Chapter 15 Cholinesterase Inibitors And Their Use In Myasthenia Gravis

Front 1

What are Cholinesterase Inhibitors?

Back 1

- Drugs that prevent the degradation of acetylcholine (ACh) by acetylcholinesterase
-Viewed as indirect-acting cholinergic agonists
- lack selectivity
-Limited therapeutic applications

Front 2

What Cholinesterase inhibitors are Reversible?

Back 2

-Neostigmine
-Physostigmine
-Ambenonium, edrophonium, and pyridostigmine
-Echothiphate
-Drugs for Alzheimer's disease

Front 3

Neostigmine (reversible cholinesterase inhibitor):

Back 3

- Cannot readily cross cell membranes due to a Quaternary nitrogen atom giving it a positive charge
- Is absorbed poorly with ORAL administration
- Has minimal effects on brain and fetus
- poor substrate for Cholinesterase

Front 4

How does Neostigmine work?

Back 4

Cholinesterase splits neostigmine more slowly than it splits Acetylcholine- once neostigmine becomes bound to the active center of cholinesterase the drug remains in place for a long time, thereby preventing cholinesterase from catalyzing the breakdown of acetylcholine

Front 5

What does the blocking of Acetylcholine do?

Back 5

neostigmine and the other cholinesterase inhibitors can intensify transmission
-they can produce skeletal stimulation, ganglionic stimulation, activation of peripheral muscarinic receptors, and activation of cholinergic receptors in the CNS

Front 6

What does Neostigmine do to
-Muscarinic Responses
-Neuromuscular Effects
- CNS

Back 6

- same as muscarinic agonists- bradycardia, bronchial constriction, urinary urgency, increased glandular secretions, increased tone and motility of GI, smooth muscle, miosis, and focusing of the lens for near vision

- increase force of contraction (too much will reduce force of contraction)

- mild stimulation (too much can depress the CNS, including respiration) - first must go through blood brain barrier

Front 7

Therapeutic uses of Neostigmine

Back 7

-Myasthenia Gravis
-Reversal of nondepolarizing neuromuscluar blockade
-used post op
-treatment of an overdose
-likely to elicit substantial muscarinic responses
- may need to administer atropine (muscarinic antagonist

Front 8

Neostigmine
-adverse effects/ acute toxcitiy
- Treatment

Back 8

Adverse effects
- Excessive muscarinic stimulation (excessive salivation, gatric secretions, increased tone and motility of GI tract, urinary urgency, bradycardia, sweating, miosis, and spasm of accomodation)
-Neurmuscular blockade- paralysis of respiratory muscles


Treat both with antangonist

Front 9

Neostigmine
-Precautions and Contraindications

Back 9

- obstruction of GI or urinary tract
-peptic ulcer disease
-asthma
-coronary insufficiency
-hyperthyroidism

Front 10

Irreversible Cholinesterase Inhibitors are:

Back 10

-Highly toxic
-Only clinical application is glaucoma
- All contain an atom of phosphorus
- Almost all are highly lipid soluble
- Readily absorbed from several routes
- Potential use in chemical warfare

Front 11

What do irreversible cholinesterase inhibitors do?

Back 11

Bind to the active center of cholinesterase preventing the enzyme from hydrolyzing ACh. They still can be split from Che but it take a very long time
-effects persist until new molecules of cholinesterase can be synthesized

Front 12

Cholinergic crisis symptoms

Back 12

-excessive muscarinic stimulation
-depolarizing neuromuscular blockade
-- results in profuse secretions from salivary and bronchial glands, involuntary urination and defecation, laryngospasm, and bronchoconstriction, convulsions of CNS which are followed by oaralysis and death by apnea

Front 13

How do you treat it?

Back 13

-Mechanical ventilation
-Pralidoxime- antidote for poisoning by IRREVERSIBLE cholinesterase inhibitors - effective if administered early
- diazepam- suppress convulsions

Front 14

What is Myasthenia Gravis?

Back 14

-Characterized by fluctuating muscle weakness and predisposition to rapid fatigue
-Autoimmune process in which antibodies attack nicotinicM receptors on skeletal muscles

Front 15

Common S/S of Myasthenia Gravis

Back 15

Ptosis
Dysphagia
Weakness of skeletal muscles

Front 16

Beneficial effects of Cholinesterase Inhibitors on Myasthenia Gravis

Back 16

increase muscle strenght
produce symptomatic relief
therapy is life long

Front 17

Side effects of Cholinesterase inhibitors with Myasthenia Gravis

Back 17

ACh accumulation- excessive muscarinic response

Front 18

Dosage adjustments for myasthenia Gravis : Cholinesterase Inhibitors

Back 18

-Start smalland adjust to patient response
-May need to modify dosage in anticipation of exertion
-SIgns of undermedication
---ptosis, difficulty swallowing
-Signs of overmedication
---excessive salivation and other muscarinic responses

Front 19

Distinguishing Myasthenic crisis from cholinergic crisis

Back 19

-history of medication use or signs of excessive muscarinic stimulation assist with differential diagnosis

--WEAR A MEDICAL ALERT BRACELET

Front 20

Promoting Compliance:

Back 20

Infrom patients that Myasthenia Gravis is not usually curable and hence treatment is life long. Encourage patients to take their meds as prescribed and to play an active role in dosage adjustment (s/s of too much or not enough)