6⃣ MPA EM ANIMAIS (Anticolinérgicos e Agonistas alfa-2) | Anestesia é o Básico #6

Premedication - Anticholinergics and alpha-2 adrenergic agonists What's up NAVE crew! In this Anaesthesia Unravelled lesson we're going to keep talking about premedication, but now about alpha-2 adrenergic agonists. Those who didn't watch the first video, on which we talked about the purposes of premedication, benzodiazepines and phenothiazines, I suggest you go watch it later, alright?

Well, but before we talk about alpha-2 adrenergic agonists, we need to talk about another group that used to be very popular in premedication, but today it is rarely used, the anticholinergics. You will understand why in a moment. Anticholinergics The anticholinergics' group consists basically of three drugs, atropine, hyoscine and glycopyrrolate, which is unavailable here at the moment.

Now, why was this group so popular 30, 40 years ago? It's basically because xylazine, thiopental and ether were the a bases of anaesthesia at the time, and all these drugs promote increased salivation and bradycardia. For that reason, it was very common for people to use atropine as premedication.

As we can see in the mechanism of action of anticholinergics, they are acetylcholine competitive blockers of muscarinic receptors, thus, they inhibit the parasympathetic system, causing the sympathetic system to stand out. In that case we’ll observe all the adrenergic effects, as tachycardia, decreased salivation, mydriasis, bronchodilation and decreased intestinal motility. As I told you before, the main effects that people were after with the use of atropine were tachycardia, in order to compensate for the bradycardia, and also the decrease in salivation.

It's worth remembering that anticholinergics don't reduce salivation directly, in fact, they only decrease its water fraction, so that the saliva gets a little more viscous. Nowadays, we have no real need for using anticholinergics, we will understand this later on, especially because, today, we have much better drugs available, so that we are going to use anticholinergic drugs in premedication very rarely, perhaps in patients with a tendency to bradycardia, as with hypothyroidism, or undergoing a cervical surgery with possibility of stimulation of the vagus nerve, but I really do not recommend using atropine as premedication. This group will be important during emergencies, when we intend, for instance, to revert bradycardia in an animal during the surgical procedure.

Then it's fine. We must not forget that anticholinergics should be used with a lot of caution in large animals, because they decrease gastrointestinal motility so, for example, atropine must be used in ruminants and horses only as a last resort. If you have to do it, It's better to opt for scopolamine, that has an interesting effect on the heart rate and the impact over the digestive system is not as hard as atropine.

If it's necessary to use atropine in small animals, the dose is: and can be done intravenously or intramuscularly. The onset of action is of 1 minute and the effect can last for up to 30 minutes. In the case of large animals, we choose scopolamine.

The dose is: also intravenously or intramuscularly. The onset of action is the same, but the effect can last for up to 90 minutes. Something curious is that, sometimes, we get slight, moderate bradycardia, and then we decide to use half the dose of atropine, just to slightly improve the heart rate, but the opposite happens.

We get bradycardia and worsen the situation. How's that? Well, that's believed to happen due to an inhibition of the uptake of acetylcholine, so that acetylcholine accumulates in the synaptic cleft, resulting in bradycardia.

If this happens, you can just administer the second half of the dose, then you will end up having given the entire dose, right? And we will have the desired tachycardia. It's worth remembering that anticholinergics have virtually no effect on blood pressure.

This group has an antagonist, neostigmine, that blocks acetylcholinesterase, which is an enzyme that breaks down acetylcholine, resulting in more acetylcholine in the cleft, pushing atropine out of the receptor and acting. The dose of neostigmine is: and can also be done intravenously or intramuscularly. Alpha-2 adrenergic agonists The alpha-2 adrenergic agonists deserve a highlight, because it's is an extremely versatile group, we will see that they are used for various things.

Regarding premedication, they're important because they promote intense sedation and also analgesia. The main alpha-2 used in the veterinary are xylazine, romifidine, detomidine and dexmedetomidine. We also have clonidine and medetomidine, but they are used less frequently.

As their name says, they are alpha-2 receptor agonists, so they will act on the alpha-2 receptor and trigger its effects. This is why they're excellent, but also slightly problematic. The mechanism of action for the alpha-2 adrenergic agonists is, perhaps, easy to comprehend.

In order to understand it a little better, we need to remember that there are two types of alpha receptors: alpha-1 and alpha-2. Generally, alpha-1 receptors are postsynaptic and alpha-2 receptors are presynaptic. There are some postsynaptic alfa-2 receptors, but they are very few and usually in the veins.

So, as we can see in this picture, both norepinephrine and alpha-2 adrenergic agonists will act on the presynaptic alpha-2 receptor. When this receptor is stimulated, it triggers a negative feedback, causing a decreased release of norepinephrine in the cleft. This mechanism triggers a myriad of different effects, depending on the location, so let's start talking about the benefic effects.

The alpha-2 activation in the brain, more precisely at the locus ceruleus, promotes intense sedation. Analgesia is obtained through the activation of the alpha-2 in the spinal cord and also due to the intense myorelaxation. There comes the part that may be a little less interesting.

Alpha-2 agonists are basically differentiated by their selectivity towards the alpha-2 receptor, the less selective is xylazine, that acts on 160 alpha-2 receptors for each alpha-1. Then, there's detomidine, that acts on 260 for 1, romifidine, 340 for 1 and, finally, medetomidine and dexmedetomidine, that work on 1620 alpha-2 receptors for each alpha-1. As we can see again in the picture, there are alpha-1 receptors that are in the postsynapse, and they are the ones that will cause the main problem.

The activation of the alpha-1 receptor will trigger hypertension, with increased peripheral vascular resistance. This increased vascular resistance will cause stimulation of the vagus nerve, decreasing the heart rate in an attempt to compensate the cardiovascular physiology. With that, we already have a problem, because we have a patient with hypertension and bradycardia, but it will get worse, because the hypertension is only temporary, then it decreases.

The problem is that the heart rate does not increase to compensate this effect. So, depending on the medication, at some point we will have bradycardia and hypotension. You can imagine what happens to the cardiac output.

This effect is more intense with the less selective medications, like xylazine. But Adriano, I've seen a bunch of people giving atropine before the alpha-2 agonist to prevent this effect. You are right, if we use an anticholinergic beforehand, we can reduce this effect somewhat.

It's a trap, Bino. Only it's not true, my friend. So, why do people have the habit of using an anticholinergic before the alpha-2 adrenergic agonist?

Because they will, theoretically, cancel that reflex bradycardia effect secondary to hypertension, so, the impact, theoretically, will be reduced. However, recent studies have shown that it is much worse to use anticholinergic agents before the alpha-2 adrenergic agonist. As we can see in this research, it was observed that when we do an anticholinergic before the alpha-2 adrenergic agonist, the peripheral vascular resistance increases even more.

So, in this case, we will have an animal with extremely high hypertension and tachycardia. We mustn't forget that the heart gets its oxygen during the diastole, what means that the faster it beats, the lower the oxygenation of the myocardium will be, so when we use an anticholinergic before an alpha-2 adrenergic agonist, we're causing a huge impact on the cardiovascular system. Okay, so I don't need to tell you that the use of alpha-2 adrenergic agonists in the cardiac patient will most likely be fatal.

What about in hypotension? Well, we don’t have time to discuss all the possibilities and effects of alpha-2 adrenergic agonists in each patient specifically, but they can be interesting in some patients and, generally those with hypotension, but we need to understand that when there's an increase in the peripheral vascular resistance, we are not favouring the blood flow. The blood vessel is narrowed to the point of increasing blood pressure, but this arterial pressure is deceiving because it is not favouring the flow to peripheral tissues, so, the alpha-2 adrenergic agonists should not be the first option of medication to increase blood pressure.

Beyond these effects, we still have another two interesting ones: first, the inhibition of the production of the antidiuretic hormone, causing the animal to urinate more. The other is the hyperglycemic response, because we have alpha-2 receptors in the beta cells of the pancreas. With that, there's inhibition of the insulin release.

Considering all this information, we need to ponder when to use or not the alpha-2 adrenergic agonists. For premedication, the dose of xylazine is: intramuscularly or intravenously, in horses and small animals. In ruminants, this dose can be ten times lower.

The use of romifidine is only permitted in horses and the dose is: intravenously. The same goes for detomidine, and the dose is: intramuscularly or intravenously. The dose of dexmedetomidine in small animals is: intramuscularly or intravenously.

In horses: intravenously. Something I forgot to tell you is that detomidine-induced analgesia is better than that of xylazine and, consequently, that of dex is better than detomidine. As I already told you, alpha-2 adrenergic agonists are extremely versatile, so we don't use it only as premedication, today is common to use alpha-2 agonists both in trans and postoperative periods.

Briefly addressing the continuous infusion of alpha-2 adrenergic agonists, we can see that, in horses, it's used: in small animals, is more common today the infusion of dexmedetomidine. Something cool about this drug group is that they have drugs that revert their effects, which gives us more safety. We have basically the yohimbine and atipamezole.

The atipamezole is better because it's more specific for alpha-2 receptors. The dose of yohimbine is: intramuscularly or intravenously, and of atipamezole is: As a conclusion of this video lesson, we have that anticholinergics cause, mainly, tachycardia, and they should not be used as premedication. The alpha-2 agonists adrenergic are one of the main groups used in premedication especially because they promote sedation and analgesia, but we need to remember that they cause an important impact on the cardiovascular system, and this should be considered.

Well guys, as usual, I'll leave some study material below, a few links in the description for those who want to know more about the topic, and before leaving, please don't forget to like it, to share and also to subscribe to our channel, OK? See you soon! So now we're going to joke a bit.

. . I already said that.

. . [unintelligible] but today is f* hard OK, now it will work.

I'll. . .

start over. From the beginning.