want do we want the peripheral or the central conversion of dopamine we want the central right because the problem is decreased dopamine in the central nervous system so we want increase dopamine in the central nervous system why would we not want increased dopamine in the peripheral nervous system peripheral dopamine makes you sick
It causes nausea vomiting really just out of control side-effects so that can make it incredibly unpleasant to be taking this drug and can make people stop taking it so this is why we don’t just give l-dopa by itself because if we gave al joba by itself sure oops sure some of that dopamine would cross the blood-brain barrier and some of that el doble would cross
The blood-brain barrier and turn into central dopamine like we want it to but some of it would turn into peripheral dopamine which a is not going to help us treat our parkinson’s symptoms because that dopamine can’t cross the blood-brain barrier it just stays in the circulation and it makes you sick so that’s why we combine levodopa with carbidopa carbidopa
Inhibits dd c so it decreases this conversion peripheral conversion of l-dopa into dopamine which has two effects a it decreases the side effects but b it it leads to a higher concentration of l-dopa in the circulation which allows more l-dopa to cross the blood-brain barrier and more of it to be converted into dopamine so with all that in mind what’s the answer
To this question well let’s try it’s the the question has two parts we want to think about peripheral and central conversion of l-dopa into dopamine so just start with the carbidopa part with the carbidopa will we have increased peripheral conversion or decreased peripheral conversion of l-dopa into dopamine decreased peripheral conversion right because that’s
The whole point of giving the carbidopa is that the carbidopa prevents this step right here it prevents conversion peripheral conversion of l-dopa into dopamine so we know that we can get rid of a and b because those both say that there’s increased peripheral conversion and we know that it’s decreased so next we need to think about if there is we have increased
Or decreased central conversion of l-dopa into dopamine now remember that l-dopa what when we give levodopa were not affecting this enzyme here we’re not activating the enzyme that converts l-dopa into dopamine centrally we’re not really doing anything to that enzyme however we are increasing the amount of l-dopa that’s in the cns right because we’re giving
L-dopa and again like we said by blocking the peripheral to conversion of l-dopa into dopamine were even increasing we kind of have two mechanisms for increasing the peripheral l-dopa one because we’re giving it directly and two because we’re decreasing its conversion into dopamine so we’re increasing or even further increasing the amount of l-dopa that’s in
The perfect more l-dopa in the periphery means more l-dopa which gets into the cns which means there’s more l-dopa around to be converted into dopamine resulting in more dopamine so we are even though we’re not affecting the enzyme by affecting the concentration of the substrate we are increasing per central conversion of l-dopa to dopamine that increases our
Central concentration of dopamine which relieves our parkinson’s symptoms so that’s the answer is that given yet when you give carbidopa levodopa therapy you decrease peripheral conversion of l-dopa into dopamine and you increase central conversion of l-dopa into dope and that was this week’s question of the week which was for usmle step 1
Transcribed from video
Dopamine Metabolism for USMLE By MedSchoolCoach
