Cholinergic Drugs

[sharifhs]

DOES ANYONE HAVE ANY CONTRADICTORY IDEA WITH THE STATEMENT BELOW?

''prolonged muscle relaxation in some subjects after receiving a cholinergic drug was explained by an inherited deficiency of a plasma cholinesterase''

-Applied Biopharmaceutics & Pharmacokinetics by Leon Shargel, 5th Edition, page: 361

WHAT I UNDERSTAND ABOUT CHOLINERGIC DRUGS: If a patient receives a cholinergic drug he or she may experience some contractile effects of muscles. In addition, if a patient lacks cholinesterase enzyme he or she will not have cholinergic-drugs metabolizing ability. As a result, the patient may experience prolonged muscle contractile effects. For example, cholinergic pilocarpine has contractile activity on iris and GI smooth muscle.

[elrowley]

Acetylcholine is released at the neuromuscular junction (following an action potential down a nerve) and stimulates contraction of the muscles. Cholinergic drugs increase the amount of acetylcholine at the neuromuscular junction (whether by 1) blocking the breakdown of acetylcholine, thereby prolonging the action, or 2) increasing the amount of acetylcholine released at the neuromuscular junction). Hence, cholinergic drugs will increase the amount of contraction of a muscle (e.g. the iris).

Cholinesterase is the enzyme that breaksdown acetylcholine. It is present at every neuromuscular junction and normally acts just after the acetylcholine has caused a contraction, to stop any prolonged, unnecessary stimulation. Plasma cholinesterase (or pseudocholinesterase) is a similar enzyme, that breaksdown exogenous choline-like molecules, and has no physiological function (i.e. just metabolises drugs/exogenous molecules).

So, if a patient lacks the pseudocholinesterase enzyme [pseudocholinesterase deficiency], they can breakdown acetylcholine at the neuromuscular junction (as it uses cholinesterase), but not in the plasma [i.e. a cholinergic drug]. When a healthy patient is given a cholinergic drug, they can breakdown 90% of it in the plasma before it reaches the neuromuscular junction, and 10% will get through and flood the receptors leading to prolonged depolarization and a flaccid paralysis state in the patient's muscles for about 3 minutes. In a patient that lacks pseudocholinesterase, you can see that if 10% of the cholinergic drug leads to a few minutes' of muscle relaxation, 100% of the cholinergic dose will lead to paralysis for up to 8 hours.

It seems very illogical that a muscle-stimulating drug can lead to over-relaxed muscle paralysis! Hope this helps? Look up pseudocholinesterase deficiency for more.

elrowley

[sharifhs]

Thanks elrowley. I'm reviewing your reply.

[sharifhs]

So, if a patient lacks the pseudocholinesterase enzyme [pseudocholinesterase deficiency], they can breakdown acetylcholine at the neuromuscular junction (as it uses cholinesterase), but not in the plasma [i.e. a cholinergic drug]. When a healthy patient is given a cholinergic drug, they can breakdown 90% of it in the plasma before it reaches the neuromuscular junction, and 10% will get through and flood the receptors leading to prolonged depolarization and a flaccid paralysis state in the patient's muscles for about 3 minutes. In a patient that lacks pseudocholinesterase, you can see that if 10% of the cholinergic drug leads to a few minutes' of muscle relaxation, 100% of the cholinergic dose will lead to paralysis for up to 8 hours.

It seems very illogical that a muscle-stimulating drug can lead to over-relaxed muscle paralysis! Hope this helps? Look up pseudocholinesterase deficiency for more.

elrowley

Elrowley, I understand that over-flooding with acetylcholine in the receptor site causes prolonged contraction of muscle (spastic paralysis) rather than, as stated by the author, prolonged relaxation of muscle (flaccid paralysis). Which side are you on?