Neostigmine - Mechanism of action, indications and side effects

This lecture is about what is the neostigmine and what are its medical uses, mechanism of action and side effects.

Neostigmine is a cholinesterase inhibitor used in the symptomatic treatment of myasthenia gravis by improving muscle tone.

Neostigmine is in the cholinergic family of medications. It works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine.

Neostigmine: Cholinesterase inhibitor = ↑ ACh

Neostigmine is an anticholinesterase inhibitor and inhibits the hydrolysis of acetylcholine by competing with acetylcholine for binding to acetylcholinesterase at the site of cholinergic transmission. By reducing the hydrolysis of acetylcholine, the transmission of nerve impulses is facilitated.

At the end of surgery, neostigmine has been given for the reversal of neuromuscular blocking agents with several adverse effects such as bradycardia and profuse secretion.

Atropine has been used to prevent those side effects of neostigmine.

Side effects titles as review:
.
Nausea, headache, insomnia, dry mouth, dizziness, vomiting, allergic reactions, skin rash, hot flashes, joint pain, stroke, weakness, muscle cramps, frequent urination

Neostigmine is rapidly absorbed after intramuscular injection (IM). Neostigmine binding to human serum albumin is approximately 15 to 25%.

Neostigmine is metabolized in the liver by microsomal enzymes. The apparent excretory half-life of neostigmine is between 24 and 113 minutes.

Presented by: Mohammadsaleh Moallem

1. Mohammad salehMoallem
SHANDONG UNIVERSITY

2. What is the neostigmine? Please talk about
its medical uses, mechanism of action and
side effects.
Question

3. Neostigmine
Neostigmineis a medication used to treat
myasthenia gravis, Ogilvie syndrome, and
urinary retention without the presence of a
blockage.
It is also used in Anaesthesiato end the effects
of non-depolarizing neuromuscular blocking
medication. It is given by injectioneither into a
vein, muscle, or under the skin. After injection
effects are generally greatest within 30
minutesand last up to 4 hours.

4. Indications of Neostigmine
Myasthenia gravis (MG) is a chronic
autoimmune disorder in which antibodies
destroy the communication between nerves
and muscle, resulting in weaknessof the
skeletal muscles.
Myasthenia gravis affects the voluntary
muscles of the body, especially those that
control the eyes, mouth, throatand limbs.

5. Indications of Neostigmine
Ogilvie syndrome is the acute dilatation
of the colon in the absence of any
mechanical obstruction in severely ill
patients. Ogilvie syndrome may occur
after surgery, especially following
coronary artery bypass surgery and
total joint replacement.
Drugsthat disturb colonic motility (such as anticholinergics or opioid analgesics)
contribute to the development of this condition.

6. Neostigmine Neostigmine is a cholinesteraseinhibitorused
in the symptomatic treatment of myasthenia
gravisby improving muscle tone.
Cholinesteraseis a family of enzymes that
catalyzes the hydrolysis of the neurotransmitter
acetylcholine (ACh) into choline and acetic
acid, a reaction necessary to allow a
cholinergic neuron to return to its resting state
after activation. So cholinesterase decrease
the amount of Ach

7. Description
Acetylcholine is the chief neurotransmitter of the
parasympatheticnervous system, the part of the
autonomic nervous system (a branch of PNS) that
contracts smooth muscles, dilates blood vessels,
increases bodily secretions, and slows heart rate.
In most people with myasthenia gravis, the immune
system blocks or damages these acetylcholine receptors.
The acetylcholine cannotthen attach to the receptor and
so the muscle is less able to contract.

8. Description
Cholinergicdrugs stimulate the activationof
the parasympathetic nervous system by
activating receptors for acetylcholine.
Anticholinergicdrugs inhibitthe
parasympathetic nervous system by blocking
the action of acetylcholine so that it cannot
bind to receptors that initiate the
parasympathetic response.

9. Neostigmine
Neostigmine is a cholinesteraseinhibitorused
in the symptomatic treatment of myasthenia
gravisby improving muscle tone.
Neostigmine is in the cholinergicfamily of
medications. It works by blocking the action of
acetylcholinesterase and therefore increases
the levels of acetylcholine.
Neostigmine: Cholinesterase inhibitor =↑ACh

10. Neostigmine
Neostigmine: Cholinesterase inhibitor =↑Ach
Neostigmine works by slowingthe breakdown
of acetylcholine when it is released from nerve
endings. This means that there is more
acetylcholine availableto attach to the muscle
receptors and this improves the strength of
your muscles.
Neostigmine, unlike physostigmine, does not
cross the blood-brain barrier.

11. Neostigmine
Neostigmine is a parasympathomimetic, specifically,
a reversible cholinesterase inhibitor. The drug inhibits
acetylcholinesterase which is responsible for the
degradation of acetylcholine.
So, with acetylcholinesterase inhibited, more
acetylcholine is present By interfering with the
breakdown of acetylcholine, neostigmine indirectly
stimulates both nicotinic and muscarinic receptors
which are involved in muscle contraction. It does not
cross the blood-brain barrier.

12. Howit acts as anticholinesterase?
Neostigmine is an anticholinesteraseinhibitorand
inhibits the hydrolysis of acetylcholine by competing
with acetylcholine for binding to acetylcholinesterase
at the site of cholinergic transmission. By reducing the
hydrolysis of acetylcholine, the transmission of nerve
impulses is facilitated.

13. Why neostigmine is given with atropinein myasthenia gravis?
At the end of surgery, neostigminehas been given
for the reversal of neuromuscular blocking agents
with several adverse effects such as bradycardia
and profuse secretion.
Atropinehas been used to preventthose side
effects of neostigmine.

14. Usage after surgery
The use of neostigmine significantly reduces the risk
that a patient will be left with muscle weakness in the
recovery room. Many anesthesiologists routinelyuse
neostigmine because postoperative muscle weakness
may lead to adverse events after surgery. Neostigmine
also relieves gastric contraction after surgery by
increasing the stimulation and tone of gastric muscles.
Atropinehas been used to preventthose side effects of
neostigmine.

15. Neostigmine Neostigmine can induce generic ocular side effects
including: headache, brow pain, blurred vision,
phacodonesis, pericornealinjection, congestive iritis,
various allergic reactions, and rarely, retinal
detachment.
Neostigmine has a wide variety of side-effects such
as reduced heart rate (bradycardia), due to the
increase of acetylcholine at nerve terminals. For this
reason it is usually given along with an anti-
cholinergic drug such as atropineor glycopyrrolate.

16. Neostigmine
Gastrointestinalsymptoms occur earliest after
ingestion and include anorexia, nausea, vomiting,
abdominal cramps, and diarrhea.
Side effects titles as review:
.
Nausea, headache, insomnia, dry mouth,
dizziness, vomiting, allergic reactions, skin rash,
hot flashes, joint pain, stroke, weakness, muscle
cramps, frequent urination

17. Pharmacokinetics of drug
Neostigmine is rapidly absorbed after intramuscular
injection (IM). Neostigmine binding to human serum
albumin is approximately 15 to 25%.
Neostigmine is metabolized in the liverby
microsomal enzymes. The apparent excretory half-
life of neostigmine is between 24 and 113 minutes.

18. Mohammad salehMoallem
SHANDONG UNIVERSITY
默汉201816230152