Yep when dopamine goes down acetylcholine goes up. Parkinsonism is a degenerative problem. The dopamingergic neurons degenerate = low dopamine
Schizophrenia is a problem of overshooting of dopaminergic neurons = excessive dopamine.

Here is what I know.

Ach has a big role in Alzheimer's disease and Dementia.
Ach circuits are in equilibrium with dopamine circuits in the corpus striatum. If one goes up the other goes down.

There are three important dopamine pathways

1. Nigrostriatal Pathway (movement disorders)
If these neurons degenerate, dopamine goes down and Ach goes up

2. Meso limbic cortico pathway (Psychosis)
Overshooting of neurons here causes Schizophrenia. Antipsychotics bring dopamine down.

3. Tuberoinfundibular System
if dopamine goes down prolactin goes up. Thats why certain antipsychotics can lead to hyperprolactinemia. Prolactin is a rough indicator of dopamine activity in the brain.

In NMS, excessive dopamine blockade makes Ach go up----> Autonomic instability
Also EPS are usually present in NMS. So yeah they are etiologically related but with different presentations.
Similarly excessive Levodopa can cause Schizophrenia-like psychosis too.

To keep a person normal, both dopamine and Ach should be in equilibrium.
Hope it helped.

 

Thanks for the reply. You confirmed a lot of my suspicious.

However, one thing I just recently learned that confused me even more was the side effect (Anticholinergic crisis) to the treatment (trihexyphenidyl) to the side effect (EPS) of the drug (Neuroleptics).

So we have so far elucidated that Anti-Psychotics give EPS and the treatment is Anti-Ach. But that treatment in itself has a side effect - AntiCholinergic crisis.

Which isn't logical or rational at all. NMS/EPS are characterized by sympathetic instability. Basically extreme fight or flight mode. You give a drug that blocks Ach and you get a side effect that also is sympathetic instability!

Anticholinergic crisis is known for "red as a beet, hot as a hare, dry as a bone, mad as a hatter, blind as a bat, and full as a flask". Basically - too much SANS.

So how can too much Acetylcholine (NMS) cause extreme SANS as well as too little (Anticholinergic crisis) ALSO cause extreme SANS?

 

Both EPS and NMS occur because of dopamine antagonist use. (In EPS, which is a chronic presentation we get Parkinson like symptoms too. which we can attribute to Dopamine blockade.
NMS is acute. includes all the cholinergic symptoms you mentioned.

To counteract that, Anti-Ach are given. Ach goes down (NMS resolves). Dopamine goes up (EPS resolves).
But dopamine going up more than its supposed to means inhibition of Ach. So here comes the side effect ----> anticholinergic crisis.

Its a sensetive equilibrium and the drugs that we give can mess this balance up. and so can the disease that we're giving the drug for. This is all I could make of it.

If you keep the equilibrium of Ach and dopamine in mind you will find it easier to get the picture. Even I dont get the entire picture because these pathways are complex. plus the adrenals also kick in.

 

Both EPS and NMS occur because of dopamine antagonist use. (In EPS, which is a chronic presentation we get Parkinson like symptoms too. which we can attribute to Dopamine blockade.
NMS is acute. includes all the cholinergic symptoms you mentioned.

To counteract that, Anti-Ach are given. Ach goes down (NMS resolves). Dopamine goes up (EPS resolves).
But dopamine going up more than its supposed to means inhibition of Ach. So here comes the side effect ----> anticholinergic crisis.

Its a sensetive equilibrium and the drugs that we give can mess this balance up. and so can the disease that we're giving the drug for. This is all I could make of it.

If you keep the equilibrium of Ach and dopamine in mind you will find it easier to get the picture. Even I dont get the entire picture because these pathways are complex. plus the adrenals also kick in.

Lets back up just a moment.

Acetylcholine - its known as a PANS agonist. Basically, Ach = rest and digest type stuff. At least, the drugs that affect it/block it affect the PANS.

So lets run 2 scenarios:

1) Parkinsons

Dz: Nigrostriatal: Too little Dopa (Extrapyramidal System: Too much Ach)

Tx: Nigrostriatal: Give Dopa (EPS: Block Ach to stop EPS symptoms - ie Benztropine)

Adverse Effect of Tx: EPS Tx causes Anticholinergic Crisis = too little PANS/too much SANS

So far so good. Everything is still rational and logical.

Scenario 2:

2) Schizophrenia

Dz: Too much Dopa

Tx: Neuroleptics - Block Dopa

Adverse Effect of Tx: Unopposed Ach causes EPS

Tx for Adverse Effect of Tx: Give Anti-Ach

Everything up till now is still logical and rational. Unopposed Ach causes EPS. Ach controls PANS.

The only problem then is NMS. Because it is ALSO due to unopposed Ach. BUT, and here is the big logical breakdown - NMS has symptoms of too much SANS! A problem that is caused by too much Ach has effects of too much SANS? Anticholinergic effect in Scenario 1 is too much SANS, while cholinergic effect of NMS is ALSO SANS?

Look in the Pathophysiology section for NMS on emedicine. It states that the mechanism of Neuroleptics is to block dopa. Which would conclude that there would also be unopposed Ach. But in that same page after it talks about neuroleptic's Dopa blocking mechanism - it states that one consequence of the drug is Anticholinergic effects.

EPS and NMS can't be related etiologically then. One is due to too much Ach (EPS) and one is due to too little (NMS). OR Ach works in 2 different ways. In scenario, too little Ach causes too much SANS and in scenario 2, too much Ach causes too much SANS.

Also, is Alzheimer's at all related by any of this?

 

Lets back up just a moment.

Acetylcholine - its known as a PANS agonist. Basically, Ach = rest and digest type stuff. At least, the drugs that affect it/block it affect the PANS.

So lets run 2 scenarios:

1) Parkinsons

Dz: Nigrostriatal: Too little Dopa (Extrapyramidal System: Too much Ach)

Tx: Nigrostriatal: Give Dopa (EPS: Block Ach to stop EPS symptoms - ie Benztropine)

Adverse Effect of Tx: EPS Tx causes Anticholinergic Crisis = too little PANS/too much SANS

So far so good. Everything is still rational and logical.

Scenario 2:

2) Schizophrenia

Dz: Too much Dopa

Tx: Neuroleptics - Block Dopa

Adverse Effect of Tx: Unopposed Ach causes EPS

Tx for Adverse Effect of Tx: Give Anti-Ach

Everything up till now is still logical and rational. Unopposed Ach causes EPS. Ach controls PANS.

The only problem then is NMS. Because it is ALSO due to unopposed Ach. BUT, and here is the big logical breakdown - NMS has symptoms of too much SANS! A problem that is caused by too much Ach has effects of too much SANS? Anticholinergic effect in Scenario 1 is too much SANS, while cholinergic effect of NMS is ALSO SANS?

http://emedicine.medscape.com/article/815881-overview#a0104

Look in the Pathophysiology section. It states that the mechanism of Neuroleptics is to block dopa. Which would conclude that there would also be unopposed Ach. But in that same page after it talks about neuroleptic's Dopa blocking mechanism - it states that one consequence of the drug is Anticholinergic effects.

EPS and NMS can't be related etiologically then. One is due to too much Ach (EPS) and one is due to too little (NMS).

 

Here is the emedicine pathophysiology of NMS you mentioned.

The most widely accepted mechanism by which antipsychotics cause neuroleptic malignant syndrome is that of dopamine D2 receptor antagonism. In this widely accepted model, central D2 receptor blockade in the hypothalamus, nigrostriatal pathways, and spinal cord leads to increased muscle rigidity and tremor via extrapyramidal pathways. Hypothalamic D2 receptor blockade results in an elevated temperature set point and impairment of heat-dissipating mechanisms. Peripherally, antipsychotics lead to increased calcium release from the sarcoplasmic reticulum, resulting in increased contractility, which can contribute to hyperthermia, rigidity, and muscle cell breakdown.

Beyond these direct effects, D2 receptor blockade might cause neuroleptic malignant syndrome by removing tonic inhibition from the sympathetic nervous system. The resulting sympathoadrenal hyperactivity and dysregulation leads to autonomic dysfunction. This model suggests that patients with baseline high levels of sympathoadrenal activity might be at increased risk. While this has not been proven in controlled studies, several such states have been proposed as risk factors for neuroleptic malignant syndrome.[3]

Direct muscle toxicity also has been proposed as a mechanism of neuroleptic malignant syndrome.

___________________________________________________

Acetylcholine is the preganglionic neurotransmitter for both divisions of the ANS, as well as the postganglionic neurotransmitter of parasympathetic neurons.

I believe that is why you got confused. You are forgetting here that Ach centrally acts as a neurotransmitter for both systems.

So increased Ach as a result of dopamine blockade can mess up/increase either of the two SANS or PSNS as you say.

EPS and NMS are related etiologically because the cause (antipsychotic) and the effect (dopamine blockade) are the same.

The pathways are different though.

Im appreciate you are going to such lengths to clear your concepts

 

Torticollis as a side effect of anti parkinson drug with Dopamine agonist

Thank you guys for your helpful conversation, this topic is really complicated. I've encountered a new challenge in a question on Kaplan Q bank:
Parkinson patient developing Torticollis due to a Dopamine agonist drug regimen! I was convinced that Dystonia is a side effect of anti Dopaminergics like neuroleptics but here it is the opposite!
In the answer it says treatment for Torticollis is Diphenhydramine or Carbidopa/Levodopa which the latter is the same as the drug that caused Torticollis in the first place in this patient!
I'm totally confused and need help.
This is my first time in Forums so forgive me if I posted this in a wrong spot!