Why do anticholinergics cause sedation?

[Ace844]

Ace844, I am not sure. I have not heard that Valium is specifically contraindicated. However, in very severe cases benzos may not work and the use of Physostigmine may be required. Here is a good article covering toxicity of antihistamines.

http://www.emedicine.com/EMERG/topic38.htm

Take care,

chbare.

Thanks, I just had the following rationale stuck in my brain for soemreason. This is that the mulit-receptor effects of the Diphyenhydramine, and the valium, and other anti-seizure meds would cause an excess of neurotransmitters in the CNS, as well as potentially inducing seritonergic syndrome...not sure, but I'll look it up and check the link, thanks again,

ACE844

[Ridryder 911]

I refer you back to http://www.emtcity.com/phpBB2/viewtopic.ph...68bc2b3345a6f52 Cookies post on Jimson's overdose aka : acetylcholine overdose, which Benadryl can cause and also increased nicotinic and muscarinic receptors to have a false sensitization as a acetylcholine. Sometimes mimicking nicotinic overload.

My partner a Paramedic student was with me and we had a female that ingested approximately 30 count of 25 mg Benadryl and the classic :"Red as a beet, dry as a bone, blind as a bat, mad as a hatter" syndrome. The complexity of this case was as well she had a history of thyroid cancer, with a recent history (<10 months) of thyroidectomy, radiation, chemo, etc.. Now, my concern as well as the O.D. was possible thyroid storm, with the notable hypertension and erythematous sclera...history of increasing agitation, depression, weight loss of >18 pounds in 1 week, tachycardia, inability to maintain eye contact and diffused concentration level. This female was from a very influential section and was a professional with no past mental history as well. Described as "just wanting to sleep"... (almost post manic phase) ...very intersting case of chicken or the egg, philosophy.

R/r 911

[fiznat]

Very good information about benadryl here. Some good study material, for sure.

Still, this isnt exactly what I'm asking. I used benadryl as an example simply because it is the drug that led me to the question, which is: why does antagonism of the parasympathetic system cause sedation, when logically it seems as if it should not?

I understand about the blood brain barrier, and how some "older" antihistimines can behave in an anticholonergic manner, but what I am not getting is how an anticholonergic causes sedation, when you would think that an anti-parasympathetic would also be anti-sedative. (Anti "feed and breed")

Maybe Im not asking the question right?

[chbare]

Fiznat, perhaps you are not looking at this in broad enough terms. Antagonism of the parasympathetic nervous system is only one the actions of Benadryl. You must take in to account all of the other physiologic interactions of this medication to fully appreciate some of the other side effects. Please do not fall into the trap of thinking sympathetic = awake and active and parasympathetic = relaxed and "chillin." The sympathetic nervous system reacts to changes in consciousness and to CNS stimuli. So, if I need more energy to wake up and fight that tiger, my brain activates the sympathetic nervous system to help provide more cardiac output, produce and use energy, and redistribute blood to vital organs. I hope this helps.

Take care,

chbare.

[AZCEP]

Perhaps this might help.

Sympathetic system is the gas pedal. Parasympathetic is the brakes. If you take your foot off the brake, but don't apply the gas, the best response you can get is to not slow down.

Now, when the body releases histamine the sympathetic system responds by releasing it's agents into action. When this happens, the CNS becomes more active along with everything else. If the histamine release is blunted, then the SNS does not need to go to work. Therefore, no increased activity. Because the PNS has been activated, the body can more easily respond to the need for action, the brakes have not been applied.

[Ace844]

Here's a link to a PPT lecture which should help as well:

http://www.sh.lsuhsc.edu/intragrad/211/Int...,50,Therapeutic Uses of Antimuscarinic Drugs

Also, here's a great article on anti-hystamine Tox:

http://www.aspca.org/site/DocServer/toxbri...ddInterest=1101

And Here's some info which i was refering to with the valium, and yes I know it uses dogs in the article{and that it is a primary vetrinary study} as an example.

(Antihistamine Toxicosis

by

Lisa Murphy @ VMD)

Symptomatic patients

As with any emergency situation, address life-threatening signs first. Diazepam (0.5 to 1 mg/kg

intravenously to effect) 1 is probably the most practical first-choice anticonvulsant to control seizures

associated with antihistamine overdose in animals. Give diazepam slowly intravenously or intramuscularly

to avoid the adverse paradoxical CNS excitement sometimes associated with its administration, particularly

in dogs.1 Barbitautes or isoflurane may also be needed to control signs in animals refractory to diazepam.

Vasopressors such as dopamine or norepinephrine may be needed for some patients with unresponsive

hypotention, 6 but avoid epinephrine because it may lower blood pressure further. Phenothiazines such as

acepromazine maleate should probably be avoided or used with caution for the same reason.

There is some evidence that guaifenesin may be useful in controlling seizures. A 59-lb (27-k) dog

exhibiting moderate to severe generalized muscle tremors, hyperthermia, and hyperesthesia that had

ingested about 67 mg/kg of diphenhydramine and was unresponsive to intravenous diazepam (0.7 mg/kg)

rapidly responded to an intravenous guaifenesin bolus (30 ml of 5% solution mixed into 5% dextrose in

water) followed by a constant-rate infusion of guaifenesin (5% solution mixed into 5% dextrose in water at

1 ml/kg/hr for three hours, then 0.5 ml/kg/hr for another six hours). The dog was discharged 24 hours after

admission and had no apparent residual effects two days after discharge. Methocarbamol (55 to 220 mg/kg

intravenously; not to exceed 330 mg/kg/day) 1 may help control seizures, though its potential effectiveness

in this situation is currently unknown.

Next here's some further discription of an anti-cholinergics activity and mechanisim in the CNS..This also describes the sedation process.

http://www.brooksidepress.org/Products/Ope...tingAgents.html