okay welcome to neuropsych pharmacology three we have three topics in this section
uh parkinson's disease agents alzheimer's disease agents and anti-epileptic agents the
first parkinson's disease disease agent we'll talk about is levodopa carbidopa and saline so
how these work is we have to kind of go back to the parkinson's disease pathology
in the substantia nigra we have an accelerator and brake pedal for the motor cortex of the brain
so dopamine is the accelerator gaba a neurotransmitter is a break so the normal
dopaminergic neuron it releases dopamine and then the gabaergic neuron releases GABA okay
and when that happens that way then we get smooth movement green light everything's working fine
with the pathology that comes along with Parkinson's disease we get low dopamine and
elevated acetylcholine and then if that's the case then we're going to see that the movement is not
smooth that the body is very jerky and we're going to see some very specific movements that go along
with Parkinson's so Parkinson's disease presents as postural impairment, it's difficult to maintain
straight posture tremors rigidity of the limbs in the body and then just like bradycardia is a slow
heartbeat brady is low bradycardia is less than 60 beats per minute bradykinesia
just like kinesiology is a kinesiology major majors in study of movement bradykinesia is
a very slow movement there's feet shuffling but it's very distinctive the Parkinson's presentation
the treatment or the goal is to restore dopamine levels in the brain but it's
not as simple as just saying okay we'll just put some dopamine in their brain
the problem is that dopamine does not cross the blood-brain barrier the bbb or triple b
as we grow or as we're born our blood-brain barrier protects us from
many different toxic substances but unfortunately with many neuro drugs
it actually prevents something that could really help us from getting there so the solution is
to give a dopamine precursor that does cross the blood-brain barrier and that precursor is called
levodopa it's also known as l-dopa all Parkinson's disease patients eventually require levodopa
it crosses the blood-brain barrier no problem and it's converted to dopamine in the brain we
have a second problem though in that it converts the dopamine in the peripheral tissues before it
even gets to the brain by an enzyme called dopa decarboxylase and this is kind of a deal breaker
until we add dopa decarboxylase inhibitor to stop the conversion
that's called carbidopa so carbidopa is the dopa inhibitor blocking the enzyme
in a little bit of a different way it's structurally really similar to levodopa
and because of that it kind of distracts the enzyme to target carbidopa instead of levodopa
so it's like over here and then levodopa makes it to the finish line makes it to the brain
so we have is this combination of levodopa-carbidopa (Sinemet) we adjust the dose based on the symptom
response and then over time patients will report on and off as the response diminishes
on is the medication working we've got good movement
off the medication is not working we've got tremors rigidity slowness returns
it should not be given to those with psychosis of any kind because what we're doing is we're
adding dopamine and this could be a really bad thing if someone has psychosis it takes months
to see full effects and then there could be a hypertensive crisis if given with non-selective
MAOIs so those are the three caveats to watch out for with carbidopa or levodopa carbidopa
another drug that we can use is selegiline and in the brand name you can see Eldepryl and they were
going for elderly that many elderly find this Parkinson's disease is something that they have
and monoamine oxidase B it's a monoamine B inhibitor and the a isomer of the enzyme breaks
down norepinephrine serotonin or 5th and dopamine the b isomer breaks down dopamine selectively
so it slows the breakdown of this dopamine in the brain
and it allows for lower doses of levodopa so two different ways of approaching parkinson's
disease in both cases we want to make sure we can get more dopamine in the brain
it should not be given alone and levodopa
carbidopa must also be given to be effective in Parkinson's disease
Alzheimer's disease agents so we're just going to talk about two of them donepezil and memantine
the thing about Alzheimer's disease is you can never really know
until after someone has passed if the person had Alzheimer's disease
you have to actually look at their brain and see you know okay well this is what we're seeing and
we'll see what the pathology looks like in the next slide but the exact cause we still don't
know there's some anomalies or things wrong within the hippocampus the current treatments
can slow disease progression but there's no cure yet and diagnosis to death can occur
in four to eight years or it could be a bit longer it depends on who you're reading
symptoms a lot of times we think just about the memory loss and Alzheimer's and that is certainly
one of the things that happen with it but there's also impaired thinking there's a cognitive decline
and then the inability to perform activities of daily living so it's extremely hard on the
patient certainly but it's also extremely hard on the partner or paragraph or caregiver as well
the pathology so we have this neuron and we're going to have these amyloid plaques which is
in hallmark anatomy of Alzheimer's decreased acetylcholine levels these deformed microtubules
and the neurons are just kind of a mess okay so what can we do with it well
two classes of medications we'll talk about are cholinesterase inhibitors and NMDA receptor
antagonists so the first thing we'll talk about is how a cholinesterase inhibitor works much like
Parkinson's where we can't just give dopamine we can't just give acetylcholine so instead of
giving acetylcholine with donepezil brand Aricept which is for mild to moderate symptoms it prevents
the breakdown of acetylcholine which is a common neurotransmitter and by preventing the breakdown
what we do is allow more acetylcholine to be around the thing is is that if you allow
more acetylcholine to be around you're going to see that we're going to have cholinergic
adverse drug reactions we're going to see maybe nausea vomiting diarrhea some dyspepsia as some of
the side effects and as you can see in the graphic it's only effective for 1 in 12 patients so
not the best prognosis for a medication another drug momentine or namenda is an
NMDA receptor antagonist and you can see the n the memantine the brain name Namenda
and it regulates calcium levels in the neurons by binding to these NMDA receptors so high calcium in
the neurons is implicit for alzheimer's disease we have decreased learning and memory ability neuron
degradation regulated calcium in the neurons increased or normalized learning memorability
increased neuron lifespan but those are the two alzheimer's disease medications
anti-epileptic agents we're going to first talk a little bit about epilepsy itself kind of
just a very big view of some of the conditions that someone can have
and then we'll talk about the two divisions of the anti-epileptic agents so epilepsy
is a chronic seizure condition we have hyperexcitability of the neurons in the brain
and 70 percent of the time it's primary it's idiopathic we have no idea what's going on
uh maybe genetic cns normalities but we need chronic treatment with medications
so these are for partial focal simple and complex generalized tonic clonic absence myoclonic febrile
or fever seizures and status epileptics secondary or symptomatic are caused by illnesses and so a
temporary anti-epileptic treatment is needed until the underlying cause is corrected so
these seizures can happen um and it's really figuring out is it the illness
that's causing it or is it something that we're just not sure about but
really the anti-epileptic treatment for each type is pretty much the same and a term that I want
you to know though is that the seizure focus that's where the beginning of the seizure is
so in terms of the anti-epileptic agents they decrease neuronal activity during the
seizure focus they slow or stop the spread of the seizure from the focus to other areas of the brain
but there's these two terms that we want to make sure we're clear about
a seizure is any type of epileptic event whereas a convulsion it's just an abnormal motor phenomena
so these are just a little bit different but let's look at some of the medications that we can use
so as far as the older medications carbamazepine is one of them and it inhibits sodium channels
on hyperactive neurons and it prevents sodium from entering the neuron and it stops the action
potential but we have serious adverse drug reactions including bone marrow suppression
grapefruit juice can increase levels Divalproex or Depakote
works in three ways it inhibits sodium channels on the hyperactive neurons just like carbamazepine
it inhibits calcium influx into the neurons and it promotes gaba activity and release but there's
some serious adverse drug reactions in hepatic and pancreatic taxes toxicities teratogenicity and
then it would interact with phenytoin the third of the traditional anti-epileptics we'll talk about
phenytoin or dilatin it inhibits sodium channels on the hyperactive neurons it
prevents sodium from entering the neuron stopping the action potential the same as
carbamazepine but it requires lots of monitoring small dose increases can cause toxicities
and small dose increases can cause therapy failure or decreases can cause therapy failure
so what we want to do is we want to make sure that we're monitoring appropriately but we want
to make sure that with phenytoin especially that we're keeping it at the right levels
and then two of the newers just to give you some examples so there are many many of the the newer
anti-epileptics gabapentin which is Neurontin and pregabalin which is Lyrica pregabalin happens to
be the metabolite of gabapentin and both work as adjunct therapy for epilepsies but common adverse
drug reactions drowsiness blurry vision peripheral edema but that's really how you want to divide
them the older drugs which we know quite a bit about have a lot more history and then the newer
drugs may have a little bit less than the adverse drug reactions but we're not necessarily as
confident sometimes with the newer ones in terms of what we know about what seizures they work for