ADHD Stimulants: General Considerations and Mechanisms of Action

00:00 Hi, I'm Doctor Rhonda Lawes and this is a discussion on stimulants in the use of ADHD.

00:06 Now, stimulants are considered first line therapy for a few reasons.

00:10 So let's get into that first.

00:12 Now you can use these on clients who are at least six years of age.

00:15 And it's also used in adults.

00:17 Now it starts to kick in and has a rapid onset, and it has a long record of safety and efficacy. You're going to get a larger treatment effect with a stimulant than you will with non stimulants.

00:28 In fact, 70 to 80% of patients show a response in the core symptoms when they receive stimulants.

00:35 Now there's just two major types of stimulants methylphenidate and amphetamine.

00:41 Now these are the things you want to be thinking about before you consider prescribing a stimulant.

00:46 Three main categories you want to look at growth a cardiovascular screen and their vital signs. So as a provider, as you're thinking about prescribing you want to think through these three categories.

00:59 First of all growth.

01:01 You want to make sure that you have an assessment that's a baseline.

01:04 Height and weight.

01:05 It's especially important in children that has an appetite suppressant effect.

01:09 So you want to make sure you keep a close eye on that.

01:12 So they have safe growth and development.

01:14 Now when they come in and see you you're going to want to track that weight at every subsequent visit to make sure you're keeping a close eye on their growth and development.

01:23 The second category is a cardiovascular screen.

01:25 Now, as a provider, you're going to want to do a very detailed assessment here, a focused assessment. So you're going to need a personal history of the patient has had any heart disease.

01:35 They've had syncope chest pains or palpitations.

01:38 You also want to get a thorough family history, particularly if the if there's a family history of sudden cardiac death that required resuscitation.

01:46 Any family history of arrhythmias or the long QT syndrome.

01:50 Now also the third category vital signs you want to take their blood pressure and their pulse. Now, if you have any positive signs for cardiovascular risk, make sure that you get clearance from a primary care physician or a cardiologist.

02:04 And also consider getting an ECG.

02:07 In addition to the three categories of assessment growth, cardiovascular screening, and their vital signs.

02:13 There's other concerns that you'll have before prescribing.

02:16 Now, in the US, stimulants have the following boxed warning due to their high potential for abuse, misuse and addiction.

02:24 Now these can result in overdose or death and the risk increases with higher doses or unapproved methods of administration.

02:32 So it's going to be important that you carefully assess each patient's risk for abuse, misuse and addiction.

02:38 And this includes family members.

02:40 You're going to need to educate the patients and their families about the following the risks of the medication.

02:46 How to properly store the medication, how to properly dispose of any unused drug.

02:51 And as a provider, you're going to want to frequently monitor for signs and symptoms of abuse, misuse and addiction.

02:59 On this slide, I've listed the two major types of stimulants the categories of methylphenidate and amphetamine.

03:05 Now I've got the names there that they are marketed by.

03:08 Just to give you an idea of which medications are which type of stimulant.

03:12 Let's look at the mechanism of action of methylphenidate.

03:16 Now methylphenidate non-competitively blocks the reuptake of two things dopamine and noradrenaline. Now it blocks the reuptake of these two neurotransmitters into the terminal because it blocks the dopamine transporter and the noradrenaline transporter.

03:32 And this leads to increasing levels of both dopamine and noradrenaline in the synaptic cleft. Remember, more of these substances in the synaptic cleft makes more of them available to the brain to use.

03:45 Now that I've told you what to expect, let's walk through it on the images.

03:49 Now you can see in the drawing you see where the dopamine transporters and the norepinephrine transporters are.

03:55 The methylphenidate binds at that site because it's again a and noncompetitive inhibitor. Now, when it binds at the sites of the dopamine and norepinephrine, that's where it blocks the reuptake of the dopamine and norepinephrine into the synaptic terminals. So look at the graphic.

04:13 You see what you have there.

04:14 It's bounded those sites.

04:15 And it's going to block the reuptake of dopamine and norepinephrine.

04:20 And make sure you can see that in the graphic.

04:23 Now when this happens it's bound at the sites.

04:26 They're not re-uptake those neurotransmitters.

04:28 This is what leads to the extra synaptic availability of dopamine and norepinephrine.

04:34 So look at the synaptic cleft.

04:36 You see there's a lot more little neurotransmitters in there.

04:38 Again that's how the mechanism of action of methylphenidate works.

04:44 The mechanism of action for amphetamine is different than methylphenidate.

04:47 And we're going to use this graphic to help illustrate it.

04:50 Now you'll see on screen you have a presynaptic dopamine neuron.

04:54 Or it could also be a norepinephrine.

04:56 And you've got a postsynaptic neuron.

04:59 So those are those are just all a matter of context.

05:00 Remember, of where you are in the process.

05:03 So you have two neurons the postsynaptic and the presynaptic.

05:07 Now taking a look at the labels, you see those little tiny circles are going to be the amphetamine. And we're going to talk about how the amphetamine gets back inside and ends up releasing extra dopamine.

05:19 So here's how it happens.

05:21 You've got the presynaptic and the postsynaptic neuron.

05:25 Now amphetamine is a competitive inhibitor.

05:28 Now it's going to work at the Dat and the net.

05:30 Remember that's the dopamine transporter and the norepinephrine transporter.

05:35 So that's how the amphetamine is going to gain entry.

05:39 So little circles are the amphetamines.

05:41 Those little tiny squarish things are looking more like a little rectangle.

05:46 Those are the transporters the dopamine transporters and the norepinephrine transporters. Now as the amphetamine is taken into the dopamine terminal through that transporter, you see that it's now entering the neuron.

06:00 Now the amphetamine, once it's in there, is going to compete with the monoamines.

06:05 It's going to compete with the monoamines to be uptaken into the vesicle via the vesicular monoamine transporters.

06:12 So again it's other transporters.

06:14 Right. Remember the amphetamine got in there through the dopamine and norepinephrine transporters. And now it's going to compete with the monoamines to go into the vesicle via the vesicular monoamine transporters the vmats.

06:29 Now we're still not done to know how this ends up with extra dopamine available for the client. Now because of this because they've gone through those vmats now we have increased level of monoamines in the cytoplasm.

06:44 Okay. That's how we got there.

06:46 So pause for just a second and let's quickly review.

06:49 Because sometimes it's easy to get lost in this.

06:52 We're talking about how amphetamines work.

06:55 We know it's a competitive inhibitor.

06:57 It enters through the dots and the knots.

07:00 Right. The transporters for dopamine and norepinephrine.

07:03 Once it gets inside, because it's taken into the dopamine terminal through the dopamine transporters, then it competes with the monoamines to be taken up into the vesicles from the Vmats.

07:15 When that happens, that's how we end up with increased level of monoamines in the cytoplasm. Now eventually you're going to hit a critical threshold of dopamine.

07:26 Now look what happens in the next picture.

07:29 Boom. You're going to have massive dumping of dopamine into the synapse.

07:34 This is how amphetamines work in the treatment of ADHD.

07:38 You have extra dopamine available in that synaptic cleft that patient's brain for it to use. Now also you've got a reversal of the Dats right of the dopamine transporters.

07:49 Instead of them bringing it in they're pushing it out.

07:52 That's the way you end up with the extra dopamine.

07:56 Stimulants stimulate the sympathetic nervous system? So when you're thinking about the physiological effects of stimulants, you're going to think about the sympathetic nervous system.

08:05 That's why patients have appetite suppression.

08:08 Remember, the parasympathetic is the one where you sit back and get comfortable and eat that big Thanksgiving meal.

08:14 But when the sympathetic nervous system is stimulated, you end up with appetite suppression. This can be particularly difficult with children with growth and development. Now, because you're stimulated, you have that increased wakefulness and alertness. People feel like they have a lot of energy.

08:30 They could also have elevated mood and they have more energy and almost a euphoria.

08:36 One of the things that puts the patient at risk for abusing the medication is that feeling of euphoria.

08:42 Now it does improve cognitive function, which is fantastic when you're helping treat a patient with ADHD, and it activates the reward system, which will help with motivation, but it can also have a potential for dependance and addiction.